Diversity in Medicine

TOPLINE:

Researchers identified thousands of census tracts as priority zones where improving the screening of colorectal cancer (CRC) may benefit Hispanic or Latino communities.

METHODOLOGY:

• Hispanic or Latino individuals have the lowest rate of CRC screening among the six broader census-designated racial or ethnic groups in the United States, while they face a high proportion of cancer deaths due to CRC.
• Researchers performed a cross-sectional ecologic study using 2021 Centers for Disease Control and Prevention PLACES and 2019 American Community Survey data to identify priority zones for CRC screening where intervention programs may be targeted.
• They analyzed a total of 72,136 US census tracts, representing 98.7% of all US census tracts.
• Nine race and ethnic groups were selected on the basis of the population size and categorizations used in prior research on health or cancer disparity: non-Hispanic Black, non-Hispanic White, Asian, Mexican, Puerto Rican, Cuban, Dominican, Central or South American, and “other race.”
• Geographically weighted regression and Getis-Ord Gi* hot spot procedures were used to identify the screening priority zones for all Hispanic or Latino groups.

TAKEAWAY:

• The analysis identified 6519 hot spot tracts for Mexican, 3477 for Puerto Rican, 3522 for Central or South American, 1069 for Dominican, and 1424 for Cuban individuals. The average rates of screening for CRC were 57.2%, 59.9%, 59.3%, 58.9%, and 60.4%, respectively.
• The percentage of Cuban individuals showed a positive association with the CRC screening rate, while the percentage of Mexican, Puerto Rican, Dominican, and Central or South American Hispanic or Latino individuals and of the uninsured showed a negative association with the CRC screening rate.
• The priority zones for Mexican communities were primarily located in Texas and southwestern United States, while those for Puerto Rican, Central or South American, and other populations were located in southern Florida and the metro areas of New York City and Texas.

IN PRACTICE:

“Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefiting specific H/L [Hispanic or Latino] communities in the United States,” the authors wrote. “These data can inform more precise neighborhood-level interventions to increase CRC screening considering unique characteristics important for these H/L [Hispanic or Latino] groups.”

SOURCE:

The study, led by R. Blake Buchalter, PhD, MPH, Center for Populations Health Research, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, was published online in the American Journal of Public Health.

LIMITATIONS: 

The study’s cross-sectional design limited the ability to infer causality. The use of census tract-level data did not capture individual-level screening behaviors. The study did not account for nativity status or years of migration owing to the lack of data. The Centers for Disease Control and Prevention PLACES dataset may not represent the actual screening delivered as it is based on survey data. 

DISCLOSURES:

The National Cancer Institute partially supported this study. The authors declared no conflicts of interest.

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 first appeared on Medscape.com.

TOPLINE:

Researchers identified thousands of census tracts as priority zones where improving the screening of colorectal cancer (CRC) may benefit Hispanic or Latino communities.

METHODOLOGY:

• Hispanic or Latino individuals have the lowest rate of CRC screening among the six broader census-designated racial or ethnic groups in the United States, while they face a high proportion of cancer deaths due to CRC.
• Researchers performed a cross-sectional ecologic study using 2021 Centers for Disease Control and Prevention PLACES and 2019 American Community Survey data to identify priority zones for CRC screening where intervention programs may be targeted.
• They analyzed a total of 72,136 US census tracts, representing 98.7% of all US census tracts.
• Nine race and ethnic groups were selected on the basis of the population size and categorizations used in prior research on health or cancer disparity: non-Hispanic Black, non-Hispanic White, Asian, Mexican, Puerto Rican, Cuban, Dominican, Central or South American, and “other race.”
• Geographically weighted regression and Getis-Ord Gi* hot spot procedures were used to identify the screening priority zones for all Hispanic or Latino groups.

TAKEAWAY:

• The analysis identified 6519 hot spot tracts for Mexican, 3477 for Puerto Rican, 3522 for Central or South American, 1069 for Dominican, and 1424 for Cuban individuals. The average rates of screening for CRC were 57.2%, 59.9%, 59.3%, 58.9%, and 60.4%, respectively.
• The percentage of Cuban individuals showed a positive association with the CRC screening rate, while the percentage of Mexican, Puerto Rican, Dominican, and Central or South American Hispanic or Latino individuals and of the uninsured showed a negative association with the CRC screening rate.
• The priority zones for Mexican communities were primarily located in Texas and southwestern United States, while those for Puerto Rican, Central or South American, and other populations were located in southern Florida and the metro areas of New York City and Texas.

IN PRACTICE:

“Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefiting specific H/L [Hispanic or Latino] communities in the United States,” the authors wrote. “These data can inform more precise neighborhood-level interventions to increase CRC screening considering unique characteristics important for these H/L [Hispanic or Latino] groups.”

SOURCE:

The study, led by R. Blake Buchalter, PhD, MPH, Center for Populations Health Research, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, was published online in the American Journal of Public Health.

LIMITATIONS: 

The study’s cross-sectional design limited the ability to infer causality. The use of census tract-level data did not capture individual-level screening behaviors. The study did not account for nativity status or years of migration owing to the lack of data. The Centers for Disease Control and Prevention PLACES dataset may not represent the actual screening delivered as it is based on survey data. 

DISCLOSURES:

The National Cancer Institute partially supported this study. The authors declared no conflicts of interest.

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 first appeared on Medscape.com.

TOPLINE:

Researchers identified thousands of census tracts as priority zones where improving the screening of colorectal cancer (CRC) may benefit Hispanic or Latino communities.

METHODOLOGY:

• Hispanic or Latino individuals have the lowest rate of CRC screening among the six broader census-designated racial or ethnic groups in the United States, while they face a high proportion of cancer deaths due to CRC.
• Researchers performed a cross-sectional ecologic study using 2021 Centers for Disease Control and Prevention PLACES and 2019 American Community Survey data to identify priority zones for CRC screening where intervention programs may be targeted.
• They analyzed a total of 72,136 US census tracts, representing 98.7% of all US census tracts.
• Nine race and ethnic groups were selected on the basis of the population size and categorizations used in prior research on health or cancer disparity: non-Hispanic Black, non-Hispanic White, Asian, Mexican, Puerto Rican, Cuban, Dominican, Central or South American, and “other race.”
• Geographically weighted regression and Getis-Ord Gi* hot spot procedures were used to identify the screening priority zones for all Hispanic or Latino groups.

TAKEAWAY:

• The analysis identified 6519 hot spot tracts for Mexican, 3477 for Puerto Rican, 3522 for Central or South American, 1069 for Dominican, and 1424 for Cuban individuals. The average rates of screening for CRC were 57.2%, 59.9%, 59.3%, 58.9%, and 60.4%, respectively.
• The percentage of Cuban individuals showed a positive association with the CRC screening rate, while the percentage of Mexican, Puerto Rican, Dominican, and Central or South American Hispanic or Latino individuals and of the uninsured showed a negative association with the CRC screening rate.
• The priority zones for Mexican communities were primarily located in Texas and southwestern United States, while those for Puerto Rican, Central or South American, and other populations were located in southern Florida and the metro areas of New York City and Texas.

IN PRACTICE:

“Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefiting specific H/L [Hispanic or Latino] communities in the United States,” the authors wrote. “These data can inform more precise neighborhood-level interventions to increase CRC screening considering unique characteristics important for these H/L [Hispanic or Latino] groups.”

SOURCE:

The study, led by R. Blake Buchalter, PhD, MPH, Center for Populations Health Research, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, was published online in the American Journal of Public Health.

LIMITATIONS: 

The study’s cross-sectional design limited the ability to infer causality. The use of census tract-level data did not capture individual-level screening behaviors. The study did not account for nativity status or years of migration owing to the lack of data. The Centers for Disease Control and Prevention PLACES dataset may not represent the actual screening delivered as it is based on survey data. 

DISCLOSURES:

The National Cancer Institute partially supported this study. The authors declared no conflicts of interest.

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 first appeared on Medscape.com.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Melasma (also known as chloasma faciei) is a common chronic skin disorder that results in well-demarcated, hyperpigmented, tan to dark patches that mostly appear in sun-exposed areas such as the face and neck and sometimes the arms. The exact prevalence or incidence is not known but is estimated to be 1% to 50% overall depending on the ethnic population and geographic location.^1,2 Melasma predominantly affects women, but research has shown that approximately 10% to 20% of men are affected by this condition.^3,4 Although melasma can affect patients of all skin types, it primarily affects those with darker skin tones.⁵ The groups most often affected are women of Black, Hispanic, Middle Eastern, and Southeast Asian ethnicity. Although the pathogenesis is complex and not fully understood, multiple pathways and etiologies have been theorized to cause melasma. Potential causes include exposure to UV radiation, oral contraceptives, hormonal changes, medications, thyroid dysfunction, genetics, and pregnancy.^6,7 Cytokines and growth factors, including adipokine and angiopoietin, synthesized by sebaceous glands play a role in the pathogenic mechanism of melasma. Cytokines and growth factors are hypothesized to modulate the function of melanocytes.⁸ Both melanocytes and sebocytes are controlled by α–melanocyte-stimulating hormone. Therefore, overexpression of α–melanocyte-stimulating hormone will result in overproduction of these 2 cell types, resulting in melasma. Melasma can be classified into 4 subtypes using Wood lamp examination: epidermal, dermal, mixed, or indeterminate.³ Furthermore, melasma is divided into subgroups based on the location: malar region, mandibular region, and centrofacial patch pattern.^9,10 The involvement of sebaceous glands in the pathogenesis of melasma may explain the predilection for the centrofacial region, which is the most common pattern.

The severity of melasma can be assessed using the melasma area and severity index (MASI), which is calculated by subjective assessment of 3 main factors: (1) facial area of involvement; (2) darkness of affected region; and (3) homogeneity, with the extent of melasma indicated by a score ranging from 0 to 48.¹¹ The modified MASI (mMASI) subsequently was introduced to assist with assessing the severity of melasma and creating distinct ranges for mild, moderate, and severe cases, ranging from 0 (mild) to 24 (severe).¹² Both indices are used in research to assess the improvement of melasma with treatment.

Patients with melasma report a decrease in quality of life, increased emotional stress, and lower self-esteem due to cosmesis.¹³ Treatment of melasma can be highly challenging and often is complicated by relapsing. Historically, the treatment of melasma has included the use of chemical lightening agents. Additional treatment options include the use of lasers and complex chemical peels,^9,10 but these interventions may result in adverse outcomes for individuals with darker skin tones. The current gold-standard treatment is topical hydroquinone and broad-spectrum sunscreen. Although hydroquinone is effective in the treatment of melasma, relapse is common. The goal of melasma management is not only to treat acute hyperpigmentation but also to prevent relapse. Other therapies that currently are being explored for the clinically sustained treatment of melasma include tranexamic acid (TXA)(trans-4-[aminomethyl]cyclohexanecarboxylic acid),^9,10 an antifibrinolytic agent routinely used to prevent blood loss during surgery and in the management of menorrhagia. It is a synthetic derivative of lysine and serves as a potent plasmin inhibitor by blocking the lysine-binding sites of plasminogen molecules, thus preventing the conversion of plasminogen to plasmin. It also prevents fibrinolysis and blood loss.

In addition to its hemostatic properties, TXA has been found to have hypopigmentation properties.^14,15 Plasminogen also can be found in human epidermal basal cells and human keratinocytes, and it is postulated that TXA’s interaction with these cells explains its hypopigmentation properties. Both UV radiation and hormones activate plasminogen into plasmin, resulting in the activation of tyrosinase and melanogenesis.^14,15 Tranexamic acid is postulated to inhibit the keratinocyte-plasminogen pathway, thus leading to the inhibition of UV-induced and hormone-induced pigmentation. Also, TXA serves as a competitive inhibitor for tyrosinase due to its structural similarity to tyrosine.¹⁵ The combination of these 2 mechanisms contributes to the skin-lightening effects of TXA, making it a potential treatment for melasma.

Furthermore, the use of microneedling is being explored as a treatment option for melasma. Microneedling creates microscopic punctures in the skin using tiny needles, resulting in a wound-healing response and skin resurfacing. The microneedling technique is utilized to create small holes in the skin, with needle depths that can be adjusted from 0.5 to 3.5 mm to target different layers of the dermis and allow for discreet application of TXA.¹⁶ We sought to look at the current literature on the use and effectiveness of microneedling in combination with TXA to treat melasma and prevent relapse.

Methods

A systematic review was performed of PubMed articles indexed for MEDLINE and Embase in November 2021 to compile available articles that studied TXA and microneedling as a treatment for melasma. The PubMed search terms were (melasma) AND (microneedling* OR ‘tranexamic acid’ OR TXA or TA). The Embase search terms were (cholasma OR melasma) AND (tranexamic acid OR TXA) AND (microneedling)(Figure). The search was then limited to ”randomized controlled trial” and ”clinical trial” in English-language journals. Duplicates were excluded. After thorough evaluation, articles that discussed the use of TXA in combination with treatment options other than microneedling also were excluded.

Results

The literature search yielded a total of 12 articles that assessed the effectiveness of TXA and microneedling for the treatment of melasma (Table).^17-28 Several articles concluded that TXA was equally effective at reducing melasma lesions when compared with the standard treatment of hydroquinone. Some of the reviewed articles also demonstrated the effectiveness of microneedling in improving melasma lesions as a stand-alone treatment. These studies highlighted the enhanced efficacy of the combined treatment of TXA and microneedling compared with their individual uses.^17-28

Comment

Melasma is a common chronic hyperpigmentation disorder, making its treatment clinically challenging. Many patients experience symptom relapses, and limited effective treatment options make achieving complete clearance difficult, underscoring the need for improved therapeutic approaches. Recently, researchers have explored alternative treatments to address the challenges of melasma management. Tranexamic acid is an antifibrinolytic used to prevent blood loss and has emerged as a potential treatment for melasma. Similarly, microneedling—a technique in which multiple punctures are made in the skin to activate and stimulate wound healing and skin rejuvenation—shows promise for melasma.

Oral TXA for Melasma—Oral TXA has been shown to reduce melasma lesions. Del Rosario et al¹⁷ recruited 44 women (39 of whom completed the study) with moderate to severe melasma and randomized them into 2 groups: oral TXA and placebo. This study demonstrated a 49% reduction in the mMASI score in all participants taking oral TXA (250 mg twice daily [BID]) compared with an 18% reduction in the control group (placebo capsule BID) after 3 months of treatment. In patients with moderate and severe melasma, 45% and 51% mMASI score reductions were reported in the treatment group, respectively, vs 16% and 19% score reductions in placebo group, respectively. These researchers concluded that oral TXA may be effective at treating moderate to severe melasma. Although patients with severe melasma had a better response to treatment, their improvement was not sustained compared with patients with moderate melasma after a 3-month posttreatment follow-up.¹⁷

Microneedling Plus TXA for Melasma—Microneedling alone has been shown to be effective for melasma. El Attar et al¹⁸ conducted a split-face study of microneedling (1.5-mm depth) plus topical TXA (0.5 mL)(right side of the face[treatment arm]) compared with microneedling (1.5-mm depth) plus topical vitamin C (0.5 mL)(left side of the face [control group]) in 20 women with melasma. The sessions were repeated every 2 weeks for a total of 6 sessions. Although researchers found no statistically significant differences between the 2 treatment sides, microneedling plus TXA showed a slight advantage over microneedling plus vitamin C in dermoscopic examination. Both sides showed improvement in pigmented lesions, but vitamin C–treated lesions did not show an improvement in vascularity vs TXA.¹⁸

Saleh et al¹⁹ further showed that combination treatment with microneedling and TXA may improve clinical outcomes better than microneedling alone. Their study demonstrated a reduction in MASI score that was significantly higher in the combination treatment group compared with the microneedling alone group (P=.001). There was a significant reduction in melanoma antigen recognized by T cells 1 (MART-1)–positive cells in the combination treatment group compared with the microneedling alone group (P=.001). Lastly, combined therapy improved melasma patches better than microneedling alone.¹⁹

Xu et al²⁰ conducted a split-face study (N=28) exploring the effectiveness of transdermal application of topical TXA using a microarray pen with microneedles (vibration at 3000×/min) plus topical TXA on one side of the face, while the other side received only topical TXA as a control. After 12 weeks of treatment, combination therapy with microneedling and TXA decreased brown spot scores, lowered melanin index (MI) values, improved blinded physician assessment, and improved patient satisfaction vs TXA therapy alone.²⁰

Kaur et al²¹ conducted a split-face, randomized, controlled trial of microneedling (1-mm depth) with TXA solution 10% vs microneedling (1-mm depth) with distilled water alone for 8 weeks (N=40). They graded participant responses to treatment using reductions in mMASI scores¹² at every 2 weeks of follow-up (no response, minimal or poor response=0%–25%; partial or fair response=26%–50%; good response=51%–75%; and excellent response=>75%). They reported an overall reduction in mMASI scores for both the treatment side and the control side in all participants, showing a 65.92% improvement in mean mMASI scores on the treatment side vs 20.75% improvement on the control side at week 8. Both sides showed statistically significant reductions in mean mMASI scores (P<.05). Clinically, 40% (16/40) of participants showed an excellent response to combined treatment compared with 0% (0/40) to microneedling alone. Overall, patient satisfaction was similar across both groups. This study demonstrated that microneedling alone improves melasma, but a combination of microneedling plus TXA showed a better clinical reduction in melasma. However, the researchers did not follow up with participants posttreatment, so it remains unclear if the improved clinical outcomes were sustained long-term.²¹

Ebrahim et al²² reported that the combination of 0.5 mL TXA (4 mg/mL) and microneedling (0.25- to 1-mm depth) was effective for melasma. Although there was improvement within microneedling and TXA, the study also showed that intradermal injection of TXA was significant in reducing mean mMASI scores and improving melasma (P<.001). The reduction in mMASI scores for the group receiving intradermal injections of TXA (left side; 74.8% reduction in mean mMASI score) vs the group receiving microneedling application of TXA (right side; 73.6% reduction in mean mMASI score) was not statistically significant. These findings suggest that the mode of TXA application may not be critical in determining clinical responses to TXA treatment. Although there was no reported statistically significant difference in clinical outcomes between the 2 treatments, patient satisfaction was higher on the microneedling side. Only 8 of 50 participants (16%) experienced recurrence 3 months posttreatment.²²

Saki et al²³ compared the efficacy of topical hydroquinone (2%) to intradermal TXA injections in treating melasma. They found intradermal TXA injections to be a clinically effective mode of treatment.²³

Sharma et al²⁴ explored the efficacy and safety of oral TXA by randomly assigning 100 Indian patients (20 of whom withdrew before study completion) with melasma into 2 groups: group A received TXA 250 mg twice daily, and group B received intradermal microinjections of TXA (4 mg/mL) every 4 weeks. The MASI scores were assessed at 4-week intervals for a total of 12 weeks. There was a decrease in MASI scores in both groups, and there was no statistically significant difference in mean percentage reduction in MASI scores between the 2 routes of drug administration, further suggesting the effectiveness of TXA independent of administration route. Two patients in group A relapsed at 24 weeks, and there were no relapses in group B, which may suggest a minimal superiority of TXA plus microneedling at providing more sustainable results compared with oral TXA alone. A notable limitation of this study was a high dropout rate as well as lack of long-term follow-up with participants, limiting the generalizability of the conclusions.²⁴

Cassiano et al²⁵ assigned 64 women with melasma to 1 of 3 treatment groups or a control group to compare the effectiveness of microneedling (M group: 1.5 mm; 2 sessions), oral TXA (T group: 250 mg/d twice daily for 60 days), and a combination of microneedling (2 sessions) and oral TXA (MT group: 250 mg/d twice daily for 60 days)with placebo for clinically reducing melasma lesions. The intervention period was 60 days followed by a 60-day maintenance phase for a total study period of 120 days. The researchers evaluated mMASI scores, quality of life, and difference in colorimetric luminosity. All treatment groups showed a reduction in mMASI scores at both 30 days and 60 days, indicating improved melasma severity. The MT and T groups had more significant improvement at 30 days compared with the control group (P<.03), suggesting that microneedling plus TXA and TXA alone promote faster improvement in melasma lesions. By 60 days, the M, T, and MT groups outperformed the control group, with no significant differences between the M, T, and MT groups. However, at the 120-day maintenance follow-up, the T group did not maintain its improvement compared with the control group. The M and MT groups showed no significance difference in effectiveness at 120 days, suggesting that microneedling may promote less frequent relapse and sustained remission compared to TXA alone.²⁵

Hydroquinone for Melasma—Additional studies on the use of TXA treatments show that TXA may be an equally effective alternative to the standard use of hydroquinone treatment. Shamsi Meymandi et al²⁶ did not find a statistically significant difference in treatment with TXA plus microneedling vs the standard regimen of hydroquinone. More importantly, patient and physician satisfaction assessments were similar between the 2 groups. Compared to hydroquinone, nightly treatment is not necessary with microneedling and TXA.²⁶

Xing et al²⁷ supported these conclusions with their study. They compared 3 study arms for a duration of 12 weeks: group A received topical 1.8% liposomal TXA BID, group B received stamp-mode electric microneedling with 5% TXA weekly, and group C applied 2% ­hydroquinone cream nightly. The study concluded that all 3 groups showed a significant reduction in mean MI by the end of the study, but a better MI improvement was observed in groups B and C (both P<.001) compared with group A (P<.01).²⁷

Zaky et al²⁸ showed that both hydroquinone and combination treatment of TXA plus microneedling are effective at improving melasma lesions. Further studies are needed to definitively conclude if combination treatment is more efficacious than hydroquinone; if the combination is more effective, it provides a treatment option for patients with melasma who may not be good candidates for hydroquinone treatment.

Study Limitations—One limitation in all the studies evaluated is the sample size. Because they all had small sample sizes, it is difficult to definitively conclude that the combination TXA and microneedling is an effective and appropriate treatment for patients with melasma. Furthermore, the quality of these studies was mostly dependent on subjectivity of the mMASI scores. Future large randomized controlled trials with a diverse participant population are needed to assess the effectiveness of TXA and microneedling in melasma treatment.

Another limitation is that many of the studies did not follow the patients longitudinally, which did not allow for an evaluation of whether patients had a relapse of melasma. Due to the chronic nature of melasma and frequent disease recurrence, future longitudinal studies are needed to monitor for disease recurrence.

Conclusion

Tranexamic acid and microneedling are potential treatment options for patients with melasma, and combination therapy appears more effective than either TXA or microneedling alone at providing sustained improvement of melasma lesions. Combination therapy appears safe and well tolerated, but its effect on reducing long-term disease recurrence is yet to be established.

Melasma (also known as chloasma faciei) is a common chronic skin disorder that results in well-demarcated, hyperpigmented, tan to dark patches that mostly appear in sun-exposed areas such as the face and neck and sometimes the arms. The exact prevalence or incidence is not known but is estimated to be 1% to 50% overall depending on the ethnic population and geographic location.^1,2 Melasma predominantly affects women, but research has shown that approximately 10% to 20% of men are affected by this condition.^3,4 Although melasma can affect patients of all skin types, it primarily affects those with darker skin tones.⁵ The groups most often affected are women of Black, Hispanic, Middle Eastern, and Southeast Asian ethnicity. Although the pathogenesis is complex and not fully understood, multiple pathways and etiologies have been theorized to cause melasma. Potential causes include exposure to UV radiation, oral contraceptives, hormonal changes, medications, thyroid dysfunction, genetics, and pregnancy.^6,7 Cytokines and growth factors, including adipokine and angiopoietin, synthesized by sebaceous glands play a role in the pathogenic mechanism of melasma. Cytokines and growth factors are hypothesized to modulate the function of melanocytes.⁸ Both melanocytes and sebocytes are controlled by α–melanocyte-stimulating hormone. Therefore, overexpression of α–melanocyte-stimulating hormone will result in overproduction of these 2 cell types, resulting in melasma. Melasma can be classified into 4 subtypes using Wood lamp examination: epidermal, dermal, mixed, or indeterminate.³ Furthermore, melasma is divided into subgroups based on the location: malar region, mandibular region, and centrofacial patch pattern.^9,10 The involvement of sebaceous glands in the pathogenesis of melasma may explain the predilection for the centrofacial region, which is the most common pattern.

The severity of melasma can be assessed using the melasma area and severity index (MASI), which is calculated by subjective assessment of 3 main factors: (1) facial area of involvement; (2) darkness of affected region; and (3) homogeneity, with the extent of melasma indicated by a score ranging from 0 to 48.¹¹ The modified MASI (mMASI) subsequently was introduced to assist with assessing the severity of melasma and creating distinct ranges for mild, moderate, and severe cases, ranging from 0 (mild) to 24 (severe).¹² Both indices are used in research to assess the improvement of melasma with treatment.

Patients with melasma report a decrease in quality of life, increased emotional stress, and lower self-esteem due to cosmesis.¹³ Treatment of melasma can be highly challenging and often is complicated by relapsing. Historically, the treatment of melasma has included the use of chemical lightening agents. Additional treatment options include the use of lasers and complex chemical peels,^9,10 but these interventions may result in adverse outcomes for individuals with darker skin tones. The current gold-standard treatment is topical hydroquinone and broad-spectrum sunscreen. Although hydroquinone is effective in the treatment of melasma, relapse is common. The goal of melasma management is not only to treat acute hyperpigmentation but also to prevent relapse. Other therapies that currently are being explored for the clinically sustained treatment of melasma include tranexamic acid (TXA)(trans-4-[aminomethyl]cyclohexanecarboxylic acid),^9,10 an antifibrinolytic agent routinely used to prevent blood loss during surgery and in the management of menorrhagia. It is a synthetic derivative of lysine and serves as a potent plasmin inhibitor by blocking the lysine-binding sites of plasminogen molecules, thus preventing the conversion of plasminogen to plasmin. It also prevents fibrinolysis and blood loss.

In addition to its hemostatic properties, TXA has been found to have hypopigmentation properties.^14,15 Plasminogen also can be found in human epidermal basal cells and human keratinocytes, and it is postulated that TXA’s interaction with these cells explains its hypopigmentation properties. Both UV radiation and hormones activate plasminogen into plasmin, resulting in the activation of tyrosinase and melanogenesis.^14,15 Tranexamic acid is postulated to inhibit the keratinocyte-plasminogen pathway, thus leading to the inhibition of UV-induced and hormone-induced pigmentation. Also, TXA serves as a competitive inhibitor for tyrosinase due to its structural similarity to tyrosine.¹⁵ The combination of these 2 mechanisms contributes to the skin-lightening effects of TXA, making it a potential treatment for melasma.

Furthermore, the use of microneedling is being explored as a treatment option for melasma. Microneedling creates microscopic punctures in the skin using tiny needles, resulting in a wound-healing response and skin resurfacing. The microneedling technique is utilized to create small holes in the skin, with needle depths that can be adjusted from 0.5 to 3.5 mm to target different layers of the dermis and allow for discreet application of TXA.¹⁶ We sought to look at the current literature on the use and effectiveness of microneedling in combination with TXA to treat melasma and prevent relapse.

Methods

A systematic review was performed of PubMed articles indexed for MEDLINE and Embase in November 2021 to compile available articles that studied TXA and microneedling as a treatment for melasma. The PubMed search terms were (melasma) AND (microneedling* OR ‘tranexamic acid’ OR TXA or TA). The Embase search terms were (cholasma OR melasma) AND (tranexamic acid OR TXA) AND (microneedling)(Figure). The search was then limited to ”randomized controlled trial” and ”clinical trial” in English-language journals. Duplicates were excluded. After thorough evaluation, articles that discussed the use of TXA in combination with treatment options other than microneedling also were excluded.

Results

The literature search yielded a total of 12 articles that assessed the effectiveness of TXA and microneedling for the treatment of melasma (Table).^17-28 Several articles concluded that TXA was equally effective at reducing melasma lesions when compared with the standard treatment of hydroquinone. Some of the reviewed articles also demonstrated the effectiveness of microneedling in improving melasma lesions as a stand-alone treatment. These studies highlighted the enhanced efficacy of the combined treatment of TXA and microneedling compared with their individual uses.^17-28

Comment

Melasma is a common chronic hyperpigmentation disorder, making its treatment clinically challenging. Many patients experience symptom relapses, and limited effective treatment options make achieving complete clearance difficult, underscoring the need for improved therapeutic approaches. Recently, researchers have explored alternative treatments to address the challenges of melasma management. Tranexamic acid is an antifibrinolytic used to prevent blood loss and has emerged as a potential treatment for melasma. Similarly, microneedling—a technique in which multiple punctures are made in the skin to activate and stimulate wound healing and skin rejuvenation—shows promise for melasma.

Oral TXA for Melasma—Oral TXA has been shown to reduce melasma lesions. Del Rosario et al¹⁷ recruited 44 women (39 of whom completed the study) with moderate to severe melasma and randomized them into 2 groups: oral TXA and placebo. This study demonstrated a 49% reduction in the mMASI score in all participants taking oral TXA (250 mg twice daily [BID]) compared with an 18% reduction in the control group (placebo capsule BID) after 3 months of treatment. In patients with moderate and severe melasma, 45% and 51% mMASI score reductions were reported in the treatment group, respectively, vs 16% and 19% score reductions in placebo group, respectively. These researchers concluded that oral TXA may be effective at treating moderate to severe melasma. Although patients with severe melasma had a better response to treatment, their improvement was not sustained compared with patients with moderate melasma after a 3-month posttreatment follow-up.¹⁷

Microneedling Plus TXA for Melasma—Microneedling alone has been shown to be effective for melasma. El Attar et al¹⁸ conducted a split-face study of microneedling (1.5-mm depth) plus topical TXA (0.5 mL)(right side of the face[treatment arm]) compared with microneedling (1.5-mm depth) plus topical vitamin C (0.5 mL)(left side of the face [control group]) in 20 women with melasma. The sessions were repeated every 2 weeks for a total of 6 sessions. Although researchers found no statistically significant differences between the 2 treatment sides, microneedling plus TXA showed a slight advantage over microneedling plus vitamin C in dermoscopic examination. Both sides showed improvement in pigmented lesions, but vitamin C–treated lesions did not show an improvement in vascularity vs TXA.¹⁸

Saleh et al¹⁹ further showed that combination treatment with microneedling and TXA may improve clinical outcomes better than microneedling alone. Their study demonstrated a reduction in MASI score that was significantly higher in the combination treatment group compared with the microneedling alone group (P=.001). There was a significant reduction in melanoma antigen recognized by T cells 1 (MART-1)–positive cells in the combination treatment group compared with the microneedling alone group (P=.001). Lastly, combined therapy improved melasma patches better than microneedling alone.¹⁹

Xu et al²⁰ conducted a split-face study (N=28) exploring the effectiveness of transdermal application of topical TXA using a microarray pen with microneedles (vibration at 3000×/min) plus topical TXA on one side of the face, while the other side received only topical TXA as a control. After 12 weeks of treatment, combination therapy with microneedling and TXA decreased brown spot scores, lowered melanin index (MI) values, improved blinded physician assessment, and improved patient satisfaction vs TXA therapy alone.²⁰

Kaur et al²¹ conducted a split-face, randomized, controlled trial of microneedling (1-mm depth) with TXA solution 10% vs microneedling (1-mm depth) with distilled water alone for 8 weeks (N=40). They graded participant responses to treatment using reductions in mMASI scores¹² at every 2 weeks of follow-up (no response, minimal or poor response=0%–25%; partial or fair response=26%–50%; good response=51%–75%; and excellent response=>75%). They reported an overall reduction in mMASI scores for both the treatment side and the control side in all participants, showing a 65.92% improvement in mean mMASI scores on the treatment side vs 20.75% improvement on the control side at week 8. Both sides showed statistically significant reductions in mean mMASI scores (P<.05). Clinically, 40% (16/40) of participants showed an excellent response to combined treatment compared with 0% (0/40) to microneedling alone. Overall, patient satisfaction was similar across both groups. This study demonstrated that microneedling alone improves melasma, but a combination of microneedling plus TXA showed a better clinical reduction in melasma. However, the researchers did not follow up with participants posttreatment, so it remains unclear if the improved clinical outcomes were sustained long-term.²¹

Ebrahim et al²² reported that the combination of 0.5 mL TXA (4 mg/mL) and microneedling (0.25- to 1-mm depth) was effective for melasma. Although there was improvement within microneedling and TXA, the study also showed that intradermal injection of TXA was significant in reducing mean mMASI scores and improving melasma (P<.001). The reduction in mMASI scores for the group receiving intradermal injections of TXA (left side; 74.8% reduction in mean mMASI score) vs the group receiving microneedling application of TXA (right side; 73.6% reduction in mean mMASI score) was not statistically significant. These findings suggest that the mode of TXA application may not be critical in determining clinical responses to TXA treatment. Although there was no reported statistically significant difference in clinical outcomes between the 2 treatments, patient satisfaction was higher on the microneedling side. Only 8 of 50 participants (16%) experienced recurrence 3 months posttreatment.²²

Saki et al²³ compared the efficacy of topical hydroquinone (2%) to intradermal TXA injections in treating melasma. They found intradermal TXA injections to be a clinically effective mode of treatment.²³

Sharma et al²⁴ explored the efficacy and safety of oral TXA by randomly assigning 100 Indian patients (20 of whom withdrew before study completion) with melasma into 2 groups: group A received TXA 250 mg twice daily, and group B received intradermal microinjections of TXA (4 mg/mL) every 4 weeks. The MASI scores were assessed at 4-week intervals for a total of 12 weeks. There was a decrease in MASI scores in both groups, and there was no statistically significant difference in mean percentage reduction in MASI scores between the 2 routes of drug administration, further suggesting the effectiveness of TXA independent of administration route. Two patients in group A relapsed at 24 weeks, and there were no relapses in group B, which may suggest a minimal superiority of TXA plus microneedling at providing more sustainable results compared with oral TXA alone. A notable limitation of this study was a high dropout rate as well as lack of long-term follow-up with participants, limiting the generalizability of the conclusions.²⁴

Cassiano et al²⁵ assigned 64 women with melasma to 1 of 3 treatment groups or a control group to compare the effectiveness of microneedling (M group: 1.5 mm; 2 sessions), oral TXA (T group: 250 mg/d twice daily for 60 days), and a combination of microneedling (2 sessions) and oral TXA (MT group: 250 mg/d twice daily for 60 days)with placebo for clinically reducing melasma lesions. The intervention period was 60 days followed by a 60-day maintenance phase for a total study period of 120 days. The researchers evaluated mMASI scores, quality of life, and difference in colorimetric luminosity. All treatment groups showed a reduction in mMASI scores at both 30 days and 60 days, indicating improved melasma severity. The MT and T groups had more significant improvement at 30 days compared with the control group (P<.03), suggesting that microneedling plus TXA and TXA alone promote faster improvement in melasma lesions. By 60 days, the M, T, and MT groups outperformed the control group, with no significant differences between the M, T, and MT groups. However, at the 120-day maintenance follow-up, the T group did not maintain its improvement compared with the control group. The M and MT groups showed no significance difference in effectiveness at 120 days, suggesting that microneedling may promote less frequent relapse and sustained remission compared to TXA alone.²⁵

Hydroquinone for Melasma—Additional studies on the use of TXA treatments show that TXA may be an equally effective alternative to the standard use of hydroquinone treatment. Shamsi Meymandi et al²⁶ did not find a statistically significant difference in treatment with TXA plus microneedling vs the standard regimen of hydroquinone. More importantly, patient and physician satisfaction assessments were similar between the 2 groups. Compared to hydroquinone, nightly treatment is not necessary with microneedling and TXA.²⁶

Xing et al²⁷ supported these conclusions with their study. They compared 3 study arms for a duration of 12 weeks: group A received topical 1.8% liposomal TXA BID, group B received stamp-mode electric microneedling with 5% TXA weekly, and group C applied 2% ­hydroquinone cream nightly. The study concluded that all 3 groups showed a significant reduction in mean MI by the end of the study, but a better MI improvement was observed in groups B and C (both P<.001) compared with group A (P<.01).²⁷

Zaky et al²⁸ showed that both hydroquinone and combination treatment of TXA plus microneedling are effective at improving melasma lesions. Further studies are needed to definitively conclude if combination treatment is more efficacious than hydroquinone; if the combination is more effective, it provides a treatment option for patients with melasma who may not be good candidates for hydroquinone treatment.

Study Limitations—One limitation in all the studies evaluated is the sample size. Because they all had small sample sizes, it is difficult to definitively conclude that the combination TXA and microneedling is an effective and appropriate treatment for patients with melasma. Furthermore, the quality of these studies was mostly dependent on subjectivity of the mMASI scores. Future large randomized controlled trials with a diverse participant population are needed to assess the effectiveness of TXA and microneedling in melasma treatment.

Another limitation is that many of the studies did not follow the patients longitudinally, which did not allow for an evaluation of whether patients had a relapse of melasma. Due to the chronic nature of melasma and frequent disease recurrence, future longitudinal studies are needed to monitor for disease recurrence.

Conclusion

Tranexamic acid and microneedling are potential treatment options for patients with melasma, and combination therapy appears more effective than either TXA or microneedling alone at providing sustained improvement of melasma lesions. Combination therapy appears safe and well tolerated, but its effect on reducing long-term disease recurrence is yet to be established.

Melasma (also known as chloasma faciei) is a common chronic skin disorder that results in well-demarcated, hyperpigmented, tan to dark patches that mostly appear in sun-exposed areas such as the face and neck and sometimes the arms. The exact prevalence or incidence is not known but is estimated to be 1% to 50% overall depending on the ethnic population and geographic location.^1,2 Melasma predominantly affects women, but research has shown that approximately 10% to 20% of men are affected by this condition.^3,4 Although melasma can affect patients of all skin types, it primarily affects those with darker skin tones.⁵ The groups most often affected are women of Black, Hispanic, Middle Eastern, and Southeast Asian ethnicity. Although the pathogenesis is complex and not fully understood, multiple pathways and etiologies have been theorized to cause melasma. Potential causes include exposure to UV radiation, oral contraceptives, hormonal changes, medications, thyroid dysfunction, genetics, and pregnancy.^6,7 Cytokines and growth factors, including adipokine and angiopoietin, synthesized by sebaceous glands play a role in the pathogenic mechanism of melasma. Cytokines and growth factors are hypothesized to modulate the function of melanocytes.⁸ Both melanocytes and sebocytes are controlled by α–melanocyte-stimulating hormone. Therefore, overexpression of α–melanocyte-stimulating hormone will result in overproduction of these 2 cell types, resulting in melasma. Melasma can be classified into 4 subtypes using Wood lamp examination: epidermal, dermal, mixed, or indeterminate.³ Furthermore, melasma is divided into subgroups based on the location: malar region, mandibular region, and centrofacial patch pattern.^9,10 The involvement of sebaceous glands in the pathogenesis of melasma may explain the predilection for the centrofacial region, which is the most common pattern.

The severity of melasma can be assessed using the melasma area and severity index (MASI), which is calculated by subjective assessment of 3 main factors: (1) facial area of involvement; (2) darkness of affected region; and (3) homogeneity, with the extent of melasma indicated by a score ranging from 0 to 48.¹¹ The modified MASI (mMASI) subsequently was introduced to assist with assessing the severity of melasma and creating distinct ranges for mild, moderate, and severe cases, ranging from 0 (mild) to 24 (severe).¹² Both indices are used in research to assess the improvement of melasma with treatment.

Patients with melasma report a decrease in quality of life, increased emotional stress, and lower self-esteem due to cosmesis.¹³ Treatment of melasma can be highly challenging and often is complicated by relapsing. Historically, the treatment of melasma has included the use of chemical lightening agents. Additional treatment options include the use of lasers and complex chemical peels,^9,10 but these interventions may result in adverse outcomes for individuals with darker skin tones. The current gold-standard treatment is topical hydroquinone and broad-spectrum sunscreen. Although hydroquinone is effective in the treatment of melasma, relapse is common. The goal of melasma management is not only to treat acute hyperpigmentation but also to prevent relapse. Other therapies that currently are being explored for the clinically sustained treatment of melasma include tranexamic acid (TXA)(trans-4-[aminomethyl]cyclohexanecarboxylic acid),^9,10 an antifibrinolytic agent routinely used to prevent blood loss during surgery and in the management of menorrhagia. It is a synthetic derivative of lysine and serves as a potent plasmin inhibitor by blocking the lysine-binding sites of plasminogen molecules, thus preventing the conversion of plasminogen to plasmin. It also prevents fibrinolysis and blood loss.

In addition to its hemostatic properties, TXA has been found to have hypopigmentation properties.^14,15 Plasminogen also can be found in human epidermal basal cells and human keratinocytes, and it is postulated that TXA’s interaction with these cells explains its hypopigmentation properties. Both UV radiation and hormones activate plasminogen into plasmin, resulting in the activation of tyrosinase and melanogenesis.^14,15 Tranexamic acid is postulated to inhibit the keratinocyte-plasminogen pathway, thus leading to the inhibition of UV-induced and hormone-induced pigmentation. Also, TXA serves as a competitive inhibitor for tyrosinase due to its structural similarity to tyrosine.¹⁵ The combination of these 2 mechanisms contributes to the skin-lightening effects of TXA, making it a potential treatment for melasma.

Furthermore, the use of microneedling is being explored as a treatment option for melasma. Microneedling creates microscopic punctures in the skin using tiny needles, resulting in a wound-healing response and skin resurfacing. The microneedling technique is utilized to create small holes in the skin, with needle depths that can be adjusted from 0.5 to 3.5 mm to target different layers of the dermis and allow for discreet application of TXA.¹⁶ We sought to look at the current literature on the use and effectiveness of microneedling in combination with TXA to treat melasma and prevent relapse.

Methods

A systematic review was performed of PubMed articles indexed for MEDLINE and Embase in November 2021 to compile available articles that studied TXA and microneedling as a treatment for melasma. The PubMed search terms were (melasma) AND (microneedling* OR ‘tranexamic acid’ OR TXA or TA). The Embase search terms were (cholasma OR melasma) AND (tranexamic acid OR TXA) AND (microneedling)(Figure). The search was then limited to ”randomized controlled trial” and ”clinical trial” in English-language journals. Duplicates were excluded. After thorough evaluation, articles that discussed the use of TXA in combination with treatment options other than microneedling also were excluded.

Results

The literature search yielded a total of 12 articles that assessed the effectiveness of TXA and microneedling for the treatment of melasma (Table).^17-28 Several articles concluded that TXA was equally effective at reducing melasma lesions when compared with the standard treatment of hydroquinone. Some of the reviewed articles also demonstrated the effectiveness of microneedling in improving melasma lesions as a stand-alone treatment. These studies highlighted the enhanced efficacy of the combined treatment of TXA and microneedling compared with their individual uses.^17-28

Comment

Melasma is a common chronic hyperpigmentation disorder, making its treatment clinically challenging. Many patients experience symptom relapses, and limited effective treatment options make achieving complete clearance difficult, underscoring the need for improved therapeutic approaches. Recently, researchers have explored alternative treatments to address the challenges of melasma management. Tranexamic acid is an antifibrinolytic used to prevent blood loss and has emerged as a potential treatment for melasma. Similarly, microneedling—a technique in which multiple punctures are made in the skin to activate and stimulate wound healing and skin rejuvenation—shows promise for melasma.

Oral TXA for Melasma—Oral TXA has been shown to reduce melasma lesions. Del Rosario et al¹⁷ recruited 44 women (39 of whom completed the study) with moderate to severe melasma and randomized them into 2 groups: oral TXA and placebo. This study demonstrated a 49% reduction in the mMASI score in all participants taking oral TXA (250 mg twice daily [BID]) compared with an 18% reduction in the control group (placebo capsule BID) after 3 months of treatment. In patients with moderate and severe melasma, 45% and 51% mMASI score reductions were reported in the treatment group, respectively, vs 16% and 19% score reductions in placebo group, respectively. These researchers concluded that oral TXA may be effective at treating moderate to severe melasma. Although patients with severe melasma had a better response to treatment, their improvement was not sustained compared with patients with moderate melasma after a 3-month posttreatment follow-up.¹⁷

Microneedling Plus TXA for Melasma—Microneedling alone has been shown to be effective for melasma. El Attar et al¹⁸ conducted a split-face study of microneedling (1.5-mm depth) plus topical TXA (0.5 mL)(right side of the face[treatment arm]) compared with microneedling (1.5-mm depth) plus topical vitamin C (0.5 mL)(left side of the face [control group]) in 20 women with melasma. The sessions were repeated every 2 weeks for a total of 6 sessions. Although researchers found no statistically significant differences between the 2 treatment sides, microneedling plus TXA showed a slight advantage over microneedling plus vitamin C in dermoscopic examination. Both sides showed improvement in pigmented lesions, but vitamin C–treated lesions did not show an improvement in vascularity vs TXA.¹⁸

Saleh et al¹⁹ further showed that combination treatment with microneedling and TXA may improve clinical outcomes better than microneedling alone. Their study demonstrated a reduction in MASI score that was significantly higher in the combination treatment group compared with the microneedling alone group (P=.001). There was a significant reduction in melanoma antigen recognized by T cells 1 (MART-1)–positive cells in the combination treatment group compared with the microneedling alone group (P=.001). Lastly, combined therapy improved melasma patches better than microneedling alone.¹⁹

Xu et al²⁰ conducted a split-face study (N=28) exploring the effectiveness of transdermal application of topical TXA using a microarray pen with microneedles (vibration at 3000×/min) plus topical TXA on one side of the face, while the other side received only topical TXA as a control. After 12 weeks of treatment, combination therapy with microneedling and TXA decreased brown spot scores, lowered melanin index (MI) values, improved blinded physician assessment, and improved patient satisfaction vs TXA therapy alone.²⁰

Kaur et al²¹ conducted a split-face, randomized, controlled trial of microneedling (1-mm depth) with TXA solution 10% vs microneedling (1-mm depth) with distilled water alone for 8 weeks (N=40). They graded participant responses to treatment using reductions in mMASI scores¹² at every 2 weeks of follow-up (no response, minimal or poor response=0%–25%; partial or fair response=26%–50%; good response=51%–75%; and excellent response=>75%). They reported an overall reduction in mMASI scores for both the treatment side and the control side in all participants, showing a 65.92% improvement in mean mMASI scores on the treatment side vs 20.75% improvement on the control side at week 8. Both sides showed statistically significant reductions in mean mMASI scores (P<.05). Clinically, 40% (16/40) of participants showed an excellent response to combined treatment compared with 0% (0/40) to microneedling alone. Overall, patient satisfaction was similar across both groups. This study demonstrated that microneedling alone improves melasma, but a combination of microneedling plus TXA showed a better clinical reduction in melasma. However, the researchers did not follow up with participants posttreatment, so it remains unclear if the improved clinical outcomes were sustained long-term.²¹

Ebrahim et al²² reported that the combination of 0.5 mL TXA (4 mg/mL) and microneedling (0.25- to 1-mm depth) was effective for melasma. Although there was improvement within microneedling and TXA, the study also showed that intradermal injection of TXA was significant in reducing mean mMASI scores and improving melasma (P<.001). The reduction in mMASI scores for the group receiving intradermal injections of TXA (left side; 74.8% reduction in mean mMASI score) vs the group receiving microneedling application of TXA (right side; 73.6% reduction in mean mMASI score) was not statistically significant. These findings suggest that the mode of TXA application may not be critical in determining clinical responses to TXA treatment. Although there was no reported statistically significant difference in clinical outcomes between the 2 treatments, patient satisfaction was higher on the microneedling side. Only 8 of 50 participants (16%) experienced recurrence 3 months posttreatment.²²

Saki et al²³ compared the efficacy of topical hydroquinone (2%) to intradermal TXA injections in treating melasma. They found intradermal TXA injections to be a clinically effective mode of treatment.²³

Sharma et al²⁴ explored the efficacy and safety of oral TXA by randomly assigning 100 Indian patients (20 of whom withdrew before study completion) with melasma into 2 groups: group A received TXA 250 mg twice daily, and group B received intradermal microinjections of TXA (4 mg/mL) every 4 weeks. The MASI scores were assessed at 4-week intervals for a total of 12 weeks. There was a decrease in MASI scores in both groups, and there was no statistically significant difference in mean percentage reduction in MASI scores between the 2 routes of drug administration, further suggesting the effectiveness of TXA independent of administration route. Two patients in group A relapsed at 24 weeks, and there were no relapses in group B, which may suggest a minimal superiority of TXA plus microneedling at providing more sustainable results compared with oral TXA alone. A notable limitation of this study was a high dropout rate as well as lack of long-term follow-up with participants, limiting the generalizability of the conclusions.²⁴

Cassiano et al²⁵ assigned 64 women with melasma to 1 of 3 treatment groups or a control group to compare the effectiveness of microneedling (M group: 1.5 mm; 2 sessions), oral TXA (T group: 250 mg/d twice daily for 60 days), and a combination of microneedling (2 sessions) and oral TXA (MT group: 250 mg/d twice daily for 60 days)with placebo for clinically reducing melasma lesions. The intervention period was 60 days followed by a 60-day maintenance phase for a total study period of 120 days. The researchers evaluated mMASI scores, quality of life, and difference in colorimetric luminosity. All treatment groups showed a reduction in mMASI scores at both 30 days and 60 days, indicating improved melasma severity. The MT and T groups had more significant improvement at 30 days compared with the control group (P<.03), suggesting that microneedling plus TXA and TXA alone promote faster improvement in melasma lesions. By 60 days, the M, T, and MT groups outperformed the control group, with no significant differences between the M, T, and MT groups. However, at the 120-day maintenance follow-up, the T group did not maintain its improvement compared with the control group. The M and MT groups showed no significance difference in effectiveness at 120 days, suggesting that microneedling may promote less frequent relapse and sustained remission compared to TXA alone.²⁵

Hydroquinone for Melasma—Additional studies on the use of TXA treatments show that TXA may be an equally effective alternative to the standard use of hydroquinone treatment. Shamsi Meymandi et al²⁶ did not find a statistically significant difference in treatment with TXA plus microneedling vs the standard regimen of hydroquinone. More importantly, patient and physician satisfaction assessments were similar between the 2 groups. Compared to hydroquinone, nightly treatment is not necessary with microneedling and TXA.²⁶

Xing et al²⁷ supported these conclusions with their study. They compared 3 study arms for a duration of 12 weeks: group A received topical 1.8% liposomal TXA BID, group B received stamp-mode electric microneedling with 5% TXA weekly, and group C applied 2% ­hydroquinone cream nightly. The study concluded that all 3 groups showed a significant reduction in mean MI by the end of the study, but a better MI improvement was observed in groups B and C (both P<.001) compared with group A (P<.01).²⁷

Zaky et al²⁸ showed that both hydroquinone and combination treatment of TXA plus microneedling are effective at improving melasma lesions. Further studies are needed to definitively conclude if combination treatment is more efficacious than hydroquinone; if the combination is more effective, it provides a treatment option for patients with melasma who may not be good candidates for hydroquinone treatment.

Study Limitations—One limitation in all the studies evaluated is the sample size. Because they all had small sample sizes, it is difficult to definitively conclude that the combination TXA and microneedling is an effective and appropriate treatment for patients with melasma. Furthermore, the quality of these studies was mostly dependent on subjectivity of the mMASI scores. Future large randomized controlled trials with a diverse participant population are needed to assess the effectiveness of TXA and microneedling in melasma treatment.

Another limitation is that many of the studies did not follow the patients longitudinally, which did not allow for an evaluation of whether patients had a relapse of melasma. Due to the chronic nature of melasma and frequent disease recurrence, future longitudinal studies are needed to monitor for disease recurrence.

Conclusion

Tranexamic acid and microneedling are potential treatment options for patients with melasma, and combination therapy appears more effective than either TXA or microneedling alone at providing sustained improvement of melasma lesions. Combination therapy appears safe and well tolerated, but its effect on reducing long-term disease recurrence is yet to be established.

Click to view more from Federal Health Care Data Trends 2024.

Click to view more from Federal Health Care Data Trends 2024.

Click to view more from Federal Health Care Data Trends 2024.

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Only one third of pediatric patients were correctly triaged at emergency departments (EDs) in a northern California health care system, according to a multicenter retrospective study published in JAMA Pediatrics. Researchers also identified gender, age, race, ethnicity, and comorbidity disparities in those who were undertriaged.

The researchers found that only 34.1% of visits were correctly triaged while 58.5% were overtriaged and 7.4% were undertriaged. The findings were based on analysis of more than 1 million pediatric emergency visits over a 5-year period that used the Emergency Severity Index (ESI) version 4 for triage.

“The ESI had poor sensitivity in identifying a critically ill pediatric patient, and undertriage occurred in 1 in 14 children,” wrote Dana R. Sax, MD, a senior emergency physician at The Permanente Medical Group in northern California, and her colleagues.

Disparities in Emergency Care

The results underscore the need for more work to address disparities in emergency care, wrote Warren D. Frankenberger, PhD, RN, a nurse scientist at Children’s Hospital of Philadelphia, and two colleagues in an accompanying editorial.

“Decisions in triage can have significant downstream effects on subsequent care during the ED visit,” they wrote in their editorial. “Given that the triage process in most instances is fully executed by nurses, nurse researchers are in a key position to evaluate these and other covariates to influence further improvements in triage.” They suggested that use of clinical decision support tools and artificial intelligence (AI) may improve the triage process, albeit with the caveat that AI often relies on models with pre-existing historical bias that may perpetuate structural inequalities.
 

Study Methodology

The researchers analyzed 1,016,816 pediatric visits at 21 emergency departments in Kaiser Permanente Northern California between January 2016 and December 2020. The patients were an average 7 years old, and 47% were female. The researchers excluded visits that lacked ESI data or had incomplete ED time variables as well as those with patients who left against medical advice, were not seen, or were transferred from another ED.

The study relied on novel definitions of ESI undertriage and overtriage developed through a modified Delphi process by a team of four emergency physicians, one pediatric emergency physician, two emergency nurses, and one pediatric ICU physician. The definition involved comparing ESI levels to the clinical outcomes and resource use.

Resources included laboratory analysis, electrocardiography, radiography, CT, MRI, diagnostic ultrasonography (not point of care), angiography, IV fluids, and IV, intramuscular, or nebulized medications. Resources did not include “oral medications, tetanus immunizations, point-of-care testing, history and physical examination, saline or heparin lock, prescription refills, simple wound care, crutches, splints, and slings.”

Level 1 events were those requiring time-sensitive, critical intervention, including high-risk sepsis. Level 2 events included most level 1 events that occurred after the first hour (except operating room admission or hospital transfer) as well as respiratory therapy, toxicology consult, lumbar puncture, suicidality as chief concern, at least 2 doses of albuterol or continuous albuterol nebulization, a skeletal survey x-ray order, and medical social work consult with an ED length of stay of at least 2 hours. Level 3 events included IV mediation order, any CT order, OR admission or hospital transfer after one hour, or any pediatric hospitalist consult.
 

Analyzing the ED Visits

Overtriaged cases were ESI level 1 or 2 cases in which fewer than 2 resources were used; level 3 cases where fewer than 2 resources were used and no level 1 or 2 events occurred; and level 4 cases where no resources were used.

Undertriaged cases were defined as the following:

• ESI level 5 cases where any resource was used and any level 1, 2, or 3 events occurred.
• Level 4 cases where more than 1 resource was used and any level 1, 2, or 3 events occurred.
• Level 3 cases where any level 1 event occurred, more than one level 2 event occurred, or any level 2 event occurred and more than one additional ED resource type was used.
• Level 2 cases where any level 1 event occurred.

About half the visits (51%) were assigned ESI 3, which was the category with the highest proportion of mistriage. After adjusting for study facility and triage vital signs, the researchers found that children age 6 and older were more likely to be undertriaged than those younger than 6, particularly those age 15 and older (relative risk [RR], 1.36).

Undertriage was also modestly more likely with male patients (female patients’ RR, 0.93), patients with comorbidities (RR, 1.11-1.2), patients who arrived by ambulance (RR, 1.04), and patients who were Asian (RR, 1.10), Black (RR, 1.05), or Hispanic (RR, 1.04). Undertriage became gradually less likely with each additional year in the study period, with an RR of 0.89 in 2019 and 2020.

Among the study’s limitations were use of ESI version 4, instead of the currently used 5, and the omission of common procedures from the outcome definition that “may systematically bias the analysis toward overtriage,” the editorial noted. The authors also did not include pain as a variable in the analysis, which can often indicate patient acuity.

Further, this study was unable to include covariates identified in other research that may influence clinical decision-making, such as “the presenting illness or injury, children with complex medical needs, and language proficiency,” Dr. Frankenberger and colleagues wrote. “Furthermore, environmental stressors, such as ED volume and crowding, can influence how a nurse prioritizes care and may increase bias in decision-making and/or increase practice variability.”

The study was funded by the Kaiser Permanente Northern California (KPNC) Community Health program. One author had consulting payments from CSL Behring and Abbott Point-of-Care, and six of the authors have received grant funding from the KPNC Community Health program. The editorial authors reported no conflicts of interest.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Lifetime skin cancer prevalence in sexual minority (SM) Americans varied by race, ethnicity, and individual sexual identity, compared with that in heterosexual peers, according to a large cross-sectional study. Addressing dynamics of each SM subgroup will require increasingly tailored prevention, screening, and research efforts, the study authors said.

“We identified specific subgroups within the sexual minority community who are at higher risk for skin cancer, specifically White gay males and Hispanic and non-Hispanic Black SM men and women — particularly individuals who identify as bisexual,” senior author Matthew Mansh, MD, said in an interview. He is an assistant professor of dermatology at the University of California, San Francisco. The study was published online in JAMA Dermatology.

Using data of adults in the US general population from the Behavioral Risk Factor Surveillance System from January 2014 to December 2021, investigators included more than 1.5 million respondents. The proportions of SM women and men (who self-identified as bisexual, lesbian, gay, “something else,” or other) were 2.6% and 2.0%, respectively.

Lifetime skin cancer prevalence was higher among SM men than among heterosexual men (7.4% vs 6.8%; adjusted odds ratio [aOR], 1.16). In analyses stratified by racial and ethnic group, AORs for non-Hispanic Black and Hispanic SM men vs their heterosexual counterparts were 2.18 and 3.81, respectively. The corresponding figures for non-Hispanic Black and Hispanic SM women were 2.33 and 2.46, respectively.

When investigators combined all minority respondents along gender lines, lifetime skin cancer prevalence was higher in bisexual men (aOR, 3.94), bisexual women (aOR, 1.51), and women identifying as something else or other (aOR, 2.70) than in their heterosexual peers.

“I wasn’t expecting that Hispanic or non-Hispanic Black SMs would be at higher risk for skin cancer,” Dr. Mansh said. Even if these groups have more behavioral risk factors for UV radiation (UVR) exposure, he explained, UVR exposure is less strongly linked with skin cancer in darker skin than in lighter skin. Reasons for the counterintuitive finding could include different screening habits among SM people of different racial and ethnic groups, he said, and analyzing such factors will require further research.

Although some effect sizes were modest, the authors wrote, their findings may have important implications for population-based research and public health efforts aimed at early skin cancer detection and prevention. Presently, the United States lacks established guidelines for skin cancer screening. In a 2023 statement published in JAMA, the US Preventive Services Task Force said that there is insufficient evidence to determine the benefit-harm balance of skin cancer screening in asymptomatic people.

“So there has been a lot of recent talk and a need to identify which subset groups of patients might be higher risk for skin cancer and might benefit from more screening,” Dr. Mansh said in an interview. “Understanding more about the high-risk demographic and clinical features that predispose someone to skin cancer helps identify these high-risk populations that could be used to develop better screening guidelines.”

Identifying groups at a higher risk for skin cancer also allows experts to design more targeted counseling or public health interventions focused on these groups, Dr. Mansh added. Absent screening guidelines, experts emphasize changing modifiable risk factors such as UVR exposure, smoking, and alcohol use. “And we know that the message that might change behaviors in a cisgender heterosexual man might be different than in a gay White male or a Hispanic bisexual male.”

A 2017 review showed that interventions to reduce behaviors involving UVR exposure, such as indoor tanning, among young cisgender women focused largely on aging and appearance-based concerns. A 2019 study showed that messages focused on avoiding skin cancer may help motivate SM men to reduce tanning behaviors.

Furthermore, said Dr. Mansh, all electronic health record products available in the United States must provide data fields for sexual orientation. “I don’t believe many dermatologists, depending on the setting, collect that information routinely. Integrating sexual orientation and/or gender identity data into patient intake forms so that it can be integrated into the electronic health record is probably very helpful, not only for your clinical practice but also for future research studies.”

Asked to comment on the results, Rebecca I. Hartman, MD, MPH, who was not involved with the study, said that its impact on clinical practice will be challenging to ascertain. She is chief of dermatology with the VA Boston Healthcare System, assistant professor of dermatology at Harvard Medical School, and director of melanoma epidemiology at Brigham and Women’s Hospital, all in Boston, Massachusetts.

“The study found significant adjusted odds ratios,” Dr. Hartman explained, “but for some of the different populations, the overall lifetime rate of skin cancer is still quite low.” For example, 1.0% for SM non-Hispanic Black men or a difference of 2.1% vs 1.8% in SM Hispanic women. “Thus, I am not sure specific screening recommendations are warranted, although some populations, such as Hispanic sexual minority males, seemed to have a much higher risk (3.8-fold on adjusted analysis) that warrants further investigation.”

For now, she advised assessing patients’ risks for skin cancer based on well-established risk factors such as sun exposure/indoor tanning, skin phototype, immunosuppression, and age.

Dr. Mansh reported no relevant conflicts or funding sources for the study. Dr. Hartman reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Margin-controlled surgery for squamous cell carcinoma (SCC) on the lower lip was first performed by Dr. Frederic Mohs on June 30, 1936. Since then, thousands of skin cancer surgeons have refined and adopted the technique. Due to the high cure rate and sparing of normal tissue, Mohs micrographic surgery (MMS) has become the gold standard treatment for facial and special-site nonmelanoma skin cancer worldwide. Mohs micrographic surgery is performed on more than 876,000 tumors annually in the United States.¹ Among 3.5 million Americans diagnosed with nonmelanoma skin cancer in 2006, one-quarter were treated with MMS.² In Japan, basal cell carcinoma (BCC) is the most common skin malignancy, with an incidence of 3.34 cases per 100,000 individuals; SCC is the second most common, with an incidence of 2.5 cases per 100,000 individuals.³

The essential element that makes MMS unique is the careful microscopic examination of the entire margin of the removed specimen. Tissue processing is done with careful en face orientation to ensure that circumferential and deep margins are entirely visible. The surgeon interprets the slides and proceeds to remove the additional tumor as necessary. Because the same physician performs both the surgery and the pathologic assessment throughout the procedure, a precise correlation between the microscopic and surgical findings can be made. The surgeon can begin with smaller margins, removing minimal healthy tissue while removing all the cancer cells, which results in the smallest-possible skin defect and the best prognosis for the malignancy (Figure 1).

At the only facility in Japan offering MMS, the lead author (S.S.) has treated 52 lesions with MMS in 46 patients (2020-2022). Of these patients, 40 were White, 5 were Japanese, and 1 was of African descent. In this case series, we present 5 Japanese patients who had BCC treated with MMS.

Case Series

Patient 1—A 50-year-old Japanese woman presented to dermatology with a brown papule on the nasal tip of 1.25 year’s duration (Figure 2). A biopsy revealed infiltrative BCC (Figure 3), and the patient was referred to the dermatology department at a nearby university hospital. Because the BCC was an aggressive variant, wide local excision (WLE) with subsequent flap reconstruction was recommended as well as radiation therapy. The patient learned about MMS through an internet search and refused both options, seeking MMS treatment at our clinic. Although Japanese health insurance does not cover MMS, the patient had supplemental private insurance that did cover the cost. She provided consent to undergo the procedure. Physical examination revealed a 7.5×6-mm, brown-red macule with ill-defined borders on the tip of the nose. We used a 1.5-mm margin for the first stage of MMS (Figure 4A). The frozen section revealed that the tumor had been entirely excised in the first stage, leaving only a 10.5×9-mm skin defect that was reconstructed with a Dufourmentel flap (Figure 4B). No signs of recurrence were noted at 3.5-year follow-up, and the cosmetic outcome was favorable (Figure 4C). National Comprehensive Cancer Network guidelines recommend a margin greater than 4 mm for infiltrative BCCs⁴; therefore, our technique reduced the total defect by at least 4 mm in a cosmetically sensitive area. The patient also did not need radiation therapy, which reduced morbidity. She continues to be recurrence free at 3.5-year follow-up.

Patient 2—A 63-year-old Japanese man presented to dermatology with a brown macule on the right lower eyelid of 2 years’ duration. A biopsy of the lesion was positive for nodular BCC. After being advised to undergo WLE and extensive reconstruction with plastic surgery, the patient learned of MMS through an internet search and found our clinic. Physical examination revealed a 7×5-mm brown macule on the right lower eyelid. The patient had supplemental private insurance that covered the cost of MMS, and he provided consent for the procedure. A 1.5-mm margin was taken for the first stage, resulting in a 10×8-mm defect superficial to the orbicularis oculi muscle. The frozen section revealed residual tumor exposure in the dermis at the 9- to 10-o’clock position. A second-stage excision was performed to remove an additional 1.5 mm of skin at the 9- to 12-o’clock position with a thin layer of the orbicularis oculi muscle. The subsequent histologic examination revealed no residual BCC, and the final 13×9-mm skin defect was reconstructed with a rotation flap. There were no signs of recurrence at 2.5-year follow-up with an excellent cosmetic outcome.

Patient 3—A 73-year-old Japanese man presented to a local university dermatology clinic with a new papule on the nose. The dermatologist suggested WLE with 4-mm margins and reconstruction of the skin defect 2 weeks later by a plastic surgeon. The patient was not satisfied with the proposed surgical plan, which led him to learn about MMS on the internet; he subsequently found our clinic. Physical examination revealed a 4×3.5-mm brown papule on the tip of the nose. He understood the nature of MMS and chose to pay out-of-pocket because Japanese health insurance did not cover the procedure. We used a 2-mm margin for the first stage, which created a 7.5×7-mm skin defect. The frozen section pathology revealed no residual BCC at the cut surface. The skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Patient 4—A 45-year-old man presented to a dermatology clinic with a papule on the right side of the nose of 1 year’s duration. A biopsy revealed the lesion was a nodular BCC. The dermatologist recommended WLE at a general hospital, but the patient refused after learning about MMS. He subsequently made an appointment with our clinic. Physical examination revealed a 7×4-mm white papule on the right side of the nose. The patient had private insurance that covered the cost of MMS. The first stage was performed with 1.5-mm margins and was clear of residual tumor. A Limberg rhombic flap from the adjacent cheek was used to repair the final 10×7-mm skin defect. There were no signs of recurrence at 1 year and 9 months’ follow-up with a favorable cosmetic outcome.

Patient 5—A 76-year-old Japanese woman presented to a university hospital near Tokyo with a black papule on the left cutaneous lip of 5 years’ duration. A biopsy revealed nodular BCC, and WLE with flap reconstruction was recommended. The patient’s son learned about MMS through internet research and referred her to our clinic. Physical examination revealed a 7×5-mm black papule on the left upper lip. The patient’s private insurance covered the cost of MMS, and she consented to the procedure. We used a 2-mm initial margin, and the immediate frozen section revealed no signs of BCC at the cut surface. The 11×9-mm skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Comment

We presented 5 cases of MMS in Japanese patients with BCC. More than 7000 new cases of nonmelanoma skin cancer occur every year in Japan.³ Only 0.04% of these cases—the 5 cases presented here—were treated with MMS in Japan in 2020 and 2021, in contrast to 25% in the United States in 2006.²

MMS vs Other BCC Treatments—Mohs micrographic surgery offers 2 distinct advantages over conventional excision: an improved cure rate while achieving a smaller final defect size, generally leading to better cosmetic outcomes. Overall 5-year recurrence rates of BCC are 10% for conventional surgical excision vs 1% for MMS, while the recurrence rates for SCC are 8% and 3%, respectively.⁵ A study of well-demarcated BCCs smaller than 2 cm that were treated with MMS with 2-mm increments revealed that 95% of the cases were free of malignancy within a 4-mm margin of the normal-appearing skin surrounding the tumor.⁶ Several articles have reported a 95% cure rate or higher with conventional excision of localized BCC,⁷ but 4- to 5-mm excision margins are required, resulting in a greater skin defect and a lower cure rate compared to MMS.

Aggressive subtypes of BCC have a higher recurrence rate. Rowe et al⁸ reported the following 5-year recurrence rates: 5.6% for MMS, 17.4% for conventional surgical excision, 40.0% for curettage and electrodesiccation, and 9.8% for radiation therapy. Primary BCCs with high-risk histologic subtypes has a 10-year recurrence rate of 4.4% with MMS vs 12.2% with conventional excision.⁹ These findings reveal that MMS yields a better prognosis compared to traditional treatment methods for recurrent BCCs and BCCs of high-risk histologic subtypes.

The primary reason for the excellent cure rate seen in MMS is the ability to perform complete margin assessment. Peripheral and deep en face margin assessment (PDEMA) is crucial in achieving high cure rates with narrow margins. In WLE (Figure 1), vertical sectioning (also known as bread-loafing) does not achieve direct visualization of the entire surgical margin, as this technique only evaluates random sections and does not achieve PDEMA.¹⁰ The bread-loafing method is used almost exclusively in Japan and visualizes only 0.1% of the entire margin compared to 100% with MMS.¹¹ Beyond the superior cure rate, the MMS technique often yields smaller final defects compared to WLE. All 5 of our patients achieved complete tumor removal while sparing more normal tissue compared to conventional WLE, which takes at least a 4-mm margin in all directions.

Barriers to Adopting MMS in Japan—There are many barriers to the broader adoption of MMS in Japan. A guideline of the Japanese Dermatological Association says, MMS “is complicated, requires special training for acquisition, and requires time and labor for implementation of a series of processes, and it has not gained wide acceptance in Japan because of these disadvantages.”³ There currently are no MMS training programs in Japan. We refute this statement from the Japanese Dermatological Association because, in our experience, only 1 surgeon plus a single histotechnician familiar with MMS is sufficient for a facility to offer the procedure (the lead author of this study [S.S.] acts as both the surgeon and the histotechnician). Another misconception among some physicians in Japan is that cancer on ethnically Japanese skin is uniquely suited to excision without microscopic verification of tumor clearance because the borders of the tumors are easily identified, which was based on good cure rates for the excision of well-demarcated pigmented BCCs in a Japanese cohort. This study of a Japanese cohort investigated the specimens with the conventional bread-loafing technique but not with the PDEMA.¹²

Eighty percent (4/5) of our patients presented with nodular BCC, and only 1 required a second stage. In comparison, we also treated 16 White patients with nodular BCC with MMS during the same period, and 31% (5/16) required more than 1 stage, with 1 patient requiring 3 stages. This cohort, however, is too small to demonstrate a statistically significant difference (S.S., unpublished data, 2020-2022).

A study in Singapore reported the postsurgical complication rate and 5-year recurrence rate for 481 tumors (92% BCC and 7.5% SCC). The median follow-up duration after MMS was 36 months, and the recurrence rate was 0.6%. The postsurgical complications included 11 (2.3%) cases with superficial tip necrosis of surgical flaps/grafts, 2 (0.4%) with mild wound dehiscence, 1 (0.2%) with minor surgical site bleeding, and 1 (0.2%) with minor wound infection.¹³ This study supports the notion that MMS is equally effective for Asian patients.

Awareness of MMS in Japan is lacking, and most Japanese dermatologists do not know about the technique. All 5 patients in our case series asked their dermatologists about alternative treatment options and were not offered MMS. In each case, the patients learned of the technique through internet research.

The lack of insurance reimbursement for MMS in Japan is another barrier. Because the national health insurance does not reimburse for MMS, the procedure is relatively unavailable to most Japanese citizens who cannot pay out-of-pocket for the treatment and do not have supplemental insurance. Mohs micrographic surgery may seem expensive compared to WLE followed by repair; however, in the authors’ experience, in Japan, excision without MMS may require general sedation and multiple surgeries to reconstruct larger skin defects, leading to greater morbidity and risk for the patient.

Conclusion

Mohs micrographic surgery in Japan is in its infancy, and further studies showing recurrence rates and long-term prognosis are needed. Such data should help increase awareness of MMS among Japanese physicians as an excellent treatment option for their patients. Furthermore, as Japan becomes more heterogenous as a society and the US Military increases its presence in the region, the need for MMS is likely to increase.

Acknowledgments—We appreciate the proofreading support by Mark Bivens, MBA, MSc (Tokyo, Japan), as well as the technical support from Ben Tallon, MBChB, and Robyn Mason (both in Tauranga, New Zealand) to start MMS at our clinic.

Margin-controlled surgery for squamous cell carcinoma (SCC) on the lower lip was first performed by Dr. Frederic Mohs on June 30, 1936. Since then, thousands of skin cancer surgeons have refined and adopted the technique. Due to the high cure rate and sparing of normal tissue, Mohs micrographic surgery (MMS) has become the gold standard treatment for facial and special-site nonmelanoma skin cancer worldwide. Mohs micrographic surgery is performed on more than 876,000 tumors annually in the United States.¹ Among 3.5 million Americans diagnosed with nonmelanoma skin cancer in 2006, one-quarter were treated with MMS.² In Japan, basal cell carcinoma (BCC) is the most common skin malignancy, with an incidence of 3.34 cases per 100,000 individuals; SCC is the second most common, with an incidence of 2.5 cases per 100,000 individuals.³

The essential element that makes MMS unique is the careful microscopic examination of the entire margin of the removed specimen. Tissue processing is done with careful en face orientation to ensure that circumferential and deep margins are entirely visible. The surgeon interprets the slides and proceeds to remove the additional tumor as necessary. Because the same physician performs both the surgery and the pathologic assessment throughout the procedure, a precise correlation between the microscopic and surgical findings can be made. The surgeon can begin with smaller margins, removing minimal healthy tissue while removing all the cancer cells, which results in the smallest-possible skin defect and the best prognosis for the malignancy (Figure 1).

At the only facility in Japan offering MMS, the lead author (S.S.) has treated 52 lesions with MMS in 46 patients (2020-2022). Of these patients, 40 were White, 5 were Japanese, and 1 was of African descent. In this case series, we present 5 Japanese patients who had BCC treated with MMS.

Case Series

Patient 1—A 50-year-old Japanese woman presented to dermatology with a brown papule on the nasal tip of 1.25 year’s duration (Figure 2). A biopsy revealed infiltrative BCC (Figure 3), and the patient was referred to the dermatology department at a nearby university hospital. Because the BCC was an aggressive variant, wide local excision (WLE) with subsequent flap reconstruction was recommended as well as radiation therapy. The patient learned about MMS through an internet search and refused both options, seeking MMS treatment at our clinic. Although Japanese health insurance does not cover MMS, the patient had supplemental private insurance that did cover the cost. She provided consent to undergo the procedure. Physical examination revealed a 7.5×6-mm, brown-red macule with ill-defined borders on the tip of the nose. We used a 1.5-mm margin for the first stage of MMS (Figure 4A). The frozen section revealed that the tumor had been entirely excised in the first stage, leaving only a 10.5×9-mm skin defect that was reconstructed with a Dufourmentel flap (Figure 4B). No signs of recurrence were noted at 3.5-year follow-up, and the cosmetic outcome was favorable (Figure 4C). National Comprehensive Cancer Network guidelines recommend a margin greater than 4 mm for infiltrative BCCs⁴; therefore, our technique reduced the total defect by at least 4 mm in a cosmetically sensitive area. The patient also did not need radiation therapy, which reduced morbidity. She continues to be recurrence free at 3.5-year follow-up.

Patient 2—A 63-year-old Japanese man presented to dermatology with a brown macule on the right lower eyelid of 2 years’ duration. A biopsy of the lesion was positive for nodular BCC. After being advised to undergo WLE and extensive reconstruction with plastic surgery, the patient learned of MMS through an internet search and found our clinic. Physical examination revealed a 7×5-mm brown macule on the right lower eyelid. The patient had supplemental private insurance that covered the cost of MMS, and he provided consent for the procedure. A 1.5-mm margin was taken for the first stage, resulting in a 10×8-mm defect superficial to the orbicularis oculi muscle. The frozen section revealed residual tumor exposure in the dermis at the 9- to 10-o’clock position. A second-stage excision was performed to remove an additional 1.5 mm of skin at the 9- to 12-o’clock position with a thin layer of the orbicularis oculi muscle. The subsequent histologic examination revealed no residual BCC, and the final 13×9-mm skin defect was reconstructed with a rotation flap. There were no signs of recurrence at 2.5-year follow-up with an excellent cosmetic outcome.

Patient 3—A 73-year-old Japanese man presented to a local university dermatology clinic with a new papule on the nose. The dermatologist suggested WLE with 4-mm margins and reconstruction of the skin defect 2 weeks later by a plastic surgeon. The patient was not satisfied with the proposed surgical plan, which led him to learn about MMS on the internet; he subsequently found our clinic. Physical examination revealed a 4×3.5-mm brown papule on the tip of the nose. He understood the nature of MMS and chose to pay out-of-pocket because Japanese health insurance did not cover the procedure. We used a 2-mm margin for the first stage, which created a 7.5×7-mm skin defect. The frozen section pathology revealed no residual BCC at the cut surface. The skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Patient 4—A 45-year-old man presented to a dermatology clinic with a papule on the right side of the nose of 1 year’s duration. A biopsy revealed the lesion was a nodular BCC. The dermatologist recommended WLE at a general hospital, but the patient refused after learning about MMS. He subsequently made an appointment with our clinic. Physical examination revealed a 7×4-mm white papule on the right side of the nose. The patient had private insurance that covered the cost of MMS. The first stage was performed with 1.5-mm margins and was clear of residual tumor. A Limberg rhombic flap from the adjacent cheek was used to repair the final 10×7-mm skin defect. There were no signs of recurrence at 1 year and 9 months’ follow-up with a favorable cosmetic outcome.

Patient 5—A 76-year-old Japanese woman presented to a university hospital near Tokyo with a black papule on the left cutaneous lip of 5 years’ duration. A biopsy revealed nodular BCC, and WLE with flap reconstruction was recommended. The patient’s son learned about MMS through internet research and referred her to our clinic. Physical examination revealed a 7×5-mm black papule on the left upper lip. The patient’s private insurance covered the cost of MMS, and she consented to the procedure. We used a 2-mm initial margin, and the immediate frozen section revealed no signs of BCC at the cut surface. The 11×9-mm skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Comment

We presented 5 cases of MMS in Japanese patients with BCC. More than 7000 new cases of nonmelanoma skin cancer occur every year in Japan.³ Only 0.04% of these cases—the 5 cases presented here—were treated with MMS in Japan in 2020 and 2021, in contrast to 25% in the United States in 2006.²

MMS vs Other BCC Treatments—Mohs micrographic surgery offers 2 distinct advantages over conventional excision: an improved cure rate while achieving a smaller final defect size, generally leading to better cosmetic outcomes. Overall 5-year recurrence rates of BCC are 10% for conventional surgical excision vs 1% for MMS, while the recurrence rates for SCC are 8% and 3%, respectively.⁵ A study of well-demarcated BCCs smaller than 2 cm that were treated with MMS with 2-mm increments revealed that 95% of the cases were free of malignancy within a 4-mm margin of the normal-appearing skin surrounding the tumor.⁶ Several articles have reported a 95% cure rate or higher with conventional excision of localized BCC,⁷ but 4- to 5-mm excision margins are required, resulting in a greater skin defect and a lower cure rate compared to MMS.

Aggressive subtypes of BCC have a higher recurrence rate. Rowe et al⁸ reported the following 5-year recurrence rates: 5.6% for MMS, 17.4% for conventional surgical excision, 40.0% for curettage and electrodesiccation, and 9.8% for radiation therapy. Primary BCCs with high-risk histologic subtypes has a 10-year recurrence rate of 4.4% with MMS vs 12.2% with conventional excision.⁹ These findings reveal that MMS yields a better prognosis compared to traditional treatment methods for recurrent BCCs and BCCs of high-risk histologic subtypes.

The primary reason for the excellent cure rate seen in MMS is the ability to perform complete margin assessment. Peripheral and deep en face margin assessment (PDEMA) is crucial in achieving high cure rates with narrow margins. In WLE (Figure 1), vertical sectioning (also known as bread-loafing) does not achieve direct visualization of the entire surgical margin, as this technique only evaluates random sections and does not achieve PDEMA.¹⁰ The bread-loafing method is used almost exclusively in Japan and visualizes only 0.1% of the entire margin compared to 100% with MMS.¹¹ Beyond the superior cure rate, the MMS technique often yields smaller final defects compared to WLE. All 5 of our patients achieved complete tumor removal while sparing more normal tissue compared to conventional WLE, which takes at least a 4-mm margin in all directions.

Barriers to Adopting MMS in Japan—There are many barriers to the broader adoption of MMS in Japan. A guideline of the Japanese Dermatological Association says, MMS “is complicated, requires special training for acquisition, and requires time and labor for implementation of a series of processes, and it has not gained wide acceptance in Japan because of these disadvantages.”³ There currently are no MMS training programs in Japan. We refute this statement from the Japanese Dermatological Association because, in our experience, only 1 surgeon plus a single histotechnician familiar with MMS is sufficient for a facility to offer the procedure (the lead author of this study [S.S.] acts as both the surgeon and the histotechnician). Another misconception among some physicians in Japan is that cancer on ethnically Japanese skin is uniquely suited to excision without microscopic verification of tumor clearance because the borders of the tumors are easily identified, which was based on good cure rates for the excision of well-demarcated pigmented BCCs in a Japanese cohort. This study of a Japanese cohort investigated the specimens with the conventional bread-loafing technique but not with the PDEMA.¹²

Eighty percent (4/5) of our patients presented with nodular BCC, and only 1 required a second stage. In comparison, we also treated 16 White patients with nodular BCC with MMS during the same period, and 31% (5/16) required more than 1 stage, with 1 patient requiring 3 stages. This cohort, however, is too small to demonstrate a statistically significant difference (S.S., unpublished data, 2020-2022).

A study in Singapore reported the postsurgical complication rate and 5-year recurrence rate for 481 tumors (92% BCC and 7.5% SCC). The median follow-up duration after MMS was 36 months, and the recurrence rate was 0.6%. The postsurgical complications included 11 (2.3%) cases with superficial tip necrosis of surgical flaps/grafts, 2 (0.4%) with mild wound dehiscence, 1 (0.2%) with minor surgical site bleeding, and 1 (0.2%) with minor wound infection.¹³ This study supports the notion that MMS is equally effective for Asian patients.

Awareness of MMS in Japan is lacking, and most Japanese dermatologists do not know about the technique. All 5 patients in our case series asked their dermatologists about alternative treatment options and were not offered MMS. In each case, the patients learned of the technique through internet research.

The lack of insurance reimbursement for MMS in Japan is another barrier. Because the national health insurance does not reimburse for MMS, the procedure is relatively unavailable to most Japanese citizens who cannot pay out-of-pocket for the treatment and do not have supplemental insurance. Mohs micrographic surgery may seem expensive compared to WLE followed by repair; however, in the authors’ experience, in Japan, excision without MMS may require general sedation and multiple surgeries to reconstruct larger skin defects, leading to greater morbidity and risk for the patient.

Conclusion

Mohs micrographic surgery in Japan is in its infancy, and further studies showing recurrence rates and long-term prognosis are needed. Such data should help increase awareness of MMS among Japanese physicians as an excellent treatment option for their patients. Furthermore, as Japan becomes more heterogenous as a society and the US Military increases its presence in the region, the need for MMS is likely to increase.

Acknowledgments—We appreciate the proofreading support by Mark Bivens, MBA, MSc (Tokyo, Japan), as well as the technical support from Ben Tallon, MBChB, and Robyn Mason (both in Tauranga, New Zealand) to start MMS at our clinic.

Margin-controlled surgery for squamous cell carcinoma (SCC) on the lower lip was first performed by Dr. Frederic Mohs on June 30, 1936. Since then, thousands of skin cancer surgeons have refined and adopted the technique. Due to the high cure rate and sparing of normal tissue, Mohs micrographic surgery (MMS) has become the gold standard treatment for facial and special-site nonmelanoma skin cancer worldwide. Mohs micrographic surgery is performed on more than 876,000 tumors annually in the United States.¹ Among 3.5 million Americans diagnosed with nonmelanoma skin cancer in 2006, one-quarter were treated with MMS.² In Japan, basal cell carcinoma (BCC) is the most common skin malignancy, with an incidence of 3.34 cases per 100,000 individuals; SCC is the second most common, with an incidence of 2.5 cases per 100,000 individuals.³

The essential element that makes MMS unique is the careful microscopic examination of the entire margin of the removed specimen. Tissue processing is done with careful en face orientation to ensure that circumferential and deep margins are entirely visible. The surgeon interprets the slides and proceeds to remove the additional tumor as necessary. Because the same physician performs both the surgery and the pathologic assessment throughout the procedure, a precise correlation between the microscopic and surgical findings can be made. The surgeon can begin with smaller margins, removing minimal healthy tissue while removing all the cancer cells, which results in the smallest-possible skin defect and the best prognosis for the malignancy (Figure 1).

At the only facility in Japan offering MMS, the lead author (S.S.) has treated 52 lesions with MMS in 46 patients (2020-2022). Of these patients, 40 were White, 5 were Japanese, and 1 was of African descent. In this case series, we present 5 Japanese patients who had BCC treated with MMS.

Case Series

Patient 1—A 50-year-old Japanese woman presented to dermatology with a brown papule on the nasal tip of 1.25 year’s duration (Figure 2). A biopsy revealed infiltrative BCC (Figure 3), and the patient was referred to the dermatology department at a nearby university hospital. Because the BCC was an aggressive variant, wide local excision (WLE) with subsequent flap reconstruction was recommended as well as radiation therapy. The patient learned about MMS through an internet search and refused both options, seeking MMS treatment at our clinic. Although Japanese health insurance does not cover MMS, the patient had supplemental private insurance that did cover the cost. She provided consent to undergo the procedure. Physical examination revealed a 7.5×6-mm, brown-red macule with ill-defined borders on the tip of the nose. We used a 1.5-mm margin for the first stage of MMS (Figure 4A). The frozen section revealed that the tumor had been entirely excised in the first stage, leaving only a 10.5×9-mm skin defect that was reconstructed with a Dufourmentel flap (Figure 4B). No signs of recurrence were noted at 3.5-year follow-up, and the cosmetic outcome was favorable (Figure 4C). National Comprehensive Cancer Network guidelines recommend a margin greater than 4 mm for infiltrative BCCs⁴; therefore, our technique reduced the total defect by at least 4 mm in a cosmetically sensitive area. The patient also did not need radiation therapy, which reduced morbidity. She continues to be recurrence free at 3.5-year follow-up.

Patient 2—A 63-year-old Japanese man presented to dermatology with a brown macule on the right lower eyelid of 2 years’ duration. A biopsy of the lesion was positive for nodular BCC. After being advised to undergo WLE and extensive reconstruction with plastic surgery, the patient learned of MMS through an internet search and found our clinic. Physical examination revealed a 7×5-mm brown macule on the right lower eyelid. The patient had supplemental private insurance that covered the cost of MMS, and he provided consent for the procedure. A 1.5-mm margin was taken for the first stage, resulting in a 10×8-mm defect superficial to the orbicularis oculi muscle. The frozen section revealed residual tumor exposure in the dermis at the 9- to 10-o’clock position. A second-stage excision was performed to remove an additional 1.5 mm of skin at the 9- to 12-o’clock position with a thin layer of the orbicularis oculi muscle. The subsequent histologic examination revealed no residual BCC, and the final 13×9-mm skin defect was reconstructed with a rotation flap. There were no signs of recurrence at 2.5-year follow-up with an excellent cosmetic outcome.

Patient 3—A 73-year-old Japanese man presented to a local university dermatology clinic with a new papule on the nose. The dermatologist suggested WLE with 4-mm margins and reconstruction of the skin defect 2 weeks later by a plastic surgeon. The patient was not satisfied with the proposed surgical plan, which led him to learn about MMS on the internet; he subsequently found our clinic. Physical examination revealed a 4×3.5-mm brown papule on the tip of the nose. He understood the nature of MMS and chose to pay out-of-pocket because Japanese health insurance did not cover the procedure. We used a 2-mm margin for the first stage, which created a 7.5×7-mm skin defect. The frozen section pathology revealed no residual BCC at the cut surface. The skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Patient 4—A 45-year-old man presented to a dermatology clinic with a papule on the right side of the nose of 1 year’s duration. A biopsy revealed the lesion was a nodular BCC. The dermatologist recommended WLE at a general hospital, but the patient refused after learning about MMS. He subsequently made an appointment with our clinic. Physical examination revealed a 7×4-mm white papule on the right side of the nose. The patient had private insurance that covered the cost of MMS. The first stage was performed with 1.5-mm margins and was clear of residual tumor. A Limberg rhombic flap from the adjacent cheek was used to repair the final 10×7-mm skin defect. There were no signs of recurrence at 1 year and 9 months’ follow-up with a favorable cosmetic outcome.

Patient 5—A 76-year-old Japanese woman presented to a university hospital near Tokyo with a black papule on the left cutaneous lip of 5 years’ duration. A biopsy revealed nodular BCC, and WLE with flap reconstruction was recommended. The patient’s son learned about MMS through internet research and referred her to our clinic. Physical examination revealed a 7×5-mm black papule on the left upper lip. The patient’s private insurance covered the cost of MMS, and she consented to the procedure. We used a 2-mm initial margin, and the immediate frozen section revealed no signs of BCC at the cut surface. The 11×9-mm skin defect was reconstructed with a Limberg rhombic flap. There were no signs of recurrence at 1.5-year follow-up with a favorable cosmetic outcome.

Comment

We presented 5 cases of MMS in Japanese patients with BCC. More than 7000 new cases of nonmelanoma skin cancer occur every year in Japan.³ Only 0.04% of these cases—the 5 cases presented here—were treated with MMS in Japan in 2020 and 2021, in contrast to 25% in the United States in 2006.²

MMS vs Other BCC Treatments—Mohs micrographic surgery offers 2 distinct advantages over conventional excision: an improved cure rate while achieving a smaller final defect size, generally leading to better cosmetic outcomes. Overall 5-year recurrence rates of BCC are 10% for conventional surgical excision vs 1% for MMS, while the recurrence rates for SCC are 8% and 3%, respectively.⁵ A study of well-demarcated BCCs smaller than 2 cm that were treated with MMS with 2-mm increments revealed that 95% of the cases were free of malignancy within a 4-mm margin of the normal-appearing skin surrounding the tumor.⁶ Several articles have reported a 95% cure rate or higher with conventional excision of localized BCC,⁷ but 4- to 5-mm excision margins are required, resulting in a greater skin defect and a lower cure rate compared to MMS.

Aggressive subtypes of BCC have a higher recurrence rate. Rowe et al⁸ reported the following 5-year recurrence rates: 5.6% for MMS, 17.4% for conventional surgical excision, 40.0% for curettage and electrodesiccation, and 9.8% for radiation therapy. Primary BCCs with high-risk histologic subtypes has a 10-year recurrence rate of 4.4% with MMS vs 12.2% with conventional excision.⁹ These findings reveal that MMS yields a better prognosis compared to traditional treatment methods for recurrent BCCs and BCCs of high-risk histologic subtypes.

The primary reason for the excellent cure rate seen in MMS is the ability to perform complete margin assessment. Peripheral and deep en face margin assessment (PDEMA) is crucial in achieving high cure rates with narrow margins. In WLE (Figure 1), vertical sectioning (also known as bread-loafing) does not achieve direct visualization of the entire surgical margin, as this technique only evaluates random sections and does not achieve PDEMA.¹⁰ The bread-loafing method is used almost exclusively in Japan and visualizes only 0.1% of the entire margin compared to 100% with MMS.¹¹ Beyond the superior cure rate, the MMS technique often yields smaller final defects compared to WLE. All 5 of our patients achieved complete tumor removal while sparing more normal tissue compared to conventional WLE, which takes at least a 4-mm margin in all directions.

Barriers to Adopting MMS in Japan—There are many barriers to the broader adoption of MMS in Japan. A guideline of the Japanese Dermatological Association says, MMS “is complicated, requires special training for acquisition, and requires time and labor for implementation of a series of processes, and it has not gained wide acceptance in Japan because of these disadvantages.”³ There currently are no MMS training programs in Japan. We refute this statement from the Japanese Dermatological Association because, in our experience, only 1 surgeon plus a single histotechnician familiar with MMS is sufficient for a facility to offer the procedure (the lead author of this study [S.S.] acts as both the surgeon and the histotechnician). Another misconception among some physicians in Japan is that cancer on ethnically Japanese skin is uniquely suited to excision without microscopic verification of tumor clearance because the borders of the tumors are easily identified, which was based on good cure rates for the excision of well-demarcated pigmented BCCs in a Japanese cohort. This study of a Japanese cohort investigated the specimens with the conventional bread-loafing technique but not with the PDEMA.¹²

Eighty percent (4/5) of our patients presented with nodular BCC, and only 1 required a second stage. In comparison, we also treated 16 White patients with nodular BCC with MMS during the same period, and 31% (5/16) required more than 1 stage, with 1 patient requiring 3 stages. This cohort, however, is too small to demonstrate a statistically significant difference (S.S., unpublished data, 2020-2022).

A study in Singapore reported the postsurgical complication rate and 5-year recurrence rate for 481 tumors (92% BCC and 7.5% SCC). The median follow-up duration after MMS was 36 months, and the recurrence rate was 0.6%. The postsurgical complications included 11 (2.3%) cases with superficial tip necrosis of surgical flaps/grafts, 2 (0.4%) with mild wound dehiscence, 1 (0.2%) with minor surgical site bleeding, and 1 (0.2%) with minor wound infection.¹³ This study supports the notion that MMS is equally effective for Asian patients.

Awareness of MMS in Japan is lacking, and most Japanese dermatologists do not know about the technique. All 5 patients in our case series asked their dermatologists about alternative treatment options and were not offered MMS. In each case, the patients learned of the technique through internet research.

The lack of insurance reimbursement for MMS in Japan is another barrier. Because the national health insurance does not reimburse for MMS, the procedure is relatively unavailable to most Japanese citizens who cannot pay out-of-pocket for the treatment and do not have supplemental insurance. Mohs micrographic surgery may seem expensive compared to WLE followed by repair; however, in the authors’ experience, in Japan, excision without MMS may require general sedation and multiple surgeries to reconstruct larger skin defects, leading to greater morbidity and risk for the patient.

Conclusion

Mohs micrographic surgery in Japan is in its infancy, and further studies showing recurrence rates and long-term prognosis are needed. Such data should help increase awareness of MMS among Japanese physicians as an excellent treatment option for their patients. Furthermore, as Japan becomes more heterogenous as a society and the US Military increases its presence in the region, the need for MMS is likely to increase.

Acknowledgments—We appreciate the proofreading support by Mark Bivens, MBA, MSc (Tokyo, Japan), as well as the technical support from Ben Tallon, MBChB, and Robyn Mason (both in Tauranga, New Zealand) to start MMS at our clinic.