Nonmelanoma Skin Cancer

The term tanorexia describes compulsive use of a tanning bed, a disorder often identified in White patients. This compulsion is driven by underlying psychological distress that typically correlates with another psychiatric disorder, such as anxiety, body dysmorphic disorder, or an eating disorder. ¹ Severe anorexia combined with excessive indoor tanning led to a notable burden of cutaneous squamous cell carcinomas (SCCs) and keratoacanthomas in one of our patients. We discuss the management and approach to patient care in this difficult situation, which we have coined TANS syndrome (for T anorexia, A norexia, and N onmelanoma s kin cancer).

A Patient With TANS Syndrome

A 35-year-old cachectic woman, who appeared much older than her chronologic age, presented for management of numerous painful bleeding skin lesions. Diffuse, erythematous, tender nodules with central keratotic cores, some several centimeters in diameter, were scattered on the abdomen, chest, and extremities (Figure 1); similar lesions were noted on the neck (Figure 2). Numerous erythematous scaly papules and plaques consistent with actinic keratoses were noted throughout the body.

The patient reported that the cutaneous SCCs presented over the last few years, whereas her eating disorder began in adolescence and persisted despite multiple intensive outpatient and inpatient programs. The patient adamantly refused repeat hospitalization, against repeated suggestions by health care providers and her family. Comorbidities related to her anorexia included severe renal insufficiency, iron deficiency anemia, hypertriglyceridemia, kwashiorkor, and pellagra.

Within the last year, the patient had several biopsies showing SCC, keratoacanthoma type. The largest tumors had been treated by Mohs micrographic surgery, excision, and electrodesiccation or curettage. Adjuvant therapy over the last 2 years consisted of tazarotene cream 0.1%, imiquimod cream 5%, oral nicotinamide 500 mg twice daily, and acitretin 10 to 20 mg daily. Human papillomavirus 9-valent vaccine, recombinant, also had been tried as a chemopreventive and treatment, based on a published report of 2 patients in whom keratinocytic carcinomas decreased after such vaccination.² The dose of acitretin was kept low because of the patient’s severe renal insufficiency and lack of supporting data for its use in this setting. Despite these modalities, our patient continued to develop new cutaneous SCCs.

We considered starting intralesional methotrexate but deferred this course of action, given the patient’s deteriorating renal function. Our plan was to initiate intralesional 5-fluorouracil; however, the patient was admitted to the hospital and subsequently died due to cardiovascular complications of anorexia.

UV Radiation in the Setting of Immune Compromise

Habitual tanning bed use has been recognized as a psychologic addiction.^3,4 After exposure to UV radiation, damaged DNA upregulates pro-opiomelanocortin, which posttranslationally generates β-endorphins to elevate mood.^3,5

Tanning beds deliver a higher dose of UVA radiation than UVB radiation and cause darkening of pigmentation by oxidation of preformed melanin and redistribution of melanosomes.³ UVA radiation (320–400 nm) emitted from a tanning bed is 10- to 15-times higher than the radiation emitted by the midday sun and causes DNA damage through generation of reactive oxygen species. UVA penetrates the dermis; its harmful effect on DNA contributes to the pathogenesis of melanoma.

UVB radiation (290–320 nm) is mainly restricted to the epidermis and is largely responsible for erythema of the skin. UVB specifically causes direct damage to DNA by forming pyrimidine dimers, superficially causing sunburn. Excessive exposure to UVB radiation increases the risk for nonmelanoma skin cancer.⁶

Severe starvation and chronic malnutrition, as seen in anorexia nervosa, also are known to lead to immunosuppression.⁷ Exposure to UV radiation has been shown to impair the function of antigen-presenting cells, cytokines, and suppressor T cells, and is classified as a Group 1 carcinogen by the World Health Organization.^3,8 Combining a compromised immune system in anorexia with DNA damage from frequent indoor tanning provides a dangerous milieu for carcinogenesis.⁸ Without immune surveillance, as occurs with adequate nutrition, treatment of cutaneous SCC is, at best, challenging.

Primary care physicians, dermatologists, psychiatrists, nutritionists, and public health officials should educate high-risk patients to prevent TANS syndrome.

The term tanorexia describes compulsive use of a tanning bed, a disorder often identified in White patients. This compulsion is driven by underlying psychological distress that typically correlates with another psychiatric disorder, such as anxiety, body dysmorphic disorder, or an eating disorder. ¹ Severe anorexia combined with excessive indoor tanning led to a notable burden of cutaneous squamous cell carcinomas (SCCs) and keratoacanthomas in one of our patients. We discuss the management and approach to patient care in this difficult situation, which we have coined TANS syndrome (for T anorexia, A norexia, and N onmelanoma s kin cancer).

A Patient With TANS Syndrome

A 35-year-old cachectic woman, who appeared much older than her chronologic age, presented for management of numerous painful bleeding skin lesions. Diffuse, erythematous, tender nodules with central keratotic cores, some several centimeters in diameter, were scattered on the abdomen, chest, and extremities (Figure 1); similar lesions were noted on the neck (Figure 2). Numerous erythematous scaly papules and plaques consistent with actinic keratoses were noted throughout the body.

The patient reported that the cutaneous SCCs presented over the last few years, whereas her eating disorder began in adolescence and persisted despite multiple intensive outpatient and inpatient programs. The patient adamantly refused repeat hospitalization, against repeated suggestions by health care providers and her family. Comorbidities related to her anorexia included severe renal insufficiency, iron deficiency anemia, hypertriglyceridemia, kwashiorkor, and pellagra.

Within the last year, the patient had several biopsies showing SCC, keratoacanthoma type. The largest tumors had been treated by Mohs micrographic surgery, excision, and electrodesiccation or curettage. Adjuvant therapy over the last 2 years consisted of tazarotene cream 0.1%, imiquimod cream 5%, oral nicotinamide 500 mg twice daily, and acitretin 10 to 20 mg daily. Human papillomavirus 9-valent vaccine, recombinant, also had been tried as a chemopreventive and treatment, based on a published report of 2 patients in whom keratinocytic carcinomas decreased after such vaccination.² The dose of acitretin was kept low because of the patient’s severe renal insufficiency and lack of supporting data for its use in this setting. Despite these modalities, our patient continued to develop new cutaneous SCCs.

We considered starting intralesional methotrexate but deferred this course of action, given the patient’s deteriorating renal function. Our plan was to initiate intralesional 5-fluorouracil; however, the patient was admitted to the hospital and subsequently died due to cardiovascular complications of anorexia.

UV Radiation in the Setting of Immune Compromise

Habitual tanning bed use has been recognized as a psychologic addiction.^3,4 After exposure to UV radiation, damaged DNA upregulates pro-opiomelanocortin, which posttranslationally generates β-endorphins to elevate mood.^3,5

Tanning beds deliver a higher dose of UVA radiation than UVB radiation and cause darkening of pigmentation by oxidation of preformed melanin and redistribution of melanosomes.³ UVA radiation (320–400 nm) emitted from a tanning bed is 10- to 15-times higher than the radiation emitted by the midday sun and causes DNA damage through generation of reactive oxygen species. UVA penetrates the dermis; its harmful effect on DNA contributes to the pathogenesis of melanoma.

UVB radiation (290–320 nm) is mainly restricted to the epidermis and is largely responsible for erythema of the skin. UVB specifically causes direct damage to DNA by forming pyrimidine dimers, superficially causing sunburn. Excessive exposure to UVB radiation increases the risk for nonmelanoma skin cancer.⁶

Severe starvation and chronic malnutrition, as seen in anorexia nervosa, also are known to lead to immunosuppression.⁷ Exposure to UV radiation has been shown to impair the function of antigen-presenting cells, cytokines, and suppressor T cells, and is classified as a Group 1 carcinogen by the World Health Organization.^3,8 Combining a compromised immune system in anorexia with DNA damage from frequent indoor tanning provides a dangerous milieu for carcinogenesis.⁸ Without immune surveillance, as occurs with adequate nutrition, treatment of cutaneous SCC is, at best, challenging.

Primary care physicians, dermatologists, psychiatrists, nutritionists, and public health officials should educate high-risk patients to prevent TANS syndrome.

The term tanorexia describes compulsive use of a tanning bed, a disorder often identified in White patients. This compulsion is driven by underlying psychological distress that typically correlates with another psychiatric disorder, such as anxiety, body dysmorphic disorder, or an eating disorder. ¹ Severe anorexia combined with excessive indoor tanning led to a notable burden of cutaneous squamous cell carcinomas (SCCs) and keratoacanthomas in one of our patients. We discuss the management and approach to patient care in this difficult situation, which we have coined TANS syndrome (for T anorexia, A norexia, and N onmelanoma s kin cancer).

A Patient With TANS Syndrome

A 35-year-old cachectic woman, who appeared much older than her chronologic age, presented for management of numerous painful bleeding skin lesions. Diffuse, erythematous, tender nodules with central keratotic cores, some several centimeters in diameter, were scattered on the abdomen, chest, and extremities (Figure 1); similar lesions were noted on the neck (Figure 2). Numerous erythematous scaly papules and plaques consistent with actinic keratoses were noted throughout the body.

The patient reported that the cutaneous SCCs presented over the last few years, whereas her eating disorder began in adolescence and persisted despite multiple intensive outpatient and inpatient programs. The patient adamantly refused repeat hospitalization, against repeated suggestions by health care providers and her family. Comorbidities related to her anorexia included severe renal insufficiency, iron deficiency anemia, hypertriglyceridemia, kwashiorkor, and pellagra.

Within the last year, the patient had several biopsies showing SCC, keratoacanthoma type. The largest tumors had been treated by Mohs micrographic surgery, excision, and electrodesiccation or curettage. Adjuvant therapy over the last 2 years consisted of tazarotene cream 0.1%, imiquimod cream 5%, oral nicotinamide 500 mg twice daily, and acitretin 10 to 20 mg daily. Human papillomavirus 9-valent vaccine, recombinant, also had been tried as a chemopreventive and treatment, based on a published report of 2 patients in whom keratinocytic carcinomas decreased after such vaccination.² The dose of acitretin was kept low because of the patient’s severe renal insufficiency and lack of supporting data for its use in this setting. Despite these modalities, our patient continued to develop new cutaneous SCCs.

We considered starting intralesional methotrexate but deferred this course of action, given the patient’s deteriorating renal function. Our plan was to initiate intralesional 5-fluorouracil; however, the patient was admitted to the hospital and subsequently died due to cardiovascular complications of anorexia.

UV Radiation in the Setting of Immune Compromise

Habitual tanning bed use has been recognized as a psychologic addiction.^3,4 After exposure to UV radiation, damaged DNA upregulates pro-opiomelanocortin, which posttranslationally generates β-endorphins to elevate mood.^3,5

Tanning beds deliver a higher dose of UVA radiation than UVB radiation and cause darkening of pigmentation by oxidation of preformed melanin and redistribution of melanosomes.³ UVA radiation (320–400 nm) emitted from a tanning bed is 10- to 15-times higher than the radiation emitted by the midday sun and causes DNA damage through generation of reactive oxygen species. UVA penetrates the dermis; its harmful effect on DNA contributes to the pathogenesis of melanoma.

UVB radiation (290–320 nm) is mainly restricted to the epidermis and is largely responsible for erythema of the skin. UVB specifically causes direct damage to DNA by forming pyrimidine dimers, superficially causing sunburn. Excessive exposure to UVB radiation increases the risk for nonmelanoma skin cancer.⁶

Severe starvation and chronic malnutrition, as seen in anorexia nervosa, also are known to lead to immunosuppression.⁷ Exposure to UV radiation has been shown to impair the function of antigen-presenting cells, cytokines, and suppressor T cells, and is classified as a Group 1 carcinogen by the World Health Organization.^3,8 Combining a compromised immune system in anorexia with DNA damage from frequent indoor tanning provides a dangerous milieu for carcinogenesis.⁸ Without immune surveillance, as occurs with adequate nutrition, treatment of cutaneous SCC is, at best, challenging.

Primary care physicians, dermatologists, psychiatrists, nutritionists, and public health officials should educate high-risk patients to prevent TANS syndrome.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

Using sunscreen and following other sun-protective behaviors such as wearing long sleeves or staying in the shade do not decrease bone mineral density overall or increase the risk of osteoporotic fracture, according to a new study that included more than 3,000 men and women.

Aja Koska/Getty Images

“We have objective data for the first time, and in a large-scale representative population of the U.S. adults, to indicate sun protection is not associated with negative bone-related outcomes,” said study lead author Mohsen Afarideh, MD, MPH, a postdoctoral research fellow at the autoimmune skin diseases unit at the University of Pennsylvania, Philadelphia.

The study, published online in JAMA Dermatology, goes a step further than previous research by others that has found sunscreen use does not compromise vitamin D synthesis and has little effect on circulating 25-hydroxyvitamin D levels.

In the new study, researchers looked at three sun-protective behaviors – sunscreen use, staying in the shade, wearing long sleeves – and their effects on bone mineral density and the risk of fractures.

While the effects of sun-protective habits on blood levels of vitamin D and BMD scores are important, ‘’what we are more interested to know is if the sun-protective behaviors actually cause or increase the risk of fracture,” Dr. Afarideh said in an interview. “The answer to that is a firm ‘No.’ These data are very reassuring and will help clinicians to keep recommending sun protection to the public.”

Study details

Dr. Afarideh and his colleagues from the Mayo Clinic in Rochester, Minn., looked at data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018, obtaining final information on 3,403 men and women, ages 20-59, who completed a dermatology questionnaire The men and women reported on the three sun-protective habits, and noted whether they followed these practices always or most of the time, sometimes, or never or rarely.

The frequency of the three behaviors was not widespread. Frequent staying in the shade was reported by 31.6% of the sample, wearing long sleeves by 11.8%, and sunscreen use by 26.1%.

The researchers also had data on the participants’ bone mineral density (BMD) scores along with dietary information such as milk consumption, vitamin D supplement use, taking steroid drugs, and exercise activity.

“Moderate sunscreen use was linked with a slightly lower lumbar BMD score,” Dr. Afarideh said, which was “the only significant association that could be interpreted as concerning.” And this was more likely to be seen in older respondents, he said.

However, otherwise they found the practice of the three behaviors was not associated with lower total or site-specific BMD z scores, nor was it linked with an increased risk of osteoporotic fractures. (The BMD z score compares an individual’s bone density to the average bone density of someone their same age and gender.)

The focus on fracture risk is the more important outcome, Dr. Afarideh said. And they found no increased risk overall of osteoporotic fractures in those who practiced sun-protective behaviors.

Moderate to frequent staying in the shade was actually linked with a reduced prevalence of spine fractures in the multivariate model (odds ratio, 0.19; 95% confidence interval, 0.04-0.86, P = .02). The researchers say that may be attributable to these respondents also being careful in other areas of life, such as avoiding falls and not participating in high-risk activities that would increase the chance of fractures. “However, this is just an assumption,” Dr. Afarideh said.

Expert perspectives

Other dermatologists not involved in the new research said the study results provide some “real-world” information that’s valuable for clinicians to share with patients.

“I think this is an important study on multiple levels,” said Henry W. Lim, MD, a former president of the American Academy of Dermatology who is a member of the department of dermatology and senior vice president of academic affairs at Henry Ford Health System, Detroit. “It is a well-done study, involving a large number. It is a real-life situation, asking people their photo protective behaviors and then looking at their bone mineral density.” The bottom line, he said: “Bone health is not affected by photo protection habits in real life.”

The findings are important but not surprising, said Antony R. Young, PhD, emeritus professor of experimental photobiology at St. John’s Institute of Dermatology, King’s College, London, who has researched sunscreens and vitamin D status. “My study showed that correct sunscreen use, albeit with a relatively low SPF of 15, did prevent sunburn in a high UVR [ultraviolet radiation] environment but did allow very good vitamin D synthesis. I think this is because the necessary dose of UVB is very low.”

Michele Green, MD, a New York dermatologist and clinical staff member at Lenox Hill Hospital there, said she often hears concerns about bone health from patients. “Every week, patients ask, ‘Why would I wear sunblock? Don’t I need sun for bone health? Don’t I need it for vitamin D?’’’

Now, she said, ‘’Dermatologists can point to the study and say ‘Don’t worry.’ It clarifies that using sunscreen won’t cause you to have osteoporosis.’’

Dr. Afarideh, who was a postdoctoral research fellow at the Mayo Clinic, and his coauthors, Megha M. Tollefson, MD, and Julio C. Sartori-Valinotti, of the Mayo Clinic, and Dr. Green had no disclosures. Dr. Lim and Dr. Young consult for the sunscreen industry.

Using sunscreen and following other sun-protective behaviors such as wearing long sleeves or staying in the shade do not decrease bone mineral density overall or increase the risk of osteoporotic fracture, according to a new study that included more than 3,000 men and women.

Aja Koska/Getty Images

“We have objective data for the first time, and in a large-scale representative population of the U.S. adults, to indicate sun protection is not associated with negative bone-related outcomes,” said study lead author Mohsen Afarideh, MD, MPH, a postdoctoral research fellow at the autoimmune skin diseases unit at the University of Pennsylvania, Philadelphia.

The study, published online in JAMA Dermatology, goes a step further than previous research by others that has found sunscreen use does not compromise vitamin D synthesis and has little effect on circulating 25-hydroxyvitamin D levels.

In the new study, researchers looked at three sun-protective behaviors – sunscreen use, staying in the shade, wearing long sleeves – and their effects on bone mineral density and the risk of fractures.

While the effects of sun-protective habits on blood levels of vitamin D and BMD scores are important, ‘’what we are more interested to know is if the sun-protective behaviors actually cause or increase the risk of fracture,” Dr. Afarideh said in an interview. “The answer to that is a firm ‘No.’ These data are very reassuring and will help clinicians to keep recommending sun protection to the public.”

Study details

Dr. Afarideh and his colleagues from the Mayo Clinic in Rochester, Minn., looked at data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018, obtaining final information on 3,403 men and women, ages 20-59, who completed a dermatology questionnaire The men and women reported on the three sun-protective habits, and noted whether they followed these practices always or most of the time, sometimes, or never or rarely.

The frequency of the three behaviors was not widespread. Frequent staying in the shade was reported by 31.6% of the sample, wearing long sleeves by 11.8%, and sunscreen use by 26.1%.

The researchers also had data on the participants’ bone mineral density (BMD) scores along with dietary information such as milk consumption, vitamin D supplement use, taking steroid drugs, and exercise activity.

“Moderate sunscreen use was linked with a slightly lower lumbar BMD score,” Dr. Afarideh said, which was “the only significant association that could be interpreted as concerning.” And this was more likely to be seen in older respondents, he said.

However, otherwise they found the practice of the three behaviors was not associated with lower total or site-specific BMD z scores, nor was it linked with an increased risk of osteoporotic fractures. (The BMD z score compares an individual’s bone density to the average bone density of someone their same age and gender.)

The focus on fracture risk is the more important outcome, Dr. Afarideh said. And they found no increased risk overall of osteoporotic fractures in those who practiced sun-protective behaviors.

Moderate to frequent staying in the shade was actually linked with a reduced prevalence of spine fractures in the multivariate model (odds ratio, 0.19; 95% confidence interval, 0.04-0.86, P = .02). The researchers say that may be attributable to these respondents also being careful in other areas of life, such as avoiding falls and not participating in high-risk activities that would increase the chance of fractures. “However, this is just an assumption,” Dr. Afarideh said.

Expert perspectives

Other dermatologists not involved in the new research said the study results provide some “real-world” information that’s valuable for clinicians to share with patients.

“I think this is an important study on multiple levels,” said Henry W. Lim, MD, a former president of the American Academy of Dermatology who is a member of the department of dermatology and senior vice president of academic affairs at Henry Ford Health System, Detroit. “It is a well-done study, involving a large number. It is a real-life situation, asking people their photo protective behaviors and then looking at their bone mineral density.” The bottom line, he said: “Bone health is not affected by photo protection habits in real life.”

The findings are important but not surprising, said Antony R. Young, PhD, emeritus professor of experimental photobiology at St. John’s Institute of Dermatology, King’s College, London, who has researched sunscreens and vitamin D status. “My study showed that correct sunscreen use, albeit with a relatively low SPF of 15, did prevent sunburn in a high UVR [ultraviolet radiation] environment but did allow very good vitamin D synthesis. I think this is because the necessary dose of UVB is very low.”

Michele Green, MD, a New York dermatologist and clinical staff member at Lenox Hill Hospital there, said she often hears concerns about bone health from patients. “Every week, patients ask, ‘Why would I wear sunblock? Don’t I need sun for bone health? Don’t I need it for vitamin D?’’’

Now, she said, ‘’Dermatologists can point to the study and say ‘Don’t worry.’ It clarifies that using sunscreen won’t cause you to have osteoporosis.’’

Dr. Afarideh, who was a postdoctoral research fellow at the Mayo Clinic, and his coauthors, Megha M. Tollefson, MD, and Julio C. Sartori-Valinotti, of the Mayo Clinic, and Dr. Green had no disclosures. Dr. Lim and Dr. Young consult for the sunscreen industry.

Using sunscreen and following other sun-protective behaviors such as wearing long sleeves or staying in the shade do not decrease bone mineral density overall or increase the risk of osteoporotic fracture, according to a new study that included more than 3,000 men and women.

Aja Koska/Getty Images

“We have objective data for the first time, and in a large-scale representative population of the U.S. adults, to indicate sun protection is not associated with negative bone-related outcomes,” said study lead author Mohsen Afarideh, MD, MPH, a postdoctoral research fellow at the autoimmune skin diseases unit at the University of Pennsylvania, Philadelphia.

The study, published online in JAMA Dermatology, goes a step further than previous research by others that has found sunscreen use does not compromise vitamin D synthesis and has little effect on circulating 25-hydroxyvitamin D levels.

In the new study, researchers looked at three sun-protective behaviors – sunscreen use, staying in the shade, wearing long sleeves – and their effects on bone mineral density and the risk of fractures.

While the effects of sun-protective habits on blood levels of vitamin D and BMD scores are important, ‘’what we are more interested to know is if the sun-protective behaviors actually cause or increase the risk of fracture,” Dr. Afarideh said in an interview. “The answer to that is a firm ‘No.’ These data are very reassuring and will help clinicians to keep recommending sun protection to the public.”

Study details

Dr. Afarideh and his colleagues from the Mayo Clinic in Rochester, Minn., looked at data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018, obtaining final information on 3,403 men and women, ages 20-59, who completed a dermatology questionnaire The men and women reported on the three sun-protective habits, and noted whether they followed these practices always or most of the time, sometimes, or never or rarely.

The frequency of the three behaviors was not widespread. Frequent staying in the shade was reported by 31.6% of the sample, wearing long sleeves by 11.8%, and sunscreen use by 26.1%.

The researchers also had data on the participants’ bone mineral density (BMD) scores along with dietary information such as milk consumption, vitamin D supplement use, taking steroid drugs, and exercise activity.

“Moderate sunscreen use was linked with a slightly lower lumbar BMD score,” Dr. Afarideh said, which was “the only significant association that could be interpreted as concerning.” And this was more likely to be seen in older respondents, he said.

However, otherwise they found the practice of the three behaviors was not associated with lower total or site-specific BMD z scores, nor was it linked with an increased risk of osteoporotic fractures. (The BMD z score compares an individual’s bone density to the average bone density of someone their same age and gender.)

The focus on fracture risk is the more important outcome, Dr. Afarideh said. And they found no increased risk overall of osteoporotic fractures in those who practiced sun-protective behaviors.

Moderate to frequent staying in the shade was actually linked with a reduced prevalence of spine fractures in the multivariate model (odds ratio, 0.19; 95% confidence interval, 0.04-0.86, P = .02). The researchers say that may be attributable to these respondents also being careful in other areas of life, such as avoiding falls and not participating in high-risk activities that would increase the chance of fractures. “However, this is just an assumption,” Dr. Afarideh said.

Expert perspectives

Other dermatologists not involved in the new research said the study results provide some “real-world” information that’s valuable for clinicians to share with patients.

“I think this is an important study on multiple levels,” said Henry W. Lim, MD, a former president of the American Academy of Dermatology who is a member of the department of dermatology and senior vice president of academic affairs at Henry Ford Health System, Detroit. “It is a well-done study, involving a large number. It is a real-life situation, asking people their photo protective behaviors and then looking at their bone mineral density.” The bottom line, he said: “Bone health is not affected by photo protection habits in real life.”

The findings are important but not surprising, said Antony R. Young, PhD, emeritus professor of experimental photobiology at St. John’s Institute of Dermatology, King’s College, London, who has researched sunscreens and vitamin D status. “My study showed that correct sunscreen use, albeit with a relatively low SPF of 15, did prevent sunburn in a high UVR [ultraviolet radiation] environment but did allow very good vitamin D synthesis. I think this is because the necessary dose of UVB is very low.”

Michele Green, MD, a New York dermatologist and clinical staff member at Lenox Hill Hospital there, said she often hears concerns about bone health from patients. “Every week, patients ask, ‘Why would I wear sunblock? Don’t I need sun for bone health? Don’t I need it for vitamin D?’’’

Now, she said, ‘’Dermatologists can point to the study and say ‘Don’t worry.’ It clarifies that using sunscreen won’t cause you to have osteoporosis.’’

Dr. Afarideh, who was a postdoctoral research fellow at the Mayo Clinic, and his coauthors, Megha M. Tollefson, MD, and Julio C. Sartori-Valinotti, of the Mayo Clinic, and Dr. Green had no disclosures. Dr. Lim and Dr. Young consult for the sunscreen industry.

Researchers writing in the British Journal of Dermatology confirm the long-term use of hydrochlorothiazide is associated with a dose-dependent, twofold increased risk of squamous cell carcinoma, compared with calcium channel blocker use.

The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.

And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma

“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.

This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.

The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.

“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.

Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.

In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.

Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.

In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.

Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.

However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.

“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.

Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.

The authors had no conflicts of interest to declare.

Researchers writing in the British Journal of Dermatology confirm the long-term use of hydrochlorothiazide is associated with a dose-dependent, twofold increased risk of squamous cell carcinoma, compared with calcium channel blocker use.

The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.

And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma

“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.

This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.

The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.

“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.

Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.

In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.

Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.

In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.

Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.

However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.

“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.

Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.

The authors had no conflicts of interest to declare.

Researchers writing in the British Journal of Dermatology confirm the long-term use of hydrochlorothiazide is associated with a dose-dependent, twofold increased risk of squamous cell carcinoma, compared with calcium channel blocker use.

The findings were originally reported in two Danish case-control studies in which physicians reported a fourfold increased risk of squamous cell carcinoma, and a moderate increased risk of basal cell carcinoma and cutaneous malignant melanoma in patients who used hydrochlorothiazide long-term.

And, while the new study did not find an increased risk of basal cell carcinoma and cutaneous malignant melanoma among long-term users of hydrochlorothiazide, they suggest that bendroflumethiazide “may be a safer alternative for patients at increased risk of skin cancer.” The long-term use of indapamide was associated with a moderately increased risk of cutaneous malignant melanoma but did not alter the risk of either squamous cell or basal cell carcinoma

“Our results suggest that bendroflumethiazide may be a safer alternative to hydrochlorothiazide and indapamide, especially for patients at increased risk of skin cancer, but future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma,” wrote authors who were led by Christoph R. Meier, PhD, a professor in pharmacy with University Hospital Basel (Switzerland) and a contributor to the Boston Collaborative Drug Surveillance Program.

This study adds to existing evidence that there is a dose-dependent increased risk of squamous cell carcinoma in users of high cumulative doses of hydrochlorothiazide, compared with non–hydrochlorothiazide users.

The study, an observational cohort study, was published earlier this year. It is based on data from the U.K.-based Clinical Practice Research Datalink. It included 271,154 new users of thiazides and thiazidelike diuretics, the majority at 87.6% having been prescribed bendroflumethiazide, 5.8% indapamide, and 3.6% hydrochlorothiazide. Outcomes were compared to those observed in 275,263 users of calcium channel blockers.

“The three primary outcomes of interest were a first-time diagnosis of cutaneous malignant melanoma, basal cell carcinoma, or squamous cell carcinoma,” the authors wrote.

Incidence rates and incidence rate ratios were estimated for both short-term and long-term users of thiazidelike diuretics and calcium channel blockers, while a propensity score (PS) analysis was done in order to control for 23 baseline covariates. The mean follow-up after PS weighting was 3.9 years for indapamide users and 5.5 years for hydrochlorothiazide users. Overall, the incidence rate ratios of squamous cell carcinoma were not markedly increased for either short-term or long-term users of thiazidelike diuretics, the authors reported.

In contrast, the incidence rate ratios of squamous cell carcinoma for hydrochlorothiazide users were increased by 29% for short-term users at an IRR of 1.29 while they were increased by almost twofold for long-term hydrochlorothiazide users at an IRR of 1.95.

Long-term use of hydrochlorothiazide was again associated with a 64% increased risk of basal cell carcinoma, compared with users of a renin-angiotensin inhibitor at a weighted IRR of 1.64.

In contrast, weighted incident rate ratios for basal cell carcinoma for both short-term and long-term thiazide users were not significantly different and results were similar for patients who took hydrochlorothiazide, indapamide, or bendroflumethiazide.

Weighted overall incident rate ratios for cutaneous malignant melanoma were not significantly different for either short-term or long-term users of thiazidelike diuretics, compared with calcium channel blocker users.

However, there was a 43% increased risk of cutaneous malignant melanoma among long-term indapamide users at a weighted IRR of 1.43, compared with calcium channel blocker users, the authors reported.

“Given the biological plausibility and the severe clinical implications of cutaneous malignant melanoma, this finding should be considered carefully,” they cautioned.

Limitations to the study include the fact that the database analyzed does not have information on sun exposure, skin characteristics, or socioeconomic status which may affect the amount of sun exposure participants received.

The authors had no conflicts of interest to declare.

Checkpoint inhibitor use as adjuvant therapy for patients with high-risk cutaneous squamous cell carcinoma (cSCC) may eventually overtake the use of cytotoxic chemotherapeutic agents, say the authors of a clinical review recently published in the journal Head and Neck.

The review, led by Jason G. Newman, MD, director of head and neck surgery at Penn Medicine, Philadelphia, includes evidence-based research findings from the last 10 years which describe the possible roles for adjuvant radiation, chemotherapy, immunotherapy, and/or targeted therapy in the management of high-risk cSCC.

Dr. Newman and colleagues wrote that more data – and high-quality data – are needed for physicians to determine with more confidence which adjuvant therapies would be best for specific patients with high-risk cSCC. But without that data, uncertainty in treatment decisions will persist.

“The requirements for and efficacy of adjuvant therapies in cutaneous squamous cell carcinoma are unclear, and the gap in evidence for practice decisions regarding adjuvant therapy in patients with high-risk cSCC has been apparent for more than a decade,” they wrote.

While surgical excision with clear margins of the primary cSCC lesion remains the standard of care, certain high-risk factors necessitate adjuvant therapy, the authors wrote. However, since the evidence consists of small retrospective studies with conflicting results, it is unclear which patients might benefit from adjuvant therapy. This review included recent and current trials in cutaneous SCC and the role of immune checkpoint inhibitors.

According to the review, adjuvant radiation therapy is usually considered with high-risk features, such as perineural invasion, lymph node metastasis and extracapsular/extranodal extension, if the patient is otherwise at high risk for metastasis or recurrence, or if further surgery is not possible.

The National Comprehensive Cancer Network, the American College of Radiology, and the American Society for Radiation Oncology do not recommend adjuvant radiation therapy for most patients with cSCC. However, adjuvant radiation therapy with or without systemic therapy may be considered in locally advanced disease, when further surgery is not an option, or if there is regional lymph node metastasis, but multidisciplinary consultation is recommended.

Regarding checkpoint inhibitors, the NCCN, ACR, and ASTRO do not recommend the use of systemic therapy for local disease amenable to surgery. Potential use of a checkpoint inhibitor with radiation therapy in a clinical trial is recommended for residual disease in locally advanced cSCC as palliative care when other options are not available. While the use of cemiplimab or pembrolizumab are preferred in regional recurrence when curative surgery and radiation therapy are not an option, a targeted therapy can be considered if this is not feasible.

“Given the current activity of checkpoint inhibition in this disease, enthusiasm for the addition of cytotoxic chemotherapeutic agents in the adjuvant setting may be on the decline,” the authors wrote. “Multidisciplinary approaches will most likely continue to be recommended in complicated cases, including those involving immunosuppression.”

The authors said that further study is needed on prognostic testing, such as gene expression profile testing or sentinel lymph node biopsy, as such testing early in disease could identify patients who would likely benefit from adjuvant therapy. They added that the need to identify patients at early stages of disease who are at high risk for metastasis continues to remain critical.

Checkpoint inhibitor use as adjuvant therapy for patients with high-risk cutaneous squamous cell carcinoma (cSCC) may eventually overtake the use of cytotoxic chemotherapeutic agents, say the authors of a clinical review recently published in the journal Head and Neck.

The review, led by Jason G. Newman, MD, director of head and neck surgery at Penn Medicine, Philadelphia, includes evidence-based research findings from the last 10 years which describe the possible roles for adjuvant radiation, chemotherapy, immunotherapy, and/or targeted therapy in the management of high-risk cSCC.

Dr. Newman and colleagues wrote that more data – and high-quality data – are needed for physicians to determine with more confidence which adjuvant therapies would be best for specific patients with high-risk cSCC. But without that data, uncertainty in treatment decisions will persist.

“The requirements for and efficacy of adjuvant therapies in cutaneous squamous cell carcinoma are unclear, and the gap in evidence for practice decisions regarding adjuvant therapy in patients with high-risk cSCC has been apparent for more than a decade,” they wrote.

While surgical excision with clear margins of the primary cSCC lesion remains the standard of care, certain high-risk factors necessitate adjuvant therapy, the authors wrote. However, since the evidence consists of small retrospective studies with conflicting results, it is unclear which patients might benefit from adjuvant therapy. This review included recent and current trials in cutaneous SCC and the role of immune checkpoint inhibitors.

According to the review, adjuvant radiation therapy is usually considered with high-risk features, such as perineural invasion, lymph node metastasis and extracapsular/extranodal extension, if the patient is otherwise at high risk for metastasis or recurrence, or if further surgery is not possible.

The National Comprehensive Cancer Network, the American College of Radiology, and the American Society for Radiation Oncology do not recommend adjuvant radiation therapy for most patients with cSCC. However, adjuvant radiation therapy with or without systemic therapy may be considered in locally advanced disease, when further surgery is not an option, or if there is regional lymph node metastasis, but multidisciplinary consultation is recommended.

Regarding checkpoint inhibitors, the NCCN, ACR, and ASTRO do not recommend the use of systemic therapy for local disease amenable to surgery. Potential use of a checkpoint inhibitor with radiation therapy in a clinical trial is recommended for residual disease in locally advanced cSCC as palliative care when other options are not available. While the use of cemiplimab or pembrolizumab are preferred in regional recurrence when curative surgery and radiation therapy are not an option, a targeted therapy can be considered if this is not feasible.

“Given the current activity of checkpoint inhibition in this disease, enthusiasm for the addition of cytotoxic chemotherapeutic agents in the adjuvant setting may be on the decline,” the authors wrote. “Multidisciplinary approaches will most likely continue to be recommended in complicated cases, including those involving immunosuppression.”

The authors said that further study is needed on prognostic testing, such as gene expression profile testing or sentinel lymph node biopsy, as such testing early in disease could identify patients who would likely benefit from adjuvant therapy. They added that the need to identify patients at early stages of disease who are at high risk for metastasis continues to remain critical.

Checkpoint inhibitor use as adjuvant therapy for patients with high-risk cutaneous squamous cell carcinoma (cSCC) may eventually overtake the use of cytotoxic chemotherapeutic agents, say the authors of a clinical review recently published in the journal Head and Neck.

The review, led by Jason G. Newman, MD, director of head and neck surgery at Penn Medicine, Philadelphia, includes evidence-based research findings from the last 10 years which describe the possible roles for adjuvant radiation, chemotherapy, immunotherapy, and/or targeted therapy in the management of high-risk cSCC.

Dr. Newman and colleagues wrote that more data – and high-quality data – are needed for physicians to determine with more confidence which adjuvant therapies would be best for specific patients with high-risk cSCC. But without that data, uncertainty in treatment decisions will persist.

“The requirements for and efficacy of adjuvant therapies in cutaneous squamous cell carcinoma are unclear, and the gap in evidence for practice decisions regarding adjuvant therapy in patients with high-risk cSCC has been apparent for more than a decade,” they wrote.

While surgical excision with clear margins of the primary cSCC lesion remains the standard of care, certain high-risk factors necessitate adjuvant therapy, the authors wrote. However, since the evidence consists of small retrospective studies with conflicting results, it is unclear which patients might benefit from adjuvant therapy. This review included recent and current trials in cutaneous SCC and the role of immune checkpoint inhibitors.

According to the review, adjuvant radiation therapy is usually considered with high-risk features, such as perineural invasion, lymph node metastasis and extracapsular/extranodal extension, if the patient is otherwise at high risk for metastasis or recurrence, or if further surgery is not possible.

The National Comprehensive Cancer Network, the American College of Radiology, and the American Society for Radiation Oncology do not recommend adjuvant radiation therapy for most patients with cSCC. However, adjuvant radiation therapy with or without systemic therapy may be considered in locally advanced disease, when further surgery is not an option, or if there is regional lymph node metastasis, but multidisciplinary consultation is recommended.

Regarding checkpoint inhibitors, the NCCN, ACR, and ASTRO do not recommend the use of systemic therapy for local disease amenable to surgery. Potential use of a checkpoint inhibitor with radiation therapy in a clinical trial is recommended for residual disease in locally advanced cSCC as palliative care when other options are not available. While the use of cemiplimab or pembrolizumab are preferred in regional recurrence when curative surgery and radiation therapy are not an option, a targeted therapy can be considered if this is not feasible.

“Given the current activity of checkpoint inhibition in this disease, enthusiasm for the addition of cytotoxic chemotherapeutic agents in the adjuvant setting may be on the decline,” the authors wrote. “Multidisciplinary approaches will most likely continue to be recommended in complicated cases, including those involving immunosuppression.”

The authors said that further study is needed on prognostic testing, such as gene expression profile testing or sentinel lymph node biopsy, as such testing early in disease could identify patients who would likely benefit from adjuvant therapy. They added that the need to identify patients at early stages of disease who are at high risk for metastasis continues to remain critical.

Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

Head and neck cutaneous squamous cell carcinoma (SCC) has an excellent prognosis but around 5% of patients develop nodal metastasis. In cutaneous SCC, metastasis is associated with a 50% decrease in 5-year survival. However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.

In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.

Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.

“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.

Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.

Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.

“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”

Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.

Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.

“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.

Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.

“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”

No disclosures were disclosed for the authors.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

Bloodroot (Sanguinaria canadensis) is a member of the family Papaveraceae.¹ This North American plant commonly is found in widespread distribution from Nova Scotia, Canada, to Florida and from the Great Lakes to Mississippi.² Historically, Native Americans used bloodroot as a skin dye and as a medicine for many ailments.³

Bloodroot blooms for only a few days, starting in March, and fruits in June. The flowers comprise 8 to 10 white petals, surrounding a bed of yellow stamens (Figure). The plant thrives in wooded areas and grows to 12 inches tall. In its off-season, the plant remains dormant and can survive below-freezing temperatures.⁴

Chemical Constituents

Bloodroot gets its colloquial name from its red sap, which is released when the plant’s rhizome is cut. This sap contains a high concentration of alkaloids that are used for protection against predators. The rhizome itself has a rusty, red-brown color; the roots are a brighter red-orange.⁴

The rhizome of S canadensis contains the highest concentration of active alkaloids; the roots also contain these chemicals, though to a lesser degree; and the leaves, flowers, and fruits harvest approximately 1% of the alkaloids found in the roots.⁴ The concentration of alkaloids can vary from one plant to the next, depending on environmental conditions.^5,6

The major alkaloids in S canadensis include both quaternary benzophenanthridine alkaloids (eg, sanguinarine, chelerythrine, sanguilutine, chelilutine, sanguirubine, chelirubine) and protopin alkaloids (eg, protopine, allocryptopine).^3,7 Of these, sanguinarine and chelerythrine typically are the most potent.¹ Oral ingestion or topical application of these molecules can have therapeutic and toxic effects.⁸

Biophysiological Effects

Bloodroot has been shown to have remarkable antimicrobial effects.⁹ The plant produces hydrogen peroxide and superoxide anion.¹⁰ These mediators cause oxidative stress, thus inducing destruction of cellular DNA and the cell membrane.¹¹ Although these effects can be helpful when fighting infection, they are not necessarily selective against healthy cells.¹²

Alkaloids of bloodroot also have cardiovascular therapeutic effects. Sanguinarine blocks angiotensin II and causes vasodilation, thus helping treat hypertension.¹³ It also acts as an inotrope by blocking the Na⁺/K⁺ ATPase pump. These effects in a patient who is already taking digoxin can cause notable cardiotoxicity because the 2 drugs share a mechanism of action.¹⁴

Chelerythrine blocks production of cyclooxygenase 2 and prostaglandin E₂.¹⁵ This pathway modification results in anti-inflammatory effects that can help treat arthritis, edema, and other inflammatory conditions.¹⁶ Moreover, sanguinarine has demonstrated efficacy in numerous anticancer pathways,¹⁷ including downregulation of intercellular adhesion molecules, vascular cell adhesion molecules, and vascular endothelial growth factor (VEGF).^18-20 Blocking VEGF is one way to inhibit angiogenesis,²¹ which is upregulated in tumor formation, thus sanguinarine can have an antiproliferative anticancer effect.²² Sanguinarine also upregulates molecules such as nuclear factor–κB and the protease enzymes known as caspases to cause proapoptotic effects, furthering its antitumor potential.^23,24

Treatment of Dermatologic Conditions

The initial technique of Mohs micrographic surgery employed a chemopaste that utilized an extract of S canadensis to preserve tissue.²⁵ Outside the dermatologist’s office, bloodroot is used as a topical home remedy for a variety of cutaneous conditions, including cancer, skin tags, and warts.²⁶ Bloodroot is advertised as black salve, an alternative anticancer treatment.^27,28

As useful as this natural agent sounds, it has a pitfall: The alkaloids of S canadensis are nonspecific in their cytotoxicity, damaging neoplastic and healthy tissue.²⁹ This cytotoxic effect can cause escharification through diffuse tissue destruction and has been observed to result in formation of a keloid scar.³⁰ The alkaloids in black salve also have been shown to cause skin erosions and cellular atypia.^28,31 Therefore, the utility of this escharotic in medical treatment is limited.³² Fortuitously, oral antibiotics and wound care can help address this adverse effect.²⁸

Bloodroot was once used as a mouth rinse and toothpaste to treat gingivitis, but this application was later associated with oral leukoplakia, a premalignant condition.³³ Leukoplakia associated with S canadensis extract often is unremitting. Immediate discontinuation of the offending agent produces little regression, suggesting that cellular damage is irreversible.³⁴

Final Thoughts

Although bloodroot demonstrates efficacy as a phytotherapeutic, it does come with notable toxicity. Physicians should warn patients of the unwanted cosmetic effects of black salve, especially oral products that incorporate sanguinarine. Adverse effects on the oropharynx can be irreversible, though the eschar associated with black salve can be treated with a topical or oral corticosteroid.²⁹

Bloodroot (Sanguinaria canadensis) is a member of the family Papaveraceae.¹ This North American plant commonly is found in widespread distribution from Nova Scotia, Canada, to Florida and from the Great Lakes to Mississippi.² Historically, Native Americans used bloodroot as a skin dye and as a medicine for many ailments.³

Bloodroot blooms for only a few days, starting in March, and fruits in June. The flowers comprise 8 to 10 white petals, surrounding a bed of yellow stamens (Figure). The plant thrives in wooded areas and grows to 12 inches tall. In its off-season, the plant remains dormant and can survive below-freezing temperatures.⁴

Chemical Constituents

Bloodroot gets its colloquial name from its red sap, which is released when the plant’s rhizome is cut. This sap contains a high concentration of alkaloids that are used for protection against predators. The rhizome itself has a rusty, red-brown color; the roots are a brighter red-orange.⁴

The rhizome of S canadensis contains the highest concentration of active alkaloids; the roots also contain these chemicals, though to a lesser degree; and the leaves, flowers, and fruits harvest approximately 1% of the alkaloids found in the roots.⁴ The concentration of alkaloids can vary from one plant to the next, depending on environmental conditions.^5,6

The major alkaloids in S canadensis include both quaternary benzophenanthridine alkaloids (eg, sanguinarine, chelerythrine, sanguilutine, chelilutine, sanguirubine, chelirubine) and protopin alkaloids (eg, protopine, allocryptopine).^3,7 Of these, sanguinarine and chelerythrine typically are the most potent.¹ Oral ingestion or topical application of these molecules can have therapeutic and toxic effects.⁸

Biophysiological Effects

Bloodroot has been shown to have remarkable antimicrobial effects.⁹ The plant produces hydrogen peroxide and superoxide anion.¹⁰ These mediators cause oxidative stress, thus inducing destruction of cellular DNA and the cell membrane.¹¹ Although these effects can be helpful when fighting infection, they are not necessarily selective against healthy cells.¹²

Alkaloids of bloodroot also have cardiovascular therapeutic effects. Sanguinarine blocks angiotensin II and causes vasodilation, thus helping treat hypertension.¹³ It also acts as an inotrope by blocking the Na⁺/K⁺ ATPase pump. These effects in a patient who is already taking digoxin can cause notable cardiotoxicity because the 2 drugs share a mechanism of action.¹⁴

Chelerythrine blocks production of cyclooxygenase 2 and prostaglandin E₂.¹⁵ This pathway modification results in anti-inflammatory effects that can help treat arthritis, edema, and other inflammatory conditions.¹⁶ Moreover, sanguinarine has demonstrated efficacy in numerous anticancer pathways,¹⁷ including downregulation of intercellular adhesion molecules, vascular cell adhesion molecules, and vascular endothelial growth factor (VEGF).^18-20 Blocking VEGF is one way to inhibit angiogenesis,²¹ which is upregulated in tumor formation, thus sanguinarine can have an antiproliferative anticancer effect.²² Sanguinarine also upregulates molecules such as nuclear factor–κB and the protease enzymes known as caspases to cause proapoptotic effects, furthering its antitumor potential.^23,24

Treatment of Dermatologic Conditions

The initial technique of Mohs micrographic surgery employed a chemopaste that utilized an extract of S canadensis to preserve tissue.²⁵ Outside the dermatologist’s office, bloodroot is used as a topical home remedy for a variety of cutaneous conditions, including cancer, skin tags, and warts.²⁶ Bloodroot is advertised as black salve, an alternative anticancer treatment.^27,28

As useful as this natural agent sounds, it has a pitfall: The alkaloids of S canadensis are nonspecific in their cytotoxicity, damaging neoplastic and healthy tissue.²⁹ This cytotoxic effect can cause escharification through diffuse tissue destruction and has been observed to result in formation of a keloid scar.³⁰ The alkaloids in black salve also have been shown to cause skin erosions and cellular atypia.^28,31 Therefore, the utility of this escharotic in medical treatment is limited.³² Fortuitously, oral antibiotics and wound care can help address this adverse effect.²⁸

Bloodroot was once used as a mouth rinse and toothpaste to treat gingivitis, but this application was later associated with oral leukoplakia, a premalignant condition.³³ Leukoplakia associated with S canadensis extract often is unremitting. Immediate discontinuation of the offending agent produces little regression, suggesting that cellular damage is irreversible.³⁴

Final Thoughts

Although bloodroot demonstrates efficacy as a phytotherapeutic, it does come with notable toxicity. Physicians should warn patients of the unwanted cosmetic effects of black salve, especially oral products that incorporate sanguinarine. Adverse effects on the oropharynx can be irreversible, though the eschar associated with black salve can be treated with a topical or oral corticosteroid.²⁹

Bloodroot (Sanguinaria canadensis) is a member of the family Papaveraceae.¹ This North American plant commonly is found in widespread distribution from Nova Scotia, Canada, to Florida and from the Great Lakes to Mississippi.² Historically, Native Americans used bloodroot as a skin dye and as a medicine for many ailments.³

Bloodroot blooms for only a few days, starting in March, and fruits in June. The flowers comprise 8 to 10 white petals, surrounding a bed of yellow stamens (Figure). The plant thrives in wooded areas and grows to 12 inches tall. In its off-season, the plant remains dormant and can survive below-freezing temperatures.⁴

Chemical Constituents

Bloodroot gets its colloquial name from its red sap, which is released when the plant’s rhizome is cut. This sap contains a high concentration of alkaloids that are used for protection against predators. The rhizome itself has a rusty, red-brown color; the roots are a brighter red-orange.⁴

The rhizome of S canadensis contains the highest concentration of active alkaloids; the roots also contain these chemicals, though to a lesser degree; and the leaves, flowers, and fruits harvest approximately 1% of the alkaloids found in the roots.⁴ The concentration of alkaloids can vary from one plant to the next, depending on environmental conditions.^5,6

The major alkaloids in S canadensis include both quaternary benzophenanthridine alkaloids (eg, sanguinarine, chelerythrine, sanguilutine, chelilutine, sanguirubine, chelirubine) and protopin alkaloids (eg, protopine, allocryptopine).^3,7 Of these, sanguinarine and chelerythrine typically are the most potent.¹ Oral ingestion or topical application of these molecules can have therapeutic and toxic effects.⁸

Biophysiological Effects

Bloodroot has been shown to have remarkable antimicrobial effects.⁹ The plant produces hydrogen peroxide and superoxide anion.¹⁰ These mediators cause oxidative stress, thus inducing destruction of cellular DNA and the cell membrane.¹¹ Although these effects can be helpful when fighting infection, they are not necessarily selective against healthy cells.¹²

Alkaloids of bloodroot also have cardiovascular therapeutic effects. Sanguinarine blocks angiotensin II and causes vasodilation, thus helping treat hypertension.¹³ It also acts as an inotrope by blocking the Na⁺/K⁺ ATPase pump. These effects in a patient who is already taking digoxin can cause notable cardiotoxicity because the 2 drugs share a mechanism of action.¹⁴

Chelerythrine blocks production of cyclooxygenase 2 and prostaglandin E₂.¹⁵ This pathway modification results in anti-inflammatory effects that can help treat arthritis, edema, and other inflammatory conditions.¹⁶ Moreover, sanguinarine has demonstrated efficacy in numerous anticancer pathways,¹⁷ including downregulation of intercellular adhesion molecules, vascular cell adhesion molecules, and vascular endothelial growth factor (VEGF).^18-20 Blocking VEGF is one way to inhibit angiogenesis,²¹ which is upregulated in tumor formation, thus sanguinarine can have an antiproliferative anticancer effect.²² Sanguinarine also upregulates molecules such as nuclear factor–κB and the protease enzymes known as caspases to cause proapoptotic effects, furthering its antitumor potential.^23,24

Treatment of Dermatologic Conditions

The initial technique of Mohs micrographic surgery employed a chemopaste that utilized an extract of S canadensis to preserve tissue.²⁵ Outside the dermatologist’s office, bloodroot is used as a topical home remedy for a variety of cutaneous conditions, including cancer, skin tags, and warts.²⁶ Bloodroot is advertised as black salve, an alternative anticancer treatment.^27,28

As useful as this natural agent sounds, it has a pitfall: The alkaloids of S canadensis are nonspecific in their cytotoxicity, damaging neoplastic and healthy tissue.²⁹ This cytotoxic effect can cause escharification through diffuse tissue destruction and has been observed to result in formation of a keloid scar.³⁰ The alkaloids in black salve also have been shown to cause skin erosions and cellular atypia.^28,31 Therefore, the utility of this escharotic in medical treatment is limited.³² Fortuitously, oral antibiotics and wound care can help address this adverse effect.²⁸

Bloodroot was once used as a mouth rinse and toothpaste to treat gingivitis, but this application was later associated with oral leukoplakia, a premalignant condition.³³ Leukoplakia associated with S canadensis extract often is unremitting. Immediate discontinuation of the offending agent produces little regression, suggesting that cellular damage is irreversible.³⁴

Final Thoughts

Although bloodroot demonstrates efficacy as a phytotherapeutic, it does come with notable toxicity. Physicians should warn patients of the unwanted cosmetic effects of black salve, especially oral products that incorporate sanguinarine. Adverse effects on the oropharynx can be irreversible, though the eschar associated with black salve can be treated with a topical or oral corticosteroid.²⁹

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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

Many patients with cancer, as well as doctors in fields other than oncology, are unaware of just how much progress has been made in recent years in the treatment of cancer, particularly with immunotherapy.

This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.

The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.

When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.

Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.

“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.

After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”

Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.

Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.

He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.

“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.

That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.

For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
 

Findings from the patient survey

It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.

“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients

The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.

The survey asked them about how immunotherapy works, what it costs, and its side effects.

Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”

Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.

“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.

A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.

“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.

Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
 

Results of the doctor survey

The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.

Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).

Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.

Both groups of doctors had a hard time estimating the survival of common cancers.

Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.

However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.

“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.

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