Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.

"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”

Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.

“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”

Treatment options, treatment challenges

Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.

“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”

Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.

“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”

The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
 

Looking ahead

Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.

Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
 

An agenda for the future

In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.

Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.

“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.

Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
 

‘A beacon of hope’

“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.

While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.

Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.

"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”

Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.

“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”

Treatment options, treatment challenges

Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.

“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”

Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.

“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”

The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
 

Looking ahead

Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.

Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
 

An agenda for the future

In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.

Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.

“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.

Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
 

‘A beacon of hope’

“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.

While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.

Prior to 1993, a multiple sclerosis (MS) diagnosis could often mean an abbreviated lifespan marked by progressive disability and loss of function. That changed when the Food and Drug Administration approved interferon beta-1b (Betaseron) in 1993, which revolutionized MS therapy and gave hope to the entire MS community.

"The most surprising thing about MS management over the last 30 years is that we’ve been able to treat MS – especially relapsing MS,” said Fred D. Lublin, MD, professor of neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in Mount Sinai in New York. “The approval of interferon was a major therapeutic advancement because it was the first treatment for what was an untreatable disease.”

Mark Gudesblatt, MD, medical director of the Comprehensive MS Care Center of South Shore Neurologic Associates in Patchogue, N.Y., agrees.

“For people with MS, it’s an extraordinarily lucky and amazingly optimistic time,” he said. “Before interferon beta-1b, MS was called ‘the crippler of young adults’ because more than 50% of these people would require a walker 10 years after diagnosis, and a large number of young and middle-age patients with MS were residing in nursing homes.”

Treatment options, treatment challenges

Dr. Gudesblatt points out that having numerous therapies from which to choose is both a blessing and a problem.

“The good news is that there are so many options for treating relapsing MS today,” he said. “The bad news is there are so many options. Like doctors who are treating high blood pressure, doctors managing patients with MS often struggle to determine which medication is best for individual patients.”

Despite the promise of vastly better outcomes and prolonged lifespan, MS therapy still faces its share of challenges, including effective therapies for progressive MS and reparative-restorative therapies.

“Choice in route of administration and timing of administration allow for larger and broader discussions to try to meet patients’ needs,” Dr. Lublin said. “We’ve been extremely successful at treating relapses, but not as successful in treating progressive disease.”

The unclear mechanism of pathogenesis amplifies the challenges clinicians face in successful management of patients with MS. For example, experts agree that the therapies for progressive MS have only proven moderately effective at best. The paucity of therapies available for progressive MS and the limitations of the current therapies further limit the outcomes.
 

Looking ahead

Experts expressed optimistic views about the future of MS therapy as a whole. From Dr. Lublin’s perspective, the MS community stands to gain valuable insights from emerging research focused on treating progressive disease along with new testing to understand the underlying mechanism of progressive disease. Enhanced understanding of the underlying pathogenesis of progressive MS coupled with the ability to diagnose MS – such as improved MRI techniques – have facilitated this process.

Among the therapies with novel mechanisms of action in the pipeline include agents that generate myelin sheath repair. Another potential therapeutic class on the horizon, known as TPK inhibitors, addresses the smoldering of the disease. With these and other therapeutic advances, Dr. Lublin hopes to see better control of progressive disease.
 

An agenda for the future

In addition, barriers such as access to care, cost, insurance coverage, and tolerance remain ongoing stressors that will likely continue weighing on the MS community and its stakeholders into the future.

Dr. Gudesblatt concluded that advancing MS outcomes in the future hinges on several additional factors.

“We need medicines that are better for relapse and progression; medicines that are better tolerated and safer; and better medicine to address the underlying disease as well as its symptoms. But we also need to appreciate, recognize, and address cognitive impairment along the MS continuum and develop effective reparative options,” he said.

Regardless, he emphasized that these “amazing advancements” in MS therapy have renewed hope that research may identify and expand effective treatments for multiple other neurologic conditions such as muscular dystrophies, neurodegenerative and genetic disorders, movement disorders, and dysautonomia-related diseases. Like MS, all of these conditions have limited therapies, some of which have minimal efficacy. But none of these other disorders has disease-modifying therapies currently available.
 

‘A beacon of hope’

“MS is the beacon of hope for multiple disease states because it’s cracked the door wide open,” Dr. Gudesblatt said. Relapse no longer gauges the prognosis of today’s MS patient – a prognosis both experts think will only continue to improve with forthcoming innovations.

While the challenges for MS still exist, the bright future that lies ahead may eventually eclipse them.

The field of gender-affirming surgery is one of the fastest growing surgical specialties in the country. Within the last few years, the number of procedures has increased markedly – with a total of 16,353 performed in 2020 compared with 8,304 in 2017.^1,2 As the number of surgeries increases, so does the need for a standardized approach to preoperative evaluation and patient preparation.

Gender-affirming genital surgery for transfeminine individuals encompasses a spectrum of procedures that includes removal of the testicles (orchiectomy), creation of a neovaginal canal (full-depth vaginoplasty), and creation of external vulvar structures without a vaginal canal (zero-depth vaginoplasty). Each of these requires different levels of preoperative preparedness and medical optimization, and has unique postoperative challenges. Often, these postoperative complications can be mitigated with adequate patient education.

Many centers that offer genital gender-affirming surgery have a multidisciplinary team composed of a social worker, mental health providers, care coordinators, primary care providers, and surgeons. This team is essential to providing supportive services within their respective scope of practices.

The role of the mental health provider cannot be understated. While the updated standards of care from the World Professional Association for Transgender Health no longer require two letters from mental health providers prior to genital surgery, it is important to recognize that many insurance companies have not yet updated their policies and still require two letters. Even when insurance companies adjust their policies to reflect current standards, a mental health assessment is still necessary to determine if patients have any mental health issues that could negatively affect their surgical outcome.³ Furthermore, a continued relationship with a mental health provider is beneficial for patients as they go through a stressful and life-changing procedure.⁴

As with any surgery, understanding patient goals and expectations is a key element in achieving optimal patient satisfaction. Patients with high esthetic or functional expectations experience higher rates of disappointment after surgery and have more difficulty coping with complications.⁵

Decisions about proceeding with a particular type of genital surgery should consider a patient’s desire to have vaginal-receptive intercourse, their commitment to dilation, financial stability, a safe environment for recovery, a support network, and the ability to understand and cope with potential complications.⁴ Patients will present with a wide variety of educational backgrounds and medical literacy, and will have differing intellectual capabilities.⁴ Consultations should take into account potential challenges these factors may play in patients’ ability to understand this complex surgery.

An adequate amount of time should be allotted to addressing these challenges. In my practice, a consultation for a gender-affirming genital surgery takes approximately 60 minutes. A preoperative packet with information is mailed to the patient ahead of time that will be reviewed at the time of the visit. During the consultation, I utilize a visual presentation that details the preoperative requirements and different types of surgical procedures, shows preoperative and postoperative surgical results, and discusses potential complications. Before the consultation, I advise that patients bring a support person (ideally the person who will assist in postoperative care) and a list of questions that they may have.

Both full- and shallow-depth procedures are reviewed at the time of initial consultation. For patients who seek a full-depth vaginoplasty procedure, it is important to determine whether patients are committed to dilation and have a safe, supportive environment to do so. Patients may have physical limitations, such as obesity or mobility issues, that could make dilation difficult or even impossible. Patients may not have stable housing, may experience financial restrictions that would impede their ability to purchase necessary supplies, and lack a support person who can care for them in the immediate postoperative period. Many patients are unaware of the importance these social factors play in a successful outcome. Social workers and care coordinators are important resources when these challenges are encountered.

Medical optimization is not unlike other gynecologic procedures with a few exceptions. Obesity, diabetes, and smoking play larger roles in surgical complications than in other surgeries as vaginoplasty techniques use pedicled flaps that rely on adequate blood supply. Obesity, poorly controlled diabetes, and smoking are associated with increased rates of wound infection, poor wound healing, and graft loss. Smoking cessation for 8 weeks prior to surgery and for 4 weeks afterward is mandatory.

For patients with a history of smoking, a nicotine test is performed within 4 weeks of surgery. Many surgeons have body mass index requirements, typically ranging between 20 and 30 kg/m², despite limited data. This paradigm is shifting to consider body fat distribution rather than BMI alone. Extensive body fat in the mons or groin area can increase the difficulty of pelvic floor dissection during surgery and impede visualization for dilation in the postoperative period. There are reports of patients dilating into their rectum or neourethra, which can have catastrophic consequences. For these patients, a zero-depth vaginoplasty or orchiectomy may initially be a safer option.

Many patients are justifiably excited to undergo the procedures as quality of life is typically improved after surgery. However, even with adequate counseling, many patients often underestimate the extensive recovery process. This surgical procedure requires extensive planning and adequate resources.⁴ Patients must be able to take off from work for prolonged periods of time (typically 6 weeks), which can serve as a source of financial stress. To maintain the integrity of suture lines in the genital region, prolonged or limited mobilization is recommended. This can create boredom and forces patients to rely on a caregiver for activities of daily living, such as household chores, cooking meals, and transportation.

Gender-affirming genital surgery is not only a complex surgical procedure but also requires extensive preoperative education and postoperative support. As this field continues to grow, patients, providers, and caregivers should work toward further developing a collaborative care model to optimize surgical outcomes and patient satisfaction.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender affirming surgeon in West Reading, Pa.

References

1. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2020.

2. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2017.

3. Coleman E et al. Standards of care for the health of transgender and gender diverse people. Version 8. Int J Transgender Health. 23(S1):S1-S258. doi :10.1080/26895269.2022.2100644.

4. Penkin A et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:37-44.

5. Waljee J et al. Surgery. 2014;155:799-808.

The field of gender-affirming surgery is one of the fastest growing surgical specialties in the country. Within the last few years, the number of procedures has increased markedly – with a total of 16,353 performed in 2020 compared with 8,304 in 2017.^1,2 As the number of surgeries increases, so does the need for a standardized approach to preoperative evaluation and patient preparation.

Gender-affirming genital surgery for transfeminine individuals encompasses a spectrum of procedures that includes removal of the testicles (orchiectomy), creation of a neovaginal canal (full-depth vaginoplasty), and creation of external vulvar structures without a vaginal canal (zero-depth vaginoplasty). Each of these requires different levels of preoperative preparedness and medical optimization, and has unique postoperative challenges. Often, these postoperative complications can be mitigated with adequate patient education.

Many centers that offer genital gender-affirming surgery have a multidisciplinary team composed of a social worker, mental health providers, care coordinators, primary care providers, and surgeons. This team is essential to providing supportive services within their respective scope of practices.

The role of the mental health provider cannot be understated. While the updated standards of care from the World Professional Association for Transgender Health no longer require two letters from mental health providers prior to genital surgery, it is important to recognize that many insurance companies have not yet updated their policies and still require two letters. Even when insurance companies adjust their policies to reflect current standards, a mental health assessment is still necessary to determine if patients have any mental health issues that could negatively affect their surgical outcome.³ Furthermore, a continued relationship with a mental health provider is beneficial for patients as they go through a stressful and life-changing procedure.⁴

As with any surgery, understanding patient goals and expectations is a key element in achieving optimal patient satisfaction. Patients with high esthetic or functional expectations experience higher rates of disappointment after surgery and have more difficulty coping with complications.⁵

Decisions about proceeding with a particular type of genital surgery should consider a patient’s desire to have vaginal-receptive intercourse, their commitment to dilation, financial stability, a safe environment for recovery, a support network, and the ability to understand and cope with potential complications.⁴ Patients will present with a wide variety of educational backgrounds and medical literacy, and will have differing intellectual capabilities.⁴ Consultations should take into account potential challenges these factors may play in patients’ ability to understand this complex surgery.

An adequate amount of time should be allotted to addressing these challenges. In my practice, a consultation for a gender-affirming genital surgery takes approximately 60 minutes. A preoperative packet with information is mailed to the patient ahead of time that will be reviewed at the time of the visit. During the consultation, I utilize a visual presentation that details the preoperative requirements and different types of surgical procedures, shows preoperative and postoperative surgical results, and discusses potential complications. Before the consultation, I advise that patients bring a support person (ideally the person who will assist in postoperative care) and a list of questions that they may have.

Both full- and shallow-depth procedures are reviewed at the time of initial consultation. For patients who seek a full-depth vaginoplasty procedure, it is important to determine whether patients are committed to dilation and have a safe, supportive environment to do so. Patients may have physical limitations, such as obesity or mobility issues, that could make dilation difficult or even impossible. Patients may not have stable housing, may experience financial restrictions that would impede their ability to purchase necessary supplies, and lack a support person who can care for them in the immediate postoperative period. Many patients are unaware of the importance these social factors play in a successful outcome. Social workers and care coordinators are important resources when these challenges are encountered.

Medical optimization is not unlike other gynecologic procedures with a few exceptions. Obesity, diabetes, and smoking play larger roles in surgical complications than in other surgeries as vaginoplasty techniques use pedicled flaps that rely on adequate blood supply. Obesity, poorly controlled diabetes, and smoking are associated with increased rates of wound infection, poor wound healing, and graft loss. Smoking cessation for 8 weeks prior to surgery and for 4 weeks afterward is mandatory.

For patients with a history of smoking, a nicotine test is performed within 4 weeks of surgery. Many surgeons have body mass index requirements, typically ranging between 20 and 30 kg/m², despite limited data. This paradigm is shifting to consider body fat distribution rather than BMI alone. Extensive body fat in the mons or groin area can increase the difficulty of pelvic floor dissection during surgery and impede visualization for dilation in the postoperative period. There are reports of patients dilating into their rectum or neourethra, which can have catastrophic consequences. For these patients, a zero-depth vaginoplasty or orchiectomy may initially be a safer option.

Many patients are justifiably excited to undergo the procedures as quality of life is typically improved after surgery. However, even with adequate counseling, many patients often underestimate the extensive recovery process. This surgical procedure requires extensive planning and adequate resources.⁴ Patients must be able to take off from work for prolonged periods of time (typically 6 weeks), which can serve as a source of financial stress. To maintain the integrity of suture lines in the genital region, prolonged or limited mobilization is recommended. This can create boredom and forces patients to rely on a caregiver for activities of daily living, such as household chores, cooking meals, and transportation.

Gender-affirming genital surgery is not only a complex surgical procedure but also requires extensive preoperative education and postoperative support. As this field continues to grow, patients, providers, and caregivers should work toward further developing a collaborative care model to optimize surgical outcomes and patient satisfaction.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender affirming surgeon in West Reading, Pa.

References

1. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2020.

2. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2017.

3. Coleman E et al. Standards of care for the health of transgender and gender diverse people. Version 8. Int J Transgender Health. 23(S1):S1-S258. doi :10.1080/26895269.2022.2100644.

4. Penkin A et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:37-44.

5. Waljee J et al. Surgery. 2014;155:799-808.

The field of gender-affirming surgery is one of the fastest growing surgical specialties in the country. Within the last few years, the number of procedures has increased markedly – with a total of 16,353 performed in 2020 compared with 8,304 in 2017.^1,2 As the number of surgeries increases, so does the need for a standardized approach to preoperative evaluation and patient preparation.

Gender-affirming genital surgery for transfeminine individuals encompasses a spectrum of procedures that includes removal of the testicles (orchiectomy), creation of a neovaginal canal (full-depth vaginoplasty), and creation of external vulvar structures without a vaginal canal (zero-depth vaginoplasty). Each of these requires different levels of preoperative preparedness and medical optimization, and has unique postoperative challenges. Often, these postoperative complications can be mitigated with adequate patient education.

Many centers that offer genital gender-affirming surgery have a multidisciplinary team composed of a social worker, mental health providers, care coordinators, primary care providers, and surgeons. This team is essential to providing supportive services within their respective scope of practices.

The role of the mental health provider cannot be understated. While the updated standards of care from the World Professional Association for Transgender Health no longer require two letters from mental health providers prior to genital surgery, it is important to recognize that many insurance companies have not yet updated their policies and still require two letters. Even when insurance companies adjust their policies to reflect current standards, a mental health assessment is still necessary to determine if patients have any mental health issues that could negatively affect their surgical outcome.³ Furthermore, a continued relationship with a mental health provider is beneficial for patients as they go through a stressful and life-changing procedure.⁴

As with any surgery, understanding patient goals and expectations is a key element in achieving optimal patient satisfaction. Patients with high esthetic or functional expectations experience higher rates of disappointment after surgery and have more difficulty coping with complications.⁵

Decisions about proceeding with a particular type of genital surgery should consider a patient’s desire to have vaginal-receptive intercourse, their commitment to dilation, financial stability, a safe environment for recovery, a support network, and the ability to understand and cope with potential complications.⁴ Patients will present with a wide variety of educational backgrounds and medical literacy, and will have differing intellectual capabilities.⁴ Consultations should take into account potential challenges these factors may play in patients’ ability to understand this complex surgery.

An adequate amount of time should be allotted to addressing these challenges. In my practice, a consultation for a gender-affirming genital surgery takes approximately 60 minutes. A preoperative packet with information is mailed to the patient ahead of time that will be reviewed at the time of the visit. During the consultation, I utilize a visual presentation that details the preoperative requirements and different types of surgical procedures, shows preoperative and postoperative surgical results, and discusses potential complications. Before the consultation, I advise that patients bring a support person (ideally the person who will assist in postoperative care) and a list of questions that they may have.

Both full- and shallow-depth procedures are reviewed at the time of initial consultation. For patients who seek a full-depth vaginoplasty procedure, it is important to determine whether patients are committed to dilation and have a safe, supportive environment to do so. Patients may have physical limitations, such as obesity or mobility issues, that could make dilation difficult or even impossible. Patients may not have stable housing, may experience financial restrictions that would impede their ability to purchase necessary supplies, and lack a support person who can care for them in the immediate postoperative period. Many patients are unaware of the importance these social factors play in a successful outcome. Social workers and care coordinators are important resources when these challenges are encountered.

Medical optimization is not unlike other gynecologic procedures with a few exceptions. Obesity, diabetes, and smoking play larger roles in surgical complications than in other surgeries as vaginoplasty techniques use pedicled flaps that rely on adequate blood supply. Obesity, poorly controlled diabetes, and smoking are associated with increased rates of wound infection, poor wound healing, and graft loss. Smoking cessation for 8 weeks prior to surgery and for 4 weeks afterward is mandatory.

For patients with a history of smoking, a nicotine test is performed within 4 weeks of surgery. Many surgeons have body mass index requirements, typically ranging between 20 and 30 kg/m², despite limited data. This paradigm is shifting to consider body fat distribution rather than BMI alone. Extensive body fat in the mons or groin area can increase the difficulty of pelvic floor dissection during surgery and impede visualization for dilation in the postoperative period. There are reports of patients dilating into their rectum or neourethra, which can have catastrophic consequences. For these patients, a zero-depth vaginoplasty or orchiectomy may initially be a safer option.

Many patients are justifiably excited to undergo the procedures as quality of life is typically improved after surgery. However, even with adequate counseling, many patients often underestimate the extensive recovery process. This surgical procedure requires extensive planning and adequate resources.⁴ Patients must be able to take off from work for prolonged periods of time (typically 6 weeks), which can serve as a source of financial stress. To maintain the integrity of suture lines in the genital region, prolonged or limited mobilization is recommended. This can create boredom and forces patients to rely on a caregiver for activities of daily living, such as household chores, cooking meals, and transportation.

Gender-affirming genital surgery is not only a complex surgical procedure but also requires extensive preoperative education and postoperative support. As this field continues to grow, patients, providers, and caregivers should work toward further developing a collaborative care model to optimize surgical outcomes and patient satisfaction.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender affirming surgeon in West Reading, Pa.

References

1. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2020.

2. American Society of Plastic Surgeons. Plastic Surgery Statistics Report–2017.

3. Coleman E et al. Standards of care for the health of transgender and gender diverse people. Version 8. Int J Transgender Health. 23(S1):S1-S258. doi :10.1080/26895269.2022.2100644.

4. Penkin A et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:37-44.

5. Waljee J et al. Surgery. 2014;155:799-808.

Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.

An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.

Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.

“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added. “We would suggest that clinicians use COPD as a flag for other conditions to ensure that all modifiable risk factors are optimized prior to surgery.”

The study was published online in the Canadian Medical Association Journal.
 

Additional recovery support

The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.

The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.

The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.

The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.

A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.

During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).

For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.

Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.

“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
 

Shared decision-making

Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”

One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”

Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”

Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.

“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”

The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.

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

Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.

An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.

Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.

“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added. “We would suggest that clinicians use COPD as a flag for other conditions to ensure that all modifiable risk factors are optimized prior to surgery.”

The study was published online in the Canadian Medical Association Journal.
 

Additional recovery support

The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.

The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.

The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.

The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.

A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.

During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).

For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.

Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.

“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
 

Shared decision-making

Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”

One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”

Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”

Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.

“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”

The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.

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

Patients with chronic obstructive pulmonary disease (COPD) are more likely to die within a year of undergoing elective surgery and to incur higher health care costs than are similar patients without COPD, data suggest.

An analysis of close to a million patient records found that, after adjustment for sociodemographic factors, procedure type, and comorbidities, patients with COPD were 26% more likely to die in the year after surgery than were those without COPD. Moreover, COPD was associated with a 4.6% increase in health care costs.

Previous studies have evaluated outcomes for the first 30 days after surgery. Those data “may not adequately capture the overall burden of surgery and how long it may take patients to recover,” study author Ashwin Sankar, MD, a clinician-investigator at St. Michael’s Hospital and assistant professor of anesthesia at the University of Toronto, told this news organization.

“We found that COPD often coexists with other conditions, like diabetes, coronary artery disease, and frailty,” Dr. Sankar added. “We would suggest that clinicians use COPD as a flag for other conditions to ensure that all modifiable risk factors are optimized prior to surgery.”

The study was published online in the Canadian Medical Association Journal.
 

Additional recovery support

The authors analyzed data from 932,616 patients who underwent intermediate-risk to high-risk elective noncardiac surgeries from 2005 to 2019 in Ontario. Procedures included carotid endarterectomy, open or endovascular abdominal aortic aneurysm repair, peripheral arterial bypass, total hip replacement, total knee replacement, shoulder surgery, large-bowel surgery, partial liver resection, pancreaticoduodenectomy, gastrectomy, esophagectomy, nephrectomy, cystectomy, prostatectomy, and hysterectomy.

The researchers quantified the associations of COPD with survival and costs. Their analyses included partial adjustment for sociodemographic factors and procedure type and full adjustment, which included comorbidities.

The primary outcome was all-cause death in the year after surgery; the secondary outcome was total health care costs in that year.

The mean age of the population was 65 years, and 60% of patients were women. A total of 170,482 (18%) patients had COPD. Compared with those without COPD, the patients with COPD were older and were more likely to be male, to be in a lower income quintile, to be residents of long-term care facilities, and to have been admitted to the hospital before surgery. They were also more likely to have comorbidities, including coronary artery disease, heart failure, and lung cancer.

A larger proportion of patients with COPD had frailty and medium to high comorbidity. They also more frequently underwent orthopedic, open upper abdominal, and vascular surgery.

During the year after surgery, 52,021 (5.6%) patients died, including 18,007 (10.6%) with COPD and 34,014 (4.5%) without. Those with COPD were more likely to die within 30 days of surgery (3.4% vs 1.2%).

For patients with COPD, the partially adjusted hazard ratio (HR) was 1.61 for risk of death; the fully adjusted HR was 1.26. COPD also was associated with a partially adjusted relative increase of 13.1% in health care costs and an increase of 4.6% with full adjustment.

Frailty, cancer, and procedure type were factors that modified the association between COPD and outcomes. “Procedures such as open aortic and upper abdominal surgery are associated with higher postoperative risks irrespective of COPD status, whereas others, such as orthopedic and lower abdominal surgery, may be of significantly greater risk for patients with COPD,” the authors wrote. “Our results suggest that perioperative management of patients with COPD requires careful consideration of the multiple domains that contribute to their elevated perioperative risk.

“Our finding that patients with COPD are at risk beyond 30 days after surgery suggests that it may be worthwhile to additionally support these patients’ recovery well beyond the first month after the procedure,” said Dr. Sankar.
 

Shared decision-making

Commenting on the study, William Whalen, MD, a pulmonary critical care specialist at Weill Cornell Medicine in New York, said, “I echo the authors’ sentiments that these findings highlight how chronically ill COPD patients are, which may be playing a role in the elevated mortality seen in this study.”

One caveat is in regard to the interpretation of the interaction effects of the study, he said. “Clinicians are unlikely to send patients who are frail or have multiple comorbidities to overly complex surgeries. Therefore, these effects may be misestimated due to selection bias.”

Two questions remain after reading the study, he added. “The first is how the degree of obstruction (i.e., the severity of COPD) impacts long-term mortality. Previous observational studies in nonsurgical COPD patients have shown increased mortality as the severity of obstruction increases. The second is how much of the long-term mortality observed in this study is related to respiratory disease from COPD. Patients with COPD are complex, and many die from nonrespiratory-related causes.”

Dr. Whalen suggests that discussion be held with the surgical team about the long-term morbidity and mortality with and without surgical intervention. Such a discussion could inform a shared decision-making process with the patient.

“Some procedures may be necessary to reduce immediate mortality, such as aortic aneurysmal repair, so [the risk of] longer-term mortality may be more acceptable in this setting,” he said. “Less straightforward are procedures that may improve quality of life. Would a patient accept an increased long-term mortality [risk] if that meant living without orthopedic-related pain?”

The study was funded by the Government of Ontario. Dr. Sankar and Dr. Whalen have disclosed no relevant financial relationships.

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

Surgeon gender was not associated with maternal morbidity or severe blood loss after cesarean delivery, a large prospective cohort study from France reports. The results have important implications for the promotion of gender equality among surgeons, obstetricians in particular, wrote a team led by Hanane Bouchghoul, MD, PhD, of the department of obstetrics and gynecology at Bordeaux (France) University Hospital. The report is in JAMA Surgery.

“Our findings are significant in that they add substantially to the string of studies contradicting the age-old dogma that men are better surgeons than women,” the authors wrote. Previous research has suggested slightly better outcomes with female surgeons or higher complication rates with male surgeons.

The results support those of a recent Canadian retrospective analysis suggesting that patients treated by male or female surgeons for various elective indications experience similar surgical outcomes but with a slight, statistically significant decrease in 30-day mortality when treated by female surgeons.

“Policy makers need to combat prejudice against women in surgical careers, particularly in obstetrics and gynecology, so that women no longer experience conscious or unconscious barriers or difficulties in their professional choices, training, and relationships with colleagues or patients,” study corresponding author Loïc Sentilhes, MD, PhD, of Bordeaux University Hospital, said in an interview.

Facing such barriers, women may doubt their ability to be surgeons, their legitimacy as surgeons, and may not consider this type of career, he continued. “Moreover a teacher may not be as involved in teaching young female surgeons as young male surgeons, or the doctor-patient relationship may be more complicated in the event of complications if the patient thinks that a female surgeon has less competence than a male surgeon.”  

The analysis drew on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery 2 trial, a multicenter, randomized, placebo-controlled study conducted from March 2018 through January 2020 in mothers from 27 French maternity hospitals.

Eligible participants had a cesarean delivery before or during labor at or after 34 weeks’ gestation. The primary endpoint was the incidence of a composite maternal morbidity variable, and the secondary endpoint was the incidence of postpartum hemorrhage, defined by a calculated estimated blood loss exceeding 1,000 mL or transfusion by day 2.

Among the 4,244 women included, male surgeons performed 943 cesarean deliveries (22.2%) and female surgeons performed 3,301 (77.8%). The percentage who were attending obstetricians was higher for men at 441 of 929 (47.5%) than women at 687 of 3,239 (21.2%).

The observed risk of maternal morbidity did not differ between male and female surgeons: 119 of 837 (14.2%) vs. 476 of 2,928 (16.3%), for an adjusted risk ratio (aRR) of 0.92 (95% confidence interval [CI], 0.77-1.13). Interaction between surgeon gender and level of experience with the risk of maternal morbidity was not statistically significant; nor did the groups differ specifically by risk for postpartum hemorrhage: aRR, 0.98 (95% CI, 0.85-1.13).

Despite the longstanding stereotype that men perform surgery better than women, and the traditional preponderance of male surgeons, the authors noted, postoperative morbidity and mortality may be lower after various surgeries performed by women.

The TRAAP2 trial

In an accompanying editorial, Amanda Fader, MD, of the department of obstetrics and gynecology at Johns Hopkins School of Medicine in Baltimore, and colleagues caution that the French study’s methodology may not fully account for the complex intersection of surgeon volume, experience, gender, clinical decision-making skills, and patient-level and clinical factors affecting outcomes.

That said, appraising surgical outcomes based on gender may be an essential step toward reducing implicit bias and dispelling engendered perceptions regarding gender and technical proficiency, the commentators stated. “To definitively dispel archaic, gender-based notions about performance in clinical or surgical settings, efforts must go beyond peer-reviewed research,” Dr. Fader said in an interview. “Medical institutions and leaders of clinical departments must make concerted efforts to recruit, mentor, support, and promote women and persons of all genders in medicine – as well as confront any discriminatory perceptions and experiences concerning sex, race and ethnicity, sexual orientation, or economic class.”

This study was supported by the French Ministry of Health under its Clinical Research Hospital Program. Dr. Sentilhes reported financial relationships with Dilafor, Bayer, GlaxoSmithKline, Sigvaris, and Ferring Pharmaceuticals. The editorial commentators disclosed no funding for their commentary or conflicts of interest.

Surgeon gender was not associated with maternal morbidity or severe blood loss after cesarean delivery, a large prospective cohort study from France reports. The results have important implications for the promotion of gender equality among surgeons, obstetricians in particular, wrote a team led by Hanane Bouchghoul, MD, PhD, of the department of obstetrics and gynecology at Bordeaux (France) University Hospital. The report is in JAMA Surgery.

“Our findings are significant in that they add substantially to the string of studies contradicting the age-old dogma that men are better surgeons than women,” the authors wrote. Previous research has suggested slightly better outcomes with female surgeons or higher complication rates with male surgeons.

The results support those of a recent Canadian retrospective analysis suggesting that patients treated by male or female surgeons for various elective indications experience similar surgical outcomes but with a slight, statistically significant decrease in 30-day mortality when treated by female surgeons.

“Policy makers need to combat prejudice against women in surgical careers, particularly in obstetrics and gynecology, so that women no longer experience conscious or unconscious barriers or difficulties in their professional choices, training, and relationships with colleagues or patients,” study corresponding author Loïc Sentilhes, MD, PhD, of Bordeaux University Hospital, said in an interview.

Facing such barriers, women may doubt their ability to be surgeons, their legitimacy as surgeons, and may not consider this type of career, he continued. “Moreover a teacher may not be as involved in teaching young female surgeons as young male surgeons, or the doctor-patient relationship may be more complicated in the event of complications if the patient thinks that a female surgeon has less competence than a male surgeon.”  

The analysis drew on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery 2 trial, a multicenter, randomized, placebo-controlled study conducted from March 2018 through January 2020 in mothers from 27 French maternity hospitals.

Eligible participants had a cesarean delivery before or during labor at or after 34 weeks’ gestation. The primary endpoint was the incidence of a composite maternal morbidity variable, and the secondary endpoint was the incidence of postpartum hemorrhage, defined by a calculated estimated blood loss exceeding 1,000 mL or transfusion by day 2.

Among the 4,244 women included, male surgeons performed 943 cesarean deliveries (22.2%) and female surgeons performed 3,301 (77.8%). The percentage who were attending obstetricians was higher for men at 441 of 929 (47.5%) than women at 687 of 3,239 (21.2%).

The observed risk of maternal morbidity did not differ between male and female surgeons: 119 of 837 (14.2%) vs. 476 of 2,928 (16.3%), for an adjusted risk ratio (aRR) of 0.92 (95% confidence interval [CI], 0.77-1.13). Interaction between surgeon gender and level of experience with the risk of maternal morbidity was not statistically significant; nor did the groups differ specifically by risk for postpartum hemorrhage: aRR, 0.98 (95% CI, 0.85-1.13).

Despite the longstanding stereotype that men perform surgery better than women, and the traditional preponderance of male surgeons, the authors noted, postoperative morbidity and mortality may be lower after various surgeries performed by women.

The TRAAP2 trial

In an accompanying editorial, Amanda Fader, MD, of the department of obstetrics and gynecology at Johns Hopkins School of Medicine in Baltimore, and colleagues caution that the French study’s methodology may not fully account for the complex intersection of surgeon volume, experience, gender, clinical decision-making skills, and patient-level and clinical factors affecting outcomes.

That said, appraising surgical outcomes based on gender may be an essential step toward reducing implicit bias and dispelling engendered perceptions regarding gender and technical proficiency, the commentators stated. “To definitively dispel archaic, gender-based notions about performance in clinical or surgical settings, efforts must go beyond peer-reviewed research,” Dr. Fader said in an interview. “Medical institutions and leaders of clinical departments must make concerted efforts to recruit, mentor, support, and promote women and persons of all genders in medicine – as well as confront any discriminatory perceptions and experiences concerning sex, race and ethnicity, sexual orientation, or economic class.”

This study was supported by the French Ministry of Health under its Clinical Research Hospital Program. Dr. Sentilhes reported financial relationships with Dilafor, Bayer, GlaxoSmithKline, Sigvaris, and Ferring Pharmaceuticals. The editorial commentators disclosed no funding for their commentary or conflicts of interest.

Surgeon gender was not associated with maternal morbidity or severe blood loss after cesarean delivery, a large prospective cohort study from France reports. The results have important implications for the promotion of gender equality among surgeons, obstetricians in particular, wrote a team led by Hanane Bouchghoul, MD, PhD, of the department of obstetrics and gynecology at Bordeaux (France) University Hospital. The report is in JAMA Surgery.

“Our findings are significant in that they add substantially to the string of studies contradicting the age-old dogma that men are better surgeons than women,” the authors wrote. Previous research has suggested slightly better outcomes with female surgeons or higher complication rates with male surgeons.

The results support those of a recent Canadian retrospective analysis suggesting that patients treated by male or female surgeons for various elective indications experience similar surgical outcomes but with a slight, statistically significant decrease in 30-day mortality when treated by female surgeons.

“Policy makers need to combat prejudice against women in surgical careers, particularly in obstetrics and gynecology, so that women no longer experience conscious or unconscious barriers or difficulties in their professional choices, training, and relationships with colleagues or patients,” study corresponding author Loïc Sentilhes, MD, PhD, of Bordeaux University Hospital, said in an interview.

Facing such barriers, women may doubt their ability to be surgeons, their legitimacy as surgeons, and may not consider this type of career, he continued. “Moreover a teacher may not be as involved in teaching young female surgeons as young male surgeons, or the doctor-patient relationship may be more complicated in the event of complications if the patient thinks that a female surgeon has less competence than a male surgeon.”  

The analysis drew on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery 2 trial, a multicenter, randomized, placebo-controlled study conducted from March 2018 through January 2020 in mothers from 27 French maternity hospitals.

Eligible participants had a cesarean delivery before or during labor at or after 34 weeks’ gestation. The primary endpoint was the incidence of a composite maternal morbidity variable, and the secondary endpoint was the incidence of postpartum hemorrhage, defined by a calculated estimated blood loss exceeding 1,000 mL or transfusion by day 2.

Among the 4,244 women included, male surgeons performed 943 cesarean deliveries (22.2%) and female surgeons performed 3,301 (77.8%). The percentage who were attending obstetricians was higher for men at 441 of 929 (47.5%) than women at 687 of 3,239 (21.2%).

The observed risk of maternal morbidity did not differ between male and female surgeons: 119 of 837 (14.2%) vs. 476 of 2,928 (16.3%), for an adjusted risk ratio (aRR) of 0.92 (95% confidence interval [CI], 0.77-1.13). Interaction between surgeon gender and level of experience with the risk of maternal morbidity was not statistically significant; nor did the groups differ specifically by risk for postpartum hemorrhage: aRR, 0.98 (95% CI, 0.85-1.13).

Despite the longstanding stereotype that men perform surgery better than women, and the traditional preponderance of male surgeons, the authors noted, postoperative morbidity and mortality may be lower after various surgeries performed by women.

The TRAAP2 trial

In an accompanying editorial, Amanda Fader, MD, of the department of obstetrics and gynecology at Johns Hopkins School of Medicine in Baltimore, and colleagues caution that the French study’s methodology may not fully account for the complex intersection of surgeon volume, experience, gender, clinical decision-making skills, and patient-level and clinical factors affecting outcomes.

That said, appraising surgical outcomes based on gender may be an essential step toward reducing implicit bias and dispelling engendered perceptions regarding gender and technical proficiency, the commentators stated. “To definitively dispel archaic, gender-based notions about performance in clinical or surgical settings, efforts must go beyond peer-reviewed research,” Dr. Fader said in an interview. “Medical institutions and leaders of clinical departments must make concerted efforts to recruit, mentor, support, and promote women and persons of all genders in medicine – as well as confront any discriminatory perceptions and experiences concerning sex, race and ethnicity, sexual orientation, or economic class.”

This study was supported by the French Ministry of Health under its Clinical Research Hospital Program. Dr. Sentilhes reported financial relationships with Dilafor, Bayer, GlaxoSmithKline, Sigvaris, and Ferring Pharmaceuticals. The editorial commentators disclosed no funding for their commentary or conflicts of interest.

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

THE COMPARISON

A Vitiligo in a young Hispanic female, which spared the area under a ring. The patient has spotty return of pigment on the hand after narrowband ultraviolet B (UVB) treatment.

B Vitiligo on the hand in a young Hispanic male.

Vitiligo is a chronic autoimmune disorder characterized by areas of depigmented white patches on the skin due to the loss of melanocytes in the epidermis. Various theories on the pathogenesis of vitiligo exist; however, autoimmune destruction of melanocytes remains the leading hypothesis, followed by intrinsic defects in melanocytes.¹

Vitiligo is associated with various autoimmune diseases but is most frequently reported in conjunction with thyroid disorders.²

Epidemiology

Vitiligo affects approximately 1% of the US population and up to 8% worldwide.² There is no difference in prevalence between races or genders. Females typically acquire the disease earlier than males. Onset may occur at any age, although about half of patients will have vitiligo by 20 years of age.¹

Key clinical features in people with darker skin tones

Bright white patches are characteristic of vitiligo. The patches typically are asymptomatic and often affect the hands (FIGURES A and B), perioral skin, feet, and scalp, as well as areas more vulnerable to friction and trauma, such as the elbows and knees.² Trichrome lesions—consisting of varying zones of white (depigmented), lighter brown (hypopigmented), and normal skin—are most commonly seen in individuals with darker skin. Trichrome vitiligo is considered an actively progressing variant of vitiligo.²

An important distinction when making the diagnosis is evaluating for segmental vs nonsegmental vitiligo. Although nonsegmental vitiligo—the more common subtype—is characterized by symmetric distribution and a less predictable course, segmental vitiligo manifests in a localized and unilateral distribution, often avoiding extension past the midline. Segmental vitiligo typically manifests at a younger age and follows a more rapidly stabilizing course.³

Worth noting

Given that stark contrasts between pigmented and depigmented lesions are more prominent in darker skin tones, vitiligo can be more socially stigmatizing and psychologically devastating in these patients.^4,5

Continue to: Treatment of vitiligo...

Treatment of vitiligo includes narrowband UVB (NB-UVB) light phototherapy, excimer laser, topical corticosteroids, topical calcineurin inhibitors such as tacrolimus and pimecrolimus, and surgical melanocyte transplantation.¹ In July 2022, ruxolitinib cream 1.5% was approved by the US Food and Drug Administration (FDA) for nonsegmental vitiligo in patients ages 12 years and older.^6,7 It is the only FDA-approved therapy for vitiligo. It is thought to work by inhibiting the Janus kinase–signal transducers and activators of the transcription pathway.⁶ However, topical ruxolitinib is expensive, costing more than $2000 for 60 g.⁸

Health disparity highlight

A 2021 study reviewing the coverage policies of 15 commercial health care insurance companies, 50 BlueCross BlueShield plans, Medicaid, Medicare, and Veterans Affairs plans found inequities in the insurance coverage patterns for therapies used to treat vitiligo. There were 2 commonly cited reasons for denying coverage for therapies: vitiligo was considered cosmetic and therapies were not FDA approved.⁷ In comparison, NB-UVB light phototherapy for psoriasis is not considered cosmetic and has a much higher insurance coverage rate.^9,10 The out-of-pocket cost for a patient to purchase their own NB-UVB light phototherapy is more than $5000.¹¹ Not all patients of color are economically disadvantaged, but in the United States, Black and Hispanic populations experience disproportionately higher rates of poverty (19% and 17%, respectively) compared to their White counterparts (8%).¹²

Final thoughts

FDA approval of new drugs or new treatment indications comes after years of research discovery and large-scale trials. This pursuit of new discovery, however, is uneven. Vitiligo has historically been understudied and underfunded for research; this is common among several conditions adversely affecting people of color in the United States.¹³

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

A version of this article originally appeared on WebMD.com.

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

A version of this article originally appeared on WebMD.com.

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

A version of this article originally appeared on WebMD.com.

Fibroepithelioma of Pinkus (FeP), or Pinkus tumor, is a rare tumor with a presentation similar to benign neoplasms such as acrochordons and seborrheic keratoses. Classically, FeP presents as a nontender, solitary, flesh-colored, firm, dome-shaped papule or plaque with a predilection for the lumbosacral region rather than sun-exposed areas. This tumor typically develops in fair-skinned older adults, more often in females.¹

The association between cutaneous lesions and internal malignancies is well known to include dermatoses such as erythema repens in patients with lung cancer, or tripe palms and acanthosis nigricans in patients with gastrointestinal malignancy. Outside of paraneoplastic presentations, many syndromes have unique constellations of clinical findings that require the clinician to investigate for internal malignancy. Cancer-associated genodermatoses such as Birt-Hogg-Dubé, neurofibromatosis, and Cowden syndrome have key findings to alert the provider of potential internal malignancies.² Given the rarity and relative novelty of FeP, few studies have been performed that evaluate for an association with internal malignancies.

There potentially is a common pathophysiologic mechanism between FeP and other benign and malignant tumors. Some have noted a possible common embryonic origin, such as Merkel cells, and even a common gene mutation involving tumor protein p53 or PTCH1 gene.^3,4 Carcinoembryonic antigen is a glycoprotein often found in association with gastrointestinal tract tumors and also is elevated in some cases of FeP.⁵ A single-center retrospective study performed by Longo et al³ demonstrated an association between FeP and gastrointestinal malignancy by calculating a percentage of those with FeP who also had gastrointestinal tract tumors. Moreover, they noted that FeP preceded gastrointestinal tract tumors by up to 1 to 2 years. Using the results of this study, they suggested that a similar pathogenesis underlies the association between FeP and gastrointestinal malignancy, but a shared pathogenesis has not yet been elucidated.³

With a transition to preventive medicine and age-adjusted malignancy screening in the US medical community, the findings of FeP as a marker of gastrointestinal tract tumors could alter current recommendations of routine skin examinations and colorectal cancer screening. This study investigates the association between FeP and internal malignancy, especially gastrointestinal tract tumors.

Methods

Patient Selection—A single-center, retrospective, case-control study was designed to investigate an association between FeP and internal malignancy. The study protocol was approved by the institutional review board of the Naval Medical Center San Diego, California, in compliance with all applicable federal regulations governing the protection of human subjects. A medical record review was initiated using the Department of Defense (DoD) electronic health record to identify patients with a history of FeP. The query used a natural language search for patients who had received a histopathology report that included Fibroepithelioma of Pinkus, Pinkus, or Pinkus tumor within the diagnosis or comment section for pathology specimens processed at our institution (Naval Medical Center San Diego). A total of 45 patients evaluated at Naval Medical Center San Diego had biopsy specimens that met inclusion criteria. Only 42 electronic medical records were available to review between January 1, 2003, and March 1, 2020. Three patients were excluded from the study for absent or incomplete medical records.

Study Procedures—Data extracted by researchers were analyzed for statistical significance. All available data in current electronic health records prior to the FeP diagnosis until March 1, 2020, was reviewed for other documented malignancy or colonoscopy data. Data extracted included age, sex, date of diagnosis of FeP, location of FeP, social history, and medical and surgical history to identify prior malignancy. Colorectal cancer screening results were drawn from original reports, gastrointestinal clinic notes, biopsy results, and/or primary care provider documentation of colonoscopy results. If the exact date of internal tumor diagnosis could not be determined but the year was known, the value “July, year” was utilized as the diagnosis date.

Statistical Analysis—Data were reviewed for validity, and the Shapiro-Wilk test was used to test for normality. Graphical visualization assisted in reviewing the distribution of the data in relation to the internal tumors. The Fisher exact test was performed to test for associations, while continuous variables were assessed using the Student t test or the nonparametric Mann-Whitney U test. Analysis was conducted with StataCorp. 2017 Stata Statistical Software: Release 15 (StataCorp LLC). Significance was set at P<.05. 

Patient Demographics—Of the 42 patients with FeP included in this study, 28 (66.7%) were male and 14 (33.3%) were female. The overall mean age at FeP diagnosis was 56.83 years. The mean age (SD) at FeP diagnosis for males was 59.21 (19.00) years and 52.07 (21.61) for females (P=.2792)(Table 1). Other pertinent medical history, including alcohol and tobacco use, obesity, and diabetes mellitus, is included in Table 1.

Characterization of Tumors—The classification of the number of patients with any other nonskin neoplasm is presented in Table 2. Fifteen (35.7%) patients had 1 or more gastrointestinal tubular adenomas. Three patients were found to have colorectal adenocarcinoma. Karsenti et al⁶ published a large study of colonic adenoma detection rates in the World Journal of Gastroenterology stratified by age and found that the incidence of adenoma for those aged 55 to 59 years was 28.3% vs 35.7% in our study (P=.2978 [Fisher exact test]).

Given the number of gastrointestinal tract tumors detected, most of which were found during routine surveillance, and a prior study⁶ suggesting a relationship between FeP and gastrointestinal tract tumors, we analyzed the temporal relationship between the date of gastrointestinal tract tumor diagnosis and the date of FeP diagnosis to assess if gastrointestinal tract tumor or FeP might predict the onset of the other (Figure 1). By assigning a temporal category to each gastrointestinal tract tumor as occurring either before or after the FeP diagnosis by 0 to 3 years, 3 to 10 years, 10 to 15 years, and 15 or more years, the box plot in Figure 1 shows that gastrointestinal adenoma development had no significant temporal relationship to the presence of FeP, excluding any outliers (shown as dots). Additionally, in Figure 1, the same concept was applied to assess the relationship between the dates of all gastrointestinal tract tumors—benign, precancerous, or malignant—and the date of FeP diagnosis, which again showed that FeP and gastrointestinal tract tumors did not predict the onset of the other. Figure 2 showed the same for all nonskin tumor diagnoses and again demonstrated that FeP and all other nondermatologic tumors did not predict the onset of the other.

Comment

Malignancy Potential—The malignant potential of FeP—characterized as a trichoblastoma (an adnexal tumor) or a basal cell carcinoma (BCC) variant—has been documented.¹ Haddock and Cohen¹ noted that FeP can be considered as an intermediate variant between BCC and trichoblastomas. Furthermore, they questioned the relevance of differentiating FeP as benign or malignant.¹ There are additional elements of FeP that currently are unknown, which can be partially attributed to its rarity. If we can clarify a more accurate pathogenic model of FeP, then common mutational pathways with other malignancies may be identified.

Screening for Malignancy in FeP Patients—Until recently, FeP has not been demonstrated to be associated with other cancers or to have increased metastatic potential.¹ In a 1985 case series of 2 patients, FeP was found to be specifically overlying infiltrating ductal carcinoma of the breast. After a unilateral mastectomy, examination of the overlying skin of the breast showed a solitary, lightly pigmented nodule, which was identified as an FeP after histopathologic evaluation.⁷ There have been limited investigations of whether FeP is simply a solitary tumor or a harbinger for other malignancies, despite a study by Longo et al³ that attempted to establish this temporal relationship. They recommended that patients with FeP be clinically evaluated and screened for gastrointestinal tract tumors.³ Based on these recommendations, textbooks for dermatopathology now highlight the possible correlation of FeP and gastrointestinal malignancy,⁸ which may lead to earlier and unwarranted screening.

Comparison to the General Population—Although our analysis showed a portion of patients with FeP have gastrointestinal tract tumors, we do not detect a significant difference from the general population. The average age at the time of FeP diagnosis in our study was 56.83 years compared with the average age of 64.0 years by Longo et al,³ where they found an association with gastrointestinal adenocarcinoma and neuroendocrine tumors. As the rate of gastrointestinal adenoma and malignancy increases with age, the older population in the study by Longo et al³ may have developed colorectal cancer independent of FeP development. However, the rate of gastrointestinal or other malignancies in their study was substantially higher than that of the general population. The Longo et al³ study found that 22 of 49 patients developed nondermatologic malignancies within 2 years of FeP diagnosis. Additionally, no data were provided in the study regarding precancerous lesions.

In our study population, benign gastrointestinal tract tumors, specifically tubular adenomas, were noted in 35.7% of patients with FeP compared with 28.3% of the general population in the same age group reported by Karsenti et al.⁶ Although limited by our sample size, our study demonstrated that patients with FeP diagnosis showed no significant difference in age-stratified incidence of tubular adenoma compared with the general population (P=.2978). Figures 1 and 2 showed no obvious temporal relationship between the development of FeP and the diagnosis of gastrointestinal tumor—either precancerous or malignant lesions—suggesting that diagnosis of one does not indicate the presence of the other.

Relationship With Colonoscopy Results—By analyzing those patients with FeP who specifically had documented colonoscopy results, we did not find a correlation between FeP and gastrointestinal tubular adenoma or carcinoma at any time during the patients’ available records. Although some patients may have had undocumented colonoscopies performed outside the DoD medical system, most had evidence that these procedures were being performed by transcription into primary care provider notes, uploaded gastroenterologist clinical notes, or colonoscopy reports. It is unlikely a true colorectal or other malignancy would remain undocumented over years within the electronic medical record.

Study Limitations—Because of the nature of electronic medical records at multiple institutions, the quality and/or the quantity of medical documentation is not standardized across all patients. Not all pathology reports may include FeP as the primary diagnosis or description, as FeP may simply be reported as BCC. Despite thorough data extraction by physicians, we were limited to the data available within our electronic medical records. Colonoscopies and other specialty care often were performed by civilian providers. Documentation regarding where patients were referred for such procedures outside the DoD was not available unless reports were transmitted to the DoD or transcribed by primary care providers. Incomplete records may make it more difficult to identify and document the number and characteristics of patients’ tubular adenomas. Therefore, a complete review of civilian records was not possible, causing some patients’ medical records to be documented for a longer period of their lives than for others.

Conclusion

Our data demonstrated no statistically significant temporal relationship between the development of FeP and other benign or malignant tumors. Additionally, the prevalence of tubular adenoma or gastrointestinal malignancy is not substantially higher in those with FeP than the age-adjusted population. Current guidelines recommend that patients with FeP should be treated and return for follow up at regular intervals, similar to patients with a history of BCC. This study does not establish FeP as a risk factor for development of any type of cancer that would require earlier or more frequent intervals beyond the established age-appropriate screening guidelines.

Given the discrepancies in our findings with the previous study,³ future investigations on FeP and associated tumors should focus on integrated health care systems with longitudinal data sets for all age-appropriate cancer screenings in a larger sample size. Another related study is needed to evaluate the pathophysiologic mechanisms of FeP development relative to known cancer lines.

Fibroepithelioma of Pinkus (FeP), or Pinkus tumor, is a rare tumor with a presentation similar to benign neoplasms such as acrochordons and seborrheic keratoses. Classically, FeP presents as a nontender, solitary, flesh-colored, firm, dome-shaped papule or plaque with a predilection for the lumbosacral region rather than sun-exposed areas. This tumor typically develops in fair-skinned older adults, more often in females.¹

The association between cutaneous lesions and internal malignancies is well known to include dermatoses such as erythema repens in patients with lung cancer, or tripe palms and acanthosis nigricans in patients with gastrointestinal malignancy. Outside of paraneoplastic presentations, many syndromes have unique constellations of clinical findings that require the clinician to investigate for internal malignancy. Cancer-associated genodermatoses such as Birt-Hogg-Dubé, neurofibromatosis, and Cowden syndrome have key findings to alert the provider of potential internal malignancies.² Given the rarity and relative novelty of FeP, few studies have been performed that evaluate for an association with internal malignancies.

There potentially is a common pathophysiologic mechanism between FeP and other benign and malignant tumors. Some have noted a possible common embryonic origin, such as Merkel cells, and even a common gene mutation involving tumor protein p53 or PTCH1 gene.^3,4 Carcinoembryonic antigen is a glycoprotein often found in association with gastrointestinal tract tumors and also is elevated in some cases of FeP.⁵ A single-center retrospective study performed by Longo et al³ demonstrated an association between FeP and gastrointestinal malignancy by calculating a percentage of those with FeP who also had gastrointestinal tract tumors. Moreover, they noted that FeP preceded gastrointestinal tract tumors by up to 1 to 2 years. Using the results of this study, they suggested that a similar pathogenesis underlies the association between FeP and gastrointestinal malignancy, but a shared pathogenesis has not yet been elucidated.³

With a transition to preventive medicine and age-adjusted malignancy screening in the US medical community, the findings of FeP as a marker of gastrointestinal tract tumors could alter current recommendations of routine skin examinations and colorectal cancer screening. This study investigates the association between FeP and internal malignancy, especially gastrointestinal tract tumors.

Methods

Patient Selection—A single-center, retrospective, case-control study was designed to investigate an association between FeP and internal malignancy. The study protocol was approved by the institutional review board of the Naval Medical Center San Diego, California, in compliance with all applicable federal regulations governing the protection of human subjects. A medical record review was initiated using the Department of Defense (DoD) electronic health record to identify patients with a history of FeP. The query used a natural language search for patients who had received a histopathology report that included Fibroepithelioma of Pinkus, Pinkus, or Pinkus tumor within the diagnosis or comment section for pathology specimens processed at our institution (Naval Medical Center San Diego). A total of 45 patients evaluated at Naval Medical Center San Diego had biopsy specimens that met inclusion criteria. Only 42 electronic medical records were available to review between January 1, 2003, and March 1, 2020. Three patients were excluded from the study for absent or incomplete medical records.

Study Procedures—Data extracted by researchers were analyzed for statistical significance. All available data in current electronic health records prior to the FeP diagnosis until March 1, 2020, was reviewed for other documented malignancy or colonoscopy data. Data extracted included age, sex, date of diagnosis of FeP, location of FeP, social history, and medical and surgical history to identify prior malignancy. Colorectal cancer screening results were drawn from original reports, gastrointestinal clinic notes, biopsy results, and/or primary care provider documentation of colonoscopy results. If the exact date of internal tumor diagnosis could not be determined but the year was known, the value “July, year” was utilized as the diagnosis date.

Statistical Analysis—Data were reviewed for validity, and the Shapiro-Wilk test was used to test for normality. Graphical visualization assisted in reviewing the distribution of the data in relation to the internal tumors. The Fisher exact test was performed to test for associations, while continuous variables were assessed using the Student t test or the nonparametric Mann-Whitney U test. Analysis was conducted with StataCorp. 2017 Stata Statistical Software: Release 15 (StataCorp LLC). Significance was set at P<.05. 

Patient Demographics—Of the 42 patients with FeP included in this study, 28 (66.7%) were male and 14 (33.3%) were female. The overall mean age at FeP diagnosis was 56.83 years. The mean age (SD) at FeP diagnosis for males was 59.21 (19.00) years and 52.07 (21.61) for females (P=.2792)(Table 1). Other pertinent medical history, including alcohol and tobacco use, obesity, and diabetes mellitus, is included in Table 1.

Characterization of Tumors—The classification of the number of patients with any other nonskin neoplasm is presented in Table 2. Fifteen (35.7%) patients had 1 or more gastrointestinal tubular adenomas. Three patients were found to have colorectal adenocarcinoma. Karsenti et al⁶ published a large study of colonic adenoma detection rates in the World Journal of Gastroenterology stratified by age and found that the incidence of adenoma for those aged 55 to 59 years was 28.3% vs 35.7% in our study (P=.2978 [Fisher exact test]).

Given the number of gastrointestinal tract tumors detected, most of which were found during routine surveillance, and a prior study⁶ suggesting a relationship between FeP and gastrointestinal tract tumors, we analyzed the temporal relationship between the date of gastrointestinal tract tumor diagnosis and the date of FeP diagnosis to assess if gastrointestinal tract tumor or FeP might predict the onset of the other (Figure 1). By assigning a temporal category to each gastrointestinal tract tumor as occurring either before or after the FeP diagnosis by 0 to 3 years, 3 to 10 years, 10 to 15 years, and 15 or more years, the box plot in Figure 1 shows that gastrointestinal adenoma development had no significant temporal relationship to the presence of FeP, excluding any outliers (shown as dots). Additionally, in Figure 1, the same concept was applied to assess the relationship between the dates of all gastrointestinal tract tumors—benign, precancerous, or malignant—and the date of FeP diagnosis, which again showed that FeP and gastrointestinal tract tumors did not predict the onset of the other. Figure 2 showed the same for all nonskin tumor diagnoses and again demonstrated that FeP and all other nondermatologic tumors did not predict the onset of the other.

Comment

Malignancy Potential—The malignant potential of FeP—characterized as a trichoblastoma (an adnexal tumor) or a basal cell carcinoma (BCC) variant—has been documented.¹ Haddock and Cohen¹ noted that FeP can be considered as an intermediate variant between BCC and trichoblastomas. Furthermore, they questioned the relevance of differentiating FeP as benign or malignant.¹ There are additional elements of FeP that currently are unknown, which can be partially attributed to its rarity. If we can clarify a more accurate pathogenic model of FeP, then common mutational pathways with other malignancies may be identified.

Screening for Malignancy in FeP Patients—Until recently, FeP has not been demonstrated to be associated with other cancers or to have increased metastatic potential.¹ In a 1985 case series of 2 patients, FeP was found to be specifically overlying infiltrating ductal carcinoma of the breast. After a unilateral mastectomy, examination of the overlying skin of the breast showed a solitary, lightly pigmented nodule, which was identified as an FeP after histopathologic evaluation.⁷ There have been limited investigations of whether FeP is simply a solitary tumor or a harbinger for other malignancies, despite a study by Longo et al³ that attempted to establish this temporal relationship. They recommended that patients with FeP be clinically evaluated and screened for gastrointestinal tract tumors.³ Based on these recommendations, textbooks for dermatopathology now highlight the possible correlation of FeP and gastrointestinal malignancy,⁸ which may lead to earlier and unwarranted screening.

Comparison to the General Population—Although our analysis showed a portion of patients with FeP have gastrointestinal tract tumors, we do not detect a significant difference from the general population. The average age at the time of FeP diagnosis in our study was 56.83 years compared with the average age of 64.0 years by Longo et al,³ where they found an association with gastrointestinal adenocarcinoma and neuroendocrine tumors. As the rate of gastrointestinal adenoma and malignancy increases with age, the older population in the study by Longo et al³ may have developed colorectal cancer independent of FeP development. However, the rate of gastrointestinal or other malignancies in their study was substantially higher than that of the general population. The Longo et al³ study found that 22 of 49 patients developed nondermatologic malignancies within 2 years of FeP diagnosis. Additionally, no data were provided in the study regarding precancerous lesions.

In our study population, benign gastrointestinal tract tumors, specifically tubular adenomas, were noted in 35.7% of patients with FeP compared with 28.3% of the general population in the same age group reported by Karsenti et al.⁶ Although limited by our sample size, our study demonstrated that patients with FeP diagnosis showed no significant difference in age-stratified incidence of tubular adenoma compared with the general population (P=.2978). Figures 1 and 2 showed no obvious temporal relationship between the development of FeP and the diagnosis of gastrointestinal tumor—either precancerous or malignant lesions—suggesting that diagnosis of one does not indicate the presence of the other.

Relationship With Colonoscopy Results—By analyzing those patients with FeP who specifically had documented colonoscopy results, we did not find a correlation between FeP and gastrointestinal tubular adenoma or carcinoma at any time during the patients’ available records. Although some patients may have had undocumented colonoscopies performed outside the DoD medical system, most had evidence that these procedures were being performed by transcription into primary care provider notes, uploaded gastroenterologist clinical notes, or colonoscopy reports. It is unlikely a true colorectal or other malignancy would remain undocumented over years within the electronic medical record.

Study Limitations—Because of the nature of electronic medical records at multiple institutions, the quality and/or the quantity of medical documentation is not standardized across all patients. Not all pathology reports may include FeP as the primary diagnosis or description, as FeP may simply be reported as BCC. Despite thorough data extraction by physicians, we were limited to the data available within our electronic medical records. Colonoscopies and other specialty care often were performed by civilian providers. Documentation regarding where patients were referred for such procedures outside the DoD was not available unless reports were transmitted to the DoD or transcribed by primary care providers. Incomplete records may make it more difficult to identify and document the number and characteristics of patients’ tubular adenomas. Therefore, a complete review of civilian records was not possible, causing some patients’ medical records to be documented for a longer period of their lives than for others.

Conclusion

Our data demonstrated no statistically significant temporal relationship between the development of FeP and other benign or malignant tumors. Additionally, the prevalence of tubular adenoma or gastrointestinal malignancy is not substantially higher in those with FeP than the age-adjusted population. Current guidelines recommend that patients with FeP should be treated and return for follow up at regular intervals, similar to patients with a history of BCC. This study does not establish FeP as a risk factor for development of any type of cancer that would require earlier or more frequent intervals beyond the established age-appropriate screening guidelines.

Given the discrepancies in our findings with the previous study,³ future investigations on FeP and associated tumors should focus on integrated health care systems with longitudinal data sets for all age-appropriate cancer screenings in a larger sample size. Another related study is needed to evaluate the pathophysiologic mechanisms of FeP development relative to known cancer lines.

Fibroepithelioma of Pinkus (FeP), or Pinkus tumor, is a rare tumor with a presentation similar to benign neoplasms such as acrochordons and seborrheic keratoses. Classically, FeP presents as a nontender, solitary, flesh-colored, firm, dome-shaped papule or plaque with a predilection for the lumbosacral region rather than sun-exposed areas. This tumor typically develops in fair-skinned older adults, more often in females.¹

The association between cutaneous lesions and internal malignancies is well known to include dermatoses such as erythema repens in patients with lung cancer, or tripe palms and acanthosis nigricans in patients with gastrointestinal malignancy. Outside of paraneoplastic presentations, many syndromes have unique constellations of clinical findings that require the clinician to investigate for internal malignancy. Cancer-associated genodermatoses such as Birt-Hogg-Dubé, neurofibromatosis, and Cowden syndrome have key findings to alert the provider of potential internal malignancies.² Given the rarity and relative novelty of FeP, few studies have been performed that evaluate for an association with internal malignancies.

There potentially is a common pathophysiologic mechanism between FeP and other benign and malignant tumors. Some have noted a possible common embryonic origin, such as Merkel cells, and even a common gene mutation involving tumor protein p53 or PTCH1 gene.^3,4 Carcinoembryonic antigen is a glycoprotein often found in association with gastrointestinal tract tumors and also is elevated in some cases of FeP.⁵ A single-center retrospective study performed by Longo et al³ demonstrated an association between FeP and gastrointestinal malignancy by calculating a percentage of those with FeP who also had gastrointestinal tract tumors. Moreover, they noted that FeP preceded gastrointestinal tract tumors by up to 1 to 2 years. Using the results of this study, they suggested that a similar pathogenesis underlies the association between FeP and gastrointestinal malignancy, but a shared pathogenesis has not yet been elucidated.³

With a transition to preventive medicine and age-adjusted malignancy screening in the US medical community, the findings of FeP as a marker of gastrointestinal tract tumors could alter current recommendations of routine skin examinations and colorectal cancer screening. This study investigates the association between FeP and internal malignancy, especially gastrointestinal tract tumors.

Methods

Patient Selection—A single-center, retrospective, case-control study was designed to investigate an association between FeP and internal malignancy. The study protocol was approved by the institutional review board of the Naval Medical Center San Diego, California, in compliance with all applicable federal regulations governing the protection of human subjects. A medical record review was initiated using the Department of Defense (DoD) electronic health record to identify patients with a history of FeP. The query used a natural language search for patients who had received a histopathology report that included Fibroepithelioma of Pinkus, Pinkus, or Pinkus tumor within the diagnosis or comment section for pathology specimens processed at our institution (Naval Medical Center San Diego). A total of 45 patients evaluated at Naval Medical Center San Diego had biopsy specimens that met inclusion criteria. Only 42 electronic medical records were available to review between January 1, 2003, and March 1, 2020. Three patients were excluded from the study for absent or incomplete medical records.

Study Procedures—Data extracted by researchers were analyzed for statistical significance. All available data in current electronic health records prior to the FeP diagnosis until March 1, 2020, was reviewed for other documented malignancy or colonoscopy data. Data extracted included age, sex, date of diagnosis of FeP, location of FeP, social history, and medical and surgical history to identify prior malignancy. Colorectal cancer screening results were drawn from original reports, gastrointestinal clinic notes, biopsy results, and/or primary care provider documentation of colonoscopy results. If the exact date of internal tumor diagnosis could not be determined but the year was known, the value “July, year” was utilized as the diagnosis date.

Statistical Analysis—Data were reviewed for validity, and the Shapiro-Wilk test was used to test for normality. Graphical visualization assisted in reviewing the distribution of the data in relation to the internal tumors. The Fisher exact test was performed to test for associations, while continuous variables were assessed using the Student t test or the nonparametric Mann-Whitney U test. Analysis was conducted with StataCorp. 2017 Stata Statistical Software: Release 15 (StataCorp LLC). Significance was set at P<.05. 

Patient Demographics—Of the 42 patients with FeP included in this study, 28 (66.7%) were male and 14 (33.3%) were female. The overall mean age at FeP diagnosis was 56.83 years. The mean age (SD) at FeP diagnosis for males was 59.21 (19.00) years and 52.07 (21.61) for females (P=.2792)(Table 1). Other pertinent medical history, including alcohol and tobacco use, obesity, and diabetes mellitus, is included in Table 1.

Characterization of Tumors—The classification of the number of patients with any other nonskin neoplasm is presented in Table 2. Fifteen (35.7%) patients had 1 or more gastrointestinal tubular adenomas. Three patients were found to have colorectal adenocarcinoma. Karsenti et al⁶ published a large study of colonic adenoma detection rates in the World Journal of Gastroenterology stratified by age and found that the incidence of adenoma for those aged 55 to 59 years was 28.3% vs 35.7% in our study (P=.2978 [Fisher exact test]).

Given the number of gastrointestinal tract tumors detected, most of which were found during routine surveillance, and a prior study⁶ suggesting a relationship between FeP and gastrointestinal tract tumors, we analyzed the temporal relationship between the date of gastrointestinal tract tumor diagnosis and the date of FeP diagnosis to assess if gastrointestinal tract tumor or FeP might predict the onset of the other (Figure 1). By assigning a temporal category to each gastrointestinal tract tumor as occurring either before or after the FeP diagnosis by 0 to 3 years, 3 to 10 years, 10 to 15 years, and 15 or more years, the box plot in Figure 1 shows that gastrointestinal adenoma development had no significant temporal relationship to the presence of FeP, excluding any outliers (shown as dots). Additionally, in Figure 1, the same concept was applied to assess the relationship between the dates of all gastrointestinal tract tumors—benign, precancerous, or malignant—and the date of FeP diagnosis, which again showed that FeP and gastrointestinal tract tumors did not predict the onset of the other. Figure 2 showed the same for all nonskin tumor diagnoses and again demonstrated that FeP and all other nondermatologic tumors did not predict the onset of the other.

Comment

Malignancy Potential—The malignant potential of FeP—characterized as a trichoblastoma (an adnexal tumor) or a basal cell carcinoma (BCC) variant—has been documented.¹ Haddock and Cohen¹ noted that FeP can be considered as an intermediate variant between BCC and trichoblastomas. Furthermore, they questioned the relevance of differentiating FeP as benign or malignant.¹ There are additional elements of FeP that currently are unknown, which can be partially attributed to its rarity. If we can clarify a more accurate pathogenic model of FeP, then common mutational pathways with other malignancies may be identified.

Screening for Malignancy in FeP Patients—Until recently, FeP has not been demonstrated to be associated with other cancers or to have increased metastatic potential.¹ In a 1985 case series of 2 patients, FeP was found to be specifically overlying infiltrating ductal carcinoma of the breast. After a unilateral mastectomy, examination of the overlying skin of the breast showed a solitary, lightly pigmented nodule, which was identified as an FeP after histopathologic evaluation.⁷ There have been limited investigations of whether FeP is simply a solitary tumor or a harbinger for other malignancies, despite a study by Longo et al³ that attempted to establish this temporal relationship. They recommended that patients with FeP be clinically evaluated and screened for gastrointestinal tract tumors.³ Based on these recommendations, textbooks for dermatopathology now highlight the possible correlation of FeP and gastrointestinal malignancy,⁸ which may lead to earlier and unwarranted screening.

Comparison to the General Population—Although our analysis showed a portion of patients with FeP have gastrointestinal tract tumors, we do not detect a significant difference from the general population. The average age at the time of FeP diagnosis in our study was 56.83 years compared with the average age of 64.0 years by Longo et al,³ where they found an association with gastrointestinal adenocarcinoma and neuroendocrine tumors. As the rate of gastrointestinal adenoma and malignancy increases with age, the older population in the study by Longo et al³ may have developed colorectal cancer independent of FeP development. However, the rate of gastrointestinal or other malignancies in their study was substantially higher than that of the general population. The Longo et al³ study found that 22 of 49 patients developed nondermatologic malignancies within 2 years of FeP diagnosis. Additionally, no data were provided in the study regarding precancerous lesions.

In our study population, benign gastrointestinal tract tumors, specifically tubular adenomas, were noted in 35.7% of patients with FeP compared with 28.3% of the general population in the same age group reported by Karsenti et al.⁶ Although limited by our sample size, our study demonstrated that patients with FeP diagnosis showed no significant difference in age-stratified incidence of tubular adenoma compared with the general population (P=.2978). Figures 1 and 2 showed no obvious temporal relationship between the development of FeP and the diagnosis of gastrointestinal tumor—either precancerous or malignant lesions—suggesting that diagnosis of one does not indicate the presence of the other.

Relationship With Colonoscopy Results—By analyzing those patients with FeP who specifically had documented colonoscopy results, we did not find a correlation between FeP and gastrointestinal tubular adenoma or carcinoma at any time during the patients’ available records. Although some patients may have had undocumented colonoscopies performed outside the DoD medical system, most had evidence that these procedures were being performed by transcription into primary care provider notes, uploaded gastroenterologist clinical notes, or colonoscopy reports. It is unlikely a true colorectal or other malignancy would remain undocumented over years within the electronic medical record.

Study Limitations—Because of the nature of electronic medical records at multiple institutions, the quality and/or the quantity of medical documentation is not standardized across all patients. Not all pathology reports may include FeP as the primary diagnosis or description, as FeP may simply be reported as BCC. Despite thorough data extraction by physicians, we were limited to the data available within our electronic medical records. Colonoscopies and other specialty care often were performed by civilian providers. Documentation regarding where patients were referred for such procedures outside the DoD was not available unless reports were transmitted to the DoD or transcribed by primary care providers. Incomplete records may make it more difficult to identify and document the number and characteristics of patients’ tubular adenomas. Therefore, a complete review of civilian records was not possible, causing some patients’ medical records to be documented for a longer period of their lives than for others.

Conclusion

Our data demonstrated no statistically significant temporal relationship between the development of FeP and other benign or malignant tumors. Additionally, the prevalence of tubular adenoma or gastrointestinal malignancy is not substantially higher in those with FeP than the age-adjusted population. Current guidelines recommend that patients with FeP should be treated and return for follow up at regular intervals, similar to patients with a history of BCC. This study does not establish FeP as a risk factor for development of any type of cancer that would require earlier or more frequent intervals beyond the established age-appropriate screening guidelines.

Given the discrepancies in our findings with the previous study,³ future investigations on FeP and associated tumors should focus on integrated health care systems with longitudinal data sets for all age-appropriate cancer screenings in a larger sample size. Another related study is needed to evaluate the pathophysiologic mechanisms of FeP development relative to known cancer lines.

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The Diagnosis: Marjolin Ulcer

A skin biopsy during his prior hospital admission demonstrated an ulcer with granulation tissue and mixed inflammation, and the patient was discharged with close outpatient follow-up. Two repeat skin biopsies from the peripheral margin at the time of the outpatient follow-up confirmed an invasive, well-differentiated squamous cell carcinoma (Figure), consistent with a Marjolin ulcer. Radiography demonstrated multiple left iliac chain and inguinal lymphadenopathies with extensive subcutaneous disease overlying the left medial tibia. After tumor board discussion, surgery was not recommended due to the size and likely penetration into the muscle. The patient began treatment with cemiplimab-rwlc, a PD-1 inhibitor. Within 4 cycles of treatment, he had improved pain and ambulation, and a 3-month follow-up positron emission tomography scan revealed decreased lymph node and cutaneous metabolic activity as well as clinical improvement.

Marjolin ulcers are rare and aggressive squamous cell carcinomas that arise from chronic wounds such as burn scars or pressure ulcers.¹ Although an underlying well-differentiated squamous cell carcinoma is the most common etiology, patients also may present with underlying basal cell carcinomas, melanomas, or angiosarcomas.² The exact pathogenesis underlying the malignant degeneration is unclear but appears to be driven by chronic inflammation. Patients classically present with a nonhealing ulcer associated with raised, friable, or crusty borders, as well as surrounding scar tissue. There is a median latency of 30 years after the trauma, though acute transformation within 12 months of an injury is possible.³ The diagnosis is confirmed with a peripheral wound biopsy. Surgical excision with wide margins remains the most common and effective intervention, especially for localized disease.¹ The addition of lymph node dissection remains controversial, but treatment decisions can be guided by radiographic staging.⁴

The prognosis of Marjolin ulcers remains poor, with a predicted 5-year survival rate ranging from 43% to 58%.¹ Dermatologists and trainees should be aware of Marjolin ulcers, especially as a mimicker of other chronic ulcerating conditions. Among the differential diagnosis, ulcerative lichen planus is a condition that commonly affects the oral and genital regions; however, patients with erosive lichen planus may develop an increased risk for the subsequent development of squamous cell carcinoma in the region.⁵ Furthermore, arterial ulcers typically develop on the distal lower extremities with other signs of chronic ischemia, including absent peripheral pulses, atrophic skin, hair loss, and ankle-brachial indices less than 0.5. Conversely, a venous ulcer classically affects the medial malleolus and will have evidence of venous insufficiency, including stasis dermatitis and peripheral edema.⁶

The Diagnosis: Marjolin Ulcer

A skin biopsy during his prior hospital admission demonstrated an ulcer with granulation tissue and mixed inflammation, and the patient was discharged with close outpatient follow-up. Two repeat skin biopsies from the peripheral margin at the time of the outpatient follow-up confirmed an invasive, well-differentiated squamous cell carcinoma (Figure), consistent with a Marjolin ulcer. Radiography demonstrated multiple left iliac chain and inguinal lymphadenopathies with extensive subcutaneous disease overlying the left medial tibia. After tumor board discussion, surgery was not recommended due to the size and likely penetration into the muscle. The patient began treatment with cemiplimab-rwlc, a PD-1 inhibitor. Within 4 cycles of treatment, he had improved pain and ambulation, and a 3-month follow-up positron emission tomography scan revealed decreased lymph node and cutaneous metabolic activity as well as clinical improvement.

Marjolin ulcers are rare and aggressive squamous cell carcinomas that arise from chronic wounds such as burn scars or pressure ulcers.¹ Although an underlying well-differentiated squamous cell carcinoma is the most common etiology, patients also may present with underlying basal cell carcinomas, melanomas, or angiosarcomas.² The exact pathogenesis underlying the malignant degeneration is unclear but appears to be driven by chronic inflammation. Patients classically present with a nonhealing ulcer associated with raised, friable, or crusty borders, as well as surrounding scar tissue. There is a median latency of 30 years after the trauma, though acute transformation within 12 months of an injury is possible.³ The diagnosis is confirmed with a peripheral wound biopsy. Surgical excision with wide margins remains the most common and effective intervention, especially for localized disease.¹ The addition of lymph node dissection remains controversial, but treatment decisions can be guided by radiographic staging.⁴

The prognosis of Marjolin ulcers remains poor, with a predicted 5-year survival rate ranging from 43% to 58%.¹ Dermatologists and trainees should be aware of Marjolin ulcers, especially as a mimicker of other chronic ulcerating conditions. Among the differential diagnosis, ulcerative lichen planus is a condition that commonly affects the oral and genital regions; however, patients with erosive lichen planus may develop an increased risk for the subsequent development of squamous cell carcinoma in the region.⁵ Furthermore, arterial ulcers typically develop on the distal lower extremities with other signs of chronic ischemia, including absent peripheral pulses, atrophic skin, hair loss, and ankle-brachial indices less than 0.5. Conversely, a venous ulcer classically affects the medial malleolus and will have evidence of venous insufficiency, including stasis dermatitis and peripheral edema.⁶

The Diagnosis: Marjolin Ulcer

A skin biopsy during his prior hospital admission demonstrated an ulcer with granulation tissue and mixed inflammation, and the patient was discharged with close outpatient follow-up. Two repeat skin biopsies from the peripheral margin at the time of the outpatient follow-up confirmed an invasive, well-differentiated squamous cell carcinoma (Figure), consistent with a Marjolin ulcer. Radiography demonstrated multiple left iliac chain and inguinal lymphadenopathies with extensive subcutaneous disease overlying the left medial tibia. After tumor board discussion, surgery was not recommended due to the size and likely penetration into the muscle. The patient began treatment with cemiplimab-rwlc, a PD-1 inhibitor. Within 4 cycles of treatment, he had improved pain and ambulation, and a 3-month follow-up positron emission tomography scan revealed decreased lymph node and cutaneous metabolic activity as well as clinical improvement.

Marjolin ulcers are rare and aggressive squamous cell carcinomas that arise from chronic wounds such as burn scars or pressure ulcers.¹ Although an underlying well-differentiated squamous cell carcinoma is the most common etiology, patients also may present with underlying basal cell carcinomas, melanomas, or angiosarcomas.² The exact pathogenesis underlying the malignant degeneration is unclear but appears to be driven by chronic inflammation. Patients classically present with a nonhealing ulcer associated with raised, friable, or crusty borders, as well as surrounding scar tissue. There is a median latency of 30 years after the trauma, though acute transformation within 12 months of an injury is possible.³ The diagnosis is confirmed with a peripheral wound biopsy. Surgical excision with wide margins remains the most common and effective intervention, especially for localized disease.¹ The addition of lymph node dissection remains controversial, but treatment decisions can be guided by radiographic staging.⁴

The prognosis of Marjolin ulcers remains poor, with a predicted 5-year survival rate ranging from 43% to 58%.¹ Dermatologists and trainees should be aware of Marjolin ulcers, especially as a mimicker of other chronic ulcerating conditions. Among the differential diagnosis, ulcerative lichen planus is a condition that commonly affects the oral and genital regions; however, patients with erosive lichen planus may develop an increased risk for the subsequent development of squamous cell carcinoma in the region.⁵ Furthermore, arterial ulcers typically develop on the distal lower extremities with other signs of chronic ischemia, including absent peripheral pulses, atrophic skin, hair loss, and ankle-brachial indices less than 0.5. Conversely, a venous ulcer classically affects the medial malleolus and will have evidence of venous insufficiency, including stasis dermatitis and peripheral edema.⁶

AURORA, COLO. – Only sparse evidence supports the use of dual-targeted therapy for patients with severe, refractory inflammatory bowel disease (IBD) -- and additional evidence will be hard to come by, according to a leading IBD researcher.

Dual-targeted therapy consists of either sequential or concomitant treatment with drugs from different classes of agents with distinct, specific mechanisms of action such as the use of a drug targeted against tumor necrosis factor (anti-TNFs) with an interleukin-12/23 inhibitor.

There have been only a handful of randomized clinical trials exploring such combinations, however. In addition, there are barriers to new trials, including the costs and risks of randomized trials, the need for cooperation rather than competition between pharmaceutical companies, and identifying patients who might optimally benefit from dual-targeted therapy, Laura Targownik, MD, said in a presentation at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“In Canada we have absolutely no chance of getting coverage for this, and I imagine in hearing about the fights you have with insurers here in the [United] States, that you’re anticipating similar problems. So what do we do with this information? I think if we’re going to get answers on this question, it’s probably going to come from real-world evidence, from all of our experiences,” said Dr. Targownik of the Zane Cohen Centre for Digestive Diseases at Mount Sinai Hospital in Toronto.

Who might benefit?

Dual-targeted therapy has the potential to benefit patients with severe disease who may need intensive therapy upfront to prevent complications such as fistulas, strictures, or chronic abdominal pain. It may also benefit those who may require only short-term acute disease control; patients with meaningful yet incomplete responses to single-agent therapy who might have better outcomes with the addition of a second agent; and, patients with a unique phenotype that might be responsive to dual-targeted agents, Dr. Targownik said.

Another reason to consider dual-targeted therapy in IBD comes from applying data from recent clinical trials of upadacitinib (Rinvoq, Abbvie) for ulcerative colitis (UC) and risankizumab-rzaa (Skyrizi, Abbvie) for Crohn’s disease to hypothetical cohorts.

For example, of 1,000 persons with moderate to severe UC treated with upadacitinib, 736 would have a clinical response at the end of the induction, and at the end of the maintenance phase 191 would have endoscopic remissions, and 382 would remain in clinical remission.

Similarly, of 1,000 persons with moderate to severe Crohn’s disease treated with risankizumab, 434 would have a clinical response at the end of induction, and at the end of the maintenance phase, 172 would have endoscopic remissions, and 234 would remain in clinical remission.

“So, the vast majority of our patients are not achieving the targets that we want to hit,” she said.
 

Evidence from research clinical trials

Data from one of the few trials that have explored dual targeted therapy in IBD were presented at United European Gastroenterology Week in 2022.

The randomized double-blind phase 2a VEGA study looked at induction therapy with either a combination of the IL-23 inhibitor guselkumab (Tremfya, Janssen) and the anti-TNF monoclonal antibody golimumab (Simponi Aria, Janssen) followed by maintenance guselkumab, or each agent alone as induction monotherapy and maintenance.

The study population included 214 patients with moderate to severe UC with a modified Mayo Disease Activity Index scores of 6 or greater and endoscopy scores of 2 or 3 who had not received either anti-TNF or anti IL-23 agents.

At 12 weeks of follow-up, 36.6% of patients who started on combination therapy had clinical remissions, compared with 22.2% of patients on golimumab monotherapy and 22.1% of those on guselkumab alone, a clinically significant difference, Dr. Targownik said.

The combination also resulted in better endoscopic improvement over baseline (49.3% vs. 25% and 29.6%, respectively), although the study was not powered for this outcome.

At 38 weeks, 22.2% of patients who started on golimumab alone were in clinical remission, compared with 31% of those assigned to guselkumab monotherapy and 43.7% of those who started on the combination.

Endoscopic normalization at 38 weeks was seen in 6.9%, 15.5%, and 25.4% of patients, respectively.

“Even in the patients who went back on guselkumab monotherapy that were induced with dual therapy, there were statistically higher rates of clinical remission and endoscopic normalization at the end of the study,” Dr. Targownik said, although she noted that it’s unknown whether the benefit of the combination would be sustained over longer follow-up.

In the open-label EXPLORER Crohn’s disease trial, among 55 patients with high risk Crohn’s disease, within 24 months of diagnosis investigators looked at the triple combination therapy of the anti-integrin agent vedolizumab (Entyvio, Takeda), the anti-TNF agent adalimumab (Humira, Abbvie) and methotrexate. An interim analysis at week 26 of the 34-week trial showed clinical remissions in 54.5% of patients and endoscopic remissions in 34.5%, “which I would argue for an open-label study are not terribly high results,” she said.
 

Real-world experience

Dr. Targownik pointed to a systematic review and meta-analysis of the safety and effectiveness of combining biologic agents and small molecules in patients with IBD as evidence for how combinations work in the real world.

The analysis included data from 1 clinical trial and 12 observational studies on a total of 266 patients treated with one of seven different combinations. It showed estimates of clinical efficacy ranging from about 40% to 80%, albeit with wide and overlapping confidence intervals, making it difficult to come to any conclusions about the relatively superiority of one combination over another, Dr. Targownik said.

The authors of the meta-analysis did note, however, that the incidence of serious adverse events was relatively low, ranging from 9.6% for the combination of vedolizumab and anti-TNF, to just 1% for the JAK inhibitor tofacitinib (Xeljanz, Pfizer) plus vedolizumab.
 

Registry data may help

The use of registry data will shed more light on the potential benefits and drawbacks of dual-targeted therapy.

“If we can identify...the patient phenotypes that we want to evaluate dual therapy in, and try to catalog their experiences in a regimented way with defined outcomes and periods of follow-up, we may be able to get more meaningful information,” Dr. Targownik said.

Dr. Targownik disclosed fees, grant support, and/or scientific advisory board participation with multiple companies.

This article was updated 1/25/23.

AURORA, COLO. – Only sparse evidence supports the use of dual-targeted therapy for patients with severe, refractory inflammatory bowel disease (IBD) -- and additional evidence will be hard to come by, according to a leading IBD researcher.

Dual-targeted therapy consists of either sequential or concomitant treatment with drugs from different classes of agents with distinct, specific mechanisms of action such as the use of a drug targeted against tumor necrosis factor (anti-TNFs) with an interleukin-12/23 inhibitor.

There have been only a handful of randomized clinical trials exploring such combinations, however. In addition, there are barriers to new trials, including the costs and risks of randomized trials, the need for cooperation rather than competition between pharmaceutical companies, and identifying patients who might optimally benefit from dual-targeted therapy, Laura Targownik, MD, said in a presentation at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“In Canada we have absolutely no chance of getting coverage for this, and I imagine in hearing about the fights you have with insurers here in the [United] States, that you’re anticipating similar problems. So what do we do with this information? I think if we’re going to get answers on this question, it’s probably going to come from real-world evidence, from all of our experiences,” said Dr. Targownik of the Zane Cohen Centre for Digestive Diseases at Mount Sinai Hospital in Toronto.

Who might benefit?

Dual-targeted therapy has the potential to benefit patients with severe disease who may need intensive therapy upfront to prevent complications such as fistulas, strictures, or chronic abdominal pain. It may also benefit those who may require only short-term acute disease control; patients with meaningful yet incomplete responses to single-agent therapy who might have better outcomes with the addition of a second agent; and, patients with a unique phenotype that might be responsive to dual-targeted agents, Dr. Targownik said.

Another reason to consider dual-targeted therapy in IBD comes from applying data from recent clinical trials of upadacitinib (Rinvoq, Abbvie) for ulcerative colitis (UC) and risankizumab-rzaa (Skyrizi, Abbvie) for Crohn’s disease to hypothetical cohorts.

For example, of 1,000 persons with moderate to severe UC treated with upadacitinib, 736 would have a clinical response at the end of the induction, and at the end of the maintenance phase 191 would have endoscopic remissions, and 382 would remain in clinical remission.

Similarly, of 1,000 persons with moderate to severe Crohn’s disease treated with risankizumab, 434 would have a clinical response at the end of induction, and at the end of the maintenance phase, 172 would have endoscopic remissions, and 234 would remain in clinical remission.

“So, the vast majority of our patients are not achieving the targets that we want to hit,” she said.
 

Evidence from research clinical trials

Data from one of the few trials that have explored dual targeted therapy in IBD were presented at United European Gastroenterology Week in 2022.

The randomized double-blind phase 2a VEGA study looked at induction therapy with either a combination of the IL-23 inhibitor guselkumab (Tremfya, Janssen) and the anti-TNF monoclonal antibody golimumab (Simponi Aria, Janssen) followed by maintenance guselkumab, or each agent alone as induction monotherapy and maintenance.

The study population included 214 patients with moderate to severe UC with a modified Mayo Disease Activity Index scores of 6 or greater and endoscopy scores of 2 or 3 who had not received either anti-TNF or anti IL-23 agents.

At 12 weeks of follow-up, 36.6% of patients who started on combination therapy had clinical remissions, compared with 22.2% of patients on golimumab monotherapy and 22.1% of those on guselkumab alone, a clinically significant difference, Dr. Targownik said.

The combination also resulted in better endoscopic improvement over baseline (49.3% vs. 25% and 29.6%, respectively), although the study was not powered for this outcome.

At 38 weeks, 22.2% of patients who started on golimumab alone were in clinical remission, compared with 31% of those assigned to guselkumab monotherapy and 43.7% of those who started on the combination.

Endoscopic normalization at 38 weeks was seen in 6.9%, 15.5%, and 25.4% of patients, respectively.

“Even in the patients who went back on guselkumab monotherapy that were induced with dual therapy, there were statistically higher rates of clinical remission and endoscopic normalization at the end of the study,” Dr. Targownik said, although she noted that it’s unknown whether the benefit of the combination would be sustained over longer follow-up.

In the open-label EXPLORER Crohn’s disease trial, among 55 patients with high risk Crohn’s disease, within 24 months of diagnosis investigators looked at the triple combination therapy of the anti-integrin agent vedolizumab (Entyvio, Takeda), the anti-TNF agent adalimumab (Humira, Abbvie) and methotrexate. An interim analysis at week 26 of the 34-week trial showed clinical remissions in 54.5% of patients and endoscopic remissions in 34.5%, “which I would argue for an open-label study are not terribly high results,” she said.
 

Real-world experience

Dr. Targownik pointed to a systematic review and meta-analysis of the safety and effectiveness of combining biologic agents and small molecules in patients with IBD as evidence for how combinations work in the real world.

The analysis included data from 1 clinical trial and 12 observational studies on a total of 266 patients treated with one of seven different combinations. It showed estimates of clinical efficacy ranging from about 40% to 80%, albeit with wide and overlapping confidence intervals, making it difficult to come to any conclusions about the relatively superiority of one combination over another, Dr. Targownik said.

The authors of the meta-analysis did note, however, that the incidence of serious adverse events was relatively low, ranging from 9.6% for the combination of vedolizumab and anti-TNF, to just 1% for the JAK inhibitor tofacitinib (Xeljanz, Pfizer) plus vedolizumab.
 

Registry data may help

The use of registry data will shed more light on the potential benefits and drawbacks of dual-targeted therapy.

“If we can identify...the patient phenotypes that we want to evaluate dual therapy in, and try to catalog their experiences in a regimented way with defined outcomes and periods of follow-up, we may be able to get more meaningful information,” Dr. Targownik said.

Dr. Targownik disclosed fees, grant support, and/or scientific advisory board participation with multiple companies.

This article was updated 1/25/23.

AURORA, COLO. – Only sparse evidence supports the use of dual-targeted therapy for patients with severe, refractory inflammatory bowel disease (IBD) -- and additional evidence will be hard to come by, according to a leading IBD researcher.

Dual-targeted therapy consists of either sequential or concomitant treatment with drugs from different classes of agents with distinct, specific mechanisms of action such as the use of a drug targeted against tumor necrosis factor (anti-TNFs) with an interleukin-12/23 inhibitor.

There have been only a handful of randomized clinical trials exploring such combinations, however. In addition, there are barriers to new trials, including the costs and risks of randomized trials, the need for cooperation rather than competition between pharmaceutical companies, and identifying patients who might optimally benefit from dual-targeted therapy, Laura Targownik, MD, said in a presentation at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“In Canada we have absolutely no chance of getting coverage for this, and I imagine in hearing about the fights you have with insurers here in the [United] States, that you’re anticipating similar problems. So what do we do with this information? I think if we’re going to get answers on this question, it’s probably going to come from real-world evidence, from all of our experiences,” said Dr. Targownik of the Zane Cohen Centre for Digestive Diseases at Mount Sinai Hospital in Toronto.

Who might benefit?

Dual-targeted therapy has the potential to benefit patients with severe disease who may need intensive therapy upfront to prevent complications such as fistulas, strictures, or chronic abdominal pain. It may also benefit those who may require only short-term acute disease control; patients with meaningful yet incomplete responses to single-agent therapy who might have better outcomes with the addition of a second agent; and, patients with a unique phenotype that might be responsive to dual-targeted agents, Dr. Targownik said.

Another reason to consider dual-targeted therapy in IBD comes from applying data from recent clinical trials of upadacitinib (Rinvoq, Abbvie) for ulcerative colitis (UC) and risankizumab-rzaa (Skyrizi, Abbvie) for Crohn’s disease to hypothetical cohorts.

For example, of 1,000 persons with moderate to severe UC treated with upadacitinib, 736 would have a clinical response at the end of the induction, and at the end of the maintenance phase 191 would have endoscopic remissions, and 382 would remain in clinical remission.

Similarly, of 1,000 persons with moderate to severe Crohn’s disease treated with risankizumab, 434 would have a clinical response at the end of induction, and at the end of the maintenance phase, 172 would have endoscopic remissions, and 234 would remain in clinical remission.

“So, the vast majority of our patients are not achieving the targets that we want to hit,” she said.
 

Evidence from research clinical trials

Data from one of the few trials that have explored dual targeted therapy in IBD were presented at United European Gastroenterology Week in 2022.

The randomized double-blind phase 2a VEGA study looked at induction therapy with either a combination of the IL-23 inhibitor guselkumab (Tremfya, Janssen) and the anti-TNF monoclonal antibody golimumab (Simponi Aria, Janssen) followed by maintenance guselkumab, or each agent alone as induction monotherapy and maintenance.

The study population included 214 patients with moderate to severe UC with a modified Mayo Disease Activity Index scores of 6 or greater and endoscopy scores of 2 or 3 who had not received either anti-TNF or anti IL-23 agents.

At 12 weeks of follow-up, 36.6% of patients who started on combination therapy had clinical remissions, compared with 22.2% of patients on golimumab monotherapy and 22.1% of those on guselkumab alone, a clinically significant difference, Dr. Targownik said.

The combination also resulted in better endoscopic improvement over baseline (49.3% vs. 25% and 29.6%, respectively), although the study was not powered for this outcome.

At 38 weeks, 22.2% of patients who started on golimumab alone were in clinical remission, compared with 31% of those assigned to guselkumab monotherapy and 43.7% of those who started on the combination.

Endoscopic normalization at 38 weeks was seen in 6.9%, 15.5%, and 25.4% of patients, respectively.

“Even in the patients who went back on guselkumab monotherapy that were induced with dual therapy, there were statistically higher rates of clinical remission and endoscopic normalization at the end of the study,” Dr. Targownik said, although she noted that it’s unknown whether the benefit of the combination would be sustained over longer follow-up.

In the open-label EXPLORER Crohn’s disease trial, among 55 patients with high risk Crohn’s disease, within 24 months of diagnosis investigators looked at the triple combination therapy of the anti-integrin agent vedolizumab (Entyvio, Takeda), the anti-TNF agent adalimumab (Humira, Abbvie) and methotrexate. An interim analysis at week 26 of the 34-week trial showed clinical remissions in 54.5% of patients and endoscopic remissions in 34.5%, “which I would argue for an open-label study are not terribly high results,” she said.
 

Real-world experience

Dr. Targownik pointed to a systematic review and meta-analysis of the safety and effectiveness of combining biologic agents and small molecules in patients with IBD as evidence for how combinations work in the real world.

The analysis included data from 1 clinical trial and 12 observational studies on a total of 266 patients treated with one of seven different combinations. It showed estimates of clinical efficacy ranging from about 40% to 80%, albeit with wide and overlapping confidence intervals, making it difficult to come to any conclusions about the relatively superiority of one combination over another, Dr. Targownik said.

The authors of the meta-analysis did note, however, that the incidence of serious adverse events was relatively low, ranging from 9.6% for the combination of vedolizumab and anti-TNF, to just 1% for the JAK inhibitor tofacitinib (Xeljanz, Pfizer) plus vedolizumab.
 

Registry data may help

The use of registry data will shed more light on the potential benefits and drawbacks of dual-targeted therapy.

“If we can identify...the patient phenotypes that we want to evaluate dual therapy in, and try to catalog their experiences in a regimented way with defined outcomes and periods of follow-up, we may be able to get more meaningful information,” Dr. Targownik said.

Dr. Targownik disclosed fees, grant support, and/or scientific advisory board participation with multiple companies.

This article was updated 1/25/23.