Article

Key clinical point: Upadacitinib is effective and well-tolerated in patients with moderate-to-severe atopic dermatitis (AD) and prior failure to multiple systemic immunosuppressive and biologic therapies.

Major finding: At a median follow-up of 37.5 weeks, the median Investigator’s Global Assessment scores and Numerical Rating Scale itch scores reduced significantly from 3.00 to 1.50 and from 7.00 to 2.25, respectively (both P < .001). The adverse events reported were mostly mild in severity, with acne-like eruptions (25%) and nausea (13%) being the most common.

Study details: This prospective observational single-center study included 48 patients with moderate-to-severe AD receiving 15 mg or 30 mg upadacitinib daily, most of whom (n = 39) had failed other targeted therapies, including other Janus kinase inhibitors and biologics.

Disclosures: This study did not receive any funding. DJ Hijnen declared serving as an investigator and consultant for various sources. The other authors declared no conflicts of interest.

Source: Schlösser AR et al. Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort. J Eur Acad Dermatol Venereol. 2023 (Oct 21). doi: 10.1111/jdv.19581

Key clinical point: Upadacitinib is effective and well-tolerated in patients with moderate-to-severe atopic dermatitis (AD) and prior failure to multiple systemic immunosuppressive and biologic therapies.

Major finding: At a median follow-up of 37.5 weeks, the median Investigator’s Global Assessment scores and Numerical Rating Scale itch scores reduced significantly from 3.00 to 1.50 and from 7.00 to 2.25, respectively (both P < .001). The adverse events reported were mostly mild in severity, with acne-like eruptions (25%) and nausea (13%) being the most common.

Study details: This prospective observational single-center study included 48 patients with moderate-to-severe AD receiving 15 mg or 30 mg upadacitinib daily, most of whom (n = 39) had failed other targeted therapies, including other Janus kinase inhibitors and biologics.

Disclosures: This study did not receive any funding. DJ Hijnen declared serving as an investigator and consultant for various sources. The other authors declared no conflicts of interest.

Source: Schlösser AR et al. Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort. J Eur Acad Dermatol Venereol. 2023 (Oct 21). doi: 10.1111/jdv.19581

Key clinical point: Upadacitinib is effective and well-tolerated in patients with moderate-to-severe atopic dermatitis (AD) and prior failure to multiple systemic immunosuppressive and biologic therapies.

Major finding: At a median follow-up of 37.5 weeks, the median Investigator’s Global Assessment scores and Numerical Rating Scale itch scores reduced significantly from 3.00 to 1.50 and from 7.00 to 2.25, respectively (both P < .001). The adverse events reported were mostly mild in severity, with acne-like eruptions (25%) and nausea (13%) being the most common.

Study details: This prospective observational single-center study included 48 patients with moderate-to-severe AD receiving 15 mg or 30 mg upadacitinib daily, most of whom (n = 39) had failed other targeted therapies, including other Janus kinase inhibitors and biologics.

Disclosures: This study did not receive any funding. DJ Hijnen declared serving as an investigator and consultant for various sources. The other authors declared no conflicts of interest.

Source: Schlösser AR et al. Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort. J Eur Acad Dermatol Venereol. 2023 (Oct 21). doi: 10.1111/jdv.19581

Key clinical point: Lebrikizumab monotherapy for 16 weeks significantly reduced itch and itch-associated sleep loss in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At 16 weeks, a significantly higher number of patients from the ADvocate1 and ADvocate2 trials treated with lebrikizumab vs placebo achieved a ≥ 3-point improvement in the Pruritus Numeric Rating Scale scores (ADvocate1 54.6% vs 19.2%; ADvocate2 49.4% vs 14.0%; both P < .001) and ≥ 1-point improvement in Sleep-Loss Scale scores (ADvocate1 64.1% vs 27.2%; ADvocate2 58.1% vs 21.7%; both P < .001).

Study details: Findings are from a study including patients from the ADvocate1 (n = 424) and ADvocate2 (n = 427) trials who had moderate-to-severe AD and were randomized to receive subcutaneous lebrikizumab or placebo every 2 weeks.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Several authors declared receiving research grants or honoraria from, serving as employees and shareholders of, or having other ties with various sources, including Eli Lilly and Dermira.

Source: Yosipovitch G et al. Lebrikizumab improved itch and reduced the extent of itch interference on sleep in patients with moderate-to-severe atopic dermatitis: Two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2023 (Nov 6). doi: 10.1093/bjd/ljad435

Key clinical point: Lebrikizumab monotherapy for 16 weeks significantly reduced itch and itch-associated sleep loss in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At 16 weeks, a significantly higher number of patients from the ADvocate1 and ADvocate2 trials treated with lebrikizumab vs placebo achieved a ≥ 3-point improvement in the Pruritus Numeric Rating Scale scores (ADvocate1 54.6% vs 19.2%; ADvocate2 49.4% vs 14.0%; both P < .001) and ≥ 1-point improvement in Sleep-Loss Scale scores (ADvocate1 64.1% vs 27.2%; ADvocate2 58.1% vs 21.7%; both P < .001).

Study details: Findings are from a study including patients from the ADvocate1 (n = 424) and ADvocate2 (n = 427) trials who had moderate-to-severe AD and were randomized to receive subcutaneous lebrikizumab or placebo every 2 weeks.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Several authors declared receiving research grants or honoraria from, serving as employees and shareholders of, or having other ties with various sources, including Eli Lilly and Dermira.

Source: Yosipovitch G et al. Lebrikizumab improved itch and reduced the extent of itch interference on sleep in patients with moderate-to-severe atopic dermatitis: Two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2023 (Nov 6). doi: 10.1093/bjd/ljad435

Key clinical point: Lebrikizumab monotherapy for 16 weeks significantly reduced itch and itch-associated sleep loss in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At 16 weeks, a significantly higher number of patients from the ADvocate1 and ADvocate2 trials treated with lebrikizumab vs placebo achieved a ≥ 3-point improvement in the Pruritus Numeric Rating Scale scores (ADvocate1 54.6% vs 19.2%; ADvocate2 49.4% vs 14.0%; both P < .001) and ≥ 1-point improvement in Sleep-Loss Scale scores (ADvocate1 64.1% vs 27.2%; ADvocate2 58.1% vs 21.7%; both P < .001).

Study details: Findings are from a study including patients from the ADvocate1 (n = 424) and ADvocate2 (n = 427) trials who had moderate-to-severe AD and were randomized to receive subcutaneous lebrikizumab or placebo every 2 weeks.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Several authors declared receiving research grants or honoraria from, serving as employees and shareholders of, or having other ties with various sources, including Eli Lilly and Dermira.

Source: Yosipovitch G et al. Lebrikizumab improved itch and reduced the extent of itch interference on sleep in patients with moderate-to-severe atopic dermatitis: Two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2023 (Nov 6). doi: 10.1093/bjd/ljad435

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

Cervical cancer was the most common cancer killer of persons with a cervix in the early 1900s in the United States. Widespread adoption of the Pap test in the mid-20th century followed by large-scale outreach through programs such as the National Breast and Cervical Cancer Early Detection Program have dramatically reduced deaths from cervical cancer. The development of a highly effective vaccine that targets human papillomavirus (HPV), the virus implicated in all cervical cancers, has made prevention even more accessible and attainable. Primary prevention with HPV vaccination in conjunction with regular screening as recommended by current guidelines is the most effective way we can prevent cervical cancer.

Despite these advances, the incidence and death rates from cervical cancer have plateaued over the last decade.¹ Additionally, many fear that due to the poor attendance at screening visits since the beginning of the COVID-19 pandemic, the incidence might further rise in the United States.² Among those in the United States diagnosed with cervical cancer, more than 50% have not been screened in over 5 years or had their abnormal results not managed as recommended by current guidelines, suggesting that operational and access issues are contributors to incident cervical cancer. In addition, HPV vaccination rates have increased only slightly from year to year. According to the most recent data from the Centers for Disease Control and Prevention (CDC), coverage with 1 or more doses of HPV vaccine in 2021 increased only by 1.8% and has stagnated, with administration to about 75% of those for whom it is recommended.³ The plateauing will limit our ability to eradicate cervical cancer in the United States, permitting death from a largely preventable disease.

Establishing the framework for the eradication of cervical cancer

The World Health Organization (WHO) adopted a global strategy called the Cervical Cancer Elimination Initiative in August 2020. This initiative is a multipronged effort that focuses on vaccination (90% of girls fully vaccinated by age 15), screening (70% of women screened by age 35 with an effective test and again at age 45), and treatment (90% treatment of precancer and 90% management of women with invasive cancer).⁴

These are the numbers we need to achieve if all countries are to reach a cervical cancer incidence of less than 4 per 100,000 persons with a cervix. The WHO further suggests that each country should meet the “90-70-90” targets by 2030 if we are to achieve the low incidence by the turn of the century.⁴ To date, few regions of the world have achieved these goals, and sadly the United States is not among them.

In response to this call to action, many medical and policymaking organizations are taking inventory and implementing strategies to achieve the WHO 2030 targets for cervical cancer eradication. In the United States, the Society of Gynecologic Oncology (SGO; www.sgo.org), the American Society for Colposcopy and Cervical Pathology (ASCCP; www.ASCCP.org), the American College of Obstetricians and Gynecologists (ACOG; www.acog.org), the American Cancer Society (ACS; www.cancer.org), and many others have initiated programs in a collaborative esprit de corps with the aim of eradicating this deadly disease.

In this Update, we review several studies with evidence of screening and management strategies that show promise of accelerating the eradication of cervical cancer.

Continue to: Transitioning to primary HPV screening in the United States...

Downs LS Jr, Nayar R, Gerndt J, et al; American Cancer Society Primary HPV Screening Initiative Steering Committee. Implementation in action: collaborating on the transition to primary HPV screening for cervical cancer in the United States. CA Cancer J Clin. 2023;73:458-460.

The American Cancer Society released an updated cervical cancer screening guideline in July 2020 that recommended testing for HPV as the preferred strategy. Reasons behind the change, moving away from a Pap test as part of the initial screen, are:

• increased sensitivity of primary HPV testing when compared with conventional cervical cytology (Pap test)
• improved risk stratification to identify who is at risk for cervical cancer now and in the future
• improved efficiency in identifying those who need colposcopy, thus limiting unnecessary procedures without increasing the risk of false-negative tests, thereby missing cervical precancer or invasive cancer.

Some countries with organized screening programs have already made the switch. Self-sampling for HPV is currently being considered for an approved use in the United States, further improving access to screening for cervical cancer when the initial step can be completed by the patient at home or simplified in nontraditional health care settings.²

ACS initiative created to address barriers to primary HPV testing

Challenges to primary HPV testing remain, including laboratory implementation, payment, and operationalizing clinical workflow (for example, HPV testing with reflex cytology instead of cytology with reflex HPV testing).⁵ There are undoubtedly other unforeseen barriers in the current US health care environment.

In a recent commentary, Downs and colleagues described how the ACS has convened the Primary HPV Screening Initiative (PHSI), nested under the ACS National Roundtable on Cervical Cancer, which is charged with identifying critical barriers to, and opportunities for, transitioning to primary HPV screening.⁵ The deliverable will be a roadmap with tools and recommendations to support health systems, laboratories, providers, patients, and payers as they make this evolution.

Work groups will develop resources

Patients, particularly those who have had routine cervical cancer screening over their lifetime, also will be curious about the changes in recommendations. The Provider Needs Workgroup within the PHSI structure will develop tools and patient education materials regarding the data, workflow, benefits, and safety of this new paradigm for cervical cancer screening.

Laboratories that process and interpret tests likely will bear the heaviest load of changes. For example, not all commercially available HPV tests in the United States are approved by the US Food and Drug Administration (FDA) for primary HPV testing. Some sites will need to adapt their equipment to ensure adherence to FDA-approved tests. Laboratory workflows will need to be altered for aliquots to be tested for HPV first, and the remainder for cytology. Quality assurance and accreditation requirements for testing will need modifications, and further efforts will be needed to ensure sufficient numbers of trained cytopathologists, whose workforce is rapidly declining, for processing and reading cervical cytology.

In addition, payment for HPV testing alone, without the need for a Pap test, might not be supported by payers that support safety-net providers and sites, who arguably serve the most vulnerable patients and those most at risk for cervical cancer. Collaboration across medical professionals, societies, payers, and policymakers will provide a critical infrastructure to make the change in the most seamless fashion and limit the harm from missed opportunities for screening.

Continue to: The quest for a “molecular Pap”: Dual-stain testing as a predictor of high-grade CIN...

Magkana M, Mentzelopoulou P, Magkana E, et al. p16/Ki-67 Dual staining is a reliable biomarker for risk stratification for patients with borderline/mild cytology in cervical cancer screening. Anticancer Res. 2022;42:2599-2606.

Stanczuk G, Currie H, Forson W, et al. Clinical performance of triage strategies for Hr-HPV-positive women; a longitudinal evaluation of cytology, p16/K-67 dual stain cytology, and HPV16/18 genotyping. Cancer Epidemiol Biomarkers Prev. 2022;31:1492-1498.
 

One new technology that was recently FDA approved and recommended for management of abnormal cervical cancer screening testing is dual-stain (DS) testing. Dual-stain testing is a cytology-based test that evaluates the concurrent expression of p16, a tumor suppressor protein upregulated in HPV oncogenesis, and Ki-67, a cell proliferation marker.^6,7 Two recent studies have showcased the outstanding clinical performance of DS testing and triage strategies that incorporate DS testing.

Higher specificity, fewer colposcopies needed with DS testing

Magkana and colleagues prospectively evaluated patients with atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or negative for intraepithelial lesion or malignancy (NILM) cytology referred for colposcopy, and they compared p16/Ki-67 DS testing with high-risk HPV (HR-HPV) testing for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+); comparable sensitivities for CIN 2+ detection were seen (97.3% and 98.7%, respectively).⁸

Dual-stain testing exhibited higher specificity at 99.3% compared with HR-HPV testing at 52.2%. Incorporating DS testing into triage strategies also led to fewer colposcopies needed to detect CIN 2+ compared with current ASCCP guidelines that use traditional cervical cancer screening algorithms.

DS cytology strategy had the highest sensitivity for CIN 2+ detection

An additional study by Stanczuk and colleagues evaluated triage strategies in a cohort of HR-HPV positive patients who participated in the Scottish Papillomavirus Dumfries and Galloway study with HPV 16/18 genotyping (HPV 16/18), liquid-based cytology (LBC), and p16/Ki-67 DS cytology.⁹ Of these 3 triage strategies, DS cytology had the highest sensitivity for the detection of CIN 2+, at 77.7% (with a specificity of 74.2%), performance that is arguably better than cytology.

When evaluated in sequence as part of a triage strategy after HPV primary screening, HPV 16/18–positive patients reflexed to DS testing showed a similar sensitivity as those who would be triaged with LBC (TABLE).⁹

DS testing’s potential

These studies add to the growing body of literature that supports the use of DS testing in cervical cancer screening management guidelines and that are being incorporated into currently existing workflows. Furthermore, with advancements in digital imaging and machine learning, DS testing holds the potential for a high throughput, reproducible, and accurate risk stratification that can replace the current reliance on cytology, furthering the potential for a fully molecular Pap test.^10,11

Continue to: Cervical cancer screening in women older than age 65: Is there benefit?...

Firtina Tuncer S, Tuncer HA. Cervical cancer screening in women aged older than 65 years. J Low Genit Tract Dis. 2023;27:207-211.

Booth BB, Tranberg M, Gustafson LW, et al. Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged  ≥ 69 referred to colposcopy due to an HPV-positive screening test. BMC Cancer. 2023;23:405.
 

Current guidelines in the United States recommend that cervical cancer screening for all persons with a cervix end at age 65. These age restrictions were a change in guidelines updated in 2012 and endorsed by the US Preventive Services Task Force.^12,13 Evidence suggests that because of high likelihood of regression and slow progression of disease, risks of screening prior to age 21 outweigh its benefits. With primary HPV testing, the age at screening debut is 25 for the same reasons.¹⁴ In people with a history of CIN 2+, active surveillance should continue for at least 25 years with HPV-based screening regardless of age. In the absence of a history of CIN 2+, however, the data to support discontinuation of screening after age 65 are less clear.

HPV positivity found to be most substantial risk for CIN 2+

In a study published this year in the Journal of Lower Genital Tract Disease, Firtina Tuncer and colleagues described their experience extending “routine screening” in patients older than 65 years.¹⁵ Data including cervical cytology, HPV test results, biopsy findings, and endocervical curettage results were collected, and abnormal findings were managed according to the 2012 and 2019 ASCCP guidelines.

When compared with negative HPV testing and normal cytology, the authors found that HPV positivity and abnormal cytology increased the risk of CIN 2+(odds ratio [OR], 136.1 and 13.1, respectively). Patients whose screening prior to age 65 had been insufficient or demonstrated CIN 2+ in the preceding 10 years were similarly more likely to have findings of CIN 2+ (OR, 9.7 when compared with HPV-negative controls).

The authors concluded that, among persons with a cervix older than age 65, previous screening and abnormal cytology were important in risk stratifications for CIN 2+; however, HPV positivity conferred the most substantial risk.

Study finds cervical dysplasia is prevalent in older populations

It has been suggested that screening for cervical cancer should continue beyond age 65 as cytology-based screening may have decreased sensitivity in older patients, which may contribute to the higher rates of advanced-stage diagnoses and cancer-related death in this population.^16,17

Authors of an observational study conducted in Denmark invited persons with a cervix aged 69 and older to have one additional HPV-based screening test, and they referred them for colposcopy if HPV positive or in the presence of ASCUS or greater cytology.¹⁸ Among the 191 patients with HPV-positive results, 20% were found to have a diagnosis of CIN 2+, and 24.4% had CIN 2+ detected at another point in the study period. Notably, most patients diagnosed with CIN 2+ had no abnormalities visualized on colposcopy, and the majority of biopsies taken (65.8%) did not contain the transitional zone.

Biopsies underestimated CIN 2+ in 17.9% of cases compared with loop electrosurgical excision procedure (LEEP). These findings suggest both that high-grade cervical dysplasia is prevalent in an older population and that older populations may be susceptible to false-negative results. They also further support the use of HPV-based screening.

Harnessing the immune system to improve survival rates in recurrent cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Unfortunately, most clinical trials for recurrent or metastatic cervical cancer are negative trials or have results that show limited impact on disease outcomes. Currently, cervical cancer is treated with multiple agents, including platinum-based chemotherapy and bevacizumab, a medication that targets vascular growth. Despite these usually very effective drugs given in combination to cervical cancer patients, long-term survival remains low. Over the past few decades, many trials have been designed to help patients with this terrible disease, but few have shown significant promise.

Immune checkpoint inhibitors, such as pembrolizumab, have revolutionized care for many cancers. Checkpoint inhibitors block the proteins that cause a tumor to remain undetected by the immune system’s army of T cells. By blocking these proteins, the cancer cells can then be recognized by the immune system as foreign. Several studies have concluded that including immune checkpoint inhibitors in the comprehensive regimen for recurrent cervical cancer improves survival.

Addition of pembrolizumab increased survival

Investigators in the phase 3 double-blinded KEYNOTE-826 trial evaluated whether or not the addition of pembrolizumab to standard of care improved progression-free and overall survival in advanced, recurrent, or persistent cervical cancer.¹⁹ As part of the evaluation, the investigators measured the protein that turns off the immune system’s ability to recognize tumors, anti-programmed cell death protein-1 (PD-1).

Compared with placebo, the investigators found that, regardless of PD-1 status, the addition of pembrolizumab immunotherapy to the standard regimen increased progression-free survival and overall survival without any significantly increased adverse effects or safety concerns (FIGURE).¹⁹ At 1 year after treatment, more patients who received pembrolizumab were still alive regardless of PD-1 status, and their responses lasted longer. The most profound improvements were seen in patients whose tumors exhibited high expression of PD-L1, the target of pembrolizumab and many other immune checkpoint inhibitors.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

Cervical cancer was the most common cancer killer of persons with a cervix in the early 1900s in the United States. Widespread adoption of the Pap test in the mid-20th century followed by large-scale outreach through programs such as the National Breast and Cervical Cancer Early Detection Program have dramatically reduced deaths from cervical cancer. The development of a highly effective vaccine that targets human papillomavirus (HPV), the virus implicated in all cervical cancers, has made prevention even more accessible and attainable. Primary prevention with HPV vaccination in conjunction with regular screening as recommended by current guidelines is the most effective way we can prevent cervical cancer.

Despite these advances, the incidence and death rates from cervical cancer have plateaued over the last decade.¹ Additionally, many fear that due to the poor attendance at screening visits since the beginning of the COVID-19 pandemic, the incidence might further rise in the United States.² Among those in the United States diagnosed with cervical cancer, more than 50% have not been screened in over 5 years or had their abnormal results not managed as recommended by current guidelines, suggesting that operational and access issues are contributors to incident cervical cancer. In addition, HPV vaccination rates have increased only slightly from year to year. According to the most recent data from the Centers for Disease Control and Prevention (CDC), coverage with 1 or more doses of HPV vaccine in 2021 increased only by 1.8% and has stagnated, with administration to about 75% of those for whom it is recommended.³ The plateauing will limit our ability to eradicate cervical cancer in the United States, permitting death from a largely preventable disease.

Establishing the framework for the eradication of cervical cancer

The World Health Organization (WHO) adopted a global strategy called the Cervical Cancer Elimination Initiative in August 2020. This initiative is a multipronged effort that focuses on vaccination (90% of girls fully vaccinated by age 15), screening (70% of women screened by age 35 with an effective test and again at age 45), and treatment (90% treatment of precancer and 90% management of women with invasive cancer).⁴

These are the numbers we need to achieve if all countries are to reach a cervical cancer incidence of less than 4 per 100,000 persons with a cervix. The WHO further suggests that each country should meet the “90-70-90” targets by 2030 if we are to achieve the low incidence by the turn of the century.⁴ To date, few regions of the world have achieved these goals, and sadly the United States is not among them.

In response to this call to action, many medical and policymaking organizations are taking inventory and implementing strategies to achieve the WHO 2030 targets for cervical cancer eradication. In the United States, the Society of Gynecologic Oncology (SGO; www.sgo.org), the American Society for Colposcopy and Cervical Pathology (ASCCP; www.ASCCP.org), the American College of Obstetricians and Gynecologists (ACOG; www.acog.org), the American Cancer Society (ACS; www.cancer.org), and many others have initiated programs in a collaborative esprit de corps with the aim of eradicating this deadly disease.

In this Update, we review several studies with evidence of screening and management strategies that show promise of accelerating the eradication of cervical cancer.

Continue to: Transitioning to primary HPV screening in the United States...

Downs LS Jr, Nayar R, Gerndt J, et al; American Cancer Society Primary HPV Screening Initiative Steering Committee. Implementation in action: collaborating on the transition to primary HPV screening for cervical cancer in the United States. CA Cancer J Clin. 2023;73:458-460.

The American Cancer Society released an updated cervical cancer screening guideline in July 2020 that recommended testing for HPV as the preferred strategy. Reasons behind the change, moving away from a Pap test as part of the initial screen, are:

• increased sensitivity of primary HPV testing when compared with conventional cervical cytology (Pap test)
• improved risk stratification to identify who is at risk for cervical cancer now and in the future
• improved efficiency in identifying those who need colposcopy, thus limiting unnecessary procedures without increasing the risk of false-negative tests, thereby missing cervical precancer or invasive cancer.

Some countries with organized screening programs have already made the switch. Self-sampling for HPV is currently being considered for an approved use in the United States, further improving access to screening for cervical cancer when the initial step can be completed by the patient at home or simplified in nontraditional health care settings.²

ACS initiative created to address barriers to primary HPV testing

Challenges to primary HPV testing remain, including laboratory implementation, payment, and operationalizing clinical workflow (for example, HPV testing with reflex cytology instead of cytology with reflex HPV testing).⁵ There are undoubtedly other unforeseen barriers in the current US health care environment.

In a recent commentary, Downs and colleagues described how the ACS has convened the Primary HPV Screening Initiative (PHSI), nested under the ACS National Roundtable on Cervical Cancer, which is charged with identifying critical barriers to, and opportunities for, transitioning to primary HPV screening.⁵ The deliverable will be a roadmap with tools and recommendations to support health systems, laboratories, providers, patients, and payers as they make this evolution.

Work groups will develop resources

Patients, particularly those who have had routine cervical cancer screening over their lifetime, also will be curious about the changes in recommendations. The Provider Needs Workgroup within the PHSI structure will develop tools and patient education materials regarding the data, workflow, benefits, and safety of this new paradigm for cervical cancer screening.

Laboratories that process and interpret tests likely will bear the heaviest load of changes. For example, not all commercially available HPV tests in the United States are approved by the US Food and Drug Administration (FDA) for primary HPV testing. Some sites will need to adapt their equipment to ensure adherence to FDA-approved tests. Laboratory workflows will need to be altered for aliquots to be tested for HPV first, and the remainder for cytology. Quality assurance and accreditation requirements for testing will need modifications, and further efforts will be needed to ensure sufficient numbers of trained cytopathologists, whose workforce is rapidly declining, for processing and reading cervical cytology.

In addition, payment for HPV testing alone, without the need for a Pap test, might not be supported by payers that support safety-net providers and sites, who arguably serve the most vulnerable patients and those most at risk for cervical cancer. Collaboration across medical professionals, societies, payers, and policymakers will provide a critical infrastructure to make the change in the most seamless fashion and limit the harm from missed opportunities for screening.

Continue to: The quest for a “molecular Pap”: Dual-stain testing as a predictor of high-grade CIN...

Magkana M, Mentzelopoulou P, Magkana E, et al. p16/Ki-67 Dual staining is a reliable biomarker for risk stratification for patients with borderline/mild cytology in cervical cancer screening. Anticancer Res. 2022;42:2599-2606.

Stanczuk G, Currie H, Forson W, et al. Clinical performance of triage strategies for Hr-HPV-positive women; a longitudinal evaluation of cytology, p16/K-67 dual stain cytology, and HPV16/18 genotyping. Cancer Epidemiol Biomarkers Prev. 2022;31:1492-1498.
 

One new technology that was recently FDA approved and recommended for management of abnormal cervical cancer screening testing is dual-stain (DS) testing. Dual-stain testing is a cytology-based test that evaluates the concurrent expression of p16, a tumor suppressor protein upregulated in HPV oncogenesis, and Ki-67, a cell proliferation marker.^6,7 Two recent studies have showcased the outstanding clinical performance of DS testing and triage strategies that incorporate DS testing.

Higher specificity, fewer colposcopies needed with DS testing

Magkana and colleagues prospectively evaluated patients with atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or negative for intraepithelial lesion or malignancy (NILM) cytology referred for colposcopy, and they compared p16/Ki-67 DS testing with high-risk HPV (HR-HPV) testing for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+); comparable sensitivities for CIN 2+ detection were seen (97.3% and 98.7%, respectively).⁸

Dual-stain testing exhibited higher specificity at 99.3% compared with HR-HPV testing at 52.2%. Incorporating DS testing into triage strategies also led to fewer colposcopies needed to detect CIN 2+ compared with current ASCCP guidelines that use traditional cervical cancer screening algorithms.

DS cytology strategy had the highest sensitivity for CIN 2+ detection

An additional study by Stanczuk and colleagues evaluated triage strategies in a cohort of HR-HPV positive patients who participated in the Scottish Papillomavirus Dumfries and Galloway study with HPV 16/18 genotyping (HPV 16/18), liquid-based cytology (LBC), and p16/Ki-67 DS cytology.⁹ Of these 3 triage strategies, DS cytology had the highest sensitivity for the detection of CIN 2+, at 77.7% (with a specificity of 74.2%), performance that is arguably better than cytology.

When evaluated in sequence as part of a triage strategy after HPV primary screening, HPV 16/18–positive patients reflexed to DS testing showed a similar sensitivity as those who would be triaged with LBC (TABLE).⁹

DS testing’s potential

These studies add to the growing body of literature that supports the use of DS testing in cervical cancer screening management guidelines and that are being incorporated into currently existing workflows. Furthermore, with advancements in digital imaging and machine learning, DS testing holds the potential for a high throughput, reproducible, and accurate risk stratification that can replace the current reliance on cytology, furthering the potential for a fully molecular Pap test.^10,11

Continue to: Cervical cancer screening in women older than age 65: Is there benefit?...

Firtina Tuncer S, Tuncer HA. Cervical cancer screening in women aged older than 65 years. J Low Genit Tract Dis. 2023;27:207-211.

Booth BB, Tranberg M, Gustafson LW, et al. Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged  ≥ 69 referred to colposcopy due to an HPV-positive screening test. BMC Cancer. 2023;23:405.
 

Current guidelines in the United States recommend that cervical cancer screening for all persons with a cervix end at age 65. These age restrictions were a change in guidelines updated in 2012 and endorsed by the US Preventive Services Task Force.^12,13 Evidence suggests that because of high likelihood of regression and slow progression of disease, risks of screening prior to age 21 outweigh its benefits. With primary HPV testing, the age at screening debut is 25 for the same reasons.¹⁴ In people with a history of CIN 2+, active surveillance should continue for at least 25 years with HPV-based screening regardless of age. In the absence of a history of CIN 2+, however, the data to support discontinuation of screening after age 65 are less clear.

HPV positivity found to be most substantial risk for CIN 2+

In a study published this year in the Journal of Lower Genital Tract Disease, Firtina Tuncer and colleagues described their experience extending “routine screening” in patients older than 65 years.¹⁵ Data including cervical cytology, HPV test results, biopsy findings, and endocervical curettage results were collected, and abnormal findings were managed according to the 2012 and 2019 ASCCP guidelines.

When compared with negative HPV testing and normal cytology, the authors found that HPV positivity and abnormal cytology increased the risk of CIN 2+(odds ratio [OR], 136.1 and 13.1, respectively). Patients whose screening prior to age 65 had been insufficient or demonstrated CIN 2+ in the preceding 10 years were similarly more likely to have findings of CIN 2+ (OR, 9.7 when compared with HPV-negative controls).

The authors concluded that, among persons with a cervix older than age 65, previous screening and abnormal cytology were important in risk stratifications for CIN 2+; however, HPV positivity conferred the most substantial risk.

Study finds cervical dysplasia is prevalent in older populations

It has been suggested that screening for cervical cancer should continue beyond age 65 as cytology-based screening may have decreased sensitivity in older patients, which may contribute to the higher rates of advanced-stage diagnoses and cancer-related death in this population.^16,17

Authors of an observational study conducted in Denmark invited persons with a cervix aged 69 and older to have one additional HPV-based screening test, and they referred them for colposcopy if HPV positive or in the presence of ASCUS or greater cytology.¹⁸ Among the 191 patients with HPV-positive results, 20% were found to have a diagnosis of CIN 2+, and 24.4% had CIN 2+ detected at another point in the study period. Notably, most patients diagnosed with CIN 2+ had no abnormalities visualized on colposcopy, and the majority of biopsies taken (65.8%) did not contain the transitional zone.

Biopsies underestimated CIN 2+ in 17.9% of cases compared with loop electrosurgical excision procedure (LEEP). These findings suggest both that high-grade cervical dysplasia is prevalent in an older population and that older populations may be susceptible to false-negative results. They also further support the use of HPV-based screening.

Harnessing the immune system to improve survival rates in recurrent cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Unfortunately, most clinical trials for recurrent or metastatic cervical cancer are negative trials or have results that show limited impact on disease outcomes. Currently, cervical cancer is treated with multiple agents, including platinum-based chemotherapy and bevacizumab, a medication that targets vascular growth. Despite these usually very effective drugs given in combination to cervical cancer patients, long-term survival remains low. Over the past few decades, many trials have been designed to help patients with this terrible disease, but few have shown significant promise.

Immune checkpoint inhibitors, such as pembrolizumab, have revolutionized care for many cancers. Checkpoint inhibitors block the proteins that cause a tumor to remain undetected by the immune system’s army of T cells. By blocking these proteins, the cancer cells can then be recognized by the immune system as foreign. Several studies have concluded that including immune checkpoint inhibitors in the comprehensive regimen for recurrent cervical cancer improves survival.

Addition of pembrolizumab increased survival

Investigators in the phase 3 double-blinded KEYNOTE-826 trial evaluated whether or not the addition of pembrolizumab to standard of care improved progression-free and overall survival in advanced, recurrent, or persistent cervical cancer.¹⁹ As part of the evaluation, the investigators measured the protein that turns off the immune system’s ability to recognize tumors, anti-programmed cell death protein-1 (PD-1).

Compared with placebo, the investigators found that, regardless of PD-1 status, the addition of pembrolizumab immunotherapy to the standard regimen increased progression-free survival and overall survival without any significantly increased adverse effects or safety concerns (FIGURE).¹⁹ At 1 year after treatment, more patients who received pembrolizumab were still alive regardless of PD-1 status, and their responses lasted longer. The most profound improvements were seen in patients whose tumors exhibited high expression of PD-L1, the target of pembrolizumab and many other immune checkpoint inhibitors.

ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT

Cervical cancer was the most common cancer killer of persons with a cervix in the early 1900s in the United States. Widespread adoption of the Pap test in the mid-20th century followed by large-scale outreach through programs such as the National Breast and Cervical Cancer Early Detection Program have dramatically reduced deaths from cervical cancer. The development of a highly effective vaccine that targets human papillomavirus (HPV), the virus implicated in all cervical cancers, has made prevention even more accessible and attainable. Primary prevention with HPV vaccination in conjunction with regular screening as recommended by current guidelines is the most effective way we can prevent cervical cancer.

Despite these advances, the incidence and death rates from cervical cancer have plateaued over the last decade.¹ Additionally, many fear that due to the poor attendance at screening visits since the beginning of the COVID-19 pandemic, the incidence might further rise in the United States.² Among those in the United States diagnosed with cervical cancer, more than 50% have not been screened in over 5 years or had their abnormal results not managed as recommended by current guidelines, suggesting that operational and access issues are contributors to incident cervical cancer. In addition, HPV vaccination rates have increased only slightly from year to year. According to the most recent data from the Centers for Disease Control and Prevention (CDC), coverage with 1 or more doses of HPV vaccine in 2021 increased only by 1.8% and has stagnated, with administration to about 75% of those for whom it is recommended.³ The plateauing will limit our ability to eradicate cervical cancer in the United States, permitting death from a largely preventable disease.

Establishing the framework for the eradication of cervical cancer

The World Health Organization (WHO) adopted a global strategy called the Cervical Cancer Elimination Initiative in August 2020. This initiative is a multipronged effort that focuses on vaccination (90% of girls fully vaccinated by age 15), screening (70% of women screened by age 35 with an effective test and again at age 45), and treatment (90% treatment of precancer and 90% management of women with invasive cancer).⁴

These are the numbers we need to achieve if all countries are to reach a cervical cancer incidence of less than 4 per 100,000 persons with a cervix. The WHO further suggests that each country should meet the “90-70-90” targets by 2030 if we are to achieve the low incidence by the turn of the century.⁴ To date, few regions of the world have achieved these goals, and sadly the United States is not among them.

In response to this call to action, many medical and policymaking organizations are taking inventory and implementing strategies to achieve the WHO 2030 targets for cervical cancer eradication. In the United States, the Society of Gynecologic Oncology (SGO; www.sgo.org), the American Society for Colposcopy and Cervical Pathology (ASCCP; www.ASCCP.org), the American College of Obstetricians and Gynecologists (ACOG; www.acog.org), the American Cancer Society (ACS; www.cancer.org), and many others have initiated programs in a collaborative esprit de corps with the aim of eradicating this deadly disease.

In this Update, we review several studies with evidence of screening and management strategies that show promise of accelerating the eradication of cervical cancer.

Continue to: Transitioning to primary HPV screening in the United States...

Downs LS Jr, Nayar R, Gerndt J, et al; American Cancer Society Primary HPV Screening Initiative Steering Committee. Implementation in action: collaborating on the transition to primary HPV screening for cervical cancer in the United States. CA Cancer J Clin. 2023;73:458-460.

The American Cancer Society released an updated cervical cancer screening guideline in July 2020 that recommended testing for HPV as the preferred strategy. Reasons behind the change, moving away from a Pap test as part of the initial screen, are:

• increased sensitivity of primary HPV testing when compared with conventional cervical cytology (Pap test)
• improved risk stratification to identify who is at risk for cervical cancer now and in the future
• improved efficiency in identifying those who need colposcopy, thus limiting unnecessary procedures without increasing the risk of false-negative tests, thereby missing cervical precancer or invasive cancer.

Some countries with organized screening programs have already made the switch. Self-sampling for HPV is currently being considered for an approved use in the United States, further improving access to screening for cervical cancer when the initial step can be completed by the patient at home or simplified in nontraditional health care settings.²

ACS initiative created to address barriers to primary HPV testing

Challenges to primary HPV testing remain, including laboratory implementation, payment, and operationalizing clinical workflow (for example, HPV testing with reflex cytology instead of cytology with reflex HPV testing).⁵ There are undoubtedly other unforeseen barriers in the current US health care environment.

In a recent commentary, Downs and colleagues described how the ACS has convened the Primary HPV Screening Initiative (PHSI), nested under the ACS National Roundtable on Cervical Cancer, which is charged with identifying critical barriers to, and opportunities for, transitioning to primary HPV screening.⁵ The deliverable will be a roadmap with tools and recommendations to support health systems, laboratories, providers, patients, and payers as they make this evolution.

Work groups will develop resources

Patients, particularly those who have had routine cervical cancer screening over their lifetime, also will be curious about the changes in recommendations. The Provider Needs Workgroup within the PHSI structure will develop tools and patient education materials regarding the data, workflow, benefits, and safety of this new paradigm for cervical cancer screening.

Laboratories that process and interpret tests likely will bear the heaviest load of changes. For example, not all commercially available HPV tests in the United States are approved by the US Food and Drug Administration (FDA) for primary HPV testing. Some sites will need to adapt their equipment to ensure adherence to FDA-approved tests. Laboratory workflows will need to be altered for aliquots to be tested for HPV first, and the remainder for cytology. Quality assurance and accreditation requirements for testing will need modifications, and further efforts will be needed to ensure sufficient numbers of trained cytopathologists, whose workforce is rapidly declining, for processing and reading cervical cytology.

In addition, payment for HPV testing alone, without the need for a Pap test, might not be supported by payers that support safety-net providers and sites, who arguably serve the most vulnerable patients and those most at risk for cervical cancer. Collaboration across medical professionals, societies, payers, and policymakers will provide a critical infrastructure to make the change in the most seamless fashion and limit the harm from missed opportunities for screening.

Continue to: The quest for a “molecular Pap”: Dual-stain testing as a predictor of high-grade CIN...

Magkana M, Mentzelopoulou P, Magkana E, et al. p16/Ki-67 Dual staining is a reliable biomarker for risk stratification for patients with borderline/mild cytology in cervical cancer screening. Anticancer Res. 2022;42:2599-2606.

Stanczuk G, Currie H, Forson W, et al. Clinical performance of triage strategies for Hr-HPV-positive women; a longitudinal evaluation of cytology, p16/K-67 dual stain cytology, and HPV16/18 genotyping. Cancer Epidemiol Biomarkers Prev. 2022;31:1492-1498.
 

One new technology that was recently FDA approved and recommended for management of abnormal cervical cancer screening testing is dual-stain (DS) testing. Dual-stain testing is a cytology-based test that evaluates the concurrent expression of p16, a tumor suppressor protein upregulated in HPV oncogenesis, and Ki-67, a cell proliferation marker.^6,7 Two recent studies have showcased the outstanding clinical performance of DS testing and triage strategies that incorporate DS testing.

Higher specificity, fewer colposcopies needed with DS testing

Magkana and colleagues prospectively evaluated patients with atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or negative for intraepithelial lesion or malignancy (NILM) cytology referred for colposcopy, and they compared p16/Ki-67 DS testing with high-risk HPV (HR-HPV) testing for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+); comparable sensitivities for CIN 2+ detection were seen (97.3% and 98.7%, respectively).⁸

Dual-stain testing exhibited higher specificity at 99.3% compared with HR-HPV testing at 52.2%. Incorporating DS testing into triage strategies also led to fewer colposcopies needed to detect CIN 2+ compared with current ASCCP guidelines that use traditional cervical cancer screening algorithms.

DS cytology strategy had the highest sensitivity for CIN 2+ detection

An additional study by Stanczuk and colleagues evaluated triage strategies in a cohort of HR-HPV positive patients who participated in the Scottish Papillomavirus Dumfries and Galloway study with HPV 16/18 genotyping (HPV 16/18), liquid-based cytology (LBC), and p16/Ki-67 DS cytology.⁹ Of these 3 triage strategies, DS cytology had the highest sensitivity for the detection of CIN 2+, at 77.7% (with a specificity of 74.2%), performance that is arguably better than cytology.

When evaluated in sequence as part of a triage strategy after HPV primary screening, HPV 16/18–positive patients reflexed to DS testing showed a similar sensitivity as those who would be triaged with LBC (TABLE).⁹

DS testing’s potential

These studies add to the growing body of literature that supports the use of DS testing in cervical cancer screening management guidelines and that are being incorporated into currently existing workflows. Furthermore, with advancements in digital imaging and machine learning, DS testing holds the potential for a high throughput, reproducible, and accurate risk stratification that can replace the current reliance on cytology, furthering the potential for a fully molecular Pap test.^10,11

Continue to: Cervical cancer screening in women older than age 65: Is there benefit?...

Firtina Tuncer S, Tuncer HA. Cervical cancer screening in women aged older than 65 years. J Low Genit Tract Dis. 2023;27:207-211.

Booth BB, Tranberg M, Gustafson LW, et al. Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged  ≥ 69 referred to colposcopy due to an HPV-positive screening test. BMC Cancer. 2023;23:405.
 

Current guidelines in the United States recommend that cervical cancer screening for all persons with a cervix end at age 65. These age restrictions were a change in guidelines updated in 2012 and endorsed by the US Preventive Services Task Force.^12,13 Evidence suggests that because of high likelihood of regression and slow progression of disease, risks of screening prior to age 21 outweigh its benefits. With primary HPV testing, the age at screening debut is 25 for the same reasons.¹⁴ In people with a history of CIN 2+, active surveillance should continue for at least 25 years with HPV-based screening regardless of age. In the absence of a history of CIN 2+, however, the data to support discontinuation of screening after age 65 are less clear.

HPV positivity found to be most substantial risk for CIN 2+

In a study published this year in the Journal of Lower Genital Tract Disease, Firtina Tuncer and colleagues described their experience extending “routine screening” in patients older than 65 years.¹⁵ Data including cervical cytology, HPV test results, biopsy findings, and endocervical curettage results were collected, and abnormal findings were managed according to the 2012 and 2019 ASCCP guidelines.

When compared with negative HPV testing and normal cytology, the authors found that HPV positivity and abnormal cytology increased the risk of CIN 2+(odds ratio [OR], 136.1 and 13.1, respectively). Patients whose screening prior to age 65 had been insufficient or demonstrated CIN 2+ in the preceding 10 years were similarly more likely to have findings of CIN 2+ (OR, 9.7 when compared with HPV-negative controls).

The authors concluded that, among persons with a cervix older than age 65, previous screening and abnormal cytology were important in risk stratifications for CIN 2+; however, HPV positivity conferred the most substantial risk.

Study finds cervical dysplasia is prevalent in older populations

It has been suggested that screening for cervical cancer should continue beyond age 65 as cytology-based screening may have decreased sensitivity in older patients, which may contribute to the higher rates of advanced-stage diagnoses and cancer-related death in this population.^16,17

Authors of an observational study conducted in Denmark invited persons with a cervix aged 69 and older to have one additional HPV-based screening test, and they referred them for colposcopy if HPV positive or in the presence of ASCUS or greater cytology.¹⁸ Among the 191 patients with HPV-positive results, 20% were found to have a diagnosis of CIN 2+, and 24.4% had CIN 2+ detected at another point in the study period. Notably, most patients diagnosed with CIN 2+ had no abnormalities visualized on colposcopy, and the majority of biopsies taken (65.8%) did not contain the transitional zone.

Biopsies underestimated CIN 2+ in 17.9% of cases compared with loop electrosurgical excision procedure (LEEP). These findings suggest both that high-grade cervical dysplasia is prevalent in an older population and that older populations may be susceptible to false-negative results. They also further support the use of HPV-based screening.

Harnessing the immune system to improve survival rates in recurrent cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Unfortunately, most clinical trials for recurrent or metastatic cervical cancer are negative trials or have results that show limited impact on disease outcomes. Currently, cervical cancer is treated with multiple agents, including platinum-based chemotherapy and bevacizumab, a medication that targets vascular growth. Despite these usually very effective drugs given in combination to cervical cancer patients, long-term survival remains low. Over the past few decades, many trials have been designed to help patients with this terrible disease, but few have shown significant promise.

Immune checkpoint inhibitors, such as pembrolizumab, have revolutionized care for many cancers. Checkpoint inhibitors block the proteins that cause a tumor to remain undetected by the immune system’s army of T cells. By blocking these proteins, the cancer cells can then be recognized by the immune system as foreign. Several studies have concluded that including immune checkpoint inhibitors in the comprehensive regimen for recurrent cervical cancer improves survival.

Addition of pembrolizumab increased survival

Investigators in the phase 3 double-blinded KEYNOTE-826 trial evaluated whether or not the addition of pembrolizumab to standard of care improved progression-free and overall survival in advanced, recurrent, or persistent cervical cancer.¹⁹ As part of the evaluation, the investigators measured the protein that turns off the immune system’s ability to recognize tumors, anti-programmed cell death protein-1 (PD-1).

Compared with placebo, the investigators found that, regardless of PD-1 status, the addition of pembrolizumab immunotherapy to the standard regimen increased progression-free survival and overall survival without any significantly increased adverse effects or safety concerns (FIGURE).¹⁹ At 1 year after treatment, more patients who received pembrolizumab were still alive regardless of PD-1 status, and their responses lasted longer. The most profound improvements were seen in patients whose tumors exhibited high expression of PD-L1, the target of pembrolizumab and many other immune checkpoint inhibitors.

REVIEW

By James Greenberg, MD

Chief of Gynecology

Associate Professor, Harvard Medical School

Boston, Massachusetts
 

Guardenia: A “really great solution” for contained tissue extraction

The Guardenia Contained Extraction System, developed by Advanced Surgical Concepts (Wicklow, Ireland), offers a comprehensive approach to contained tissue extraction.

Background. Contained tissue extraction has been an integral part of laparoscopic procedures from at least the late 1980s and early 1990s. Bags of one sort or another are routinely used to remove from the abdomen all sorts of human tissues, including but not limited to ovaries, ectopic pregnancies, gallbladders, kidneys, spleens, and the list goes on. However, after the April 17, 2014, FDA Safety Communication discouraging the use of power morcellators with myomectomy or hysterectomy, the need for more robust contained tissue extraction systems has been ongoing, and there has yet to be a really good solution despite some innovative attempts.

Design/Functionality. Advanced Surgical Concepts’ Guardenia System is the latest attempt to provide a “really great solution” for surgeons to address my 3 “musts” for any system to gain traction in this niche.

1. Must #1. An easy method for getting the device into the abdomen.
2. Must #2. An easy method for getting the tissue into the bag.
3. Must #3. An easy method for getting the tissue out of the body while still containing the cells within the system.

In my opinion based on my usage, Guardenia does a pretty good job addressing all my “musts.”

The Guardenia System is a sterile, single-use device with 3 main components—an introducer with a plunger that will fit through any standard 12-mm trocar, a polyurethane film bag supported by a nitinol ring, and an opening ring with expandable semi-rigid polyethylene “Guard Petals.” When I used it in the operating room to manually morcellate a 10-cm myoma through the umbilicus, I thought it was pretty spot on. Getting the bag into the abdomen is 100% intuitive but even has a nifty up-arrow built onto the tip to make sure the bag is opened in the proper direction. The bag material and the nitinol ring, in combination with the 17.5-cm opening ring, make the process of getting the specimen into the bag and exteriorized easier than any other system I have ever used. And, the opening ring with the Guard Petals yields a very large retraction area for the incision size while providing excellent protection to the surrounding tissues. Overall, Guardenia worked better than anything else I have previously used.

Innovation. Guardenia does not really introduce any fundamentally novel ideas, but it does combine a lot of standard technologies into a product whose sum is much larger than its parts. I would like to see it combined with an occlusive top piece to allow the retractor to be used for single-port laparoscopy as well, but that would just be the cherry on top.

Summary. I have been working on inventing a really good contained tissue extraction system for a long time, and I am a bit chagrined to see someone else outsmart me (low bar), but Advanced Surgical Concepts did, and I really like Guardenia. For pathology that is appropriate for contained morcellation, this device is definitely worth a try, and I suspect many surgeons will switch to it from whatever they are currently using.

FOR MORE INFORMATION, VISIT https://advancedsurgical.ie/guardenia-contained-extraction-system/

The views of the author are personal opinions and do not necessarily represent the views of OBG Management.Dr. Greenberg personally trials all the products he reviews. Dr. Greenberg has no conflicts of interest with this product or the company that produces it. ●

REVIEW

By James Greenberg, MD

Chief of Gynecology

Associate Professor, Harvard Medical School

Boston, Massachusetts
 

Guardenia: A “really great solution” for contained tissue extraction

The Guardenia Contained Extraction System, developed by Advanced Surgical Concepts (Wicklow, Ireland), offers a comprehensive approach to contained tissue extraction.

Background. Contained tissue extraction has been an integral part of laparoscopic procedures from at least the late 1980s and early 1990s. Bags of one sort or another are routinely used to remove from the abdomen all sorts of human tissues, including but not limited to ovaries, ectopic pregnancies, gallbladders, kidneys, spleens, and the list goes on. However, after the April 17, 2014, FDA Safety Communication discouraging the use of power morcellators with myomectomy or hysterectomy, the need for more robust contained tissue extraction systems has been ongoing, and there has yet to be a really good solution despite some innovative attempts.

Design/Functionality. Advanced Surgical Concepts’ Guardenia System is the latest attempt to provide a “really great solution” for surgeons to address my 3 “musts” for any system to gain traction in this niche.

1. Must #1. An easy method for getting the device into the abdomen.
2. Must #2. An easy method for getting the tissue into the bag.
3. Must #3. An easy method for getting the tissue out of the body while still containing the cells within the system.

In my opinion based on my usage, Guardenia does a pretty good job addressing all my “musts.”

The Guardenia System is a sterile, single-use device with 3 main components—an introducer with a plunger that will fit through any standard 12-mm trocar, a polyurethane film bag supported by a nitinol ring, and an opening ring with expandable semi-rigid polyethylene “Guard Petals.” When I used it in the operating room to manually morcellate a 10-cm myoma through the umbilicus, I thought it was pretty spot on. Getting the bag into the abdomen is 100% intuitive but even has a nifty up-arrow built onto the tip to make sure the bag is opened in the proper direction. The bag material and the nitinol ring, in combination with the 17.5-cm opening ring, make the process of getting the specimen into the bag and exteriorized easier than any other system I have ever used. And, the opening ring with the Guard Petals yields a very large retraction area for the incision size while providing excellent protection to the surrounding tissues. Overall, Guardenia worked better than anything else I have previously used.

Innovation. Guardenia does not really introduce any fundamentally novel ideas, but it does combine a lot of standard technologies into a product whose sum is much larger than its parts. I would like to see it combined with an occlusive top piece to allow the retractor to be used for single-port laparoscopy as well, but that would just be the cherry on top.

Summary. I have been working on inventing a really good contained tissue extraction system for a long time, and I am a bit chagrined to see someone else outsmart me (low bar), but Advanced Surgical Concepts did, and I really like Guardenia. For pathology that is appropriate for contained morcellation, this device is definitely worth a try, and I suspect many surgeons will switch to it from whatever they are currently using.

FOR MORE INFORMATION, VISIT https://advancedsurgical.ie/guardenia-contained-extraction-system/

The views of the author are personal opinions and do not necessarily represent the views of OBG Management.Dr. Greenberg personally trials all the products he reviews. Dr. Greenberg has no conflicts of interest with this product or the company that produces it. ●

REVIEW

By James Greenberg, MD

Chief of Gynecology

Associate Professor, Harvard Medical School

Boston, Massachusetts
 

Guardenia: A “really great solution” for contained tissue extraction

The Guardenia Contained Extraction System, developed by Advanced Surgical Concepts (Wicklow, Ireland), offers a comprehensive approach to contained tissue extraction.

Background. Contained tissue extraction has been an integral part of laparoscopic procedures from at least the late 1980s and early 1990s. Bags of one sort or another are routinely used to remove from the abdomen all sorts of human tissues, including but not limited to ovaries, ectopic pregnancies, gallbladders, kidneys, spleens, and the list goes on. However, after the April 17, 2014, FDA Safety Communication discouraging the use of power morcellators with myomectomy or hysterectomy, the need for more robust contained tissue extraction systems has been ongoing, and there has yet to be a really good solution despite some innovative attempts.

Design/Functionality. Advanced Surgical Concepts’ Guardenia System is the latest attempt to provide a “really great solution” for surgeons to address my 3 “musts” for any system to gain traction in this niche.

1. Must #1. An easy method for getting the device into the abdomen.
2. Must #2. An easy method for getting the tissue into the bag.
3. Must #3. An easy method for getting the tissue out of the body while still containing the cells within the system.

In my opinion based on my usage, Guardenia does a pretty good job addressing all my “musts.”

The Guardenia System is a sterile, single-use device with 3 main components—an introducer with a plunger that will fit through any standard 12-mm trocar, a polyurethane film bag supported by a nitinol ring, and an opening ring with expandable semi-rigid polyethylene “Guard Petals.” When I used it in the operating room to manually morcellate a 10-cm myoma through the umbilicus, I thought it was pretty spot on. Getting the bag into the abdomen is 100% intuitive but even has a nifty up-arrow built onto the tip to make sure the bag is opened in the proper direction. The bag material and the nitinol ring, in combination with the 17.5-cm opening ring, make the process of getting the specimen into the bag and exteriorized easier than any other system I have ever used. And, the opening ring with the Guard Petals yields a very large retraction area for the incision size while providing excellent protection to the surrounding tissues. Overall, Guardenia worked better than anything else I have previously used.

Innovation. Guardenia does not really introduce any fundamentally novel ideas, but it does combine a lot of standard technologies into a product whose sum is much larger than its parts. I would like to see it combined with an occlusive top piece to allow the retractor to be used for single-port laparoscopy as well, but that would just be the cherry on top.

Summary. I have been working on inventing a really good contained tissue extraction system for a long time, and I am a bit chagrined to see someone else outsmart me (low bar), but Advanced Surgical Concepts did, and I really like Guardenia. For pathology that is appropriate for contained morcellation, this device is definitely worth a try, and I suspect many surgeons will switch to it from whatever they are currently using.

FOR MORE INFORMATION, VISIT https://advancedsurgical.ie/guardenia-contained-extraction-system/

The views of the author are personal opinions and do not necessarily represent the views of OBG Management.Dr. Greenberg personally trials all the products he reviews. Dr. Greenberg has no conflicts of interest with this product or the company that produces it. ●

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radio­iodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).

Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A).­ The spaces contained basophilic strands ­(FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.

The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid¹ and obstructing lymphatic microcirculation, resulting in nonpitting edema.²

There are 5 distinct clinical variants of pretibial myxedema^1,3:

• The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
• The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
• The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
• The mixed form manifests as 2 or more of the other variants.
• The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.

A rare, late manifestation

Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.⁴ The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.⁴

While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.⁵

Continue to: More serious conditions must be ruled out

The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.

Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma ­(PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type ­(PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,⁶ differing from our case.

Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.

Treatment is simple and noninvasive

Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intra­lesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.²

This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.

CONFERENCE COVERAGE

MS, DMTs, and pregnancy: Beware of over-caution regarding treatment

Randy Dotinga

MILAN—The news about multiple sclerosis (MS) and childbearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication—or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

FEATURE

Employment vs. private practice: Who’s happier?

Amanda Loudin

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Continue to: LATEST NEWS...

LATEST NEWS

Three-quarters of menopausal women report unexpected symptoms

Becky McCall

GLASGOW­—Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them—dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important. Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.” ●

CONFERENCE COVERAGE

MS, DMTs, and pregnancy: Beware of over-caution regarding treatment

Randy Dotinga

MILAN—The news about multiple sclerosis (MS) and childbearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication—or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

FEATURE

Employment vs. private practice: Who’s happier?

Amanda Loudin

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Continue to: LATEST NEWS...

LATEST NEWS

Three-quarters of menopausal women report unexpected symptoms

Becky McCall

GLASGOW­—Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them—dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important. Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.” ●

CONFERENCE COVERAGE

MS, DMTs, and pregnancy: Beware of over-caution regarding treatment

Randy Dotinga

MILAN—The news about multiple sclerosis (MS) and childbearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. Evidence suggests that MS doesn’t disrupt fertility, pregnancy, birth, or lactation. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.

Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication—or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.

Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.

While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”

FEATURE

Employment vs. private practice: Who’s happier?

Amanda Loudin

Alexandra Kharazi, MD, a California-based cardiothoracic surgeon, previously worked as an employed physician and is now in private practice. Though she appreciates that there are some trade-offs to working with her small group of three surgeons, Dr. Kharazi has no qualms about her choice.

“For me, it’s an issue of autonomy,” she said. “While I have to work a lot of hours, I don’t have to adhere to a strict schedule. I also don’t have to follow specific policies and rules.”

In contrast, Cassandra Boduch, MD, an employed psychiatrist with PsychPlus in Houston, is very satisfied with working as an employee. “I looked into private practice, but no one really prepares you for the complications that come with it,” she said. “There’s a lot more that goes into it than people realize.”

By hanging up her own shingle, Dr. Kharazi may be living a rapidly shrinking dream. According to the American Medical Association, between 2012 and 2022, the share of physicians working in private practice fell from 60% to 47%. The share of physicians working in hospitals as direct employees or contractors increased from about 6% to about 10% during the same time period.

Many factors contribute to these shifting trends, a major factor being economic stress stemming from payment cuts in Medicare. Add in rising practice costs and administrative burdens, and more doctors than ever are seeking employment, according to the AMA.

Though the traditional dream of owning your own practice may be slipping away, are employed physicians less happy than are their self-employed peers? By many measures, the answer is no.

In Medscape’s Employed Physicians Report 2023, doctors weighed in on the pros and cons of their jobs.

When asked what they like most about their jobs, employed physician respondents reported “not having to run a business” as their number-one benefit, followed closely by a stable income. The fact that employers pay for malpractice insurance ranked third, followed by work-life balance.

“We get no business classes in medical school or residency,” said one employed physician. “Having a good salary feels good,” said another. Yet another respondent chimed in: “Running a practice as a small business has become undoable over the past 10-12 years.”

And 50% of employed physicians said that they were “very satisfied/satisfied” with their degree of autonomy.

Continue to: LATEST NEWS...

LATEST NEWS

Three-quarters of menopausal women report unexpected symptoms

Becky McCall

GLASGOW­—Three-quarters of women going through perimenopause and menopause experience unexpected distressing, debilitating, and embarrassing symptoms but often fail to receive appropriate treatment, a large U.K.-based survey found.

“For too long, many people have thought of menopause as just hot flashes and vaginal dryness. But we know hormones work all over our body, so there are many symptoms beyond that,” said Daniel Reisel, MBBS, PhD, a gynecologist at University College London, who presented the survey findings at the 2023 annual meeting of the Royal College of General Practitioners.

Primary care physicians in the United Kingdom have seen an increase in cases of women presenting with symptoms associated with menopause at a time when the country’s Parliament is debating whether all women should have a menopause check-up in their early 40s, he said.

Still, only around 14% of menopausal women in the United Kingdom are prescribed hormone replacement therapy (HRT), despite national and international guidelines clearly stating the benefits of the treatment generally outweigh the risks.

Louise Newson, MBChB, who runs the U.K.’s largest menopause clinic, said many women with symptoms of menopause feel the medical system “gaslights” them—dismissing their concerns as trivial or even fabricated.

In her clinic, she typically sees many women with poor sleep, as well as muscle and joint pains. “Yet [when they visit their GPs], they are incorrectly told that it can’t be hormones because they’re still having periods,” she said.

Prescribed antidepressants often precede HRT

The new study sought to learn what women knew and experienced with respect to menopause symptoms and what they thought was important. Of the 5,744 women who responded to the survey, 79.4% were aged 40-60 years and 84.6% were White. “The survey respondents were not different from the distribution of ethnicities we see in NHS menopause care,” said Dr. Reisel, adding that “the barriers are greater for women in poorer areas and for those who are non-White.”

A total of 30.4% had two to five hospital consultations before the health care professional considered that symptoms were related to changing hormone levels; 38.5% were offered antidepressants before HRT. Nearly all (94.6%) said they had experienced negative mood changes and emotions since becoming perimenopausal or menopausal; of these, 19.1% were formally diagnosed with depression or a mood disorder.

“This all just highlights the frustrations I feel around menopause care,” Dr. Newson said. “Women are often not given the tools to properly understand what’s going on and then they don’t ask for the right treatment, and many are given antidepressants. It’s still medicalizing the menopause but in a different way.” ●