All physicians will see changes in reimbursement in 2017. A new president with a new agenda makes for an interesting time ahead for health care in the United States. However, in this time of flux, there is one constant: the Final Rule, an informal term for the annual update on how the Medicare system will function and how much you will get paid for what you do.¹ The document is 393 pages and outlines what is new in the Medicare system, with lots of supplements giving granular details about physician work, overhead, and supply and labor costs. In this column, I have taken the liberty of dissecting the Final Rule for you and to bring attention to its high and low points for dermatologists.

Changes in Relative Value Units

The conversion factor has gone up, meaning you will be paid a bit more this year for what you do; it is not enough to account for inflation or the increasing cost of unfunded mandates, but it is better than nothing. Although the conversion factor was $35.8043 in 2016, it increased by more than 0.2% on January 1, 2017, to $35.8887.¹ How is this conversion factor calculated? We go up 0.5% due to MACRA (Medicare Access and CHIP Reauthorization Act), down 0.013% due to budget neutrality, down 0.07% due to multiple procedure payment reduction changes, and down another 0.18% due to the misvalued code target.¹ The misvalued code target is related to targets established by statute for 2016 to 2018 and payment rates are reduced across the board if they are not met.

If payments suffer from reductions in work value, they may not happen all at once. If the Centers for Medicare & Medicaid Services (CMS) reduce total relative value units (RVUs) by more than 20%, reductions will take place over at least 2 years with a single year drop maximum of 19%.¹ Unfortunately, such limits do not apply to revised codes, which can take as big a hit as the CMS cares to make.

Changes to Global Periods

In 2015, we learned that 10- and 90-day global periods would be eliminated in 2017 and 2018, respectively, with great concern on the part of the government about the number and level of evaluation and management services embedded in these codes. The implementation of global policy elimination was prohibited by MACRA and the CMS was required to develop and implement a process to gather data on services furnished in the global period from a representative sample of physicians, which they will use to value surgical services beginningin 2019.¹ The CMS decided to capture this data with a new set of time-based G codes (which would be onerous for all practicing physicians), not just the unlucky folks who were to be the sample mandated under MACRA.² During the comment period, it became obvious to the CMS that this concept was flawed for many reasons and it decided to hold a town hall meeting at the CMS headquarters on August 25, 2016, on data collection on resources used in furnishing global services in which 90 minutes of live testimony in the morning was followed by another 90 minutes by telephone in the afternoon.³ This meeting, which I attended, resulted in the CMS changing the all-practitioner reporting program to a specified sample with others allowed to opt in. Practitioners in groups of less than 10 are exempt, and only physicians in Florida, Kentucky, Louisiana, Nevada, New Jersey, North Dakota, Ohio, Oregon, and Rhode Island must capture data beginning in July 2017.¹ These data only have to be captured on codes that are used by more than 100 practitioners and are furnished at least 10,000 times or have allowed charges of greater than $10,000,000 annually. If you are lucky enough to live in one of the testing states, you must start on July 1 but can start before July 1 if you wish. Practitioners in smaller practices or in other geographic areas are encouraged to report data if feasible but are not required to do so. Current Procedural Terminology (CPT) code 99024 will be used for reporting postoperative services rather than the proposed onerous set of G codes, and reporting will not be required for preoperative visits included in the global package or for services not related to the patient’s visit.

Changes to Chronic Care Management

There are new and modified chronic care management codes that are not of use to you unless you are the primary provider for the patient and you and the patient meet multiple stringent requirements.⁴ The patient must have multiple illnesses, use multiple medications, be unable to perform activities of daily living, require a caregiver, and/or have repeat admissions or emergency department visits. Typical adult patients who receive complex chronic care management services are treated with 3 or more prescription medications and may be receiving other types of therapeutic interventions (eg, physical therapy, occupational therapy). Typical pediatric patients receive 3 or more therapeutic interventions (eg, medications, nutritional support, respiratory therapy). All patients have 2 or more chronic continuous or episodic health conditions that are expected to last at least 12 months or until the death of the patient and place the patient at serious risk for death, acute exacerbation/decompensation, or functional decline.⁴

Changes to Moderate Sedation Codes

The economic value of providing moderate sedation (eg, drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation) used to be embedded in a variety of CPT codes, which is no longer the case in 2017. Diazepam or similar drugs swallowed or dissolved under the tongue are not included. The new CPT codes 99151, 99152, 99153, 99155, 99156, and 99157 are not to be used to report administration of medications for pain control or minimal sedation (anxiolysis). An independent trained observer, an individual who is qualified to monitor the patient during the procedure and who has no other duties (eg, assisting at surgery) during the procedure, must be present. If you are thinking of using these codes, read the entire section in the CPT manual,⁴ check your state laws, and consult your malpractice carrier and perhaps even your health care attorney.

Changes to Nail Procedure Codes

Current Procedural Terminology code 11752 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail], for permanent removal; with amputation of tuft of distal phalanx) is now gone, while base code 11750 remains. If you are doing nail surgery and removing underlying bone, instead use code 26236 (partial excision [craterization, saucerization, or diaphysectomy] bone [eg, osteomyelitis]; distal phalanx of finger), 28124 (partial excision [craterization, saucerization, sequestrectomy, or diaphysectomy] bone [eg, osteomyelitis or bossing]; phalanx of toe), or other codes in the same section of the CPT manual if they more precisely describe the procedure performed.

Changes to Slide Consultation Codes

The slide consultation codes 88321 (consultation and report on referred slides prepared elsewhere), 88323 (consultation and report on referred material requiring preparation of slides), and 88325 (consultation, comprehensive, with review of records and specimens, with report on referred material) were revalued this year, with the first 2 showing no change but the latter showing an increase in value from 2.50 to 2.85 RVUs.¹ None are meant to be routine. If you have every slide looked at by someone else for “quality assurance reasons,” the consultation is not reportable. If you use these consultation codes too often, the CMS might have concerns about fraud and abuse. Visit http://data.cms.gov to see how you compare to your peers.

Changes to Reflectance Confocal Microscopy Codes

Reflectance confocal microscopy had new codes for 2016, which were carrier priced, and in 2017 they have real RVUs per the CMS. The payments for these codes have a national average reimbursement of $161.85 for 96931 (reflectance confocal microscopy for cellular and subcellular imaging of skin; image acquisition and interpretation and report, first lesion), $104.80 for 96932 (image acquisition only, first lesion), and $45.94 for 96933 (interpretation and report only, first lesion).⁵ The respective add-on codes have values of $83.26 for 96934 (image acquisition and interpretation and report, each additional lesion [list separately in addition to code for primary procedure]), $35.17 for 96935 (image acquisition only, each additional lesion [list separately in addition to code for primary procedure]), and $43.78 for 96936 (interpretation and report only, each additional lesion [list separately in addition to code for primary procedure]).

Other Coding Changes

There are a whole bunch of new codes in the “Genomic Sequencing Procedures and Other Molecular Multianalyte Assays” (MMAAs) section of CPT. The important thing for you to remember is these codes are for the laboratory performing the assay to report, not the physician ordering it. There is a new Appendix O for proprietary laboratory analysis MMAAs, including those that do not have a Category I code. These MMAAs are identified in Appendix O by a 4-digit number followed by the letter M.⁴

There are some revisions to psychotherapy codes 90832 to 90847. These codes are outside our scope of practice and should only be used by psychiatrists, social workers, psychologists, or other appropriate mental health workers.

Final Thoughts

It has not been a breakout year for telehealth and we still do not have payment for store-and-forward teledermatology, except in a few designated rural areas. With the advent of the rhetoric we have heard after the presidential election, any speculation on what will happen to the brave new world of the merit-based incentive payment system, alternative payment models, and other regulations are anyone’s guess.

All physicians will see changes in reimbursement in 2017. A new president with a new agenda makes for an interesting time ahead for health care in the United States. However, in this time of flux, there is one constant: the Final Rule, an informal term for the annual update on how the Medicare system will function and how much you will get paid for what you do.¹ The document is 393 pages and outlines what is new in the Medicare system, with lots of supplements giving granular details about physician work, overhead, and supply and labor costs. In this column, I have taken the liberty of dissecting the Final Rule for you and to bring attention to its high and low points for dermatologists.

Changes in Relative Value Units

The conversion factor has gone up, meaning you will be paid a bit more this year for what you do; it is not enough to account for inflation or the increasing cost of unfunded mandates, but it is better than nothing. Although the conversion factor was $35.8043 in 2016, it increased by more than 0.2% on January 1, 2017, to $35.8887.¹ How is this conversion factor calculated? We go up 0.5% due to MACRA (Medicare Access and CHIP Reauthorization Act), down 0.013% due to budget neutrality, down 0.07% due to multiple procedure payment reduction changes, and down another 0.18% due to the misvalued code target.¹ The misvalued code target is related to targets established by statute for 2016 to 2018 and payment rates are reduced across the board if they are not met.

If payments suffer from reductions in work value, they may not happen all at once. If the Centers for Medicare & Medicaid Services (CMS) reduce total relative value units (RVUs) by more than 20%, reductions will take place over at least 2 years with a single year drop maximum of 19%.¹ Unfortunately, such limits do not apply to revised codes, which can take as big a hit as the CMS cares to make.

Changes to Global Periods

In 2015, we learned that 10- and 90-day global periods would be eliminated in 2017 and 2018, respectively, with great concern on the part of the government about the number and level of evaluation and management services embedded in these codes. The implementation of global policy elimination was prohibited by MACRA and the CMS was required to develop and implement a process to gather data on services furnished in the global period from a representative sample of physicians, which they will use to value surgical services beginningin 2019.¹ The CMS decided to capture this data with a new set of time-based G codes (which would be onerous for all practicing physicians), not just the unlucky folks who were to be the sample mandated under MACRA.² During the comment period, it became obvious to the CMS that this concept was flawed for many reasons and it decided to hold a town hall meeting at the CMS headquarters on August 25, 2016, on data collection on resources used in furnishing global services in which 90 minutes of live testimony in the morning was followed by another 90 minutes by telephone in the afternoon.³ This meeting, which I attended, resulted in the CMS changing the all-practitioner reporting program to a specified sample with others allowed to opt in. Practitioners in groups of less than 10 are exempt, and only physicians in Florida, Kentucky, Louisiana, Nevada, New Jersey, North Dakota, Ohio, Oregon, and Rhode Island must capture data beginning in July 2017.¹ These data only have to be captured on codes that are used by more than 100 practitioners and are furnished at least 10,000 times or have allowed charges of greater than $10,000,000 annually. If you are lucky enough to live in one of the testing states, you must start on July 1 but can start before July 1 if you wish. Practitioners in smaller practices or in other geographic areas are encouraged to report data if feasible but are not required to do so. Current Procedural Terminology (CPT) code 99024 will be used for reporting postoperative services rather than the proposed onerous set of G codes, and reporting will not be required for preoperative visits included in the global package or for services not related to the patient’s visit.

Changes to Chronic Care Management

There are new and modified chronic care management codes that are not of use to you unless you are the primary provider for the patient and you and the patient meet multiple stringent requirements.⁴ The patient must have multiple illnesses, use multiple medications, be unable to perform activities of daily living, require a caregiver, and/or have repeat admissions or emergency department visits. Typical adult patients who receive complex chronic care management services are treated with 3 or more prescription medications and may be receiving other types of therapeutic interventions (eg, physical therapy, occupational therapy). Typical pediatric patients receive 3 or more therapeutic interventions (eg, medications, nutritional support, respiratory therapy). All patients have 2 or more chronic continuous or episodic health conditions that are expected to last at least 12 months or until the death of the patient and place the patient at serious risk for death, acute exacerbation/decompensation, or functional decline.⁴

Changes to Moderate Sedation Codes

The economic value of providing moderate sedation (eg, drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation) used to be embedded in a variety of CPT codes, which is no longer the case in 2017. Diazepam or similar drugs swallowed or dissolved under the tongue are not included. The new CPT codes 99151, 99152, 99153, 99155, 99156, and 99157 are not to be used to report administration of medications for pain control or minimal sedation (anxiolysis). An independent trained observer, an individual who is qualified to monitor the patient during the procedure and who has no other duties (eg, assisting at surgery) during the procedure, must be present. If you are thinking of using these codes, read the entire section in the CPT manual,⁴ check your state laws, and consult your malpractice carrier and perhaps even your health care attorney.

Changes to Nail Procedure Codes

Current Procedural Terminology code 11752 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail], for permanent removal; with amputation of tuft of distal phalanx) is now gone, while base code 11750 remains. If you are doing nail surgery and removing underlying bone, instead use code 26236 (partial excision [craterization, saucerization, or diaphysectomy] bone [eg, osteomyelitis]; distal phalanx of finger), 28124 (partial excision [craterization, saucerization, sequestrectomy, or diaphysectomy] bone [eg, osteomyelitis or bossing]; phalanx of toe), or other codes in the same section of the CPT manual if they more precisely describe the procedure performed.

Changes to Slide Consultation Codes

The slide consultation codes 88321 (consultation and report on referred slides prepared elsewhere), 88323 (consultation and report on referred material requiring preparation of slides), and 88325 (consultation, comprehensive, with review of records and specimens, with report on referred material) were revalued this year, with the first 2 showing no change but the latter showing an increase in value from 2.50 to 2.85 RVUs.¹ None are meant to be routine. If you have every slide looked at by someone else for “quality assurance reasons,” the consultation is not reportable. If you use these consultation codes too often, the CMS might have concerns about fraud and abuse. Visit http://data.cms.gov to see how you compare to your peers.

Changes to Reflectance Confocal Microscopy Codes

Reflectance confocal microscopy had new codes for 2016, which were carrier priced, and in 2017 they have real RVUs per the CMS. The payments for these codes have a national average reimbursement of $161.85 for 96931 (reflectance confocal microscopy for cellular and subcellular imaging of skin; image acquisition and interpretation and report, first lesion), $104.80 for 96932 (image acquisition only, first lesion), and $45.94 for 96933 (interpretation and report only, first lesion).⁵ The respective add-on codes have values of $83.26 for 96934 (image acquisition and interpretation and report, each additional lesion [list separately in addition to code for primary procedure]), $35.17 for 96935 (image acquisition only, each additional lesion [list separately in addition to code for primary procedure]), and $43.78 for 96936 (interpretation and report only, each additional lesion [list separately in addition to code for primary procedure]).

Other Coding Changes

There are a whole bunch of new codes in the “Genomic Sequencing Procedures and Other Molecular Multianalyte Assays” (MMAAs) section of CPT. The important thing for you to remember is these codes are for the laboratory performing the assay to report, not the physician ordering it. There is a new Appendix O for proprietary laboratory analysis MMAAs, including those that do not have a Category I code. These MMAAs are identified in Appendix O by a 4-digit number followed by the letter M.⁴

There are some revisions to psychotherapy codes 90832 to 90847. These codes are outside our scope of practice and should only be used by psychiatrists, social workers, psychologists, or other appropriate mental health workers.

Final Thoughts

It has not been a breakout year for telehealth and we still do not have payment for store-and-forward teledermatology, except in a few designated rural areas. With the advent of the rhetoric we have heard after the presidential election, any speculation on what will happen to the brave new world of the merit-based incentive payment system, alternative payment models, and other regulations are anyone’s guess.

All physicians will see changes in reimbursement in 2017. A new president with a new agenda makes for an interesting time ahead for health care in the United States. However, in this time of flux, there is one constant: the Final Rule, an informal term for the annual update on how the Medicare system will function and how much you will get paid for what you do.¹ The document is 393 pages and outlines what is new in the Medicare system, with lots of supplements giving granular details about physician work, overhead, and supply and labor costs. In this column, I have taken the liberty of dissecting the Final Rule for you and to bring attention to its high and low points for dermatologists.

Changes in Relative Value Units

The conversion factor has gone up, meaning you will be paid a bit more this year for what you do; it is not enough to account for inflation or the increasing cost of unfunded mandates, but it is better than nothing. Although the conversion factor was $35.8043 in 2016, it increased by more than 0.2% on January 1, 2017, to $35.8887.¹ How is this conversion factor calculated? We go up 0.5% due to MACRA (Medicare Access and CHIP Reauthorization Act), down 0.013% due to budget neutrality, down 0.07% due to multiple procedure payment reduction changes, and down another 0.18% due to the misvalued code target.¹ The misvalued code target is related to targets established by statute for 2016 to 2018 and payment rates are reduced across the board if they are not met.

If payments suffer from reductions in work value, they may not happen all at once. If the Centers for Medicare & Medicaid Services (CMS) reduce total relative value units (RVUs) by more than 20%, reductions will take place over at least 2 years with a single year drop maximum of 19%.¹ Unfortunately, such limits do not apply to revised codes, which can take as big a hit as the CMS cares to make.

Changes to Global Periods

In 2015, we learned that 10- and 90-day global periods would be eliminated in 2017 and 2018, respectively, with great concern on the part of the government about the number and level of evaluation and management services embedded in these codes. The implementation of global policy elimination was prohibited by MACRA and the CMS was required to develop and implement a process to gather data on services furnished in the global period from a representative sample of physicians, which they will use to value surgical services beginningin 2019.¹ The CMS decided to capture this data with a new set of time-based G codes (which would be onerous for all practicing physicians), not just the unlucky folks who were to be the sample mandated under MACRA.² During the comment period, it became obvious to the CMS that this concept was flawed for many reasons and it decided to hold a town hall meeting at the CMS headquarters on August 25, 2016, on data collection on resources used in furnishing global services in which 90 minutes of live testimony in the morning was followed by another 90 minutes by telephone in the afternoon.³ This meeting, which I attended, resulted in the CMS changing the all-practitioner reporting program to a specified sample with others allowed to opt in. Practitioners in groups of less than 10 are exempt, and only physicians in Florida, Kentucky, Louisiana, Nevada, New Jersey, North Dakota, Ohio, Oregon, and Rhode Island must capture data beginning in July 2017.¹ These data only have to be captured on codes that are used by more than 100 practitioners and are furnished at least 10,000 times or have allowed charges of greater than $10,000,000 annually. If you are lucky enough to live in one of the testing states, you must start on July 1 but can start before July 1 if you wish. Practitioners in smaller practices or in other geographic areas are encouraged to report data if feasible but are not required to do so. Current Procedural Terminology (CPT) code 99024 will be used for reporting postoperative services rather than the proposed onerous set of G codes, and reporting will not be required for preoperative visits included in the global package or for services not related to the patient’s visit.

Changes to Chronic Care Management

There are new and modified chronic care management codes that are not of use to you unless you are the primary provider for the patient and you and the patient meet multiple stringent requirements.⁴ The patient must have multiple illnesses, use multiple medications, be unable to perform activities of daily living, require a caregiver, and/or have repeat admissions or emergency department visits. Typical adult patients who receive complex chronic care management services are treated with 3 or more prescription medications and may be receiving other types of therapeutic interventions (eg, physical therapy, occupational therapy). Typical pediatric patients receive 3 or more therapeutic interventions (eg, medications, nutritional support, respiratory therapy). All patients have 2 or more chronic continuous or episodic health conditions that are expected to last at least 12 months or until the death of the patient and place the patient at serious risk for death, acute exacerbation/decompensation, or functional decline.⁴

Changes to Moderate Sedation Codes

The economic value of providing moderate sedation (eg, drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation) used to be embedded in a variety of CPT codes, which is no longer the case in 2017. Diazepam or similar drugs swallowed or dissolved under the tongue are not included. The new CPT codes 99151, 99152, 99153, 99155, 99156, and 99157 are not to be used to report administration of medications for pain control or minimal sedation (anxiolysis). An independent trained observer, an individual who is qualified to monitor the patient during the procedure and who has no other duties (eg, assisting at surgery) during the procedure, must be present. If you are thinking of using these codes, read the entire section in the CPT manual,⁴ check your state laws, and consult your malpractice carrier and perhaps even your health care attorney.

Changes to Nail Procedure Codes

Current Procedural Terminology code 11752 (excision of nail and nail matrix, partial or complete [eg, ingrown or deformed nail], for permanent removal; with amputation of tuft of distal phalanx) is now gone, while base code 11750 remains. If you are doing nail surgery and removing underlying bone, instead use code 26236 (partial excision [craterization, saucerization, or diaphysectomy] bone [eg, osteomyelitis]; distal phalanx of finger), 28124 (partial excision [craterization, saucerization, sequestrectomy, or diaphysectomy] bone [eg, osteomyelitis or bossing]; phalanx of toe), or other codes in the same section of the CPT manual if they more precisely describe the procedure performed.

Changes to Slide Consultation Codes

The slide consultation codes 88321 (consultation and report on referred slides prepared elsewhere), 88323 (consultation and report on referred material requiring preparation of slides), and 88325 (consultation, comprehensive, with review of records and specimens, with report on referred material) were revalued this year, with the first 2 showing no change but the latter showing an increase in value from 2.50 to 2.85 RVUs.¹ None are meant to be routine. If you have every slide looked at by someone else for “quality assurance reasons,” the consultation is not reportable. If you use these consultation codes too often, the CMS might have concerns about fraud and abuse. Visit http://data.cms.gov to see how you compare to your peers.

Changes to Reflectance Confocal Microscopy Codes

Reflectance confocal microscopy had new codes for 2016, which were carrier priced, and in 2017 they have real RVUs per the CMS. The payments for these codes have a national average reimbursement of $161.85 for 96931 (reflectance confocal microscopy for cellular and subcellular imaging of skin; image acquisition and interpretation and report, first lesion), $104.80 for 96932 (image acquisition only, first lesion), and $45.94 for 96933 (interpretation and report only, first lesion).⁵ The respective add-on codes have values of $83.26 for 96934 (image acquisition and interpretation and report, each additional lesion [list separately in addition to code for primary procedure]), $35.17 for 96935 (image acquisition only, each additional lesion [list separately in addition to code for primary procedure]), and $43.78 for 96936 (interpretation and report only, each additional lesion [list separately in addition to code for primary procedure]).

Other Coding Changes

There are a whole bunch of new codes in the “Genomic Sequencing Procedures and Other Molecular Multianalyte Assays” (MMAAs) section of CPT. The important thing for you to remember is these codes are for the laboratory performing the assay to report, not the physician ordering it. There is a new Appendix O for proprietary laboratory analysis MMAAs, including those that do not have a Category I code. These MMAAs are identified in Appendix O by a 4-digit number followed by the letter M.⁴

There are some revisions to psychotherapy codes 90832 to 90847. These codes are outside our scope of practice and should only be used by psychiatrists, social workers, psychologists, or other appropriate mental health workers.

Final Thoughts

It has not been a breakout year for telehealth and we still do not have payment for store-and-forward teledermatology, except in a few designated rural areas. With the advent of the rhetoric we have heard after the presidential election, any speculation on what will happen to the brave new world of the merit-based incentive payment system, alternative payment models, and other regulations are anyone’s guess.

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.^1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.⁴ Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.⁵ This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.⁶

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).³ Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.⁷ Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.¹ Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.⁸

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.^1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.⁵ The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.^9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.^1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.¹¹ Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.¹² Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.¹³

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.¹⁴ Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.¹⁴ Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.¹⁵ Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.⁶

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.¹⁶ Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.¹⁷ Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.^4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.¹⁶

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.^1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.⁴ Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.⁵ This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.⁶

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).³ Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.⁷ Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.¹ Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.⁸

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.^1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.⁵ The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.^9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.^1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.¹¹ Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.¹² Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.¹³

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.¹⁴ Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.¹⁴ Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.¹⁵ Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.⁶

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.¹⁶ Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.¹⁷ Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.^4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.¹⁶

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.^1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.⁴ Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.⁵ This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.⁶

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).³ Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.⁷ Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.¹ Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.⁸

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.^1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.⁵ The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.^9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.^1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.¹¹ Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.¹² Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.¹³

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.¹⁴ Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.¹⁴ Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.¹⁵ Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.⁶

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.¹⁶ Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.¹⁷ Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.^4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.¹⁶

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

The cardiovascular comorbidities associated with psoriasis have been well documented; however, the mechanism by which psoriasis increases the risk for cardiovascular disease (CVD) remains unclear. Elevated systemic inflammatory cytokines and mediators may play a key role in their association, which prompts the questions: Do systemic medications have a protective effect? Do patients on systemic antipsoriatic treatment have a decreased risk for major adverse cardiovascular events (MACEs) compared with untreated patients?

We believe the shared inflammatory processes involved in psoriasis and atherosclerosis formation are potential targets for therapy in reducing the incidence of CVD and its associated complications. A growing amount of evidence suggests cardioprotective effects associated with antipsoriatic treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate. Gkalpakiotis et al¹ demonstrated a reduction in serum E-selectin (mean [standard deviation], 53.04 [23.54] ng/mL vs 35.32 [8.70] ng/mL; P<.001) and IL-22 (25.11 [19.9] pg/mL vs 12.83 [8.42] pg/mL; P<.001) after 3 months of adalimumab administration in patients with moderate to severe psoriasis. Both E-selectin and IL-22 are associated with the development of atherosclerosis, endothelial dysfunction, and an increased incidence of CVD. Similarly, Wu et al² demonstrated a statistically significant reduction (–5.04 mg/dL [95% confidence interval [CI], –8.24 to –2.12; P<.01) in C-reactive protein in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis after concurrent use of methotrexate and TNF inhibitors.

Solomon et al³ compared the rate of newly diagnosed diabetes mellitus among psoriasis and rheumatoid arthritis patients treated with TNF inhibitors, methotrexate, hydroxychloroquine, and other nonbiologic disease-modifying antirheumatic drugs. The authors’ findings suggest that those who take a TNF inhibitor (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91) and hydroxychloroquine (HR, 0.54; 95% CI, 0.36-0.80) are at lower risk for diabetes mellitus compared to those treated with nonbiologic disease-modifying antirheumatic drugs. Conversely, the methotrexate (HR, 0.77; 95% CI, 0.53-1.13) cohort did not show a statistically significant reduction in diabetes risk.³

Pina et al⁴ revealed improvement in endothelial function after 6 months of adalimumab use in patients with moderate to severe psoriasis. To evaluate the presence of subclinical endothelial dysfunction, the authors assessed brachial artery reactivity by measuring flow-mediated dilation and carotid artery stiffness by pulse wave velocity. Patients showed an increase in flow-mediated dilation (mean [SD], 6.19% [2.44%] vs 7.46% [2.43%]; P=.008) and reduction in pulse wave velocity (6.28 [1.04] m/s vs 5.69 [1.31] m/s; P=.03) compared to baseline measurements, indicating an improvement of endothelial function.⁴

Ahlehoff et al⁵ observed for improvements in subclinical left ventricular dysfunction in psoriasis patients after treatment with biologics. Using echocardiography, they assessed for changes in diastolic function and left ventricular systolic deformation (defined by global longitudinal strain). Of patients who received 3 months of biologic therapy (TNF inhibitor orIL-12/23 inhibitor) and maintained at minimum a psoriasis area and severity index 50 response, all demonstrated an improvement in diastolic function (mean [SD], 8.1 [2.1] vs 6.7 [1.9]; P<.001) and global longitudinal strain (mean [SD], –16.8% [2.1%] vs –18.3% [2.3%]; P<.001). Of note, patients who did not achieve a psoriasis area and severity index 50 response at follow-up did not exhibit an improvement in subclinical myocardial function.⁵

Moreover, a Danish nationwide study with up to 5-year follow-up evaluated the risk for MACE (ie, cardiovascular death, myocardial infarction, stroke) in patients with severe psoriasis receiving systemic anti-inflammatory medications and nonsystemic therapies including topical treatments, phototherapy, and climate therapy.⁶ Compared to nonsystemic therapies, methotrexate use (HR, 0.53; 95% CI, 0.34-0.83) was associated with a decreased risk for cardiovascular events. However, a protective decreased risk was not found among patients who used systemic cyclosporine (HR, 1.06; 95% CI, 0.26-4.27) or retinoids (HR, 1.80; 95% CI, 1.03-2.96). Any biological drug use had a comparable but nonsignificant reduction of cardiovascular events (HR, 0.58; 95% CI, 0.30-1.10). After multivariable adjustment, TNF inhibitors were associated with a statistically significant decreased risk for cardiovascular events (HR, 0.46; 95% CI, 0.22-0.98; P=.04) compared to nonsystemic therapies. The IL-12/23 inhibitor did not demonstrate this relationship (HR, 1.52; 95% CI, 0.47-4.94).⁶

Lastly, Wu et al⁷ compared the risk for MACE (ie, myocardial infarction, stroke, unstable angina, transient ischemic attack) between patients with psoriasis who received TNF inhibitors or methotrexate. The TNF inhibitor and methotrexate cohorts were observed for a median of 12 months and 9 months, respectively. After adjusting for potential confounding factors, they found a 45% reduction (HR, 0.55; 95% CI, 0.45-0.67) in cardiovascular event risk in the TNF inhibitor cohort compared with the methotrexate cohort. Notably, analyses also showed comparatively fewer cardiovascular events in the TNF inhibitor cohort throughout all time points—6, 12, 18, 24, 60 months—in the observation period. Regression analysis revealed an 11% reduction in cardiovascular events (HR, 0.89; 95% CI, 0.80-0.98) with each additional 6 months of cumulative TNF inhibitor exposure.

The current sum of evidence suggests cardioprotective effects of TNF inhibitor and methotrexate use. However, given the cumulative systemic toxicity and inferior cutaneous efficacy of methotrexate, TNF inhibitors will likely play a more significant role going forward. The role of methotrexate may be for its simultaneous use with biologic therapies to limit immunogenicity. Newer biologic agents such as IL-12/23 and IL-17 inhibitors have not yet been as extensively studied for their effects on cardiovascular risk as their TNF inhibitor counterparts. However, because of their shared ability to target specific immunological pathways, it is plausible that IL-12/23 and IL-17 agents may exhibit cardioprotective effects.⁸

Patients with psoriasis should be counseled and educated about the increased risk for CVD and its associated morbidity and mortality risk. Screening for modifiable risk factors and recommending therapeutic lifestyle changes also is appropriate. Future studies should help define the role of specific systemic drugs in reducing the risk for CVD in patients with psoriasis. Despite the expanding amount of evidence in the current literature implicating the use of TNF inhibitors for cardiovascular risk prevention, there is still a need for long-term, randomized, placebo-controlled trials to provide more authoritative evidence-based recommendations.

MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

[email protected]

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

[email protected]

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

[email protected]

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at [email protected].

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at [email protected].

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at [email protected].

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”