The Food and Drug Administration has approved tofacitinib and an extended-release formulation of the drug for adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to a Dec. 14 announcement from its manufacturer, Pfizer.

The approvals of tofacitinib (Xeljanz) at 5 mg twice daily and extended-release tofacitinib (Xeljanz XR) at 11 mg once daily are based on data from the phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond.

In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg twice daily in combination with a nonbiologic DMARD achieved an ACR20 response at 3 months, compared with 33% of those treated with placebo (P equal to or less than .05). In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg twice daily at 3 months, when compared with 24% of patients taking placebo (P equal to or less than .05).

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The Food and Drug Administration has approved tofacitinib and an extended-release formulation of the drug for adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to a Dec. 14 announcement from its manufacturer, Pfizer.

The approvals of tofacitinib (Xeljanz) at 5 mg twice daily and extended-release tofacitinib (Xeljanz XR) at 11 mg once daily are based on data from the phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond.

In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg twice daily in combination with a nonbiologic DMARD achieved an ACR20 response at 3 months, compared with 33% of those treated with placebo (P equal to or less than .05). In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg twice daily at 3 months, when compared with 24% of patients taking placebo (P equal to or less than .05).

[email protected]

The Food and Drug Administration has approved tofacitinib and an extended-release formulation of the drug for adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to a Dec. 14 announcement from its manufacturer, Pfizer.

The approvals of tofacitinib (Xeljanz) at 5 mg twice daily and extended-release tofacitinib (Xeljanz XR) at 11 mg once daily are based on data from the phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond.

In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg twice daily in combination with a nonbiologic DMARD achieved an ACR20 response at 3 months, compared with 33% of those treated with placebo (P equal to or less than .05). In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg twice daily at 3 months, when compared with 24% of patients taking placebo (P equal to or less than .05).

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The positive trends in drug use among adolescents appear to be continuing – overall, according to the 2017 Monitoring the Future survey.

“This year, we have very good news, because ... the pattern of drug use among teenagers in the United States is continuing to go down, and it’s most notable in the case of opioid drugs,” Nora D. Volkow, MD, director of the National Institute on Drug Abuse said in a video interview posted by NIDA. “We are observing some of the lowest rates of opioid use that we have been monitoring through the survey.”

The national survey results of 8th, 10th, and 12th graders, released Dec. 14, found that lifetime, past-year, and past-month misuse of prescription pain medications are at lows that NIDA called historic. Among high school seniors, the survey showed, Vicodin use was at its lowest point since 2002 at 2% – a decrease from its high of 10.5% in 2003. Similarly, the reported use of OxyContin among high school seniors dropped from 5.5% in 2005 to 2.7% this year.

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SOURCE: Miech RA et al. 2017 Monitoring the Future

The positive trends in drug use among adolescents appear to be continuing – overall, according to the 2017 Monitoring the Future survey.

“This year, we have very good news, because ... the pattern of drug use among teenagers in the United States is continuing to go down, and it’s most notable in the case of opioid drugs,” Nora D. Volkow, MD, director of the National Institute on Drug Abuse said in a video interview posted by NIDA. “We are observing some of the lowest rates of opioid use that we have been monitoring through the survey.”

The national survey results of 8th, 10th, and 12th graders, released Dec. 14, found that lifetime, past-year, and past-month misuse of prescription pain medications are at lows that NIDA called historic. Among high school seniors, the survey showed, Vicodin use was at its lowest point since 2002 at 2% – a decrease from its high of 10.5% in 2003. Similarly, the reported use of OxyContin among high school seniors dropped from 5.5% in 2005 to 2.7% this year.

[email protected]

SOURCE: Miech RA et al. 2017 Monitoring the Future

The positive trends in drug use among adolescents appear to be continuing – overall, according to the 2017 Monitoring the Future survey.

“This year, we have very good news, because ... the pattern of drug use among teenagers in the United States is continuing to go down, and it’s most notable in the case of opioid drugs,” Nora D. Volkow, MD, director of the National Institute on Drug Abuse said in a video interview posted by NIDA. “We are observing some of the lowest rates of opioid use that we have been monitoring through the survey.”

The national survey results of 8th, 10th, and 12th graders, released Dec. 14, found that lifetime, past-year, and past-month misuse of prescription pain medications are at lows that NIDA called historic. Among high school seniors, the survey showed, Vicodin use was at its lowest point since 2002 at 2% – a decrease from its high of 10.5% in 2003. Similarly, the reported use of OxyContin among high school seniors dropped from 5.5% in 2005 to 2.7% this year.

[email protected]

SOURCE: Miech RA et al. 2017 Monitoring the Future

Uterine transplantation is generally seen as ethical, with acceptable risk levels for both donors and recipients, according to two parallel surveys given to women’s health physicians and to the general public.

The results, presented at the annual meeting of the American Society for Reproductive Medicine (ASRM), showed that “the majority of gynecologists surveyed find uterine transplantation to be an acceptable and ethical option for patients with uterine factor infertility,” wrote Pietro Bortoletto, MD, and his coauthors.

Similarly, about two-thirds of the general public found uterine transplantation permissible and ethical, according to responses from an age- and gender-balanced nationally representative survey.

The web-based surveys were designed to assess the personal beliefs of both the public and of physicians about the permissibility of uterine transplantation, and to evaluate respondents’ concerns about perceived risks associated with the procedure. Respondents in each survey were also asked to identify any ethical concerns they might have; recipients of both surveys received background information about uterine transplantation.

Dr. Bortoletto and his colleagues sent the survey by email to physicians who were members of ASRM and AAGL. Of the 4,216 physicians who were invited to take the survey, 447 (28.4%) completed it, though results were tallied just for the 414 respondents who were United States–based physicians.

Physician respondents, when asked whether women should be allowed to donate or receive a transplanted uterus, responded mostly in the affirmative: 20% strongly agreed and 36% agreed, while 23% were neutral. The remainder disagreed or strongly disagreed.

The possibility of complications for the recipient was identified as the top concern by about 50% of physician respondents. Next most concerning was fetal outcomes, of primary concern for about 28%, followed by complications to the donor and cost, each of which was of primary concern to 10% or fewer of the physician respondents.

The risk to donors of uterine transplantation was seen as acceptable by 73.7% of AAGL members and 71.7% of ASRM members; just over half of each group saw the risk as acceptable for the recipients and the infants, however.

Though over half of physician respondents (57.9% of AAGL members and 59.5% of ASRM members) felt that uterine transplantation should be a potential treatment option for women with absolute uterine factor infertility, fewer felt it should be covered by health insurance – 35.4% of AAGL members and 40.5% of ASRM members held this opinion.

Among the general public, over three quarters (78%) felt that women should be allowed to undergo uterine transplantation. Slightly fewer (67%) respondents to the public survey felt that uterine transplantation is ethical; those who agreed had slightly higher incomes and education levels (relative risk, 1.11 and 1.09, respectively). A similar number (66%) felt that uterine transplantation was an acceptable alternative to using a gestational carrier.

As was the case for physicians, fewer members of the general public (45%) agreed that health insurance should cover the procedure; here, women and Hispanics were more likely to agree (relative risk, 1.11 and 1.18, respectively).

The results of the survey of the general public were presented by first author Eduardo Hariton, MD, a coauthor of Dr. Bortoletto’s in the study of physician survey results. Both Dr. Hariton and Dr. Bortoletto are resident physicians in the department of obstetrics, gynecology, and reproductive biology at Brigham and Women’s Hospital, Boston.

The public survey was sent to a nationally representative sample, balanced by gender and age. Of 1,444 individuals who were recruited to receive the survey, 1,337 completed it. Ninety respondents reported that they found in vitro fertilization unacceptable; these responses were excluded, Dr. Hariton said in an interview. “We wanted to get at uterine transplantation per se,” rather than assisted reproductive technology in general.

Placing the ethics of uterine transplantation in a broader context, Dr. Bortoletto said in an interview that the United States is one of just a few countries that permit gestational surrogacy, with regulations varying by state. To his knowledge, he said, Ukraine and Russia are the only other two nations that permit compensation for surrogacy. Greece and the United Kingdom permit altruistic surrogacy, while gestational surrogacy of any sort is forbidden in the European Union. Thus, in those nations, uterine transplantation will be the only option for women who wish to bear their biological children.

“I think the main takeaway is that for people who had hesitation about [uterine transplantation], it was mainly around safety,” and not ethical concerns, said Dr. Hariton. “I was a bit surprised, but also encouraged, by the degree of support.”

Neither Dr. Hariton nor Dr. Bortoletto reported any conflicts of interest. The public opinion study was funded by an Expanding the Boundaries grant.

[email protected]

Uterine transplantation is generally seen as ethical, with acceptable risk levels for both donors and recipients, according to two parallel surveys given to women’s health physicians and to the general public.

The results, presented at the annual meeting of the American Society for Reproductive Medicine (ASRM), showed that “the majority of gynecologists surveyed find uterine transplantation to be an acceptable and ethical option for patients with uterine factor infertility,” wrote Pietro Bortoletto, MD, and his coauthors.

Similarly, about two-thirds of the general public found uterine transplantation permissible and ethical, according to responses from an age- and gender-balanced nationally representative survey.

The web-based surveys were designed to assess the personal beliefs of both the public and of physicians about the permissibility of uterine transplantation, and to evaluate respondents’ concerns about perceived risks associated with the procedure. Respondents in each survey were also asked to identify any ethical concerns they might have; recipients of both surveys received background information about uterine transplantation.

Dr. Bortoletto and his colleagues sent the survey by email to physicians who were members of ASRM and AAGL. Of the 4,216 physicians who were invited to take the survey, 447 (28.4%) completed it, though results were tallied just for the 414 respondents who were United States–based physicians.

Physician respondents, when asked whether women should be allowed to donate or receive a transplanted uterus, responded mostly in the affirmative: 20% strongly agreed and 36% agreed, while 23% were neutral. The remainder disagreed or strongly disagreed.

The possibility of complications for the recipient was identified as the top concern by about 50% of physician respondents. Next most concerning was fetal outcomes, of primary concern for about 28%, followed by complications to the donor and cost, each of which was of primary concern to 10% or fewer of the physician respondents.

The risk to donors of uterine transplantation was seen as acceptable by 73.7% of AAGL members and 71.7% of ASRM members; just over half of each group saw the risk as acceptable for the recipients and the infants, however.

Though over half of physician respondents (57.9% of AAGL members and 59.5% of ASRM members) felt that uterine transplantation should be a potential treatment option for women with absolute uterine factor infertility, fewer felt it should be covered by health insurance – 35.4% of AAGL members and 40.5% of ASRM members held this opinion.

Among the general public, over three quarters (78%) felt that women should be allowed to undergo uterine transplantation. Slightly fewer (67%) respondents to the public survey felt that uterine transplantation is ethical; those who agreed had slightly higher incomes and education levels (relative risk, 1.11 and 1.09, respectively). A similar number (66%) felt that uterine transplantation was an acceptable alternative to using a gestational carrier.

As was the case for physicians, fewer members of the general public (45%) agreed that health insurance should cover the procedure; here, women and Hispanics were more likely to agree (relative risk, 1.11 and 1.18, respectively).

The results of the survey of the general public were presented by first author Eduardo Hariton, MD, a coauthor of Dr. Bortoletto’s in the study of physician survey results. Both Dr. Hariton and Dr. Bortoletto are resident physicians in the department of obstetrics, gynecology, and reproductive biology at Brigham and Women’s Hospital, Boston.

The public survey was sent to a nationally representative sample, balanced by gender and age. Of 1,444 individuals who were recruited to receive the survey, 1,337 completed it. Ninety respondents reported that they found in vitro fertilization unacceptable; these responses were excluded, Dr. Hariton said in an interview. “We wanted to get at uterine transplantation per se,” rather than assisted reproductive technology in general.

Placing the ethics of uterine transplantation in a broader context, Dr. Bortoletto said in an interview that the United States is one of just a few countries that permit gestational surrogacy, with regulations varying by state. To his knowledge, he said, Ukraine and Russia are the only other two nations that permit compensation for surrogacy. Greece and the United Kingdom permit altruistic surrogacy, while gestational surrogacy of any sort is forbidden in the European Union. Thus, in those nations, uterine transplantation will be the only option for women who wish to bear their biological children.

“I think the main takeaway is that for people who had hesitation about [uterine transplantation], it was mainly around safety,” and not ethical concerns, said Dr. Hariton. “I was a bit surprised, but also encouraged, by the degree of support.”

Neither Dr. Hariton nor Dr. Bortoletto reported any conflicts of interest. The public opinion study was funded by an Expanding the Boundaries grant.

[email protected]

Uterine transplantation is generally seen as ethical, with acceptable risk levels for both donors and recipients, according to two parallel surveys given to women’s health physicians and to the general public.

The results, presented at the annual meeting of the American Society for Reproductive Medicine (ASRM), showed that “the majority of gynecologists surveyed find uterine transplantation to be an acceptable and ethical option for patients with uterine factor infertility,” wrote Pietro Bortoletto, MD, and his coauthors.

Similarly, about two-thirds of the general public found uterine transplantation permissible and ethical, according to responses from an age- and gender-balanced nationally representative survey.

The web-based surveys were designed to assess the personal beliefs of both the public and of physicians about the permissibility of uterine transplantation, and to evaluate respondents’ concerns about perceived risks associated with the procedure. Respondents in each survey were also asked to identify any ethical concerns they might have; recipients of both surveys received background information about uterine transplantation.

Dr. Bortoletto and his colleagues sent the survey by email to physicians who were members of ASRM and AAGL. Of the 4,216 physicians who were invited to take the survey, 447 (28.4%) completed it, though results were tallied just for the 414 respondents who were United States–based physicians.

Physician respondents, when asked whether women should be allowed to donate or receive a transplanted uterus, responded mostly in the affirmative: 20% strongly agreed and 36% agreed, while 23% were neutral. The remainder disagreed or strongly disagreed.

The possibility of complications for the recipient was identified as the top concern by about 50% of physician respondents. Next most concerning was fetal outcomes, of primary concern for about 28%, followed by complications to the donor and cost, each of which was of primary concern to 10% or fewer of the physician respondents.

The risk to donors of uterine transplantation was seen as acceptable by 73.7% of AAGL members and 71.7% of ASRM members; just over half of each group saw the risk as acceptable for the recipients and the infants, however.

Though over half of physician respondents (57.9% of AAGL members and 59.5% of ASRM members) felt that uterine transplantation should be a potential treatment option for women with absolute uterine factor infertility, fewer felt it should be covered by health insurance – 35.4% of AAGL members and 40.5% of ASRM members held this opinion.

Among the general public, over three quarters (78%) felt that women should be allowed to undergo uterine transplantation. Slightly fewer (67%) respondents to the public survey felt that uterine transplantation is ethical; those who agreed had slightly higher incomes and education levels (relative risk, 1.11 and 1.09, respectively). A similar number (66%) felt that uterine transplantation was an acceptable alternative to using a gestational carrier.

As was the case for physicians, fewer members of the general public (45%) agreed that health insurance should cover the procedure; here, women and Hispanics were more likely to agree (relative risk, 1.11 and 1.18, respectively).

The results of the survey of the general public were presented by first author Eduardo Hariton, MD, a coauthor of Dr. Bortoletto’s in the study of physician survey results. Both Dr. Hariton and Dr. Bortoletto are resident physicians in the department of obstetrics, gynecology, and reproductive biology at Brigham and Women’s Hospital, Boston.

The public survey was sent to a nationally representative sample, balanced by gender and age. Of 1,444 individuals who were recruited to receive the survey, 1,337 completed it. Ninety respondents reported that they found in vitro fertilization unacceptable; these responses were excluded, Dr. Hariton said in an interview. “We wanted to get at uterine transplantation per se,” rather than assisted reproductive technology in general.

Placing the ethics of uterine transplantation in a broader context, Dr. Bortoletto said in an interview that the United States is one of just a few countries that permit gestational surrogacy, with regulations varying by state. To his knowledge, he said, Ukraine and Russia are the only other two nations that permit compensation for surrogacy. Greece and the United Kingdom permit altruistic surrogacy, while gestational surrogacy of any sort is forbidden in the European Union. Thus, in those nations, uterine transplantation will be the only option for women who wish to bear their biological children.

“I think the main takeaway is that for people who had hesitation about [uterine transplantation], it was mainly around safety,” and not ethical concerns, said Dr. Hariton. “I was a bit surprised, but also encouraged, by the degree of support.”

Neither Dr. Hariton nor Dr. Bortoletto reported any conflicts of interest. The public opinion study was funded by an Expanding the Boundaries grant.

[email protected]

The Food and Drug Administration has approved a premixed sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution (Clenpiq) for cleansing of the colon in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.

The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.

Sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.

Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.

To help your patients understand and prepare for a colonoscopy, use AGA’s patient education materials at http://www.gastro.org/patient-care/procedures/colonoscopy.

[email protected]

The Food and Drug Administration has approved a premixed sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution (Clenpiq) for cleansing of the colon in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.

The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.

Sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.

Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.

To help your patients understand and prepare for a colonoscopy, use AGA’s patient education materials at http://www.gastro.org/patient-care/procedures/colonoscopy.

[email protected]

The Food and Drug Administration has approved a premixed sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution (Clenpiq) for cleansing of the colon in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.

The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.

Sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.

Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.

To help your patients understand and prepare for a colonoscopy, use AGA’s patient education materials at http://www.gastro.org/patient-care/procedures/colonoscopy.

[email protected]

Take-Home Points

• Emergency physicians should be aware of radiological markers to avoid missing perilunate injuries.   
• They should have a low threshold to refer a suspected perilunate injury for urgent specialist assessment.
• Although majority of the injuries demonstrate the classical pattern, one should be aware of atypical injuries.
• The principles of early anatomic reduction and stable fixation remain the same.
• Salvage procedures are only indicated in extensive irreparable injuries.

Perilunate fracture-dislocations, rare injuries representing <10% of wrist injuries,¹ are part of a wide spectrum of high-energy trauma injuries. The typical mechanism of injury is a fall on a dorsiflexed and ulnar-deviated wrist with forces progressively traversing the scapholunate, lunocapitate, and lunotriquetral ligaments.²

In this article, we report a very unusual case of translunate, transradial, transtriquetral, transtrapezoid perilunate dislocation with multiple metacarpal neck fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A fit and healthy 30-year-old male software professional fell down stairs, landed on his nondominant right hand, and sustained a high-energy wrist injury. The patient also sustained a concussion, without focal neurologic deficit, and was unable to recall the exact mechanism of the wrist injury (there were no other witnesses). Radiographs of the right wrist in the emergency department showed only a nondisplaced fracture of the neck of the second, third, fourth, and fifth metacarpals and a nondisplaced fracture of the radial styloid. 

The next day, with the patient under general anesthesia, an attempt to reduce the perilunate dislocation by manipulation was unsuccessful. Open reduction and internal fixation (ORIF) were performed through a dorsal approach; the perilunate dislocation was reduced and stabilized with lunocapitate 1.2-mm Kirschner wire (K-wire). The scapholunate and lunotriquetral ligaments were found to be intact, and the significantly displaced triquetral fracture was treated with internal fixation involving 2 minifragment screws (Figure 6).

Discussion

Perilunate injuries are classified as lesser arc injuries (purely ligamentous) or greater arc injuries (osseoligamentous). Greater arc injuries involve fracture of one or more carpal bones with associated ligamentous injuries.³ The greater or lesser arc injuries described by Mayfield and colleagues² imply a specific pattern of force transmission with axial loading in a dorsiflexed and ulnar-deviated wrist with intercarpal supination. Graham⁴ introduced a concept of inferior arc injury with the forces passing through the radiocarpal joint with fracture of the radial styloid or juxta-articular margin. Similarly, lunate fracture in perilunate dislocations was explained by Bain and colleagues⁵ in the translunate arc concept in which forces pass through the lunate bone. A study involving a literature review of translunate perilunate dislocations noted associated transradial, trans-scaphoid, transcapitate, and transtriquetral fractures in order of decreasing frequency.⁶ To our knowledge, no case of translunate perilunate dislocation with multiple carpal and metacarpal fractures with radial styloid fracture has been reported in the literature.

Our patient’s associated multiple metacarpal neck fractures can be explained by the peculiar double-impact injury with initial axial loading across the hyperextended metacarpophalangeal joint, followed by axial loading across the hyperextended and ulnar-deviated wrist, causing greater arc perilunate fracture-dislocation. The mechanism of lunate injury in this case seems to be longitudinal impaction of the capitate shearing against the volar lunate in the axial plane causing a volar lip fracture (Teisen type I), and this may be accentuated by tension in the volar radiolunate ligament.^6,7 Associated triquetral fracture in perilunate dislocation is well described in the literature.⁶ However, the trapezoid fracture in our case implies a very atypical pattern of force transmission with the arc probably passing more distally through the trapezoid laterally and the triquetrum medially.

This case, which represents a very rare fracture pattern associated with perilunate dislocation, may have been caused by the variable position of the wrist and the pattern of load transmission at time of impact. Although the majority of cases demonstrate the classical pattern described in the literature, it may not be unusual to find atypical fracture patterns, especially those associated with high-energy trauma. 

Perilunate injuries have been missed in busy emergency departments and orthopedic practices. An estimated 25% of such injuries can be missed on initial presentation.⁸ In the present case, fracture of the radial styloid provided a clue to possible more complex carpal injuries involving the scaphoid, lunate, or scapholunate ligament, as Graham⁴ suggested with the concept of the “transverse pattern” of force transmission. In this case as well, the injury was initially missed, and its extent became evident only with CT. Therefore, emergency teams should have a very low threshold for suspecting and evaluating high-energy wrist injuries.

The goal in the treatment of perilunate dislocation with multiple carpal fractures is anatomical reduction and restoration of carpal alignment—which frequently require ORIF, though acute salvage procedures like proximal row carpectomy may be considered in irreparable fractures with extensive ligament injuries.⁹ For open reduction, the approach can be dorsal, volar, or a combination. The approach in our patient’s case was dorsal. His triquetral fracture, his only displaced fracture, was treated with internal fixation. All other fractures were nondisplaced, stable, and did not warrant internal fixation.

A high index of suspicion and urgent specialist consultation are essential in suspected perilunate injuries. The injury and fracture pattern may be atypical, but the principles of early anatomical reduction and stable fixation remain the same.

Take-Home Points

• Emergency physicians should be aware of radiological markers to avoid missing perilunate injuries.   
• They should have a low threshold to refer a suspected perilunate injury for urgent specialist assessment.
• Although majority of the injuries demonstrate the classical pattern, one should be aware of atypical injuries.
• The principles of early anatomic reduction and stable fixation remain the same.
• Salvage procedures are only indicated in extensive irreparable injuries.

Perilunate fracture-dislocations, rare injuries representing <10% of wrist injuries,¹ are part of a wide spectrum of high-energy trauma injuries. The typical mechanism of injury is a fall on a dorsiflexed and ulnar-deviated wrist with forces progressively traversing the scapholunate, lunocapitate, and lunotriquetral ligaments.²

In this article, we report a very unusual case of translunate, transradial, transtriquetral, transtrapezoid perilunate dislocation with multiple metacarpal neck fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A fit and healthy 30-year-old male software professional fell down stairs, landed on his nondominant right hand, and sustained a high-energy wrist injury. The patient also sustained a concussion, without focal neurologic deficit, and was unable to recall the exact mechanism of the wrist injury (there were no other witnesses). Radiographs of the right wrist in the emergency department showed only a nondisplaced fracture of the neck of the second, third, fourth, and fifth metacarpals and a nondisplaced fracture of the radial styloid. 

The next day, with the patient under general anesthesia, an attempt to reduce the perilunate dislocation by manipulation was unsuccessful. Open reduction and internal fixation (ORIF) were performed through a dorsal approach; the perilunate dislocation was reduced and stabilized with lunocapitate 1.2-mm Kirschner wire (K-wire). The scapholunate and lunotriquetral ligaments were found to be intact, and the significantly displaced triquetral fracture was treated with internal fixation involving 2 minifragment screws (Figure 6).

Discussion

Perilunate injuries are classified as lesser arc injuries (purely ligamentous) or greater arc injuries (osseoligamentous). Greater arc injuries involve fracture of one or more carpal bones with associated ligamentous injuries.³ The greater or lesser arc injuries described by Mayfield and colleagues² imply a specific pattern of force transmission with axial loading in a dorsiflexed and ulnar-deviated wrist with intercarpal supination. Graham⁴ introduced a concept of inferior arc injury with the forces passing through the radiocarpal joint with fracture of the radial styloid or juxta-articular margin. Similarly, lunate fracture in perilunate dislocations was explained by Bain and colleagues⁵ in the translunate arc concept in which forces pass through the lunate bone. A study involving a literature review of translunate perilunate dislocations noted associated transradial, trans-scaphoid, transcapitate, and transtriquetral fractures in order of decreasing frequency.⁶ To our knowledge, no case of translunate perilunate dislocation with multiple carpal and metacarpal fractures with radial styloid fracture has been reported in the literature.

Our patient’s associated multiple metacarpal neck fractures can be explained by the peculiar double-impact injury with initial axial loading across the hyperextended metacarpophalangeal joint, followed by axial loading across the hyperextended and ulnar-deviated wrist, causing greater arc perilunate fracture-dislocation. The mechanism of lunate injury in this case seems to be longitudinal impaction of the capitate shearing against the volar lunate in the axial plane causing a volar lip fracture (Teisen type I), and this may be accentuated by tension in the volar radiolunate ligament.^6,7 Associated triquetral fracture in perilunate dislocation is well described in the literature.⁶ However, the trapezoid fracture in our case implies a very atypical pattern of force transmission with the arc probably passing more distally through the trapezoid laterally and the triquetrum medially.

This case, which represents a very rare fracture pattern associated with perilunate dislocation, may have been caused by the variable position of the wrist and the pattern of load transmission at time of impact. Although the majority of cases demonstrate the classical pattern described in the literature, it may not be unusual to find atypical fracture patterns, especially those associated with high-energy trauma. 

Perilunate injuries have been missed in busy emergency departments and orthopedic practices. An estimated 25% of such injuries can be missed on initial presentation.⁸ In the present case, fracture of the radial styloid provided a clue to possible more complex carpal injuries involving the scaphoid, lunate, or scapholunate ligament, as Graham⁴ suggested with the concept of the “transverse pattern” of force transmission. In this case as well, the injury was initially missed, and its extent became evident only with CT. Therefore, emergency teams should have a very low threshold for suspecting and evaluating high-energy wrist injuries.

The goal in the treatment of perilunate dislocation with multiple carpal fractures is anatomical reduction and restoration of carpal alignment—which frequently require ORIF, though acute salvage procedures like proximal row carpectomy may be considered in irreparable fractures with extensive ligament injuries.⁹ For open reduction, the approach can be dorsal, volar, or a combination. The approach in our patient’s case was dorsal. His triquetral fracture, his only displaced fracture, was treated with internal fixation. All other fractures were nondisplaced, stable, and did not warrant internal fixation.

A high index of suspicion and urgent specialist consultation are essential in suspected perilunate injuries. The injury and fracture pattern may be atypical, but the principles of early anatomical reduction and stable fixation remain the same.

Take-Home Points

• Emergency physicians should be aware of radiological markers to avoid missing perilunate injuries.   
• They should have a low threshold to refer a suspected perilunate injury for urgent specialist assessment.
• Although majority of the injuries demonstrate the classical pattern, one should be aware of atypical injuries.
• The principles of early anatomic reduction and stable fixation remain the same.
• Salvage procedures are only indicated in extensive irreparable injuries.

Perilunate fracture-dislocations, rare injuries representing <10% of wrist injuries,¹ are part of a wide spectrum of high-energy trauma injuries. The typical mechanism of injury is a fall on a dorsiflexed and ulnar-deviated wrist with forces progressively traversing the scapholunate, lunocapitate, and lunotriquetral ligaments.²

In this article, we report a very unusual case of translunate, transradial, transtriquetral, transtrapezoid perilunate dislocation with multiple metacarpal neck fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A fit and healthy 30-year-old male software professional fell down stairs, landed on his nondominant right hand, and sustained a high-energy wrist injury. The patient also sustained a concussion, without focal neurologic deficit, and was unable to recall the exact mechanism of the wrist injury (there were no other witnesses). Radiographs of the right wrist in the emergency department showed only a nondisplaced fracture of the neck of the second, third, fourth, and fifth metacarpals and a nondisplaced fracture of the radial styloid. 

The next day, with the patient under general anesthesia, an attempt to reduce the perilunate dislocation by manipulation was unsuccessful. Open reduction and internal fixation (ORIF) were performed through a dorsal approach; the perilunate dislocation was reduced and stabilized with lunocapitate 1.2-mm Kirschner wire (K-wire). The scapholunate and lunotriquetral ligaments were found to be intact, and the significantly displaced triquetral fracture was treated with internal fixation involving 2 minifragment screws (Figure 6).

Discussion

Perilunate injuries are classified as lesser arc injuries (purely ligamentous) or greater arc injuries (osseoligamentous). Greater arc injuries involve fracture of one or more carpal bones with associated ligamentous injuries.³ The greater or lesser arc injuries described by Mayfield and colleagues² imply a specific pattern of force transmission with axial loading in a dorsiflexed and ulnar-deviated wrist with intercarpal supination. Graham⁴ introduced a concept of inferior arc injury with the forces passing through the radiocarpal joint with fracture of the radial styloid or juxta-articular margin. Similarly, lunate fracture in perilunate dislocations was explained by Bain and colleagues⁵ in the translunate arc concept in which forces pass through the lunate bone. A study involving a literature review of translunate perilunate dislocations noted associated transradial, trans-scaphoid, transcapitate, and transtriquetral fractures in order of decreasing frequency.⁶ To our knowledge, no case of translunate perilunate dislocation with multiple carpal and metacarpal fractures with radial styloid fracture has been reported in the literature.

Our patient’s associated multiple metacarpal neck fractures can be explained by the peculiar double-impact injury with initial axial loading across the hyperextended metacarpophalangeal joint, followed by axial loading across the hyperextended and ulnar-deviated wrist, causing greater arc perilunate fracture-dislocation. The mechanism of lunate injury in this case seems to be longitudinal impaction of the capitate shearing against the volar lunate in the axial plane causing a volar lip fracture (Teisen type I), and this may be accentuated by tension in the volar radiolunate ligament.^6,7 Associated triquetral fracture in perilunate dislocation is well described in the literature.⁶ However, the trapezoid fracture in our case implies a very atypical pattern of force transmission with the arc probably passing more distally through the trapezoid laterally and the triquetrum medially.

This case, which represents a very rare fracture pattern associated with perilunate dislocation, may have been caused by the variable position of the wrist and the pattern of load transmission at time of impact. Although the majority of cases demonstrate the classical pattern described in the literature, it may not be unusual to find atypical fracture patterns, especially those associated with high-energy trauma. 

Perilunate injuries have been missed in busy emergency departments and orthopedic practices. An estimated 25% of such injuries can be missed on initial presentation.⁸ In the present case, fracture of the radial styloid provided a clue to possible more complex carpal injuries involving the scaphoid, lunate, or scapholunate ligament, as Graham⁴ suggested with the concept of the “transverse pattern” of force transmission. In this case as well, the injury was initially missed, and its extent became evident only with CT. Therefore, emergency teams should have a very low threshold for suspecting and evaluating high-energy wrist injuries.

The goal in the treatment of perilunate dislocation with multiple carpal fractures is anatomical reduction and restoration of carpal alignment—which frequently require ORIF, though acute salvage procedures like proximal row carpectomy may be considered in irreparable fractures with extensive ligament injuries.⁹ For open reduction, the approach can be dorsal, volar, or a combination. The approach in our patient’s case was dorsal. His triquetral fracture, his only displaced fracture, was treated with internal fixation. All other fractures were nondisplaced, stable, and did not warrant internal fixation.

A high index of suspicion and urgent specialist consultation are essential in suspected perilunate injuries. The injury and fracture pattern may be atypical, but the principles of early anatomical reduction and stable fixation remain the same.

Complex atypical hyperplasia (CAH) of the endometrium is considered the precursor for endometrioid endometrial cancer, the most common gynecologic cancer in the United States. This disease is most frequently diagnosed by gynecologists who are evaluating symptoms of abnormal uterine bleeding in premenopausal women or in postmenopausal women who experience new bleeding. Medical therapies, typically progestin-based treatments, can be employed, particularly when fertility preservation is desired or among patients who are poor surgical candidates. However, the most definitive therapy remains surgery with total hysterectomy for two reasons: CAH is associated with a 28% risk for the development of invasive cancer, and occult invasive cancer frequently coexists with CAH.^1,2 This raises a question for gynecologists: Given the risk for occult endometrial cancer, should patients be referred to a gynecologic oncologist for their surgery?

What is the risk for cancer?

What is the significance of occult malignancy with CAH?

If surgeons are aware of endometrial cancer preoperatively or intraoperatively, decisions can be made about staging, particularly the need for lymphadenectomy. The virtues of staging in endometrial cancer is a controversial and frequently debated topic. No survival (therapeutic) benefit from lymphadenectomy has been observed in prospective trials when the information from staging results is not used to guide adjuvant therapy.⁴ However, the administration of adjuvant chemotherapy is associated with improved survival for patients with lymph node metastases.⁵ Therefore, if there is a benefit to staging with lymphadenectomy, it is its ability to identify patients who most need this life-saving systemic therapy.

Not all patients with endometrial cancer are at equal risk for harboring lymph node metastases and the majority may not benefit from lymphadenectomy. Patients with tumors that are deeply invasive, moderate or high grade, larger than 2 cm, or that have lymphovascular space invasion are at higher risk for lymph node metastases. Women with low grade, minimally invasive tumors that are smaller than 2 cm have extremely low risk for metastases.⁶ These criteria are commonly employed to stratify women at lowest risk and minimize unnecessary lymphadenectomy procedures. It should be noted that all three of these low risk features must be present to convey that negligible risk profile. The finding of a grade 1 invasive tumor alone is not enough to exclude potential lymph node metastases, particularly in the case of large or deeply invasive cancers.

How can the diagnosis be made preoperatively or intraoperatively?

The gold standard for discriminating between CAH and endometrial cancer is definitive surgical pathology. However, if surgeons wait until these results are available, they have lost the opportunity to stage the patient without subjecting them to a second surgery. The preoperative discovery of cancer may be increased by performing diagnostic curettage rather than relying on office endometrial biopsy sampling.⁷ This is likely due to the increased volume of tissue removed with dilation and curettage, and a reduction in the risk for sampling error. The addition of hysteroscopy to curettage does not improve upon the detection of cancer. Preoperative MRI to evaluate for depth of myometrial invasion has been described in cases of known endometrial cancer; however, its role in discriminating between CAH and invasive cancer is not well studied.

Intraoperative frozen section is commonly employed to evaluate the hysterectomy specimen for cancer in order to triage patients to staging during that same surgery. However, the accuracy of frozen section with definitive pathology is only approximately 50%.⁸ This means that at least half of women with CAH will have a false negative frozen section result and will have lost the opportunity for staging at the same procedure. The inaccuracy of frozen section is often overlooked by surgeons who may feel that it is a very straightforward diagnostic procedure. In reality, the characterization of CAH and invasive cancer is technically challenging and relies on multiple sectioning and significant experience in gynecologic pathology.⁹

Should all patients with CAH be referred and staged?

An alternative to relying on the frozen section process and its inherent inaccuracies would be to routinely stage all women with CAH, knowing that approximately 40% of them have occult cancer, and more than a third of those will have high risk features for lymph node metastases. However, due to the risks associated with lymphadenectomy, particularly lymphedema, most gynecologic oncologists do not routinely stage patients with preoperative CAH with complete lymphadenectomy.

An alternative to the all (complete lymphadenectomy) or none (hysterectomy alone) approach is to perform sentinel lymph node (SLN) biopsy for patients with CAH. SLN biopsy involves removing scant, but high yield lymphatic tissue, and has been shown to be extremely sensitive in detecting metastatic disease.¹⁰ This approach is commonly employed by surgeons in the treatment of ductal carcinoma in situ of the breast which, like CAH, is a stage 0 cancer that can be associated with invasive carcinoma on final pathology. In the case of ductal carcinoma in situ, the risk for upstaging is actually substantially lower (25%) than what is observed in CAH.¹¹ Therefore, it would seem even more compelling to apply this approach for endometrial pathologies. The ability to apply the SLN technique is lost after hysterectomy is performed, as there is no longer the target organ into which tracer can be injected; therefore, if SLN biopsy is to be offered to these patients, it needs to be performed using only the preoperative diagnosis of CAH. In this approach, there will be overtreatment of approximately two-thirds of patients, albeit with a less radical and morbid staging procedure.

Making the decision to refer

Ultimately, decisions to refer or not are guided by comprehensive discussions between patient and provider that outline the potential risks and benefits of various approaches. Patients frequently have strong relationships with confidence in their gynecologists who may have cared for them for many years, and may be motivated to have them perform their surgery. For others, the uncertainty and possibility of an unstaged cancer and the potential of a second surgery drives their decision to seek an oncology consultation. Clinicians should discuss the inherent uncertainties in the diagnosis of CAH and the potential for underlying cancer and lymph node metastases, and help patients determine the balance of their underlying competing concerns regarding the risk for inadequate surgery versus the risk of unnecessary surgical procedures.

Summary of recommendations

Invasive endometrial cancer will be identified in the hysterectomy specimens of approximately 40% of women with a preoperative diagnosis of complex endometrial hyperplasia. Preoperative dilation and curettage may reduce the potential for missed occult cancer. Frozen section is an option for determining which patients might benefit from staging but is associated with significant inaccuracies. Failure to diagnose malignancy pre- or intraoperatively handicaps postoperative decision making regarding the necessity of adjuvant chemotherapy, and prevents the ability to offer patients potentially less morbid staging techniques such as SLN biopsy. When gynecologists without oncology training perform these hysterectomies, they should discuss these scenarios to patients and consider referral to gynecologic oncology for patients who desire the potential for comprehensive staging if necessary.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. She reports no relevant financial disclosures.

References

1. J Clin Oncol. 2010 Feb;28:788-92.

2. Cancer. 2006 Feb;106:812-9.

3. Int J Gynecol Cancer. 2005 Jan-Feb;15:127-31.

4. Lancet. 2009 Jan;373(9658):125-36.

5. J Clin Oncol. 2006 Jan;24:36-44.

6. Gynecol Oncol 2008 Apr;109:11-8.

7. Am J Obstet Gynecol. 2010 Oct;203(4):349. e1-6.

8. Am J Obstet Gynecol. 2007 May;196(5):e40-2.

9. Obstet Gynecol. 2012 Nov;120(5):1160-75.

10. Lancet Oncol. 2017 Mar;18(3):384-92.

11. Radiology. 2011 Jul;260:119-28.

Complex atypical hyperplasia (CAH) of the endometrium is considered the precursor for endometrioid endometrial cancer, the most common gynecologic cancer in the United States. This disease is most frequently diagnosed by gynecologists who are evaluating symptoms of abnormal uterine bleeding in premenopausal women or in postmenopausal women who experience new bleeding. Medical therapies, typically progestin-based treatments, can be employed, particularly when fertility preservation is desired or among patients who are poor surgical candidates. However, the most definitive therapy remains surgery with total hysterectomy for two reasons: CAH is associated with a 28% risk for the development of invasive cancer, and occult invasive cancer frequently coexists with CAH.^1,2 This raises a question for gynecologists: Given the risk for occult endometrial cancer, should patients be referred to a gynecologic oncologist for their surgery?

What is the risk for cancer?

What is the significance of occult malignancy with CAH?

If surgeons are aware of endometrial cancer preoperatively or intraoperatively, decisions can be made about staging, particularly the need for lymphadenectomy. The virtues of staging in endometrial cancer is a controversial and frequently debated topic. No survival (therapeutic) benefit from lymphadenectomy has been observed in prospective trials when the information from staging results is not used to guide adjuvant therapy.⁴ However, the administration of adjuvant chemotherapy is associated with improved survival for patients with lymph node metastases.⁵ Therefore, if there is a benefit to staging with lymphadenectomy, it is its ability to identify patients who most need this life-saving systemic therapy.

Not all patients with endometrial cancer are at equal risk for harboring lymph node metastases and the majority may not benefit from lymphadenectomy. Patients with tumors that are deeply invasive, moderate or high grade, larger than 2 cm, or that have lymphovascular space invasion are at higher risk for lymph node metastases. Women with low grade, minimally invasive tumors that are smaller than 2 cm have extremely low risk for metastases.⁶ These criteria are commonly employed to stratify women at lowest risk and minimize unnecessary lymphadenectomy procedures. It should be noted that all three of these low risk features must be present to convey that negligible risk profile. The finding of a grade 1 invasive tumor alone is not enough to exclude potential lymph node metastases, particularly in the case of large or deeply invasive cancers.

How can the diagnosis be made preoperatively or intraoperatively?

The gold standard for discriminating between CAH and endometrial cancer is definitive surgical pathology. However, if surgeons wait until these results are available, they have lost the opportunity to stage the patient without subjecting them to a second surgery. The preoperative discovery of cancer may be increased by performing diagnostic curettage rather than relying on office endometrial biopsy sampling.⁷ This is likely due to the increased volume of tissue removed with dilation and curettage, and a reduction in the risk for sampling error. The addition of hysteroscopy to curettage does not improve upon the detection of cancer. Preoperative MRI to evaluate for depth of myometrial invasion has been described in cases of known endometrial cancer; however, its role in discriminating between CAH and invasive cancer is not well studied.

Intraoperative frozen section is commonly employed to evaluate the hysterectomy specimen for cancer in order to triage patients to staging during that same surgery. However, the accuracy of frozen section with definitive pathology is only approximately 50%.⁸ This means that at least half of women with CAH will have a false negative frozen section result and will have lost the opportunity for staging at the same procedure. The inaccuracy of frozen section is often overlooked by surgeons who may feel that it is a very straightforward diagnostic procedure. In reality, the characterization of CAH and invasive cancer is technically challenging and relies on multiple sectioning and significant experience in gynecologic pathology.⁹

Should all patients with CAH be referred and staged?

An alternative to relying on the frozen section process and its inherent inaccuracies would be to routinely stage all women with CAH, knowing that approximately 40% of them have occult cancer, and more than a third of those will have high risk features for lymph node metastases. However, due to the risks associated with lymphadenectomy, particularly lymphedema, most gynecologic oncologists do not routinely stage patients with preoperative CAH with complete lymphadenectomy.

An alternative to the all (complete lymphadenectomy) or none (hysterectomy alone) approach is to perform sentinel lymph node (SLN) biopsy for patients with CAH. SLN biopsy involves removing scant, but high yield lymphatic tissue, and has been shown to be extremely sensitive in detecting metastatic disease.¹⁰ This approach is commonly employed by surgeons in the treatment of ductal carcinoma in situ of the breast which, like CAH, is a stage 0 cancer that can be associated with invasive carcinoma on final pathology. In the case of ductal carcinoma in situ, the risk for upstaging is actually substantially lower (25%) than what is observed in CAH.¹¹ Therefore, it would seem even more compelling to apply this approach for endometrial pathologies. The ability to apply the SLN technique is lost after hysterectomy is performed, as there is no longer the target organ into which tracer can be injected; therefore, if SLN biopsy is to be offered to these patients, it needs to be performed using only the preoperative diagnosis of CAH. In this approach, there will be overtreatment of approximately two-thirds of patients, albeit with a less radical and morbid staging procedure.

Making the decision to refer

Ultimately, decisions to refer or not are guided by comprehensive discussions between patient and provider that outline the potential risks and benefits of various approaches. Patients frequently have strong relationships with confidence in their gynecologists who may have cared for them for many years, and may be motivated to have them perform their surgery. For others, the uncertainty and possibility of an unstaged cancer and the potential of a second surgery drives their decision to seek an oncology consultation. Clinicians should discuss the inherent uncertainties in the diagnosis of CAH and the potential for underlying cancer and lymph node metastases, and help patients determine the balance of their underlying competing concerns regarding the risk for inadequate surgery versus the risk of unnecessary surgical procedures.

Summary of recommendations

Invasive endometrial cancer will be identified in the hysterectomy specimens of approximately 40% of women with a preoperative diagnosis of complex endometrial hyperplasia. Preoperative dilation and curettage may reduce the potential for missed occult cancer. Frozen section is an option for determining which patients might benefit from staging but is associated with significant inaccuracies. Failure to diagnose malignancy pre- or intraoperatively handicaps postoperative decision making regarding the necessity of adjuvant chemotherapy, and prevents the ability to offer patients potentially less morbid staging techniques such as SLN biopsy. When gynecologists without oncology training perform these hysterectomies, they should discuss these scenarios to patients and consider referral to gynecologic oncology for patients who desire the potential for comprehensive staging if necessary.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. She reports no relevant financial disclosures.

References

1. J Clin Oncol. 2010 Feb;28:788-92.

2. Cancer. 2006 Feb;106:812-9.

3. Int J Gynecol Cancer. 2005 Jan-Feb;15:127-31.

4. Lancet. 2009 Jan;373(9658):125-36.

5. J Clin Oncol. 2006 Jan;24:36-44.

6. Gynecol Oncol 2008 Apr;109:11-8.

7. Am J Obstet Gynecol. 2010 Oct;203(4):349. e1-6.

8. Am J Obstet Gynecol. 2007 May;196(5):e40-2.

9. Obstet Gynecol. 2012 Nov;120(5):1160-75.

10. Lancet Oncol. 2017 Mar;18(3):384-92.

11. Radiology. 2011 Jul;260:119-28.

Complex atypical hyperplasia (CAH) of the endometrium is considered the precursor for endometrioid endometrial cancer, the most common gynecologic cancer in the United States. This disease is most frequently diagnosed by gynecologists who are evaluating symptoms of abnormal uterine bleeding in premenopausal women or in postmenopausal women who experience new bleeding. Medical therapies, typically progestin-based treatments, can be employed, particularly when fertility preservation is desired or among patients who are poor surgical candidates. However, the most definitive therapy remains surgery with total hysterectomy for two reasons: CAH is associated with a 28% risk for the development of invasive cancer, and occult invasive cancer frequently coexists with CAH.^1,2 This raises a question for gynecologists: Given the risk for occult endometrial cancer, should patients be referred to a gynecologic oncologist for their surgery?

What is the risk for cancer?

What is the significance of occult malignancy with CAH?

If surgeons are aware of endometrial cancer preoperatively or intraoperatively, decisions can be made about staging, particularly the need for lymphadenectomy. The virtues of staging in endometrial cancer is a controversial and frequently debated topic. No survival (therapeutic) benefit from lymphadenectomy has been observed in prospective trials when the information from staging results is not used to guide adjuvant therapy.⁴ However, the administration of adjuvant chemotherapy is associated with improved survival for patients with lymph node metastases.⁵ Therefore, if there is a benefit to staging with lymphadenectomy, it is its ability to identify patients who most need this life-saving systemic therapy.

Not all patients with endometrial cancer are at equal risk for harboring lymph node metastases and the majority may not benefit from lymphadenectomy. Patients with tumors that are deeply invasive, moderate or high grade, larger than 2 cm, or that have lymphovascular space invasion are at higher risk for lymph node metastases. Women with low grade, minimally invasive tumors that are smaller than 2 cm have extremely low risk for metastases.⁶ These criteria are commonly employed to stratify women at lowest risk and minimize unnecessary lymphadenectomy procedures. It should be noted that all three of these low risk features must be present to convey that negligible risk profile. The finding of a grade 1 invasive tumor alone is not enough to exclude potential lymph node metastases, particularly in the case of large or deeply invasive cancers.

How can the diagnosis be made preoperatively or intraoperatively?

The gold standard for discriminating between CAH and endometrial cancer is definitive surgical pathology. However, if surgeons wait until these results are available, they have lost the opportunity to stage the patient without subjecting them to a second surgery. The preoperative discovery of cancer may be increased by performing diagnostic curettage rather than relying on office endometrial biopsy sampling.⁷ This is likely due to the increased volume of tissue removed with dilation and curettage, and a reduction in the risk for sampling error. The addition of hysteroscopy to curettage does not improve upon the detection of cancer. Preoperative MRI to evaluate for depth of myometrial invasion has been described in cases of known endometrial cancer; however, its role in discriminating between CAH and invasive cancer is not well studied.

Intraoperative frozen section is commonly employed to evaluate the hysterectomy specimen for cancer in order to triage patients to staging during that same surgery. However, the accuracy of frozen section with definitive pathology is only approximately 50%.⁸ This means that at least half of women with CAH will have a false negative frozen section result and will have lost the opportunity for staging at the same procedure. The inaccuracy of frozen section is often overlooked by surgeons who may feel that it is a very straightforward diagnostic procedure. In reality, the characterization of CAH and invasive cancer is technically challenging and relies on multiple sectioning and significant experience in gynecologic pathology.⁹

Should all patients with CAH be referred and staged?

An alternative to relying on the frozen section process and its inherent inaccuracies would be to routinely stage all women with CAH, knowing that approximately 40% of them have occult cancer, and more than a third of those will have high risk features for lymph node metastases. However, due to the risks associated with lymphadenectomy, particularly lymphedema, most gynecologic oncologists do not routinely stage patients with preoperative CAH with complete lymphadenectomy.

An alternative to the all (complete lymphadenectomy) or none (hysterectomy alone) approach is to perform sentinel lymph node (SLN) biopsy for patients with CAH. SLN biopsy involves removing scant, but high yield lymphatic tissue, and has been shown to be extremely sensitive in detecting metastatic disease.¹⁰ This approach is commonly employed by surgeons in the treatment of ductal carcinoma in situ of the breast which, like CAH, is a stage 0 cancer that can be associated with invasive carcinoma on final pathology. In the case of ductal carcinoma in situ, the risk for upstaging is actually substantially lower (25%) than what is observed in CAH.¹¹ Therefore, it would seem even more compelling to apply this approach for endometrial pathologies. The ability to apply the SLN technique is lost after hysterectomy is performed, as there is no longer the target organ into which tracer can be injected; therefore, if SLN biopsy is to be offered to these patients, it needs to be performed using only the preoperative diagnosis of CAH. In this approach, there will be overtreatment of approximately two-thirds of patients, albeit with a less radical and morbid staging procedure.

Making the decision to refer

Ultimately, decisions to refer or not are guided by comprehensive discussions between patient and provider that outline the potential risks and benefits of various approaches. Patients frequently have strong relationships with confidence in their gynecologists who may have cared for them for many years, and may be motivated to have them perform their surgery. For others, the uncertainty and possibility of an unstaged cancer and the potential of a second surgery drives their decision to seek an oncology consultation. Clinicians should discuss the inherent uncertainties in the diagnosis of CAH and the potential for underlying cancer and lymph node metastases, and help patients determine the balance of their underlying competing concerns regarding the risk for inadequate surgery versus the risk of unnecessary surgical procedures.

Summary of recommendations

Invasive endometrial cancer will be identified in the hysterectomy specimens of approximately 40% of women with a preoperative diagnosis of complex endometrial hyperplasia. Preoperative dilation and curettage may reduce the potential for missed occult cancer. Frozen section is an option for determining which patients might benefit from staging but is associated with significant inaccuracies. Failure to diagnose malignancy pre- or intraoperatively handicaps postoperative decision making regarding the necessity of adjuvant chemotherapy, and prevents the ability to offer patients potentially less morbid staging techniques such as SLN biopsy. When gynecologists without oncology training perform these hysterectomies, they should discuss these scenarios to patients and consider referral to gynecologic oncology for patients who desire the potential for comprehensive staging if necessary.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. She reports no relevant financial disclosures.

References

1. J Clin Oncol. 2010 Feb;28:788-92.

2. Cancer. 2006 Feb;106:812-9.

3. Int J Gynecol Cancer. 2005 Jan-Feb;15:127-31.

4. Lancet. 2009 Jan;373(9658):125-36.

5. J Clin Oncol. 2006 Jan;24:36-44.

6. Gynecol Oncol 2008 Apr;109:11-8.

7. Am J Obstet Gynecol. 2010 Oct;203(4):349. e1-6.

8. Am J Obstet Gynecol. 2007 May;196(5):e40-2.

9. Obstet Gynecol. 2012 Nov;120(5):1160-75.

10. Lancet Oncol. 2017 Mar;18(3):384-92.

11. Radiology. 2011 Jul;260:119-28.

In a recent article, the New York Times publicly exposed behavior that can only be described as appalling: Some dermatologists have been using unsupervised physician assistants (PAs) and nurse practitioners (NPs) to perform dermatology services on patients, including frail nursing home patients, many with dementia or other similar cognitive impairments, to increase their profits.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

In a recent article, the New York Times publicly exposed behavior that can only be described as appalling: Some dermatologists have been using unsupervised physician assistants (PAs) and nurse practitioners (NPs) to perform dermatology services on patients, including frail nursing home patients, many with dementia or other similar cognitive impairments, to increase their profits.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

In a recent article, the New York Times publicly exposed behavior that can only be described as appalling: Some dermatologists have been using unsupervised physician assistants (PAs) and nurse practitioners (NPs) to perform dermatology services on patients, including frail nursing home patients, many with dementia or other similar cognitive impairments, to increase their profits.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

The severity of acne has a substantial negative impact on patients’ self-esteem in different age groups and cultures, with the greatest impact on women and in those with more severe acne, according to the authors of a review of studies that evaluated self-esteem in patients with acne.

Dermatologists Stephanie M. Gallitano, MD, of Columbia University, and Diane S. Berson, MD, of Cornell University, both in New York City, conducted a literature search of studies using the terms “acne vulgaris” and “self-esteem.” They identified 13 studies in 11 countries, including India, Singapore, Brazil, Greece, the United Kingdom, Egypt, South Korea, and Australia.

In the review, published in the International Journal of Women’s Dermatology, they wrote that most of the study authors determined that women with acne were more likely to have a greater degree of feelings that involved self-consciousness, lower self-esteem, and self-worth. In four studies, though, “men and women were equally affected by their disease,” and in one study in Egypt, self-esteem was significantly lower in males with acne than in women with acne, they wrote.

In all the studies, “self-esteem became lower as severity of acne increased,” they observed. There was evidence that subjective perceptions of acne severity affected self-esteem, with a few studies associating subjective evaluations of acne severity, but not objective evaluations, with lower self-esteem. They included a study of 550 students in Turkey, which found “a significant relationship between subjective acne severity and self-esteem but no relationship between objective acne severity and self-esteem.”

Most – between 70% and 80% – of patients used self-prescribed treatments, and 5% to almost 30% had seen a dermatologist. But patients with more severe acne were more likely to have seen a dermatologist, with 61% of those with moderate to severe acne having seen a dermatologist in a Greek study, for example. In addition, in an adult study and in an adolescent study, patients who felt that they had benefited from treatment also had improved self-esteem, improved quality of life, and less anxiety compared with those who did not feel they had benefited from treatment, the authors wrote.

Their review shows that acne “has a substantial negative impact on patients’ self-esteem” and that more severe acne and acne in women “tend to have the greatest impact across cultures,” they concluded.

Read the full study in the International Journal of Women’s Dermatology.

[email protected]

SOURCE: Gallitano S.M, et al. Int J Womens Dermatol 2017 Oct. doi: 10.1016/j.ijwd.2017.10.004

The severity of acne has a substantial negative impact on patients’ self-esteem in different age groups and cultures, with the greatest impact on women and in those with more severe acne, according to the authors of a review of studies that evaluated self-esteem in patients with acne.

Dermatologists Stephanie M. Gallitano, MD, of Columbia University, and Diane S. Berson, MD, of Cornell University, both in New York City, conducted a literature search of studies using the terms “acne vulgaris” and “self-esteem.” They identified 13 studies in 11 countries, including India, Singapore, Brazil, Greece, the United Kingdom, Egypt, South Korea, and Australia.

In the review, published in the International Journal of Women’s Dermatology, they wrote that most of the study authors determined that women with acne were more likely to have a greater degree of feelings that involved self-consciousness, lower self-esteem, and self-worth. In four studies, though, “men and women were equally affected by their disease,” and in one study in Egypt, self-esteem was significantly lower in males with acne than in women with acne, they wrote.

In all the studies, “self-esteem became lower as severity of acne increased,” they observed. There was evidence that subjective perceptions of acne severity affected self-esteem, with a few studies associating subjective evaluations of acne severity, but not objective evaluations, with lower self-esteem. They included a study of 550 students in Turkey, which found “a significant relationship between subjective acne severity and self-esteem but no relationship between objective acne severity and self-esteem.”

Most – between 70% and 80% – of patients used self-prescribed treatments, and 5% to almost 30% had seen a dermatologist. But patients with more severe acne were more likely to have seen a dermatologist, with 61% of those with moderate to severe acne having seen a dermatologist in a Greek study, for example. In addition, in an adult study and in an adolescent study, patients who felt that they had benefited from treatment also had improved self-esteem, improved quality of life, and less anxiety compared with those who did not feel they had benefited from treatment, the authors wrote.

Their review shows that acne “has a substantial negative impact on patients’ self-esteem” and that more severe acne and acne in women “tend to have the greatest impact across cultures,” they concluded.

Read the full study in the International Journal of Women’s Dermatology.

[email protected]

SOURCE: Gallitano S.M, et al. Int J Womens Dermatol 2017 Oct. doi: 10.1016/j.ijwd.2017.10.004

The severity of acne has a substantial negative impact on patients’ self-esteem in different age groups and cultures, with the greatest impact on women and in those with more severe acne, according to the authors of a review of studies that evaluated self-esteem in patients with acne.

Dermatologists Stephanie M. Gallitano, MD, of Columbia University, and Diane S. Berson, MD, of Cornell University, both in New York City, conducted a literature search of studies using the terms “acne vulgaris” and “self-esteem.” They identified 13 studies in 11 countries, including India, Singapore, Brazil, Greece, the United Kingdom, Egypt, South Korea, and Australia.

In the review, published in the International Journal of Women’s Dermatology, they wrote that most of the study authors determined that women with acne were more likely to have a greater degree of feelings that involved self-consciousness, lower self-esteem, and self-worth. In four studies, though, “men and women were equally affected by their disease,” and in one study in Egypt, self-esteem was significantly lower in males with acne than in women with acne, they wrote.

In all the studies, “self-esteem became lower as severity of acne increased,” they observed. There was evidence that subjective perceptions of acne severity affected self-esteem, with a few studies associating subjective evaluations of acne severity, but not objective evaluations, with lower self-esteem. They included a study of 550 students in Turkey, which found “a significant relationship between subjective acne severity and self-esteem but no relationship between objective acne severity and self-esteem.”

Most – between 70% and 80% – of patients used self-prescribed treatments, and 5% to almost 30% had seen a dermatologist. But patients with more severe acne were more likely to have seen a dermatologist, with 61% of those with moderate to severe acne having seen a dermatologist in a Greek study, for example. In addition, in an adult study and in an adolescent study, patients who felt that they had benefited from treatment also had improved self-esteem, improved quality of life, and less anxiety compared with those who did not feel they had benefited from treatment, the authors wrote.

Their review shows that acne “has a substantial negative impact on patients’ self-esteem” and that more severe acne and acne in women “tend to have the greatest impact across cultures,” they concluded.

Read the full study in the International Journal of Women’s Dermatology.

[email protected]

SOURCE: Gallitano S.M, et al. Int J Womens Dermatol 2017 Oct. doi: 10.1016/j.ijwd.2017.10.004

ATLANTA – A novel chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen showed promising efficacy with a manageable adverse event profile in heavily pretreated patients with relapsed/refractory multiple myeloma in the CRB-410 multicenter phase 1 dose escalation trial.

The product, known as bb2121, received breakthrough therapy designation from the Food and Drug Administration in November 2017 based on preliminary data from the ongoing trial. Those data showed that as of May 2017, the overall response rate at 1 month in 18 evaluable patients was 89%, whereas the response in those who received active dosing (150 x 10⁶ CAR+ T cells or higher) was 100%.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Berdeja J et al. ASH 2017 Abstract 740.

ATLANTA – A novel chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen showed promising efficacy with a manageable adverse event profile in heavily pretreated patients with relapsed/refractory multiple myeloma in the CRB-410 multicenter phase 1 dose escalation trial.

The product, known as bb2121, received breakthrough therapy designation from the Food and Drug Administration in November 2017 based on preliminary data from the ongoing trial. Those data showed that as of May 2017, the overall response rate at 1 month in 18 evaluable patients was 89%, whereas the response in those who received active dosing (150 x 10⁶ CAR+ T cells or higher) was 100%.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Berdeja J et al. ASH 2017 Abstract 740.

ATLANTA – A novel chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen showed promising efficacy with a manageable adverse event profile in heavily pretreated patients with relapsed/refractory multiple myeloma in the CRB-410 multicenter phase 1 dose escalation trial.

The product, known as bb2121, received breakthrough therapy designation from the Food and Drug Administration in November 2017 based on preliminary data from the ongoing trial. Those data showed that as of May 2017, the overall response rate at 1 month in 18 evaluable patients was 89%, whereas the response in those who received active dosing (150 x 10⁶ CAR+ T cells or higher) was 100%.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Berdeja J et al. ASH 2017 Abstract 740.

State spending on Medicaid in fiscal 2017 was up 6.1% over 2016, and the program’s share of state budgets increased for the fifth year in a row, according to the National Association of State Budget Officers.

Total spending by the states on Medicaid benefits for more than 74 million individuals was an estimated $574 billion in 2017, which represented 29% of all expenditures. That compares with 28.7% in 2016 and 23.6% in 2012 – the last year that Medicaid’s share of state spending decreased, NASBO said in its annual State Expenditure Report.

[email protected]

State spending on Medicaid in fiscal 2017 was up 6.1% over 2016, and the program’s share of state budgets increased for the fifth year in a row, according to the National Association of State Budget Officers.

Total spending by the states on Medicaid benefits for more than 74 million individuals was an estimated $574 billion in 2017, which represented 29% of all expenditures. That compares with 28.7% in 2016 and 23.6% in 2012 – the last year that Medicaid’s share of state spending decreased, NASBO said in its annual State Expenditure Report.

[email protected]

State spending on Medicaid in fiscal 2017 was up 6.1% over 2016, and the program’s share of state budgets increased for the fifth year in a row, according to the National Association of State Budget Officers.

Total spending by the states on Medicaid benefits for more than 74 million individuals was an estimated $574 billion in 2017, which represented 29% of all expenditures. That compares with 28.7% in 2016 and 23.6% in 2012 – the last year that Medicaid’s share of state spending decreased, NASBO said in its annual State Expenditure Report.

[email protected]