Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

cpalmer@mdedge.com

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

rfranki@mdedge.com

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

rfranki@mdedge.com

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

rfranki@mdedge.com

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

klennon@mdedge.com

Over the past year, major strides have been made in the treatment of gynecologic malignancies. In this Update, we highlight 3 notable studies. The first is a phase 3, multicenter, international, randomized clinical trial that demonstrated a significant improvement in both overall and failure-free survival with the use of adjuvant chemoradiation versus radiotherapy alone in patients with stage III or high-risk uterine cancer. Additionally, we describe the results of 2 phase 3, multicenter, international, randomized clinical trials in ovarian cancer treatment: use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in combination with platinum and taxane-based chemotherapy followed by the PARP inhibitor as maintenance therapy, and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian cancer.

We provide a brief overview of current treatment strategies, summarize the key findings of these trials, and establish how these findings have changed our management of these gynecologic malignancies.

Adjuvant chemotherapy and radiotherapy improves survival in women with high-risk endometrial cancer 

de Boer SM, Powell ME, Mileshkin L, et al; on behalf of the PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019;1273-1285. 

In the United States, it is estimated that more than 61,000 women were diagnosed with endometrial cancer in 2019.¹ Women with endometrial cancer usually have a favorable prognosis; more than 65% are diagnosed with early-stage disease, which is associated with a 95% 5-year survival rate.¹ However, 15% to 20% of patients have disease with high-risk features, including advanced stage (stage II-IV), high tumor grade, lymphovascular space invasion, deep myometrial invasion, or nonendometrioid histologic subtypes (serous or clear cell).² The presence of these high-risk disease features is associated with an increased incidence of distant metastases and cancer-related death. 

Adjuvant therapy in high-risk endometrial cancer 

To date, the optimal adjuvant therapy for patients with high-risk endometrial cancer remains controversial. Prior data from Gynecologic Oncology Group (GOG) protocol 122 demonstrated that chemotherapy significantly improved progression-free survival and overall survival when compared with radiotherapy in patients with advanced-stage endometrial cancer.³ As such, chemotherapy now is frequently used in this population, often in combination with radiation, although data describing the benefit of chemoradiation are limited.⁴ For women with earlier-stage disease with high-risk features, the value of chemotherapy plus radiation is uncertain.^5,6 

Continue to: Benefit observed with adjuvant chemoradiotherapy...

Benefit observed with adjuvant chemoradiotherapy 

In a multicenter, international, randomized phase 3 trial, known as the PORTEC-3 trial, de Boer and colleagues sought to determine if combined adjuvant chemoradiation improved overall survival (OS) and failure-free survival when compared with external-beam radiation therapy (EBRT) alone in the treatment of women with high-risk endometrial cancer.⁷ Women were eligible for the study if they had histologically confirmed stage I, grade 3 endometrioid endometrial cancer with deep invasion and/or lymphovascular space invasion, stage II or III disease, or stage I-III disease with serous or clear cell histology. 

Participants were randomly assigned in a 1:1 ratio; 330 women received adjuvant EBRT alone (total dose of 48.6 Gy administered in 27 fractions), and 330 received adjuvant chemotherapy during and after radiation therapy (CTRT) (2 cycles of cisplatin 50 mg/m² IV given on days 1 and 22 of EBRT followed by 4 cycles of carboplatin AUC 5 and paclitaxel 175 mg/m² IV every 3 weeks). 

At a median follow-up of 73 months, treatment with adjuvant CTRT, compared with adjuvant EBRT alone, was associated with a significant improvement in both overall survival (5-year OS: 81.4% vs 76.1%, P = .034 [FIGURE]) and failure-free survival (5-year failure-free survival: 76.5% vs 69.1%, P = .016). 

The greatest absolute benefit of adjuvant CTRT, compared with EBRT alone, in survival was among women with stage III endometrial cancer (5-year OS: 78.5% vs 68.5%, P = .043) or serous cancers (19% absolute improvement in 5-year OS), or both. Significant differences in 5-year OS and failure-free survival in women with stage I-II cancer were not observed with adjuvant CTRT when compared with adjuvant EBRT alone. At 5 years, significantly more adverse events of grade 2 or worse were reported in the adjuvant CTRT arm. 

Results from similar trials 

Since the publication of results from the updated analysis of PORTEC-3, results from 2 pertinent trials have been published.^8,9 In the GOG 249 trial, women with stage I-II endometrial cancer with high-risk features were randomly assigned to receive 3 cycles of carboplatin-paclitaxel chemotherapy with vaginal brachytherapy or EBRT.⁸ There was no difference in survival, but a significant increase in both pelvic and para-aortic recurrences were seen after the combination of chemotherapy and vaginal brachytherapy.⁸ 

In GOG 258, women with stage III-IVA endometrial cancer were randomly assigned to receive chemotherapy alone (carboplatin-paclitaxel) or adjuvant chemotherapy after EBRT.⁹ No differences in recurrence-free or overall survival were noted, but there was a significant increase in the number of vaginal and pelvic or para-aortic recurrences in patients in the chemotherapy-only arm.⁹

Role for PARP inhibitor plus first-line chemotherapy, and as maintenance therapy, in ovarian cancer treatment 

Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403-2415. 

Ovarian cancer is the leading cause of gynecologic cancer-related deaths among women in the United States.¹⁰ Treatment consists of cytoreductive surgery combined with platinum and taxane-based chemotherapy.¹¹ Despite favorable initial responses, more than 80% of patients experience a recurrence, with an 18-month median time to progression.¹² As a result, recent efforts have focused on finding novel therapeutic approaches to improve treatment outcomes and mitigate the risk of disease recurrence. 

Continue to: PARP inhibitors are changing the face of treatment...

PARP inhibitors are changing the face of treatment 

Poly(adenosine diphosphate-ribose) polymerases (PARPs) are a family of enzymes that play a critical role in DNA damage repair. These enzymes promote DNA repair by recruiting proteins involved in repairing single-strand and double-strand DNA breaks and in protecting and restarting stalled DNA replication forks.¹³ The predominant mechanisms of action of PARP inhibitors in cells with homologous-recombination deficiency (HRD) include inhibiting repair of single-strand DNA breaks and trapping PARP-DNA complexes at stalled DNA replication forks.¹⁴ 

Germline or somatic BRCA1/2 mutations and genetic alterations resulting in HRD are present in about 20% and 30% of ovarian carcinomas, respectively, and increase the susceptibility of tumors to platinum-based agents and PARP inhibitors.^15,16 Based on multiple clinical trials that demonstrated the efficacy of single-agent PARP in the treatment of recurrent ovarian carcinoma and as maintenance therapy after an initial response to platinum-based therapy, the US Food and Drug Administration approved olaparib, niraparib, and rucaparib for the treatment of high-grade epithelial ovarian cancer.^17-19 Only olaparib is approved for maintenance therapy after initial adjuvant therapy in patients with BRCA mutations.²⁰ 

Given the robust response to PARP inhibitors, there has been great interest in using these agents earlier in the disease course in combination with chemotherapy. 

Efficacy of veliparib with chemotherapy and as maintenance monotherapy 

In a randomized, double-blind, placebo-controlled phase 3 trial, Coleman and colleagues sought to determine the efficacy of the PARP inhibitor veliparib when administered with first-line carboplatin and paclitaxel induction chemotherapy and subsequently continued as maintenance monotherapy.²¹ 

Women with stage III or IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were eligible for the study. Cytoreductive surgery could be performed prior to the initiation of trial treatment or after 3 cycles of chemotherapy. 

Participants were randomized in a 1:1:1 ratio: 371 women received carboplatin and paclitaxel plus placebo followed by placebo maintenance (control arm); 376 received chemotherapy plus veliparib followed by placebo maintenance (veliparib combination-only arm); and 377 received chemotherapy plus veliparib followed by veliparib maintenance therapy (veliparib-throughout arm). Combination chemotherapy consisted of 6 cycles, and maintenance therapy was an additional 30 cycles. 

Progression-free survival extended 

At a median follow-up of 28 months, investigators observed a significant improvement in progression-free survival in the veliparib-throughout (initial and maintenance therapy) arm compared with the control arm in 3 cohorts: the BRCA-mutation cohort, the HRD cohort, and the intention-to-treat population (all participants undergoing randomization). 

In the BRCA-mutation cohort, the median progression-free survival was 12.7 months longer in the veliparib-throughout arm than in the control arm. Similarly, in the HRD cohort, the median progression-free survival was 11.4 months longer in the veliparib-throughout arm than in the control group. In the intention-to-treat population, the median progression-free survival increased from 17.3 to 23.5 months in the veliparib-throughout arm compared with the control arm. 

Women who received veliparib experienced increased rates of nausea, anemia, and fatigue and were more likely to require dose reductions and treatment interruptions. Myelodysplastic syndrome was reported in 1 patient (BRCA1 positive) in the veliparib combination-only arm.

Secondary cytoreductive surgery or chemotherapy alone for platinum-sensitive recurrent ovarian carcinoma? 

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939. 

Primary surgical cytoreduction combined with platinum and taxane-based chemotherapy remains the mainstay of ovarian cancer treatment.¹¹ The role of surgery for women with recurrent ovarian cancer, so-called secondary cytoreduction, remains controversial.²² 

Data have shown that among women who undergo secondary surgery, those with little or no postoperative residual disease benefit the most from a secondary debulking.^23-26 Prior work largely is based on small retrospective reports and is limited by substantial bias in the selection of patients undergoing surgery. Additionally, with the availability of targeted therapies such as bevacizumab and PARP inhibitors as maintenance—medical interventions with a demonstrated benefit in progression-free survival^17-19,27—the role of secondary cytoreduction in the treatment of ovarian carcinoma needs to be clarified. 

Continue to: Overall survival after secondary cytoreduction followed by chemotherapy...

Overall survival after secondary cytoreduction followed by chemotherapy 

Coleman and colleagues conducted a prospective, multicenter, international, randomized phase 3 trial to assess whether secondary cytoreductive surgery followed by chemotherapy would improve overall survival versus chemotherapy alone among women with resectable platinum-sensitive, recurrent ovarian cancer.²² Platinum sensitivity was defined as a disease-free interval of at least 6 months after the last cycle of platinum-based chemotherapy. 

All women had recurrent epithelial ovarian carcinoma considered to be amenable to complete gross surgical resection by the investigator and a history of complete response to at least 3 cycles of platinum-based chemotherapy as determined by a normal CA-125 value or negative imaging studies (if obtained). 

Participants were randomly assigned 1:1, with 240 women assigned to secondary surgical cytoreduction followed by platinum-based chemotherapy, and 245 assigned to chemotherapy alone. The type of adjuvant chemotherapy used (carboplatin-paclitaxel or carboplatin-gemcitabine) and whether or not bevacizumab was administered were at the investigators' discretion. 

Shorter survival, decline in quality of life 

Among the participants assigned to and who underwent surgery, complete gross resection was achieved in 67%. Eighty-four percent of the entire study population received platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance therapy, which was equally distributed between the 2 study arms. 

At a median follow-up of 48.1 months, median overall survival was 50.6 months in the surgery arm compared with 64.7 months in the chemotherapy arm, corresponding to a hazard ratio (HR) for death of 1.29 (95% confidence interval [CI], 0.97-1.72; P = .08). This effect was unchanged after adjusting for platinum-free interval, chemotherapy choice, and restricting the analysis to women who had a complete gross resection. 

Similarly, the adjusted HR for disease progression or death was 0.82 (95% CI, 0.66-1.01) and corresponded to a median progression-free survival of 18.9 months for the surgery group and 16.2 months for the chemotherapy group. Surgical morbidity was reported in 9% of patients who underwent surgery, and 1 patient (0.4%) died from postoperative complications. 

While a significant decline in both quality of life and patient-reported outcomes was reported immediately after surgery, significant differences were not noted between the 2 groups after the initial postoperative recovery period. 

Over the past year, major strides have been made in the treatment of gynecologic malignancies. In this Update, we highlight 3 notable studies. The first is a phase 3, multicenter, international, randomized clinical trial that demonstrated a significant improvement in both overall and failure-free survival with the use of adjuvant chemoradiation versus radiotherapy alone in patients with stage III or high-risk uterine cancer. Additionally, we describe the results of 2 phase 3, multicenter, international, randomized clinical trials in ovarian cancer treatment: use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in combination with platinum and taxane-based chemotherapy followed by the PARP inhibitor as maintenance therapy, and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian cancer.

We provide a brief overview of current treatment strategies, summarize the key findings of these trials, and establish how these findings have changed our management of these gynecologic malignancies.

Adjuvant chemotherapy and radiotherapy improves survival in women with high-risk endometrial cancer 

de Boer SM, Powell ME, Mileshkin L, et al; on behalf of the PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019;1273-1285. 

In the United States, it is estimated that more than 61,000 women were diagnosed with endometrial cancer in 2019.¹ Women with endometrial cancer usually have a favorable prognosis; more than 65% are diagnosed with early-stage disease, which is associated with a 95% 5-year survival rate.¹ However, 15% to 20% of patients have disease with high-risk features, including advanced stage (stage II-IV), high tumor grade, lymphovascular space invasion, deep myometrial invasion, or nonendometrioid histologic subtypes (serous or clear cell).² The presence of these high-risk disease features is associated with an increased incidence of distant metastases and cancer-related death. 

Adjuvant therapy in high-risk endometrial cancer 

To date, the optimal adjuvant therapy for patients with high-risk endometrial cancer remains controversial. Prior data from Gynecologic Oncology Group (GOG) protocol 122 demonstrated that chemotherapy significantly improved progression-free survival and overall survival when compared with radiotherapy in patients with advanced-stage endometrial cancer.³ As such, chemotherapy now is frequently used in this population, often in combination with radiation, although data describing the benefit of chemoradiation are limited.⁴ For women with earlier-stage disease with high-risk features, the value of chemotherapy plus radiation is uncertain.^5,6 

Continue to: Benefit observed with adjuvant chemoradiotherapy...

Benefit observed with adjuvant chemoradiotherapy 

In a multicenter, international, randomized phase 3 trial, known as the PORTEC-3 trial, de Boer and colleagues sought to determine if combined adjuvant chemoradiation improved overall survival (OS) and failure-free survival when compared with external-beam radiation therapy (EBRT) alone in the treatment of women with high-risk endometrial cancer.⁷ Women were eligible for the study if they had histologically confirmed stage I, grade 3 endometrioid endometrial cancer with deep invasion and/or lymphovascular space invasion, stage II or III disease, or stage I-III disease with serous or clear cell histology. 

Participants were randomly assigned in a 1:1 ratio; 330 women received adjuvant EBRT alone (total dose of 48.6 Gy administered in 27 fractions), and 330 received adjuvant chemotherapy during and after radiation therapy (CTRT) (2 cycles of cisplatin 50 mg/m² IV given on days 1 and 22 of EBRT followed by 4 cycles of carboplatin AUC 5 and paclitaxel 175 mg/m² IV every 3 weeks). 

At a median follow-up of 73 months, treatment with adjuvant CTRT, compared with adjuvant EBRT alone, was associated with a significant improvement in both overall survival (5-year OS: 81.4% vs 76.1%, P = .034 [FIGURE]) and failure-free survival (5-year failure-free survival: 76.5% vs 69.1%, P = .016). 

The greatest absolute benefit of adjuvant CTRT, compared with EBRT alone, in survival was among women with stage III endometrial cancer (5-year OS: 78.5% vs 68.5%, P = .043) or serous cancers (19% absolute improvement in 5-year OS), or both. Significant differences in 5-year OS and failure-free survival in women with stage I-II cancer were not observed with adjuvant CTRT when compared with adjuvant EBRT alone. At 5 years, significantly more adverse events of grade 2 or worse were reported in the adjuvant CTRT arm. 

Results from similar trials 

Since the publication of results from the updated analysis of PORTEC-3, results from 2 pertinent trials have been published.^8,9 In the GOG 249 trial, women with stage I-II endometrial cancer with high-risk features were randomly assigned to receive 3 cycles of carboplatin-paclitaxel chemotherapy with vaginal brachytherapy or EBRT.⁸ There was no difference in survival, but a significant increase in both pelvic and para-aortic recurrences were seen after the combination of chemotherapy and vaginal brachytherapy.⁸ 

In GOG 258, women with stage III-IVA endometrial cancer were randomly assigned to receive chemotherapy alone (carboplatin-paclitaxel) or adjuvant chemotherapy after EBRT.⁹ No differences in recurrence-free or overall survival were noted, but there was a significant increase in the number of vaginal and pelvic or para-aortic recurrences in patients in the chemotherapy-only arm.⁹

Role for PARP inhibitor plus first-line chemotherapy, and as maintenance therapy, in ovarian cancer treatment 

Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403-2415. 

Ovarian cancer is the leading cause of gynecologic cancer-related deaths among women in the United States.¹⁰ Treatment consists of cytoreductive surgery combined with platinum and taxane-based chemotherapy.¹¹ Despite favorable initial responses, more than 80% of patients experience a recurrence, with an 18-month median time to progression.¹² As a result, recent efforts have focused on finding novel therapeutic approaches to improve treatment outcomes and mitigate the risk of disease recurrence. 

Continue to: PARP inhibitors are changing the face of treatment...

PARP inhibitors are changing the face of treatment 

Poly(adenosine diphosphate-ribose) polymerases (PARPs) are a family of enzymes that play a critical role in DNA damage repair. These enzymes promote DNA repair by recruiting proteins involved in repairing single-strand and double-strand DNA breaks and in protecting and restarting stalled DNA replication forks.¹³ The predominant mechanisms of action of PARP inhibitors in cells with homologous-recombination deficiency (HRD) include inhibiting repair of single-strand DNA breaks and trapping PARP-DNA complexes at stalled DNA replication forks.¹⁴ 

Germline or somatic BRCA1/2 mutations and genetic alterations resulting in HRD are present in about 20% and 30% of ovarian carcinomas, respectively, and increase the susceptibility of tumors to platinum-based agents and PARP inhibitors.^15,16 Based on multiple clinical trials that demonstrated the efficacy of single-agent PARP in the treatment of recurrent ovarian carcinoma and as maintenance therapy after an initial response to platinum-based therapy, the US Food and Drug Administration approved olaparib, niraparib, and rucaparib for the treatment of high-grade epithelial ovarian cancer.^17-19 Only olaparib is approved for maintenance therapy after initial adjuvant therapy in patients with BRCA mutations.²⁰ 

Given the robust response to PARP inhibitors, there has been great interest in using these agents earlier in the disease course in combination with chemotherapy. 

Efficacy of veliparib with chemotherapy and as maintenance monotherapy 

In a randomized, double-blind, placebo-controlled phase 3 trial, Coleman and colleagues sought to determine the efficacy of the PARP inhibitor veliparib when administered with first-line carboplatin and paclitaxel induction chemotherapy and subsequently continued as maintenance monotherapy.²¹ 

Women with stage III or IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were eligible for the study. Cytoreductive surgery could be performed prior to the initiation of trial treatment or after 3 cycles of chemotherapy. 

Participants were randomized in a 1:1:1 ratio: 371 women received carboplatin and paclitaxel plus placebo followed by placebo maintenance (control arm); 376 received chemotherapy plus veliparib followed by placebo maintenance (veliparib combination-only arm); and 377 received chemotherapy plus veliparib followed by veliparib maintenance therapy (veliparib-throughout arm). Combination chemotherapy consisted of 6 cycles, and maintenance therapy was an additional 30 cycles. 

Progression-free survival extended 

At a median follow-up of 28 months, investigators observed a significant improvement in progression-free survival in the veliparib-throughout (initial and maintenance therapy) arm compared with the control arm in 3 cohorts: the BRCA-mutation cohort, the HRD cohort, and the intention-to-treat population (all participants undergoing randomization). 

In the BRCA-mutation cohort, the median progression-free survival was 12.7 months longer in the veliparib-throughout arm than in the control arm. Similarly, in the HRD cohort, the median progression-free survival was 11.4 months longer in the veliparib-throughout arm than in the control group. In the intention-to-treat population, the median progression-free survival increased from 17.3 to 23.5 months in the veliparib-throughout arm compared with the control arm. 

Women who received veliparib experienced increased rates of nausea, anemia, and fatigue and were more likely to require dose reductions and treatment interruptions. Myelodysplastic syndrome was reported in 1 patient (BRCA1 positive) in the veliparib combination-only arm.

Secondary cytoreductive surgery or chemotherapy alone for platinum-sensitive recurrent ovarian carcinoma? 

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939. 

Primary surgical cytoreduction combined with platinum and taxane-based chemotherapy remains the mainstay of ovarian cancer treatment.¹¹ The role of surgery for women with recurrent ovarian cancer, so-called secondary cytoreduction, remains controversial.²² 

Data have shown that among women who undergo secondary surgery, those with little or no postoperative residual disease benefit the most from a secondary debulking.^23-26 Prior work largely is based on small retrospective reports and is limited by substantial bias in the selection of patients undergoing surgery. Additionally, with the availability of targeted therapies such as bevacizumab and PARP inhibitors as maintenance—medical interventions with a demonstrated benefit in progression-free survival^17-19,27—the role of secondary cytoreduction in the treatment of ovarian carcinoma needs to be clarified. 

Continue to: Overall survival after secondary cytoreduction followed by chemotherapy...

Overall survival after secondary cytoreduction followed by chemotherapy 

Coleman and colleagues conducted a prospective, multicenter, international, randomized phase 3 trial to assess whether secondary cytoreductive surgery followed by chemotherapy would improve overall survival versus chemotherapy alone among women with resectable platinum-sensitive, recurrent ovarian cancer.²² Platinum sensitivity was defined as a disease-free interval of at least 6 months after the last cycle of platinum-based chemotherapy. 

All women had recurrent epithelial ovarian carcinoma considered to be amenable to complete gross surgical resection by the investigator and a history of complete response to at least 3 cycles of platinum-based chemotherapy as determined by a normal CA-125 value or negative imaging studies (if obtained). 

Participants were randomly assigned 1:1, with 240 women assigned to secondary surgical cytoreduction followed by platinum-based chemotherapy, and 245 assigned to chemotherapy alone. The type of adjuvant chemotherapy used (carboplatin-paclitaxel or carboplatin-gemcitabine) and whether or not bevacizumab was administered were at the investigators' discretion. 

Shorter survival, decline in quality of life 

Among the participants assigned to and who underwent surgery, complete gross resection was achieved in 67%. Eighty-four percent of the entire study population received platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance therapy, which was equally distributed between the 2 study arms. 

At a median follow-up of 48.1 months, median overall survival was 50.6 months in the surgery arm compared with 64.7 months in the chemotherapy arm, corresponding to a hazard ratio (HR) for death of 1.29 (95% confidence interval [CI], 0.97-1.72; P = .08). This effect was unchanged after adjusting for platinum-free interval, chemotherapy choice, and restricting the analysis to women who had a complete gross resection. 

Similarly, the adjusted HR for disease progression or death was 0.82 (95% CI, 0.66-1.01) and corresponded to a median progression-free survival of 18.9 months for the surgery group and 16.2 months for the chemotherapy group. Surgical morbidity was reported in 9% of patients who underwent surgery, and 1 patient (0.4%) died from postoperative complications. 

While a significant decline in both quality of life and patient-reported outcomes was reported immediately after surgery, significant differences were not noted between the 2 groups after the initial postoperative recovery period. 

Over the past year, major strides have been made in the treatment of gynecologic malignancies. In this Update, we highlight 3 notable studies. The first is a phase 3, multicenter, international, randomized clinical trial that demonstrated a significant improvement in both overall and failure-free survival with the use of adjuvant chemoradiation versus radiotherapy alone in patients with stage III or high-risk uterine cancer. Additionally, we describe the results of 2 phase 3, multicenter, international, randomized clinical trials in ovarian cancer treatment: use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in combination with platinum and taxane-based chemotherapy followed by the PARP inhibitor as maintenance therapy, and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian cancer.

We provide a brief overview of current treatment strategies, summarize the key findings of these trials, and establish how these findings have changed our management of these gynecologic malignancies.

Adjuvant chemotherapy and radiotherapy improves survival in women with high-risk endometrial cancer 

de Boer SM, Powell ME, Mileshkin L, et al; on behalf of the PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019;1273-1285. 

In the United States, it is estimated that more than 61,000 women were diagnosed with endometrial cancer in 2019.¹ Women with endometrial cancer usually have a favorable prognosis; more than 65% are diagnosed with early-stage disease, which is associated with a 95% 5-year survival rate.¹ However, 15% to 20% of patients have disease with high-risk features, including advanced stage (stage II-IV), high tumor grade, lymphovascular space invasion, deep myometrial invasion, or nonendometrioid histologic subtypes (serous or clear cell).² The presence of these high-risk disease features is associated with an increased incidence of distant metastases and cancer-related death. 

Adjuvant therapy in high-risk endometrial cancer 

To date, the optimal adjuvant therapy for patients with high-risk endometrial cancer remains controversial. Prior data from Gynecologic Oncology Group (GOG) protocol 122 demonstrated that chemotherapy significantly improved progression-free survival and overall survival when compared with radiotherapy in patients with advanced-stage endometrial cancer.³ As such, chemotherapy now is frequently used in this population, often in combination with radiation, although data describing the benefit of chemoradiation are limited.⁴ For women with earlier-stage disease with high-risk features, the value of chemotherapy plus radiation is uncertain.^5,6 

Continue to: Benefit observed with adjuvant chemoradiotherapy...

Benefit observed with adjuvant chemoradiotherapy 

In a multicenter, international, randomized phase 3 trial, known as the PORTEC-3 trial, de Boer and colleagues sought to determine if combined adjuvant chemoradiation improved overall survival (OS) and failure-free survival when compared with external-beam radiation therapy (EBRT) alone in the treatment of women with high-risk endometrial cancer.⁷ Women were eligible for the study if they had histologically confirmed stage I, grade 3 endometrioid endometrial cancer with deep invasion and/or lymphovascular space invasion, stage II or III disease, or stage I-III disease with serous or clear cell histology. 

Participants were randomly assigned in a 1:1 ratio; 330 women received adjuvant EBRT alone (total dose of 48.6 Gy administered in 27 fractions), and 330 received adjuvant chemotherapy during and after radiation therapy (CTRT) (2 cycles of cisplatin 50 mg/m² IV given on days 1 and 22 of EBRT followed by 4 cycles of carboplatin AUC 5 and paclitaxel 175 mg/m² IV every 3 weeks). 

At a median follow-up of 73 months, treatment with adjuvant CTRT, compared with adjuvant EBRT alone, was associated with a significant improvement in both overall survival (5-year OS: 81.4% vs 76.1%, P = .034 [FIGURE]) and failure-free survival (5-year failure-free survival: 76.5% vs 69.1%, P = .016). 

The greatest absolute benefit of adjuvant CTRT, compared with EBRT alone, in survival was among women with stage III endometrial cancer (5-year OS: 78.5% vs 68.5%, P = .043) or serous cancers (19% absolute improvement in 5-year OS), or both. Significant differences in 5-year OS and failure-free survival in women with stage I-II cancer were not observed with adjuvant CTRT when compared with adjuvant EBRT alone. At 5 years, significantly more adverse events of grade 2 or worse were reported in the adjuvant CTRT arm. 

Results from similar trials 

Since the publication of results from the updated analysis of PORTEC-3, results from 2 pertinent trials have been published.^8,9 In the GOG 249 trial, women with stage I-II endometrial cancer with high-risk features were randomly assigned to receive 3 cycles of carboplatin-paclitaxel chemotherapy with vaginal brachytherapy or EBRT.⁸ There was no difference in survival, but a significant increase in both pelvic and para-aortic recurrences were seen after the combination of chemotherapy and vaginal brachytherapy.⁸ 

In GOG 258, women with stage III-IVA endometrial cancer were randomly assigned to receive chemotherapy alone (carboplatin-paclitaxel) or adjuvant chemotherapy after EBRT.⁹ No differences in recurrence-free or overall survival were noted, but there was a significant increase in the number of vaginal and pelvic or para-aortic recurrences in patients in the chemotherapy-only arm.⁹

Role for PARP inhibitor plus first-line chemotherapy, and as maintenance therapy, in ovarian cancer treatment 

Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403-2415. 

Ovarian cancer is the leading cause of gynecologic cancer-related deaths among women in the United States.¹⁰ Treatment consists of cytoreductive surgery combined with platinum and taxane-based chemotherapy.¹¹ Despite favorable initial responses, more than 80% of patients experience a recurrence, with an 18-month median time to progression.¹² As a result, recent efforts have focused on finding novel therapeutic approaches to improve treatment outcomes and mitigate the risk of disease recurrence. 

Continue to: PARP inhibitors are changing the face of treatment...

PARP inhibitors are changing the face of treatment 

Poly(adenosine diphosphate-ribose) polymerases (PARPs) are a family of enzymes that play a critical role in DNA damage repair. These enzymes promote DNA repair by recruiting proteins involved in repairing single-strand and double-strand DNA breaks and in protecting and restarting stalled DNA replication forks.¹³ The predominant mechanisms of action of PARP inhibitors in cells with homologous-recombination deficiency (HRD) include inhibiting repair of single-strand DNA breaks and trapping PARP-DNA complexes at stalled DNA replication forks.¹⁴ 

Germline or somatic BRCA1/2 mutations and genetic alterations resulting in HRD are present in about 20% and 30% of ovarian carcinomas, respectively, and increase the susceptibility of tumors to platinum-based agents and PARP inhibitors.^15,16 Based on multiple clinical trials that demonstrated the efficacy of single-agent PARP in the treatment of recurrent ovarian carcinoma and as maintenance therapy after an initial response to platinum-based therapy, the US Food and Drug Administration approved olaparib, niraparib, and rucaparib for the treatment of high-grade epithelial ovarian cancer.^17-19 Only olaparib is approved for maintenance therapy after initial adjuvant therapy in patients with BRCA mutations.²⁰ 

Given the robust response to PARP inhibitors, there has been great interest in using these agents earlier in the disease course in combination with chemotherapy. 

Efficacy of veliparib with chemotherapy and as maintenance monotherapy 

In a randomized, double-blind, placebo-controlled phase 3 trial, Coleman and colleagues sought to determine the efficacy of the PARP inhibitor veliparib when administered with first-line carboplatin and paclitaxel induction chemotherapy and subsequently continued as maintenance monotherapy.²¹ 

Women with stage III or IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were eligible for the study. Cytoreductive surgery could be performed prior to the initiation of trial treatment or after 3 cycles of chemotherapy. 

Participants were randomized in a 1:1:1 ratio: 371 women received carboplatin and paclitaxel plus placebo followed by placebo maintenance (control arm); 376 received chemotherapy plus veliparib followed by placebo maintenance (veliparib combination-only arm); and 377 received chemotherapy plus veliparib followed by veliparib maintenance therapy (veliparib-throughout arm). Combination chemotherapy consisted of 6 cycles, and maintenance therapy was an additional 30 cycles. 

Progression-free survival extended 

At a median follow-up of 28 months, investigators observed a significant improvement in progression-free survival in the veliparib-throughout (initial and maintenance therapy) arm compared with the control arm in 3 cohorts: the BRCA-mutation cohort, the HRD cohort, and the intention-to-treat population (all participants undergoing randomization). 

In the BRCA-mutation cohort, the median progression-free survival was 12.7 months longer in the veliparib-throughout arm than in the control arm. Similarly, in the HRD cohort, the median progression-free survival was 11.4 months longer in the veliparib-throughout arm than in the control group. In the intention-to-treat population, the median progression-free survival increased from 17.3 to 23.5 months in the veliparib-throughout arm compared with the control arm. 

Women who received veliparib experienced increased rates of nausea, anemia, and fatigue and were more likely to require dose reductions and treatment interruptions. Myelodysplastic syndrome was reported in 1 patient (BRCA1 positive) in the veliparib combination-only arm.

Secondary cytoreductive surgery or chemotherapy alone for platinum-sensitive recurrent ovarian carcinoma? 

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939. 

Primary surgical cytoreduction combined with platinum and taxane-based chemotherapy remains the mainstay of ovarian cancer treatment.¹¹ The role of surgery for women with recurrent ovarian cancer, so-called secondary cytoreduction, remains controversial.²² 

Data have shown that among women who undergo secondary surgery, those with little or no postoperative residual disease benefit the most from a secondary debulking.^23-26 Prior work largely is based on small retrospective reports and is limited by substantial bias in the selection of patients undergoing surgery. Additionally, with the availability of targeted therapies such as bevacizumab and PARP inhibitors as maintenance—medical interventions with a demonstrated benefit in progression-free survival^17-19,27—the role of secondary cytoreduction in the treatment of ovarian carcinoma needs to be clarified. 

Continue to: Overall survival after secondary cytoreduction followed by chemotherapy...

Overall survival after secondary cytoreduction followed by chemotherapy 

Coleman and colleagues conducted a prospective, multicenter, international, randomized phase 3 trial to assess whether secondary cytoreductive surgery followed by chemotherapy would improve overall survival versus chemotherapy alone among women with resectable platinum-sensitive, recurrent ovarian cancer.²² Platinum sensitivity was defined as a disease-free interval of at least 6 months after the last cycle of platinum-based chemotherapy. 

All women had recurrent epithelial ovarian carcinoma considered to be amenable to complete gross surgical resection by the investigator and a history of complete response to at least 3 cycles of platinum-based chemotherapy as determined by a normal CA-125 value or negative imaging studies (if obtained). 

Participants were randomly assigned 1:1, with 240 women assigned to secondary surgical cytoreduction followed by platinum-based chemotherapy, and 245 assigned to chemotherapy alone. The type of adjuvant chemotherapy used (carboplatin-paclitaxel or carboplatin-gemcitabine) and whether or not bevacizumab was administered were at the investigators' discretion. 

Shorter survival, decline in quality of life 

Among the participants assigned to and who underwent surgery, complete gross resection was achieved in 67%. Eighty-four percent of the entire study population received platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance therapy, which was equally distributed between the 2 study arms. 

At a median follow-up of 48.1 months, median overall survival was 50.6 months in the surgery arm compared with 64.7 months in the chemotherapy arm, corresponding to a hazard ratio (HR) for death of 1.29 (95% confidence interval [CI], 0.97-1.72; P = .08). This effect was unchanged after adjusting for platinum-free interval, chemotherapy choice, and restricting the analysis to women who had a complete gross resection. 

Similarly, the adjusted HR for disease progression or death was 0.82 (95% CI, 0.66-1.01) and corresponded to a median progression-free survival of 18.9 months for the surgery group and 16.2 months for the chemotherapy group. Surgical morbidity was reported in 9% of patients who underwent surgery, and 1 patient (0.4%) died from postoperative complications. 

While a significant decline in both quality of life and patient-reported outcomes was reported immediately after surgery, significant differences were not noted between the 2 groups after the initial postoperative recovery period. 

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.

CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

CASE A patient experiences unnessary inconvenience, distress, and cost following IUD placement

Ms. J had a levonorgestrel intrauterine device (IUD) placed at her postpartum visit. Her physician asked her to return for a string check in 4 to 6 weeks. She was dismayed at the prospect of re-presenting for care, as she is losing the Medicaid coverage that paid for her pregnancy care. One month later, she arranged for a babysitter so she could obtain the recommended string check. The physician told her the strings seemed longer than expected and ordered ultrasonography. Ms. J is distressed because of the mounting cost of care but is anxious to ensure that the IUD will prevent future pregnancy.

Should the routine IUD string check be reconsidered?

The string check dissension

Intrauterine devices offer reliable contraception with a high rate of satisfaction and a remarkably low rate of complications.^1-3 With the increased uptake of IUDs, the value of “string checks” is being debated, with myriad responses from professional groups, manufacturers, and individual clinicians. For many practicing ObGyns, the question remains: Should patients be counseled about presenting for or doing their own IUD string checks?

Indeed, all IUD manufacturers recommend monthly self-examination to evaluate string presence.^4-8 Manufacturers’ websites prominently display this information in material directed toward current or potential users, so many patients may be familiar already with this recommendation before their clinician visit. Yet, the Centers for Disease Control and Prevention state that no routine follow-up or monitoring is needed.⁹

In our case scenario, follow-up is clearly burdensome and ultimately costly. Instead, clinicians can advise patients to return with rare but important to recognize complications (such as perforation, expulsion, infection), adverse effects, or desire for change. While no data are available to support in-office or at-home string checks, data do show that women reliably present when intervention is needed.

Here, we explore 5 questions relevant to IUD string checks and discuss why it is time to rethink this practice habit.

What is the purpose of a string check?

String checks serve as a surrogate for assessing an IUD’s position and function. A string check can be performed by a clinician, who observes the IUD strings on speculum exam or palpates the strings on bimanual exam, or by the patient doing a self-exam. A positive string check purportedly assures both the IUD user and the health care provider that an IUD remains in a fundal, intrauterine position, thus providing an ongoing reliable contraceptive effect.

However, string check reliability in detecting contraceptive effectiveness is uncertain. Strings that subjectively feel or appear longer than anticipated can lead to unnecessary additional evaluation and emotional distress: These are harms. By contrast, when an expulsion occurs, it often is a partial expulsion or displacement, with unclear effect on patient or physician perception of the strings on examination. One retrospective review identified women with a history of IUD placement and a positive pregnancy test; those with an intrauterine pregnancy (74%) frequently also had a malpositioned IUD (55%) and rarely identifiable string issues (16%).¹⁰ Before asking patients and clinicians to use resources for performing string evaluations, the association between this action and outcomes of interest must be elucidated.

If not for assessing risk of expulsion, IUD follow-up allows the clinician to evaluate for other complications or adverse effects and to address patient concerns. This practice often is performed when the patient is starting a new medication or medical intervention. However, a systematic review involving 4 studies of IUD follow-up visits or phone calls after contraceptive initiation generated limited data, with no notable impact on contraceptive continuation or indicated use.¹¹

Most important, data show that patients present to their clinician when issues arise with IUD use. One prospective study of 280 women compared multiple follow-up visits with a single 6-week follow-up visit after IUD placement; 10 expulsions were identified, and 8 of these were noted at unscheduled visits when patients presented with symptoms.¹² This study suggests that there is little benefit in scheduled follow-up or set self-checks.

Furthermore, in a study in Finland of more than 17,000 IUD users, the rare participants who became pregnant during IUD use promptly presented for care because of a change in menses, pain, or symptoms of pregnancy.¹³ While IUDs are touted as user independent, this overlooks the reality: Data show that device failure, although rare, is rapidly and appropriately addressed by the user.

Continue to: Does the risk of IUD expulsion warrant string checks?...

Does the risk of IUD expulsion warrant string checks?

The risk of IUD expulsion is estimated to be 1% at 1 month and 4% at 1 year, with a contraceptive failure rate of 0.4% at 1 year. The risk of expulsion does not differ by age group, including adolescents, or parity, but it is higher with use of the copper IUD (2% at 1 month, 6% at 1 year) and with prior expulsion (14%, limited by small numbers).¹ Furthermore, risk of expulsion is higher with postplacental placement and second trimester abortion.^14,15 Despite this risk, the contraceptive failure rate of all types of IUDs remains consistently lower than all other reversible methods besides the contraceptive implant.¹⁶

Furthermore, while IUD expulsion is rare, unnoticed expulsion is even more rare. In one study with more than 58,000 person-years of use, 132 pregnancies were noted, and 7 of these occurred in the setting of an unnoticed expulsion.¹³ Notably, a higher risk threshold is held for other medications. For example, statins are associated with a 3% risk of irreversible hepatic injury, yet serial liver function tests are not performed in patients without baseline liver dysfunction.¹⁷ A less than 0.1% risk of a non–life-threatening complication—unnoticed expulsion—does not warrant routine follow-up. Instead, the patient gauges the tolerability of that risk in making a follow-up plan, particularly given the varied individual preferences in patients’ management of the associated outcome of unintended pregnancy.

Are women interested in and able to perform their own string checks?

Recommendations to perform IUD string self-checks should consider whether women are willing and able to do so. In a study of 126 IUD users, 59% of women had attempted to check their IUD strings at home, and one-third were unable to do so successfully; all participants had visible strings on subsequent speculum exam.¹⁸ The women also were given the opportunity to perform a string self-check at the study visit. Overall, only 46% of participants found the exercise acceptable and were able to palpate the IUD strings.¹⁸ The authors aptly stated, “A universal recommendation for practice that is meant to identify a rare complication has no clinical utility if at least half of the women are unable to follow it.”

In which scenarios might a string check have clear utility?

The most important reason for follow-up after IUD placement or for patients to perform string self-checks is patient preference. At least anecdotally, some patients take comfort, particularly in the absence of menses, in palpating IUD strings regularly; these individuals should know that there is no necessity for but also no harm in this practice. In addition, patients may desire a string check or follow-up visit to discuss their new contraceptive’s goodness-of-fit.

While limited data show that routinely scheduling such visits does not improve contraceptive continuation, it is difficult to extrapolate these data to the select individuals who independently desire follow-up. (In addition, contraceptive continuance is hardly a metric of success, as clinicians and patients can agree that discontinuation in the setting of patient dissatisfaction is always appropriate.)

Clinicians should share with patients differing risks of IUD expulsion, and this may prompt more nuanced decisions about string checks and/or follow-up. Patients with postplacental or postabortion (second trimester) IUD placement or placement following prior expulsion may opt to perform string checks given the relatively higher risk of expulsion despite the maintained, absolutely low risk that such an event is unnoticed.

If a patient does present for a string check and strings are not visualized on exam, reasonable attempts should be made to identify the strings at that time. A cytobrush can be used to liberate and identify strings within the cervical canal. If the clinician cannot identify the strings or the patient is unable to tolerate such attempts, ultrasonography should be performed to localize the IUD. The ultrasound scan can be done in the office, if available, which is more cost-effective for women than a referral to radiology. If ultrasonography does not identify an intrauterine IUD, an x-ray is the next step to determine if the IUD has expulsed or perforated.

Continue to: Is a string check worth the cost?...

Is a string check worth the cost?

Health care providers may not be aware of the cost of care from the patient perspective. While the Affordable Care Act of 2010 mandates contraceptive coverage for women with insurance, a string check often is coded as a problem-based visit and thus may require a significant copay or out-of-pocket cost for high-deductible plans—without a proven benefit.¹⁹ Women who lack insurance coverage may forgo even necessary care due to the cost.²⁰

The bottom line

The medical community and ObGyns specifically are familiar with a practice of patient self-examination falling by the wayside, as has been the case with breast self-examination.²¹ While counseling on string checks can complement conversations about risks and patients’ personal preferences regarding follow-up, no data support routine string checks in the clinic or at home. One of the great benefits of IUD use is its lack of barriers and resources for ongoing use. Physicians need not reintroduce burdens without benefits to those who desire this contraceptive method.

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Video 2. Negative hysteroscopic view 

Vidyard Video

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Video 4. Endometrial adenocarcinoma 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Video 2. Negative hysteroscopic view 

Vidyard Video

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Video 4. Endometrial adenocarcinoma 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.

For more than 45 years, gynecologists have used hysteroscopy to diagnose endometrial carcinoma and to associate morphologic descriptive terms with visual findings.¹ Today, considerably more clinical evidence supports visual pattern recognition to assess the risk for and presence of endometrial carcinoma, improving observer-dependent biopsy of the most suspect lesions (VIDEO 1).

In this article, I discuss the clinical evolution of hysteroscopic pattern recognition of endometrial disease and review the visual findings that correlate with the likelihood of endometrial carcinoma. In addition, I have provided 9 short videos that show hysteroscopic views of various endometrial pathologies in the online version of this article at https://www.mdedge.com/obgyn.

Video 1. Endometrial carcinoma and visually directed biopsy

Vidyard Video

The negative hysteroscopic view defined

In 1989, Dr. Frank Loffer confirmed the diagnostic superiority of visually directed biopsy. He demonstrated the advantages of using hysteroscopy and directed biopsy in the evaluation of abnormal uterine bleeding (AUB) to obtain a more accurate diagnosis compared with dilation and curettage (D&C) alone (sensitivity, 98% vs 65%, respectively).²

Also derived from this work is the clinical application of the “negative hysteroscopic view” (NHV). Loffer used the following criteria to define the NHV: good visualization of the entire uterine cavity, no structural abnormalities of the cavity, and a uniformly thin, homogeneous-appearing endometrium without variations in thickness (TABLE 1). The last criterion can be expected to occur only in the early proliferative phase or in postmenopausal women.

Video 2. Negative hysteroscopic view 

Vidyard Video

Efforts in hysteroscopic classification of endometrial carcinoma

Lesion morphologic characteristics. Sugimoto was among the first to describe the hysteroscopic identification of visual morphologic features that are most likely to be associated with endometrial carcinoma.¹ Patients with AUB were evaluated with hysteroscopy as first-line management to describe lesion morphology and confirm biopsy with histopathology. Sugimoto classified endometrial carcinoma as circumscribed or exophytic with distinct forms, such as polypoid, nodular, papillary, and ulcerated (FIGURE 2). Diffuse or endophytic carcinoma is defined by an ulcerated type of lesion that indicates necrosis; this is most likely to represent an undifferentiated tumor. Sugimoto also described abnormal vascularity that often is associated with carcinoma.¹

Endometrial features. Valli and Zupi created a nomenclature and classification for hysteroscopic endometrial lesions by prospectively grading 4 features: thickness, surface, vascularization, and color.³ Features were scored based on the degree of abnormality and could be considered to be of low or high risk for the presence of carcinoma. High-risk hysteroscopic features included endometrial thickness greater than 10 mm, polymorphous surface, irregular vascularization, and white-grayish color. The sensitivity for accurately diagnosing endometrial lesions was 86.9% for mild lesions and 96% for severe lesions.³ Also, these investigators confirmed the clinical value of the NHV and associated overall risk of precancer or cancer of the endometrium.

Continue to: Amount of endometrial involvement...

Several important findings associated with this system may improve visual diagnosis. First, hysteroscopic evaluation had a 100% negative predictive value for the cervical spread of disease (FIGURE 3, VIDEO 3). Second, the hysteroscopic morphologic tumor type did not relate to surgical stage or pathologic grade. Third, when less than half of the endometrium was involved, stage I disease was found (97%, 33 of 34). Last, when more than half of the endometrium was involved, advanced disease beyond stage I was found (9 of 26, 6 of whom had poorly differentiated disease).⁴

Video 3. Cervical spread of adenocarcinoma and visually directed biopsy

Vidyard Video

Structured pattern analysis. Recently, Dueholm and co-investigators published a prospective evaluation of women with postmenopausal bleeding and an endometrial thickness of 5 mm or greater.⁵ They used a structured system of visual pattern analysis during hysteroscopy that they termed the hysteroscopic cancer (HYCA) scoring system. The HYCA scoring system is based on surface outline (uneven, polypoid, and papillary projections), necrosis (cotton candy endometrium [FIGURE 4], whitish-grayish areas without vessels on the surface), and vessel pattern (tortuous S-shaped, loops, irregular caliber, irregular branching, and irregular distribution [FIGURE 5]). Structured pattern analysis predicted cancer with higher accuracy than subjective evaluation.⁵

Video 4. Endometrial adenocarcinoma 

Vidyard Video

The scoring system for endometrial adenocarcinoma correctly classified 42 of 44 cancers (sensitivity, 95.4%; specificity, 98.2%), and AEH had a sensitivity of 63.3% and a specificity of 90.4%.⁶ These investigators also showed a high negative predictive value of 99.5% for endometrial adenocarcinoma associated with a negative view at hysteroscopy. Similar to the Dueholm data, Ianieri and colleagues’ morphologic pattern analysis predicted cancer with high accuracy.

Glomerular pattern association. Su and colleagues also showed that pattern recognition could aid in the accurate hysteroscopic diagnosis of endometrial adenocarcinoma.⁷ They used the hysteroscopic presence of a glomerular pattern to predict the association with endometrial adenocarcinoma. A glomerular pattern was described as polypoid endometrium with a papillary-like feature, containing an abnormal neovascularization feature with “intertwined neovascular vessels covered by a thin layer of endometrial tissue” (FIGURE 6). The presence of a glomerular pattern indicated grade 2 or grade 3 disease in 25 of 26 women (96%; sensitivity, 84.6%, specificity, 81.8%)⁷ (see video 4).

TABLE 2 summarizes significant morphologic findings relating to the presences of endometrial carcinoma.

Continue to: Atypical endometrial hyperplasia: A difficult diagnosis...

Atypical endometrial hyperplasia: A difficult diagnosis

The most common type of endometrial cancer is endometrioid adenocarcinoma (type 1 endometrial carcinoma), and it accounts for approximately 75% to 80% of endometrial cancer diagnoses.⁸ Risk factors include prolonged unopposed estrogen exposure, obesity, diabetes, and age. Type 1 endometrial carcinoma follows a progressive continuum of histopathologic change: from endometrial hyperplasia without atypia to endometrial hyperplasia with atypia (AEH) to well-differentiated endometrial cancer. Therefore, it is possible for endometrial carcinoma to be present simultaneously with AEH. The reported prevalence of concurrent endometrial carcinoma among patients with AEH on biopsy is between 17% and 52%.⁸ Thus, the clinical consideration is for hysterectomy, especially in the postmenopausal patient with a diagnosis of AEH.

Hysteroscopic diagnosis of AEH, however, is more difficult than identification of endometrial carcinoma because a range of morphologic characteristics exist that resemble normal endometrium as well as more progressive disease (VIDEO 5). De Franciscis and colleagues based a hysteroscopic diagnosis of hyperplasia on one or more of the following findings: focal or diffuse, papillary or polypoid, endometrial thickening; abnormal vascular patterns; evidence of glandular cysts; and abnormal architecture features of the glandular outlets (thickening, irregular gland density, or dilatation)⁹ (VIDEO 6).

Video 5. Endometrial polyp and atypical hyperplasia 

Vidyard Video

Additional studies, including that from Ianieri and colleagues, also have determined that AEH is difficult to discern visually from normal endometrium and other endometrial pathologies.⁶ In another investigation, Lasmar and coauthors reported a retrospective analysis of 4,054 hysteroscopic procedures with directed biopsies evaluating for concordance between the hysteroscopic view and histopathology.¹⁰ Agreement was 56.3% for AEH versus 94% for endometrial carcinoma. Among those with a histologic diagnosis of AEH, in 35.4% benign disease was suspected; in 2.1%, endometrial carcinoma was suspected; and in 6%, normal findings were presumed.¹⁰

Video 6. Nodular, polypoid atypical hyperplasia 

Vidyard Video

Because of the similarities in morphologic features between AEH and endometrial carcinoma, tissue biopsy under direct visualization is warranted to assure sampling of the most significantly abnormal tissue and to confirm visual interpretation of findings.

Techniques for hysteroscopic-directed biopsy

Using a visual assessment of endometrial abnormalities allows the surgeon to examine the entire uterine cavity and to biopsy the most suspicious and concerning lesions. The directed biopsy technique can involve a simple grasping maneuver: With the jaws of a small grasper open, push slightly forward to accumulate tissue within the jaw, close the jaw, and remove the tissue carefully through the cervix (VIDEO 7). The size of the sample may be limited, and multiple samples may be needed, depending on the quantity of the tissue retrieved.

Video 7. Visually directed endometrial biopsy

Vidyard Video

Another technique involves first creating a plane of tissue to be removed with scissors and subsequently grasping and removing the tissue (see video 1 and video 3). This particular technique will yield more tissue with one pass of the hysteroscope into the cavity. Careful removal of tissue through the cervix is facilitated by withdrawing the sample in the grasper and the hysteroscope together at the same time, without pulling the sample through the operative channel of the hysteroscope. Also, by turning off the inflow port, the stream of saline does not wash the sample off the grasper at hysteroscope removal from the cervix.

Blind biopsy. If visual inspection reveals a diffuse process within the uterine cavity such that no normal endometrium is noted and the abnormality is of equal degree throughout the endometrial surface, a decision can be made to replace directed biopsy with a blind biopsy. In this scenario, the blind biopsy is certain to sample the representative disease process and not potentially miss significant lesions (see video 4 and video 6). Otherwise, the hysteroscope-directed biopsy would be preferable.

Continue to: Potential for intraperitoneal dissemination of endometrial cancer...

Potential for intraperitoneal dissemination of endometrial cancer

There is some concern about intraperitoneal dissemination of endometrial carcinoma at the time of hysteroscopy and effect on disease prognosis. Chang and colleagues conducted a large meta-analysis and found that hysteroscopy performed in the presence of type 1 endometrial carcinoma statistically significantly increased the likelihood of positive intraperitoneal cytology.¹¹ In the included studies that reported survival rates (6 of 19), positive cytology did not alter the clinical outcome. The investigators recommended that hysteroscopy not be avoided for this reason, as it helps in the diagnosis of endometrial carcinoma, especially in the early stages of disease.¹¹

In a recent retrospective analysis, Namazov and colleagues included only stage I endometrial carcinoma (to exclude the adverse effect of advanced stage on survival) and evaluated the assumed isolated effect of hysteroscopy on survival.¹² They compared women in whom stage I endometrial carcinoma was diagnosed: 355 by hysteroscopy and 969 by a nonhysteroscopy method (D&C or office endometrial biopsy). Tumors were classified and grouped as low grade (endometrioid grade 1-2 and villoglandular) and high grade, consisting of endometrioid grade 3 and type 2 endometrial carcinoma (serous carcinoma, clear cell carcinoma, and carcinosarcoma) (VIDEOS 8 and 9). Positive intraperitoneal cytology at the time of surgery was 2.3% and 2.1% (P = .832), with an average interval from diagnosis to surgery of 34.6 days (range, 7–43 days).

Video 8. Carcinosarcoma 

Vidyard Video

The authors proposed several explanations for the low rate of intraperitoneal cytology with hysteroscopy. One possibility is having lower mean intrauterine pressure below 100 mm Hg for saline uterine distension, although this was not standardized for all surgeons in the study but rather was a custom of the institution. In addition, the length of time between hysteroscopy and surgery may allow the immune-reactive peritoneum to respond to the cellular insult, thus decreasing the biologic burden at the time of surgery. The median follow-up was 52 months (range, 12–120 months), and there were no differences between the hysteroscopy and the nonhysteroscopy groups in the 5-year recurrence-free survival (90.2% vs 88.2%; P = .53), disease-specific survival (93.4% vs 91.7%; P = .5), and overall survival (86.2% vs 80.6%; P = .22). The authors concluded that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.¹²

Video 9. Carcinosarcoma 

Vidyard Video

Retrospective data from Chen and colleagues regarding type 2 endometrial carcinoma indicated a statistically significant increase in positive intraperitoneal cytology for carcinomas evaluated by hysteroscopy versus D&C (30% vs 12%; P = .008).¹³ Among the patients who died, there was no difference in disease-specific survival (53 months for hysteroscopy and 63.5 months for D&C; P = .34), and there was no difference in overall recurrence rates.¹³ Compared with type 1 endometrial carcinoma, type 2 endometrial carcinoma behaves more aggressively, with a higher incidence of extrauterine disease and an increased propensity for recurrence and poor outcome even in the early stages of the disease. This makes it difficult to determine the role of hysteroscopy in the prognosis of these carcinomas, especially in this study where most patients were diagnosed at a later stage.

Key takeaways

Hysteroscopy and directed biopsy are highly effective for visual and histopathologic diagnosis of atypical endometrial hyperplasia and endometrial carcinoma, and they are recommended in the evaluation of AUB, especially in the postmenopausal woman. When the hysteroscopic view is negative, there is a high correlation with the absence of uterine cavity and endometrial pathology. Hysteroscopic diagnostic accuracy is improved with structured use of visual grading scales, well-defined descriptors of endometrial pathology, and hysteroscopist experience.

Low operating intrauterine pressure may decrease the intraperitoneal spread of carcinoma cells during hysteroscopy, and current evidence suggests that there is no change in type 1 endometrial carcinoma prognosis and overall outcomes. Type 2 endometrial carcinoma is more aggressive and is associated with poor outcomes even in early stages, and the effect on disease progression by intraperitoneal spread of carcinoma cells at hysteroscopy is not yet known. Hysteroscopic evaluation of the uterine cavity and directed biopsy is easily and safely performed in the office and adds significantly to the evaluation and management of endometrial carcinoma.