OBG Management

Claimed missteps lead to brain damage: $53M award

At 2:00 AM, a woman at 40 weeks’ gestation went to a hospital because she felt a decrease in fetal movement. At birth, the baby was not breathing. He was rushed to the neonatal intensive care unit where he was resuscitated and placed on life support. He remained in critical care for 4 weeks. The child has cerebral palsy and cannot walk, talk, or care for himself. He will need 24-hour care for the rest of his life.

PARENT’S CLAIM:

The lawsuit cited 20 alleged missteps by physicians and nurses, including failure to: react to abnormal fetal heart-rate patterns that indicated fetal distress, perform a timely cesarean delivery, and follow a chain of command. During the 12 hours that the mother was in labor at the hospital, nurses and physicians allegedly ignored her. Although the fetal heart-rate monitor showed fetal distress, the mother continued to lie unattended. At 12:40 PM, physicians called for cesarean delivery due to fetal distress, but it took an hour for the child to be born.

The negligence of the hospital staff and delay in delivery caused hypoxia, resulting in cerebral palsy. All medical records from the hospital’s neonatal clinic show that he suffered hypoxia at birth.

HOSPITAL’S DEFENSE:

The mother and child were treated for an infection, which is a recognized cause of cerebral palsy. The child was born with normal blood oxygen levels. His injury occurred before the mother came to the hospital.

VERDICT:

A $53 million Illinois verdict was returned. The hospital applied for a mistrial based on allegedly inflammatory comments by the prosecuting attorney, but that was dismissed.

Birth trauma: $2.75M settlement

A woman had her first prenatal visit at 21 weeks’ gestation. Her advanced maternal age (39 years) and poor health history, including prior delivery of a baby with intrauterine growth restriction (IUGR), put her at risk; her prenatal care was transferred to a high-risk clinic.

At her next prenatal visit, records noted that the mother’s job required excessive standing, that she tested positive for marijuana, and that she was at risk for IUGR. Notes did not say that the mother was informed of her IUGR risk nor was a plan created for additional testing to monitor IUGR.

Ultrasonography (US) performed at 25 weeks’ gestation estimated that the baby’s weight was in the 11th- to 12th-week percentile. Amniotic fluid volume was noted as normal.

The mother missed her next appointment but returned at 28 weeks’ gestation, when she reported a headache and was found to have high blood pressure. US revealed normal fetal heart anatomy but amniotic fluid volume was noted to have decreased since the first US. The mother missed the next several appointments.

When she presented at 33 weeks’ gestation, her blood pressure was 160/97 mm Hg, fetal heart-rate tones were normal, and there was positive fetal movement. Fundal height measurement revealed a 3-cm discrepancy in date and size, suggesting a small baby, decreased amniotic fluid, or both. The ObGyn ordered testing for the next day. When a nonstress test performed from 8:44 AM to 9:10 AM was nonreassuring, the mother was ordered to immediately go to the hospital. She did not arrive at the hospital until 11:13 AM, when she was placed on fetal heart-rate monitor; test results were nonreassuring. At 11:30 AM, US revealed IUGR and oligohydramnios. An urgent cesarean delivery was performed and the baby was born at 11:56 AM.

The child’s Apgar scores were 4 and 9 at 1 and 5 minutes, respectively. The baby developed white matter brain damage and grade III and IV intraventricular hemorrhages due to hypoxia, ischemia, and metabolic acidosis. A maternal drug screen was positive for marijuana. Placental pathology revealed multiple abnormalities including placental infarcts involving approximately 50% of placental tissue, abnormal vascular changes, intervillous fibrin deposition, and chronic villitis.

At trial, the child had developmental delays, cognitive defects, learning disabilities, and breakthrough seizures.

PARENT’S CLAIM:

The mother claimed that the high-risk clinic was negligent. A plan should have been put into place at her first visit to monitor for IUGR based on her history. She was not advised of her risk of having another IUGR baby. Fundal height measurement, US to test for IUGR, or assessments of fetal heart-rate tones and fetal movement were not performed regularly. If a nonstress test had been performed earlier than 33 weeks’ gestation, she might have been admitted to the hospital for monitoring and earlier delivery, resulting in a healthier baby.

DEFENDANTS’ DEFENSE:

The mother was noncompliant and missed most of her prenatal appointments. She also continued to smoke marijuana throughout her pregnancy although she was told to stop. When the mother arrived at the prenatal clinic at 33 weeks’ gestation, tests were ordered and delivery occurred in a timely fashion. Any problems suffered by the child were a result of prematurity and damage that occurred during the 5 weeks of missed prenatal appointments.

VERDICT:

A $2.75M Missouri settlement was reached.

Who should have delivered the baby?

A mother’s prenatal care was managed by her family practitioner (FP). The mother went to the FP for induction of labor, but it was unsuccessful. Three days later, the baby was delivered by the FP and began having seizures a few minutes after birth. The child is quadriplegic and has severe cerebral palsy.

PARENTS’ CLAIM:

The FP was negligent in managing labor and delivery. She should have called an ObGyn to manage the labor. She failed to monitor fetal heart-rate tracings and failed to order an emergency cesarean delivery. The FP mismanaged the baby’s condition upon delivery and seizures started.

PHYSICIAN’S DEFENSE:

The FP properly managed the delivery and postdelivery complications. The brain injury had nothing to do with the birth; it was instead caused by a stroke disorder that occurred 3 to 7 days before delivery.

VERDICT:

A Minnesota defense verdict was returned.  

Undiagnosed H1N1 influenza (swine flu) during pregnancy; mother and child die: $16.7M verdict

At 7 months’ gestation, a 27-year-old woman presented to a clinic on June 26 with a runny nose, congestion, cough, wheezing, chills, and sweats. The physician noted concern about proteinuria and that the patient reported chills and sweats, but that he was uncertain as to the symptoms’ cause. He recommended that she see her ObGyn immediately and report to the emergency department (ED) if symptoms worsened. The patient called her ObGyn to report having a temperature between 94˚F and 103˚F and taking acetaminophen. The next day, she saw a nurse practitioner in the ObGyn’s office who documented that the patient was not given antiviral medication.

On June 29, the patient was still feeling ill and went to the ED. Although a physician planned to discharge her, an ObGyn nurse recognized that the patient was too ill to leave and had her admitted.

The patient’s condition worsened overnight and she was transferred to the intensive care unit (ICU), where she was intubated and put on a ventilator. Medical notes read “as whether influenza was present was unclear…Tamiflu will be started, but the efficacy of it this late into a possible influenza episode is extremely questionable.” ICU physicians believed that the best option was to deliver the child. After the patient’s husband gave permission, the child was born by cesarean delivery. The mother never regained full consciousness and remained in a medically induced coma. She died on August 11 after the family decided to remove life support.

After being given the diagnosis of intrauterine hypoxia, the child remained in intensive care for several weeks and then was discharged home. Seven months later, the father found his daughter in bed, not breathing, which physicians believed was an episode of sudden infant death syndrome. The father performed CPR and rushed her to the hospital. Physicians tried twice to take the child off the ventilator, but she could not breathe without assistance. On February 21, life support was removed and the child died.

ESTATES’ CLAIM:

The clinic and its physician were negligent for failing to recognize that the mother had influenza; she presented with classic flu symptoms during a worldwide pandemic. In the several months before the patient’s visit, the clinic had received notices from health authorities alerting medical professionals to the dangers of H1N1 influenza, or Swine Flu. The clinic also had received, before the patient’s visit, information warning of an elevated risk of H1N1 to pregnant women, with instructions to administer oseltamivir phosphate (Tamiflu) to any pregnant woman suspected of having influenza.

DEFENDANTS’ DEFENSE:

The clinic and physician denied negligence, claiming that treatment of the mother was appropriate.

VERDICT:

A $16.7 million Washington verdict was returned.

Mother claims to being uninformed of antiepileptics’ risks

A woman with epilepsy gave birth to a child with physical and cognitive birth defects.

PARENT’S CLAIM:

The mother claimed that, although she was of child-bearing age, she had never been informed of the risk of birth defects associated with taking an antiepileptic medication. Had she known of the risk, she would not have chosen to conceive. The physicians should have prescribed a different antiepileptic drug.

DEFENDANTS’ DEFENSE:

The clinic’s physicians met the standard of care in prescribing the drug. They properly informed the mother of the risks of taking the antiepileptic drug during pregnancy. The patient was allergic to all other antiepileptic drugs available at the time, so an alternative was not available.

VERDICT:

An Illinois defense verdict was returned for the clinic.

Mother has stroke during delivery: $3M settlement

A 42-year-old woman had a hemorrhagic stroke during the delivery of her first child. She remained hospitalized for observation with a medical plan to insert a drain if her condition worsened. Initially she did well, but she then began to have episodes of decreased consciousness and loss of function and later became unresponsive. Her physicians then undertook an emergency procedure to attempt to drain blood from her brain, but the surgical measure did not prevent her from incurring significant cognitive and physical injuries.

PATIENT’S CLAIM:

The agreed-upon medical plan of treatment was not followed, resulting in severe brain damage to the patient.

DEFENDANTS’ DEFENSE:

The case was settled during the trial.

VERDICT:

A $3 million Massachusetts settlement was reached. 

Did delayed cesarean cause cognitive defects?

When fetal distress was detected, the nurse called the patient’s ObGyn at 12:30 AM. The ObGyn arrived at the hospital at 12:48 AM, ordered a cesarean delivery at 12:56 AM, and the baby was born at 1:20 AM.

PARENTS’ CLAIM:

The ObGyn was negligent for not calling for the hospital’s on-duty resident physician to become involved in the case when the nurse phoned at 12:30 AM. If the ObGyn had done so, cesarean delivery would have been ordered and completed earlier, which would have averted the child’s injuries, including cognitive and physical impairments.

PHYSICIAN’S DEFENSE:

The ObGyn asserted that, based on the information provided to her, there was no reason to request the resident’s involvement. An earlier cesarean delivery was not necessary based on fetal heart-rate monitoring strip results. The ObGyn acted in a timely manner when calling for cesarean delivery. There was no concrete evidence that any alleged delay caused the child’s injuries.

VERDICT:

An Illinois defense verdict was returned.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Claimed missteps lead to brain damage: $53M award

At 2:00 AM, a woman at 40 weeks’ gestation went to a hospital because she felt a decrease in fetal movement. At birth, the baby was not breathing. He was rushed to the neonatal intensive care unit where he was resuscitated and placed on life support. He remained in critical care for 4 weeks. The child has cerebral palsy and cannot walk, talk, or care for himself. He will need 24-hour care for the rest of his life.

PARENT’S CLAIM:

The lawsuit cited 20 alleged missteps by physicians and nurses, including failure to: react to abnormal fetal heart-rate patterns that indicated fetal distress, perform a timely cesarean delivery, and follow a chain of command. During the 12 hours that the mother was in labor at the hospital, nurses and physicians allegedly ignored her. Although the fetal heart-rate monitor showed fetal distress, the mother continued to lie unattended. At 12:40 PM, physicians called for cesarean delivery due to fetal distress, but it took an hour for the child to be born.

The negligence of the hospital staff and delay in delivery caused hypoxia, resulting in cerebral palsy. All medical records from the hospital’s neonatal clinic show that he suffered hypoxia at birth.

HOSPITAL’S DEFENSE:

The mother and child were treated for an infection, which is a recognized cause of cerebral palsy. The child was born with normal blood oxygen levels. His injury occurred before the mother came to the hospital.

VERDICT:

A $53 million Illinois verdict was returned. The hospital applied for a mistrial based on allegedly inflammatory comments by the prosecuting attorney, but that was dismissed.

Birth trauma: $2.75M settlement

A woman had her first prenatal visit at 21 weeks’ gestation. Her advanced maternal age (39 years) and poor health history, including prior delivery of a baby with intrauterine growth restriction (IUGR), put her at risk; her prenatal care was transferred to a high-risk clinic.

At her next prenatal visit, records noted that the mother’s job required excessive standing, that she tested positive for marijuana, and that she was at risk for IUGR. Notes did not say that the mother was informed of her IUGR risk nor was a plan created for additional testing to monitor IUGR.

Ultrasonography (US) performed at 25 weeks’ gestation estimated that the baby’s weight was in the 11th- to 12th-week percentile. Amniotic fluid volume was noted as normal.

The mother missed her next appointment but returned at 28 weeks’ gestation, when she reported a headache and was found to have high blood pressure. US revealed normal fetal heart anatomy but amniotic fluid volume was noted to have decreased since the first US. The mother missed the next several appointments.

When she presented at 33 weeks’ gestation, her blood pressure was 160/97 mm Hg, fetal heart-rate tones were normal, and there was positive fetal movement. Fundal height measurement revealed a 3-cm discrepancy in date and size, suggesting a small baby, decreased amniotic fluid, or both. The ObGyn ordered testing for the next day. When a nonstress test performed from 8:44 AM to 9:10 AM was nonreassuring, the mother was ordered to immediately go to the hospital. She did not arrive at the hospital until 11:13 AM, when she was placed on fetal heart-rate monitor; test results were nonreassuring. At 11:30 AM, US revealed IUGR and oligohydramnios. An urgent cesarean delivery was performed and the baby was born at 11:56 AM.

The child’s Apgar scores were 4 and 9 at 1 and 5 minutes, respectively. The baby developed white matter brain damage and grade III and IV intraventricular hemorrhages due to hypoxia, ischemia, and metabolic acidosis. A maternal drug screen was positive for marijuana. Placental pathology revealed multiple abnormalities including placental infarcts involving approximately 50% of placental tissue, abnormal vascular changes, intervillous fibrin deposition, and chronic villitis.

At trial, the child had developmental delays, cognitive defects, learning disabilities, and breakthrough seizures.

PARENT’S CLAIM:

The mother claimed that the high-risk clinic was negligent. A plan should have been put into place at her first visit to monitor for IUGR based on her history. She was not advised of her risk of having another IUGR baby. Fundal height measurement, US to test for IUGR, or assessments of fetal heart-rate tones and fetal movement were not performed regularly. If a nonstress test had been performed earlier than 33 weeks’ gestation, she might have been admitted to the hospital for monitoring and earlier delivery, resulting in a healthier baby.

DEFENDANTS’ DEFENSE:

The mother was noncompliant and missed most of her prenatal appointments. She also continued to smoke marijuana throughout her pregnancy although she was told to stop. When the mother arrived at the prenatal clinic at 33 weeks’ gestation, tests were ordered and delivery occurred in a timely fashion. Any problems suffered by the child were a result of prematurity and damage that occurred during the 5 weeks of missed prenatal appointments.

VERDICT:

A $2.75M Missouri settlement was reached.

Who should have delivered the baby?

A mother’s prenatal care was managed by her family practitioner (FP). The mother went to the FP for induction of labor, but it was unsuccessful. Three days later, the baby was delivered by the FP and began having seizures a few minutes after birth. The child is quadriplegic and has severe cerebral palsy.

PARENTS’ CLAIM:

The FP was negligent in managing labor and delivery. She should have called an ObGyn to manage the labor. She failed to monitor fetal heart-rate tracings and failed to order an emergency cesarean delivery. The FP mismanaged the baby’s condition upon delivery and seizures started.

PHYSICIAN’S DEFENSE:

The FP properly managed the delivery and postdelivery complications. The brain injury had nothing to do with the birth; it was instead caused by a stroke disorder that occurred 3 to 7 days before delivery.

VERDICT:

A Minnesota defense verdict was returned.  

Undiagnosed H1N1 influenza (swine flu) during pregnancy; mother and child die: $16.7M verdict

At 7 months’ gestation, a 27-year-old woman presented to a clinic on June 26 with a runny nose, congestion, cough, wheezing, chills, and sweats. The physician noted concern about proteinuria and that the patient reported chills and sweats, but that he was uncertain as to the symptoms’ cause. He recommended that she see her ObGyn immediately and report to the emergency department (ED) if symptoms worsened. The patient called her ObGyn to report having a temperature between 94˚F and 103˚F and taking acetaminophen. The next day, she saw a nurse practitioner in the ObGyn’s office who documented that the patient was not given antiviral medication.

On June 29, the patient was still feeling ill and went to the ED. Although a physician planned to discharge her, an ObGyn nurse recognized that the patient was too ill to leave and had her admitted.

The patient’s condition worsened overnight and she was transferred to the intensive care unit (ICU), where she was intubated and put on a ventilator. Medical notes read “as whether influenza was present was unclear…Tamiflu will be started, but the efficacy of it this late into a possible influenza episode is extremely questionable.” ICU physicians believed that the best option was to deliver the child. After the patient’s husband gave permission, the child was born by cesarean delivery. The mother never regained full consciousness and remained in a medically induced coma. She died on August 11 after the family decided to remove life support.

After being given the diagnosis of intrauterine hypoxia, the child remained in intensive care for several weeks and then was discharged home. Seven months later, the father found his daughter in bed, not breathing, which physicians believed was an episode of sudden infant death syndrome. The father performed CPR and rushed her to the hospital. Physicians tried twice to take the child off the ventilator, but she could not breathe without assistance. On February 21, life support was removed and the child died.

ESTATES’ CLAIM:

The clinic and its physician were negligent for failing to recognize that the mother had influenza; she presented with classic flu symptoms during a worldwide pandemic. In the several months before the patient’s visit, the clinic had received notices from health authorities alerting medical professionals to the dangers of H1N1 influenza, or Swine Flu. The clinic also had received, before the patient’s visit, information warning of an elevated risk of H1N1 to pregnant women, with instructions to administer oseltamivir phosphate (Tamiflu) to any pregnant woman suspected of having influenza.

DEFENDANTS’ DEFENSE:

The clinic and physician denied negligence, claiming that treatment of the mother was appropriate.

VERDICT:

A $16.7 million Washington verdict was returned.

Mother claims to being uninformed of antiepileptics’ risks

A woman with epilepsy gave birth to a child with physical and cognitive birth defects.

PARENT’S CLAIM:

The mother claimed that, although she was of child-bearing age, she had never been informed of the risk of birth defects associated with taking an antiepileptic medication. Had she known of the risk, she would not have chosen to conceive. The physicians should have prescribed a different antiepileptic drug.

DEFENDANTS’ DEFENSE:

The clinic’s physicians met the standard of care in prescribing the drug. They properly informed the mother of the risks of taking the antiepileptic drug during pregnancy. The patient was allergic to all other antiepileptic drugs available at the time, so an alternative was not available.

VERDICT:

An Illinois defense verdict was returned for the clinic.

Mother has stroke during delivery: $3M settlement

A 42-year-old woman had a hemorrhagic stroke during the delivery of her first child. She remained hospitalized for observation with a medical plan to insert a drain if her condition worsened. Initially she did well, but she then began to have episodes of decreased consciousness and loss of function and later became unresponsive. Her physicians then undertook an emergency procedure to attempt to drain blood from her brain, but the surgical measure did not prevent her from incurring significant cognitive and physical injuries.

PATIENT’S CLAIM:

The agreed-upon medical plan of treatment was not followed, resulting in severe brain damage to the patient.

DEFENDANTS’ DEFENSE:

The case was settled during the trial.

VERDICT:

A $3 million Massachusetts settlement was reached. 

Did delayed cesarean cause cognitive defects?

When fetal distress was detected, the nurse called the patient’s ObGyn at 12:30 AM. The ObGyn arrived at the hospital at 12:48 AM, ordered a cesarean delivery at 12:56 AM, and the baby was born at 1:20 AM.

PARENTS’ CLAIM:

The ObGyn was negligent for not calling for the hospital’s on-duty resident physician to become involved in the case when the nurse phoned at 12:30 AM. If the ObGyn had done so, cesarean delivery would have been ordered and completed earlier, which would have averted the child’s injuries, including cognitive and physical impairments.

PHYSICIAN’S DEFENSE:

The ObGyn asserted that, based on the information provided to her, there was no reason to request the resident’s involvement. An earlier cesarean delivery was not necessary based on fetal heart-rate monitoring strip results. The ObGyn acted in a timely manner when calling for cesarean delivery. There was no concrete evidence that any alleged delay caused the child’s injuries.

VERDICT:

An Illinois defense verdict was returned.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Claimed missteps lead to brain damage: $53M award

At 2:00 AM, a woman at 40 weeks’ gestation went to a hospital because she felt a decrease in fetal movement. At birth, the baby was not breathing. He was rushed to the neonatal intensive care unit where he was resuscitated and placed on life support. He remained in critical care for 4 weeks. The child has cerebral palsy and cannot walk, talk, or care for himself. He will need 24-hour care for the rest of his life.

PARENT’S CLAIM:

The lawsuit cited 20 alleged missteps by physicians and nurses, including failure to: react to abnormal fetal heart-rate patterns that indicated fetal distress, perform a timely cesarean delivery, and follow a chain of command. During the 12 hours that the mother was in labor at the hospital, nurses and physicians allegedly ignored her. Although the fetal heart-rate monitor showed fetal distress, the mother continued to lie unattended. At 12:40 PM, physicians called for cesarean delivery due to fetal distress, but it took an hour for the child to be born.

The negligence of the hospital staff and delay in delivery caused hypoxia, resulting in cerebral palsy. All medical records from the hospital’s neonatal clinic show that he suffered hypoxia at birth.

HOSPITAL’S DEFENSE:

The mother and child were treated for an infection, which is a recognized cause of cerebral palsy. The child was born with normal blood oxygen levels. His injury occurred before the mother came to the hospital.

VERDICT:

A $53 million Illinois verdict was returned. The hospital applied for a mistrial based on allegedly inflammatory comments by the prosecuting attorney, but that was dismissed.

Birth trauma: $2.75M settlement

A woman had her first prenatal visit at 21 weeks’ gestation. Her advanced maternal age (39 years) and poor health history, including prior delivery of a baby with intrauterine growth restriction (IUGR), put her at risk; her prenatal care was transferred to a high-risk clinic.

At her next prenatal visit, records noted that the mother’s job required excessive standing, that she tested positive for marijuana, and that she was at risk for IUGR. Notes did not say that the mother was informed of her IUGR risk nor was a plan created for additional testing to monitor IUGR.

Ultrasonography (US) performed at 25 weeks’ gestation estimated that the baby’s weight was in the 11th- to 12th-week percentile. Amniotic fluid volume was noted as normal.

The mother missed her next appointment but returned at 28 weeks’ gestation, when she reported a headache and was found to have high blood pressure. US revealed normal fetal heart anatomy but amniotic fluid volume was noted to have decreased since the first US. The mother missed the next several appointments.

When she presented at 33 weeks’ gestation, her blood pressure was 160/97 mm Hg, fetal heart-rate tones were normal, and there was positive fetal movement. Fundal height measurement revealed a 3-cm discrepancy in date and size, suggesting a small baby, decreased amniotic fluid, or both. The ObGyn ordered testing for the next day. When a nonstress test performed from 8:44 AM to 9:10 AM was nonreassuring, the mother was ordered to immediately go to the hospital. She did not arrive at the hospital until 11:13 AM, when she was placed on fetal heart-rate monitor; test results were nonreassuring. At 11:30 AM, US revealed IUGR and oligohydramnios. An urgent cesarean delivery was performed and the baby was born at 11:56 AM.

The child’s Apgar scores were 4 and 9 at 1 and 5 minutes, respectively. The baby developed white matter brain damage and grade III and IV intraventricular hemorrhages due to hypoxia, ischemia, and metabolic acidosis. A maternal drug screen was positive for marijuana. Placental pathology revealed multiple abnormalities including placental infarcts involving approximately 50% of placental tissue, abnormal vascular changes, intervillous fibrin deposition, and chronic villitis.

At trial, the child had developmental delays, cognitive defects, learning disabilities, and breakthrough seizures.

PARENT’S CLAIM:

The mother claimed that the high-risk clinic was negligent. A plan should have been put into place at her first visit to monitor for IUGR based on her history. She was not advised of her risk of having another IUGR baby. Fundal height measurement, US to test for IUGR, or assessments of fetal heart-rate tones and fetal movement were not performed regularly. If a nonstress test had been performed earlier than 33 weeks’ gestation, she might have been admitted to the hospital for monitoring and earlier delivery, resulting in a healthier baby.

DEFENDANTS’ DEFENSE:

The mother was noncompliant and missed most of her prenatal appointments. She also continued to smoke marijuana throughout her pregnancy although she was told to stop. When the mother arrived at the prenatal clinic at 33 weeks’ gestation, tests were ordered and delivery occurred in a timely fashion. Any problems suffered by the child were a result of prematurity and damage that occurred during the 5 weeks of missed prenatal appointments.

VERDICT:

A $2.75M Missouri settlement was reached.

Who should have delivered the baby?

A mother’s prenatal care was managed by her family practitioner (FP). The mother went to the FP for induction of labor, but it was unsuccessful. Three days later, the baby was delivered by the FP and began having seizures a few minutes after birth. The child is quadriplegic and has severe cerebral palsy.

PARENTS’ CLAIM:

The FP was negligent in managing labor and delivery. She should have called an ObGyn to manage the labor. She failed to monitor fetal heart-rate tracings and failed to order an emergency cesarean delivery. The FP mismanaged the baby’s condition upon delivery and seizures started.

PHYSICIAN’S DEFENSE:

The FP properly managed the delivery and postdelivery complications. The brain injury had nothing to do with the birth; it was instead caused by a stroke disorder that occurred 3 to 7 days before delivery.

VERDICT:

A Minnesota defense verdict was returned.  

Undiagnosed H1N1 influenza (swine flu) during pregnancy; mother and child die: $16.7M verdict

At 7 months’ gestation, a 27-year-old woman presented to a clinic on June 26 with a runny nose, congestion, cough, wheezing, chills, and sweats. The physician noted concern about proteinuria and that the patient reported chills and sweats, but that he was uncertain as to the symptoms’ cause. He recommended that she see her ObGyn immediately and report to the emergency department (ED) if symptoms worsened. The patient called her ObGyn to report having a temperature between 94˚F and 103˚F and taking acetaminophen. The next day, she saw a nurse practitioner in the ObGyn’s office who documented that the patient was not given antiviral medication.

On June 29, the patient was still feeling ill and went to the ED. Although a physician planned to discharge her, an ObGyn nurse recognized that the patient was too ill to leave and had her admitted.

The patient’s condition worsened overnight and she was transferred to the intensive care unit (ICU), where she was intubated and put on a ventilator. Medical notes read “as whether influenza was present was unclear…Tamiflu will be started, but the efficacy of it this late into a possible influenza episode is extremely questionable.” ICU physicians believed that the best option was to deliver the child. After the patient’s husband gave permission, the child was born by cesarean delivery. The mother never regained full consciousness and remained in a medically induced coma. She died on August 11 after the family decided to remove life support.

After being given the diagnosis of intrauterine hypoxia, the child remained in intensive care for several weeks and then was discharged home. Seven months later, the father found his daughter in bed, not breathing, which physicians believed was an episode of sudden infant death syndrome. The father performed CPR and rushed her to the hospital. Physicians tried twice to take the child off the ventilator, but she could not breathe without assistance. On February 21, life support was removed and the child died.

ESTATES’ CLAIM:

The clinic and its physician were negligent for failing to recognize that the mother had influenza; she presented with classic flu symptoms during a worldwide pandemic. In the several months before the patient’s visit, the clinic had received notices from health authorities alerting medical professionals to the dangers of H1N1 influenza, or Swine Flu. The clinic also had received, before the patient’s visit, information warning of an elevated risk of H1N1 to pregnant women, with instructions to administer oseltamivir phosphate (Tamiflu) to any pregnant woman suspected of having influenza.

DEFENDANTS’ DEFENSE:

The clinic and physician denied negligence, claiming that treatment of the mother was appropriate.

VERDICT:

A $16.7 million Washington verdict was returned.

Mother claims to being uninformed of antiepileptics’ risks

A woman with epilepsy gave birth to a child with physical and cognitive birth defects.

PARENT’S CLAIM:

The mother claimed that, although she was of child-bearing age, she had never been informed of the risk of birth defects associated with taking an antiepileptic medication. Had she known of the risk, she would not have chosen to conceive. The physicians should have prescribed a different antiepileptic drug.

DEFENDANTS’ DEFENSE:

The clinic’s physicians met the standard of care in prescribing the drug. They properly informed the mother of the risks of taking the antiepileptic drug during pregnancy. The patient was allergic to all other antiepileptic drugs available at the time, so an alternative was not available.

VERDICT:

An Illinois defense verdict was returned for the clinic.

Mother has stroke during delivery: $3M settlement

A 42-year-old woman had a hemorrhagic stroke during the delivery of her first child. She remained hospitalized for observation with a medical plan to insert a drain if her condition worsened. Initially she did well, but she then began to have episodes of decreased consciousness and loss of function and later became unresponsive. Her physicians then undertook an emergency procedure to attempt to drain blood from her brain, but the surgical measure did not prevent her from incurring significant cognitive and physical injuries.

PATIENT’S CLAIM:

The agreed-upon medical plan of treatment was not followed, resulting in severe brain damage to the patient.

DEFENDANTS’ DEFENSE:

The case was settled during the trial.

VERDICT:

A $3 million Massachusetts settlement was reached. 

Did delayed cesarean cause cognitive defects?

When fetal distress was detected, the nurse called the patient’s ObGyn at 12:30 AM. The ObGyn arrived at the hospital at 12:48 AM, ordered a cesarean delivery at 12:56 AM, and the baby was born at 1:20 AM.

PARENTS’ CLAIM:

The ObGyn was negligent for not calling for the hospital’s on-duty resident physician to become involved in the case when the nurse phoned at 12:30 AM. If the ObGyn had done so, cesarean delivery would have been ordered and completed earlier, which would have averted the child’s injuries, including cognitive and physical impairments.

PHYSICIAN’S DEFENSE:

The ObGyn asserted that, based on the information provided to her, there was no reason to request the resident’s involvement. An earlier cesarean delivery was not necessary based on fetal heart-rate monitoring strip results. The ObGyn acted in a timely manner when calling for cesarean delivery. There was no concrete evidence that any alleged delay caused the child’s injuries.

VERDICT:

An Illinois defense verdict was returned.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.

• Be comfortable taking a sexual history from their patients.
• Understand the prevalence of HSDD.
• Understand how to diagnose HSDD and distinguish it from other sexual complaints.
• Understand data from trials involving pharmacologic agents both approved and not approved in attempts to treat HSDD.
• Employ multidisciplinary communication strategies to improve quality of life in patients with PDP

This CME supplement entitles the reader to 1 free CME credit.

Click here to read supplement.

After reading the supplement, click here to access the CME posttest 

• Be comfortable taking a sexual history from their patients.
• Understand the prevalence of HSDD.
• Understand how to diagnose HSDD and distinguish it from other sexual complaints.
• Understand data from trials involving pharmacologic agents both approved and not approved in attempts to treat HSDD.
• Employ multidisciplinary communication strategies to improve quality of life in patients with PDP

This CME supplement entitles the reader to 1 free CME credit.

Click here to read supplement.

After reading the supplement, click here to access the CME posttest 

• Be comfortable taking a sexual history from their patients.
• Understand the prevalence of HSDD.
• Understand how to diagnose HSDD and distinguish it from other sexual complaints.
• Understand data from trials involving pharmacologic agents both approved and not approved in attempts to treat HSDD.
• Employ multidisciplinary communication strategies to improve quality of life in patients with PDP

This CME supplement entitles the reader to 1 free CME credit.

Click here to read supplement.

After reading the supplement, click here to access the CME posttest 

In a striking trend, the rate of contralateral prophylactic mastectomy (CPM) has risen by 30% over the last 10 years in the United States.¹ Many women undergo CPM because of the fear and anxiety of cancer recurrence and their perceived risk of contralateral breast cancer; however, few women have a medical condition that necessitates removal of the contralateral breast. The medical indications for CPM include having a pathogenic genetic mutation (eg, BRCA1 and BRCA2), a strong family history of breast cancer, or prior mediastina chest radiation.

The actual risk of contralateral breast cancer is much lower than perceived. In women without a genetic mutation, the 10-year risk of contralateral breast cancer is only 3% to 5%.¹ Also, CPM does not prevent the development of metastatic disease and offers no survival benefit over breast conservation or unilateral mastectomy.² Furthermore, compared with unilateral therapeutic mastectomy, the “upgrade” to a CPM carries a 2.7-fold risk of a major surgical complication.³ It is therefore important that patients receive appropriate counseling regarding CPM, and that this counseling include cancer stage at diagnosis, family history and genetic risk, and cancer versus surgical risk (see “Counseling patients on contralateral prophylactic mastectomy” for key points to cover in patient discussions).

Women should be made aware that there are alternatives to mastectomy that have similar, or even better, outcomes with improved quality of life. Furthermore, a multi‑disciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care. Knowledge of this team approach and of modern breast cancer treatments is essential for general ObGyns as this understanding improves the overall care and guidance—specifically regarding referral to expert, high-volume breast surgeons—provided to those women most in need.

Expanded treatment options for breast cancer

Advancements in breast surgery, better imaging, and targeted therapies are changing the paradigm of breast cancer treatment.

Image-guided biopsy is key in decision making

When an abnormality is found in the breast, surgical excision of an undiagnosed breast lesion is no longer considered an appropriate first step. Use of image-guided biopsy or minimally invasive core needle biopsy allows for accurate diagnosis of a breast lesion while avoiding a potentially breast deforming and expensive surgical operation. It is always better to go into the operating room (OR) with a diagnosis and do the right operation the first time.

A core needle biopsy, results of which demonstrate a benign lesion, helps avoid breast surgery in women who do not need it. If cancer is diagnosed on biopsy, the extent of disease can be better evaluated and decision making can be more informed, with a multidisciplinary approach used to consider the various options, including genetic counseling, plastic surgery consultation, or neoadjuvant therapy. Some lesions, such as those too close to the skin, chest wall, or an implant, may not be amenable to core needle biopsy and therefore require surgical excision for diagnosis.

Benefits of a multidisciplinary tumor conference

It is important for a multidisciplinary group of cancer specialists to review a patient’s case and discuss the ideal treatment plan prior to surgery. Some breast cancer subtypes (such as human epidermal growth factor receptor 2 [HER2]–overamplified breast cancer and many triple-negative breast cancers) are very sensitive to chemotherapy, and patients with these tumor types may benefit from receiving neoadjuvant chemotherapy prior to surgery. New types of chemotherapy may allow up to 60% of some breast cancers to diminish almost completely, with subsequent improved cosmetic results of breast surgery.⁴ It may also allow time for genetic counseling and testing prior to surgery. (See “How to code for a multidisciplinary tumor conference” for appropriate coding procedure.)

Image-guided lumpectomy

Advances in breast imaging have led to increased identification of nonpalpable breast cancers. Surgical excision of nonpalpable breast lesions requires image guidance, which can be done using a variety of techniques.

Wire-guided localization (WGL) has been used in practice for the past 40 years. The procedure involves placement of a hooked wire under local anesthesia using either mammographic or ultrasound guidance. This procedure is mostly done in the radiology department on the same day as the surgery and requires that the radiologist coordinate with the OR schedule. Besides scheduling conflicts and delays in surgery, this procedure can be complicated by wires becoming dislodged, transected, or migrated, and limits the surgeon’s ability to cosmetically hide the scar in relation to position of the wire. It is uncomfortable for the patient, who must be transported from the radiology department to the OR with a wire extruding from her breast.

An alternative localization technique is placement of a radioactive source within the tumor, which can then be identified in the OR with a gamma probe.

Iodine I 125 Radioactive seed localization (RSL) involves placing a 4-mm titanium radiolabeled seed into the breast lesion under mammographic or ultrasound guidance (FIGURES 1 and 2). The procedure can be performed a few days before surgery in the radiology department, and there is less chance for the seed to become displaced or dislodged. This technique provides scheduling flexibility for the radiologist and reduces OR delays. The surgeon uses the same gamma probe for sentinel node biopsy to find the lesion in the breast, using the setting specific for iodine I 125. Incisions can be tailored anywhere in the breast, and the seed is detected by a focal gamma signal. Once the lumpectomy is performed, the specimen is probed and radiographed to confirm removal of the seed and adequate margins.

Limitations of this procedure include potential loss of the seed during the operation and radiation safety issues regarding handling and disposal of the radioactive isotope. Once the seed has been placed in the patient’s body, it must be removed surgically, as the half-life of iodine I 125 is long (60 days).⁵ Care must therefore be taken to optimize medical clearance prior to seed placement and to avoid surgery cancellations.

Intraoperative ultrasound (IOUS) allows the surgeon to identify the lesion under general anesthesia in the OR, which is more comfortable for the patient. The surgical incision can be tailored cosmetically and the lumpectomy can be performed with real-time ultrasound visualization of the tumor during dissection. This technique eliminates the need for a separate preoperative seed or wire localization in radiology. However, it can be used only for lesions or clips that are visible by ultrasound. The excised specimen can be evaluated for confirmation of tumor removal and adequate margins via ultrasound and re-excision of close margins can be accomplished immediately if needed.

Results of a meta-analysis of WGL versus IOUS demonstrated a significant reduction of positive margins with the use of IOUS.⁶ Results of the COBALT trial, in which patients were assigned randomly to excision of palpable breast cancers with either IOUS or palpation, demonstrated a 14% reduction in positive margins in favor of IOUS.⁷ Surgeon-performed breast ultrasound requires advanced training and accreditation in breast ultrasound through a rigorous certification process offered by the American Society of Breast Surgeons (www.breastsurgeons.org).

Oncoplastic lumpectomy

This approach to lumpectomy combines adequate oncologist resection of the breast tumor with plastic surgery techniques to achieve superior cosmesis. This approach allows complete removal of the tumor with negative margins, yet maintains the normal shape and contour of the breast. Two techniques have been described: volume displacement and volume replacement.

With the volume displacement technique, the surgeon uses adjacent tissue advancement to fill the lumpectomy cavity with the patient’s own surrounding breast tissue (FIGURE 3). The volume replacement technique requires the transposition of autologous tissue from elsewhere in the body.

Oncoplastic lumpectomy allows more women with larger tumors to undergo breast conservation with better cosmetic results. It reduces the number of mastectomies performed without compromising local control and avoids the need for extensive plastic surgery reconstruction and implants. Special effort and attention must be paid to ensure adequate margins utilizing intraoperative specimen radiograph and pathology evaluation.

This procedure requires that the surgeon acquire specialized skills and knowledge of oncologic and plastic surgery techniques, and it is best performed with the collaboration of a multidisciplinary team. Compared with conventional lumpectomy or mastectomy, oncoplastic breast conservation has been shown to reduce re-excision rates, and it has similar rates of local and distant recurrence and similar disease-free survival and overall survival.^8,9

Total skin- and nipple-sparing mastectomy

Some patients do not have the option of breast conservation. Women with multicentric breast cancer (more than 1 tumor in different quadrants of the breast) are better served with mastectomy. Surgical techniques for mastectomy have improved and provide women with various options. One option is skin- and nipple-sparing mastectomy, which preserves the skin envelope overlying the breast (including the skin of the nipple and areola) while removing the glandular elements of the breast and the majority of ductal tissue beneath the nipple-areola complex (FIGURE 4). This surgery can be performed via hidden scars at the inframammary crease or periareolar and is combined with immediate reconstruction, which provides an excellent cosmetic result.

Surgical considerations include removing glandular breast tissue within its anatomic boundaries while maintaining the blood supply to the skin and nipple-areola complex. Furthermore, there must be close dissection of ductal tissue beneath the nipple-areola complex and intraoperative frozen section of the nipple margin in cancer cases. Nipple-sparing mastectomy is oncologically safe in carefully selected patients who do not have cancer near or within the skin or nipple (eg, Paget disease).¹⁰ It is also safe as a prophylactic procedure for patients with genetic mutations, such as BRCA1 and BRCA2.¹¹ The procedure is not ideal for smokers or patients with large, pendulous breasts. There is a 3% risk of breast cancer recurrence at the nipple or in the skin or muscle.¹⁰ Surgical complications include a 10% to 20% risk of skin or nipple necrosis.¹²

How do we manage the lymph nodes: Axillary dissection vs sentinel node biopsy?

Evaluation of the axillary nodes is currently part of breast cancer staging and can help the clinician determine the need for adjuvant chemotherapy. It also may assist in assessing the need for extending the radiation field beyond the breast to include the regional lymph nodes. Patients with early stage (stage I and II) breast cancer who do not have abnormal palpable lymph nodes or biopsy-proven metastasis to axillary nodes qualify for sentinel lymph node (SLN) biopsy.

Sentinel node biopsy = less morbidity with no loss of accuracy. Compared with axillary lymph node dissection (ALND; removing all the level I and II nodes in the axilla), SLN biopsy has a 98% accuracy and is associated with less morbidity from lymphedema. The procedure involves injecting the breast with 2 tracers: a radioactive isotope, injected into the breast within 24 hours of the operation, and isosulfan blue dye, injected into the breast in the OR at the time of surgery (see illustration). Both tracers travel through the breast lymphatics and concentrate in the first few lymph nodes that drain the breast. The surgery is performed through a separate axillary incision, and the blue and radioactive lymph nodes are individually dissected and removed for pathologic evaluation. On average, 2 to 4 sentinel nodes are removed, including any suspicious palpable nodes. In experienced hands, this procedure has a false-negative rate of less than 5% to 10%.¹³

Illustration: Kimberly Martens for OBG Management

Axillary node dissection no longer standard of care. The indication for a completion ALND has changed based on the results of the randomized trial, ACOSOG Z0011.¹⁴ In this trial, patients with early stage breast cancer and 1 to 2 positive SLNs who were undergoing breast conservation therapy with radiation and adjuvant systemic therapy were randomly assigned to ALND or no ALND. (The trial did not include patients who were undergoing mastectomy, neoadjuvant chemotherapy, or who had more than 2 metastatic lymph nodes.) The investigators found no difference in overall or disease-free survival or local-regional recurrence between the 2 treatment groups over 9.2 years of follow up.¹⁴

Based on this practice-changing trial result, guidelines of the National Comprehensive Cancer Network no longer recommend completion ALND for patients who meet the ACOSOG Z0011 criteria. For patients who do not meet ACOSOG Z0011 criteria, we do intraoperative pathologic lymph node assessment with either frozen section or imprint cytology, and we perform immediate ALND when results are positive.

Indications for SLN biopsy include:

• invasive breast cancer with clinically negative axillary nodes
• ductal carcinoma in situ (DCIS) with microinvasion or extensive enough to require mastectomy
• clinically negative axillary nodes after neoadjuvant chemotherapy.

Contraindications for SLN biopsy include:

• bulky palpable lymphadenopathy
• pregnancy, as the safety of radioactive isotope and blue dye is not well studied; in isotope mapping the radiation dose is small and within safety limits for pregnant patients
• inflammatory breast cancer.

Complications of any axillary surgery may include risk of lymphedema (5% with SLN biopsy and 30% to 40% with ALND).¹⁵ Other complications include neuropathy of the affected arm with chronic pain and numbness of the skin.

Positive trends: Improved patient outcomes, specialized clinician training

Management of breast cancer has changed dramatically over the past several decades. More women are surviving breast cancer thanks to improvements in early detection, an individualized treatment approach with less aggressive surgery, and more effective targeted systemic therapies. A multidisciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care.

Complexity in breast disease management has led to the development of formal fellowship training in breast surgical oncology. Studies have demonstrated that patients treated by high-volume breast surgeons are more satisfied with their care and have improved cancer outcomes.^16,17 Women should be aware that they have different options for their breast cancer care, and surgeons with advanced specialization in this field may provide optimal results and better quality of care.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In a striking trend, the rate of contralateral prophylactic mastectomy (CPM) has risen by 30% over the last 10 years in the United States.¹ Many women undergo CPM because of the fear and anxiety of cancer recurrence and their perceived risk of contralateral breast cancer; however, few women have a medical condition that necessitates removal of the contralateral breast. The medical indications for CPM include having a pathogenic genetic mutation (eg, BRCA1 and BRCA2), a strong family history of breast cancer, or prior mediastina chest radiation.

The actual risk of contralateral breast cancer is much lower than perceived. In women without a genetic mutation, the 10-year risk of contralateral breast cancer is only 3% to 5%.¹ Also, CPM does not prevent the development of metastatic disease and offers no survival benefit over breast conservation or unilateral mastectomy.² Furthermore, compared with unilateral therapeutic mastectomy, the “upgrade” to a CPM carries a 2.7-fold risk of a major surgical complication.³ It is therefore important that patients receive appropriate counseling regarding CPM, and that this counseling include cancer stage at diagnosis, family history and genetic risk, and cancer versus surgical risk (see “Counseling patients on contralateral prophylactic mastectomy” for key points to cover in patient discussions).

Women should be made aware that there are alternatives to mastectomy that have similar, or even better, outcomes with improved quality of life. Furthermore, a multi‑disciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care. Knowledge of this team approach and of modern breast cancer treatments is essential for general ObGyns as this understanding improves the overall care and guidance—specifically regarding referral to expert, high-volume breast surgeons—provided to those women most in need.

Expanded treatment options for breast cancer

Advancements in breast surgery, better imaging, and targeted therapies are changing the paradigm of breast cancer treatment.

Image-guided biopsy is key in decision making

When an abnormality is found in the breast, surgical excision of an undiagnosed breast lesion is no longer considered an appropriate first step. Use of image-guided biopsy or minimally invasive core needle biopsy allows for accurate diagnosis of a breast lesion while avoiding a potentially breast deforming and expensive surgical operation. It is always better to go into the operating room (OR) with a diagnosis and do the right operation the first time.

A core needle biopsy, results of which demonstrate a benign lesion, helps avoid breast surgery in women who do not need it. If cancer is diagnosed on biopsy, the extent of disease can be better evaluated and decision making can be more informed, with a multidisciplinary approach used to consider the various options, including genetic counseling, plastic surgery consultation, or neoadjuvant therapy. Some lesions, such as those too close to the skin, chest wall, or an implant, may not be amenable to core needle biopsy and therefore require surgical excision for diagnosis.

Benefits of a multidisciplinary tumor conference

It is important for a multidisciplinary group of cancer specialists to review a patient’s case and discuss the ideal treatment plan prior to surgery. Some breast cancer subtypes (such as human epidermal growth factor receptor 2 [HER2]–overamplified breast cancer and many triple-negative breast cancers) are very sensitive to chemotherapy, and patients with these tumor types may benefit from receiving neoadjuvant chemotherapy prior to surgery. New types of chemotherapy may allow up to 60% of some breast cancers to diminish almost completely, with subsequent improved cosmetic results of breast surgery.⁴ It may also allow time for genetic counseling and testing prior to surgery. (See “How to code for a multidisciplinary tumor conference” for appropriate coding procedure.)

Image-guided lumpectomy

Advances in breast imaging have led to increased identification of nonpalpable breast cancers. Surgical excision of nonpalpable breast lesions requires image guidance, which can be done using a variety of techniques.

Wire-guided localization (WGL) has been used in practice for the past 40 years. The procedure involves placement of a hooked wire under local anesthesia using either mammographic or ultrasound guidance. This procedure is mostly done in the radiology department on the same day as the surgery and requires that the radiologist coordinate with the OR schedule. Besides scheduling conflicts and delays in surgery, this procedure can be complicated by wires becoming dislodged, transected, or migrated, and limits the surgeon’s ability to cosmetically hide the scar in relation to position of the wire. It is uncomfortable for the patient, who must be transported from the radiology department to the OR with a wire extruding from her breast.

An alternative localization technique is placement of a radioactive source within the tumor, which can then be identified in the OR with a gamma probe.

Iodine I 125 Radioactive seed localization (RSL) involves placing a 4-mm titanium radiolabeled seed into the breast lesion under mammographic or ultrasound guidance (FIGURES 1 and 2). The procedure can be performed a few days before surgery in the radiology department, and there is less chance for the seed to become displaced or dislodged. This technique provides scheduling flexibility for the radiologist and reduces OR delays. The surgeon uses the same gamma probe for sentinel node biopsy to find the lesion in the breast, using the setting specific for iodine I 125. Incisions can be tailored anywhere in the breast, and the seed is detected by a focal gamma signal. Once the lumpectomy is performed, the specimen is probed and radiographed to confirm removal of the seed and adequate margins.

Limitations of this procedure include potential loss of the seed during the operation and radiation safety issues regarding handling and disposal of the radioactive isotope. Once the seed has been placed in the patient’s body, it must be removed surgically, as the half-life of iodine I 125 is long (60 days).⁵ Care must therefore be taken to optimize medical clearance prior to seed placement and to avoid surgery cancellations.

Intraoperative ultrasound (IOUS) allows the surgeon to identify the lesion under general anesthesia in the OR, which is more comfortable for the patient. The surgical incision can be tailored cosmetically and the lumpectomy can be performed with real-time ultrasound visualization of the tumor during dissection. This technique eliminates the need for a separate preoperative seed or wire localization in radiology. However, it can be used only for lesions or clips that are visible by ultrasound. The excised specimen can be evaluated for confirmation of tumor removal and adequate margins via ultrasound and re-excision of close margins can be accomplished immediately if needed.

Results of a meta-analysis of WGL versus IOUS demonstrated a significant reduction of positive margins with the use of IOUS.⁶ Results of the COBALT trial, in which patients were assigned randomly to excision of palpable breast cancers with either IOUS or palpation, demonstrated a 14% reduction in positive margins in favor of IOUS.⁷ Surgeon-performed breast ultrasound requires advanced training and accreditation in breast ultrasound through a rigorous certification process offered by the American Society of Breast Surgeons (www.breastsurgeons.org).

Oncoplastic lumpectomy

This approach to lumpectomy combines adequate oncologist resection of the breast tumor with plastic surgery techniques to achieve superior cosmesis. This approach allows complete removal of the tumor with negative margins, yet maintains the normal shape and contour of the breast. Two techniques have been described: volume displacement and volume replacement.

With the volume displacement technique, the surgeon uses adjacent tissue advancement to fill the lumpectomy cavity with the patient’s own surrounding breast tissue (FIGURE 3). The volume replacement technique requires the transposition of autologous tissue from elsewhere in the body.

Oncoplastic lumpectomy allows more women with larger tumors to undergo breast conservation with better cosmetic results. It reduces the number of mastectomies performed without compromising local control and avoids the need for extensive plastic surgery reconstruction and implants. Special effort and attention must be paid to ensure adequate margins utilizing intraoperative specimen radiograph and pathology evaluation.

This procedure requires that the surgeon acquire specialized skills and knowledge of oncologic and plastic surgery techniques, and it is best performed with the collaboration of a multidisciplinary team. Compared with conventional lumpectomy or mastectomy, oncoplastic breast conservation has been shown to reduce re-excision rates, and it has similar rates of local and distant recurrence and similar disease-free survival and overall survival.^8,9

Total skin- and nipple-sparing mastectomy

Some patients do not have the option of breast conservation. Women with multicentric breast cancer (more than 1 tumor in different quadrants of the breast) are better served with mastectomy. Surgical techniques for mastectomy have improved and provide women with various options. One option is skin- and nipple-sparing mastectomy, which preserves the skin envelope overlying the breast (including the skin of the nipple and areola) while removing the glandular elements of the breast and the majority of ductal tissue beneath the nipple-areola complex (FIGURE 4). This surgery can be performed via hidden scars at the inframammary crease or periareolar and is combined with immediate reconstruction, which provides an excellent cosmetic result.

Surgical considerations include removing glandular breast tissue within its anatomic boundaries while maintaining the blood supply to the skin and nipple-areola complex. Furthermore, there must be close dissection of ductal tissue beneath the nipple-areola complex and intraoperative frozen section of the nipple margin in cancer cases. Nipple-sparing mastectomy is oncologically safe in carefully selected patients who do not have cancer near or within the skin or nipple (eg, Paget disease).¹⁰ It is also safe as a prophylactic procedure for patients with genetic mutations, such as BRCA1 and BRCA2.¹¹ The procedure is not ideal for smokers or patients with large, pendulous breasts. There is a 3% risk of breast cancer recurrence at the nipple or in the skin or muscle.¹⁰ Surgical complications include a 10% to 20% risk of skin or nipple necrosis.¹²

How do we manage the lymph nodes: Axillary dissection vs sentinel node biopsy?

Evaluation of the axillary nodes is currently part of breast cancer staging and can help the clinician determine the need for adjuvant chemotherapy. It also may assist in assessing the need for extending the radiation field beyond the breast to include the regional lymph nodes. Patients with early stage (stage I and II) breast cancer who do not have abnormal palpable lymph nodes or biopsy-proven metastasis to axillary nodes qualify for sentinel lymph node (SLN) biopsy.

Sentinel node biopsy = less morbidity with no loss of accuracy. Compared with axillary lymph node dissection (ALND; removing all the level I and II nodes in the axilla), SLN biopsy has a 98% accuracy and is associated with less morbidity from lymphedema. The procedure involves injecting the breast with 2 tracers: a radioactive isotope, injected into the breast within 24 hours of the operation, and isosulfan blue dye, injected into the breast in the OR at the time of surgery (see illustration). Both tracers travel through the breast lymphatics and concentrate in the first few lymph nodes that drain the breast. The surgery is performed through a separate axillary incision, and the blue and radioactive lymph nodes are individually dissected and removed for pathologic evaluation. On average, 2 to 4 sentinel nodes are removed, including any suspicious palpable nodes. In experienced hands, this procedure has a false-negative rate of less than 5% to 10%.¹³

Illustration: Kimberly Martens for OBG Management

Axillary node dissection no longer standard of care. The indication for a completion ALND has changed based on the results of the randomized trial, ACOSOG Z0011.¹⁴ In this trial, patients with early stage breast cancer and 1 to 2 positive SLNs who were undergoing breast conservation therapy with radiation and adjuvant systemic therapy were randomly assigned to ALND or no ALND. (The trial did not include patients who were undergoing mastectomy, neoadjuvant chemotherapy, or who had more than 2 metastatic lymph nodes.) The investigators found no difference in overall or disease-free survival or local-regional recurrence between the 2 treatment groups over 9.2 years of follow up.¹⁴

Based on this practice-changing trial result, guidelines of the National Comprehensive Cancer Network no longer recommend completion ALND for patients who meet the ACOSOG Z0011 criteria. For patients who do not meet ACOSOG Z0011 criteria, we do intraoperative pathologic lymph node assessment with either frozen section or imprint cytology, and we perform immediate ALND when results are positive.

Indications for SLN biopsy include:

• invasive breast cancer with clinically negative axillary nodes
• ductal carcinoma in situ (DCIS) with microinvasion or extensive enough to require mastectomy
• clinically negative axillary nodes after neoadjuvant chemotherapy.

Contraindications for SLN biopsy include:

• bulky palpable lymphadenopathy
• pregnancy, as the safety of radioactive isotope and blue dye is not well studied; in isotope mapping the radiation dose is small and within safety limits for pregnant patients
• inflammatory breast cancer.

Complications of any axillary surgery may include risk of lymphedema (5% with SLN biopsy and 30% to 40% with ALND).¹⁵ Other complications include neuropathy of the affected arm with chronic pain and numbness of the skin.

Positive trends: Improved patient outcomes, specialized clinician training

Management of breast cancer has changed dramatically over the past several decades. More women are surviving breast cancer thanks to improvements in early detection, an individualized treatment approach with less aggressive surgery, and more effective targeted systemic therapies. A multidisciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care.

Complexity in breast disease management has led to the development of formal fellowship training in breast surgical oncology. Studies have demonstrated that patients treated by high-volume breast surgeons are more satisfied with their care and have improved cancer outcomes.^16,17 Women should be aware that they have different options for their breast cancer care, and surgeons with advanced specialization in this field may provide optimal results and better quality of care.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In a striking trend, the rate of contralateral prophylactic mastectomy (CPM) has risen by 30% over the last 10 years in the United States.¹ Many women undergo CPM because of the fear and anxiety of cancer recurrence and their perceived risk of contralateral breast cancer; however, few women have a medical condition that necessitates removal of the contralateral breast. The medical indications for CPM include having a pathogenic genetic mutation (eg, BRCA1 and BRCA2), a strong family history of breast cancer, or prior mediastina chest radiation.

The actual risk of contralateral breast cancer is much lower than perceived. In women without a genetic mutation, the 10-year risk of contralateral breast cancer is only 3% to 5%.¹ Also, CPM does not prevent the development of metastatic disease and offers no survival benefit over breast conservation or unilateral mastectomy.² Furthermore, compared with unilateral therapeutic mastectomy, the “upgrade” to a CPM carries a 2.7-fold risk of a major surgical complication.³ It is therefore important that patients receive appropriate counseling regarding CPM, and that this counseling include cancer stage at diagnosis, family history and genetic risk, and cancer versus surgical risk (see “Counseling patients on contralateral prophylactic mastectomy” for key points to cover in patient discussions).

Women should be made aware that there are alternatives to mastectomy that have similar, or even better, outcomes with improved quality of life. Furthermore, a multi‑disciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care. Knowledge of this team approach and of modern breast cancer treatments is essential for general ObGyns as this understanding improves the overall care and guidance—specifically regarding referral to expert, high-volume breast surgeons—provided to those women most in need.

Expanded treatment options for breast cancer

Advancements in breast surgery, better imaging, and targeted therapies are changing the paradigm of breast cancer treatment.

Image-guided biopsy is key in decision making

When an abnormality is found in the breast, surgical excision of an undiagnosed breast lesion is no longer considered an appropriate first step. Use of image-guided biopsy or minimally invasive core needle biopsy allows for accurate diagnosis of a breast lesion while avoiding a potentially breast deforming and expensive surgical operation. It is always better to go into the operating room (OR) with a diagnosis and do the right operation the first time.

A core needle biopsy, results of which demonstrate a benign lesion, helps avoid breast surgery in women who do not need it. If cancer is diagnosed on biopsy, the extent of disease can be better evaluated and decision making can be more informed, with a multidisciplinary approach used to consider the various options, including genetic counseling, plastic surgery consultation, or neoadjuvant therapy. Some lesions, such as those too close to the skin, chest wall, or an implant, may not be amenable to core needle biopsy and therefore require surgical excision for diagnosis.

Benefits of a multidisciplinary tumor conference

It is important for a multidisciplinary group of cancer specialists to review a patient’s case and discuss the ideal treatment plan prior to surgery. Some breast cancer subtypes (such as human epidermal growth factor receptor 2 [HER2]–overamplified breast cancer and many triple-negative breast cancers) are very sensitive to chemotherapy, and patients with these tumor types may benefit from receiving neoadjuvant chemotherapy prior to surgery. New types of chemotherapy may allow up to 60% of some breast cancers to diminish almost completely, with subsequent improved cosmetic results of breast surgery.⁴ It may also allow time for genetic counseling and testing prior to surgery. (See “How to code for a multidisciplinary tumor conference” for appropriate coding procedure.)

Image-guided lumpectomy

Advances in breast imaging have led to increased identification of nonpalpable breast cancers. Surgical excision of nonpalpable breast lesions requires image guidance, which can be done using a variety of techniques.

Wire-guided localization (WGL) has been used in practice for the past 40 years. The procedure involves placement of a hooked wire under local anesthesia using either mammographic or ultrasound guidance. This procedure is mostly done in the radiology department on the same day as the surgery and requires that the radiologist coordinate with the OR schedule. Besides scheduling conflicts and delays in surgery, this procedure can be complicated by wires becoming dislodged, transected, or migrated, and limits the surgeon’s ability to cosmetically hide the scar in relation to position of the wire. It is uncomfortable for the patient, who must be transported from the radiology department to the OR with a wire extruding from her breast.

An alternative localization technique is placement of a radioactive source within the tumor, which can then be identified in the OR with a gamma probe.

Iodine I 125 Radioactive seed localization (RSL) involves placing a 4-mm titanium radiolabeled seed into the breast lesion under mammographic or ultrasound guidance (FIGURES 1 and 2). The procedure can be performed a few days before surgery in the radiology department, and there is less chance for the seed to become displaced or dislodged. This technique provides scheduling flexibility for the radiologist and reduces OR delays. The surgeon uses the same gamma probe for sentinel node biopsy to find the lesion in the breast, using the setting specific for iodine I 125. Incisions can be tailored anywhere in the breast, and the seed is detected by a focal gamma signal. Once the lumpectomy is performed, the specimen is probed and radiographed to confirm removal of the seed and adequate margins.

Limitations of this procedure include potential loss of the seed during the operation and radiation safety issues regarding handling and disposal of the radioactive isotope. Once the seed has been placed in the patient’s body, it must be removed surgically, as the half-life of iodine I 125 is long (60 days).⁵ Care must therefore be taken to optimize medical clearance prior to seed placement and to avoid surgery cancellations.

Intraoperative ultrasound (IOUS) allows the surgeon to identify the lesion under general anesthesia in the OR, which is more comfortable for the patient. The surgical incision can be tailored cosmetically and the lumpectomy can be performed with real-time ultrasound visualization of the tumor during dissection. This technique eliminates the need for a separate preoperative seed or wire localization in radiology. However, it can be used only for lesions or clips that are visible by ultrasound. The excised specimen can be evaluated for confirmation of tumor removal and adequate margins via ultrasound and re-excision of close margins can be accomplished immediately if needed.

Results of a meta-analysis of WGL versus IOUS demonstrated a significant reduction of positive margins with the use of IOUS.⁶ Results of the COBALT trial, in which patients were assigned randomly to excision of palpable breast cancers with either IOUS or palpation, demonstrated a 14% reduction in positive margins in favor of IOUS.⁷ Surgeon-performed breast ultrasound requires advanced training and accreditation in breast ultrasound through a rigorous certification process offered by the American Society of Breast Surgeons (www.breastsurgeons.org).

Oncoplastic lumpectomy

This approach to lumpectomy combines adequate oncologist resection of the breast tumor with plastic surgery techniques to achieve superior cosmesis. This approach allows complete removal of the tumor with negative margins, yet maintains the normal shape and contour of the breast. Two techniques have been described: volume displacement and volume replacement.

With the volume displacement technique, the surgeon uses adjacent tissue advancement to fill the lumpectomy cavity with the patient’s own surrounding breast tissue (FIGURE 3). The volume replacement technique requires the transposition of autologous tissue from elsewhere in the body.

Oncoplastic lumpectomy allows more women with larger tumors to undergo breast conservation with better cosmetic results. It reduces the number of mastectomies performed without compromising local control and avoids the need for extensive plastic surgery reconstruction and implants. Special effort and attention must be paid to ensure adequate margins utilizing intraoperative specimen radiograph and pathology evaluation.

This procedure requires that the surgeon acquire specialized skills and knowledge of oncologic and plastic surgery techniques, and it is best performed with the collaboration of a multidisciplinary team. Compared with conventional lumpectomy or mastectomy, oncoplastic breast conservation has been shown to reduce re-excision rates, and it has similar rates of local and distant recurrence and similar disease-free survival and overall survival.^8,9

Total skin- and nipple-sparing mastectomy

Some patients do not have the option of breast conservation. Women with multicentric breast cancer (more than 1 tumor in different quadrants of the breast) are better served with mastectomy. Surgical techniques for mastectomy have improved and provide women with various options. One option is skin- and nipple-sparing mastectomy, which preserves the skin envelope overlying the breast (including the skin of the nipple and areola) while removing the glandular elements of the breast and the majority of ductal tissue beneath the nipple-areola complex (FIGURE 4). This surgery can be performed via hidden scars at the inframammary crease or periareolar and is combined with immediate reconstruction, which provides an excellent cosmetic result.

Surgical considerations include removing glandular breast tissue within its anatomic boundaries while maintaining the blood supply to the skin and nipple-areola complex. Furthermore, there must be close dissection of ductal tissue beneath the nipple-areola complex and intraoperative frozen section of the nipple margin in cancer cases. Nipple-sparing mastectomy is oncologically safe in carefully selected patients who do not have cancer near or within the skin or nipple (eg, Paget disease).¹⁰ It is also safe as a prophylactic procedure for patients with genetic mutations, such as BRCA1 and BRCA2.¹¹ The procedure is not ideal for smokers or patients with large, pendulous breasts. There is a 3% risk of breast cancer recurrence at the nipple or in the skin or muscle.¹⁰ Surgical complications include a 10% to 20% risk of skin or nipple necrosis.¹²

How do we manage the lymph nodes: Axillary dissection vs sentinel node biopsy?

Evaluation of the axillary nodes is currently part of breast cancer staging and can help the clinician determine the need for adjuvant chemotherapy. It also may assist in assessing the need for extending the radiation field beyond the breast to include the regional lymph nodes. Patients with early stage (stage I and II) breast cancer who do not have abnormal palpable lymph nodes or biopsy-proven metastasis to axillary nodes qualify for sentinel lymph node (SLN) biopsy.

Sentinel node biopsy = less morbidity with no loss of accuracy. Compared with axillary lymph node dissection (ALND; removing all the level I and II nodes in the axilla), SLN biopsy has a 98% accuracy and is associated with less morbidity from lymphedema. The procedure involves injecting the breast with 2 tracers: a radioactive isotope, injected into the breast within 24 hours of the operation, and isosulfan blue dye, injected into the breast in the OR at the time of surgery (see illustration). Both tracers travel through the breast lymphatics and concentrate in the first few lymph nodes that drain the breast. The surgery is performed through a separate axillary incision, and the blue and radioactive lymph nodes are individually dissected and removed for pathologic evaluation. On average, 2 to 4 sentinel nodes are removed, including any suspicious palpable nodes. In experienced hands, this procedure has a false-negative rate of less than 5% to 10%.¹³

Illustration: Kimberly Martens for OBG Management

Axillary node dissection no longer standard of care. The indication for a completion ALND has changed based on the results of the randomized trial, ACOSOG Z0011.¹⁴ In this trial, patients with early stage breast cancer and 1 to 2 positive SLNs who were undergoing breast conservation therapy with radiation and adjuvant systemic therapy were randomly assigned to ALND or no ALND. (The trial did not include patients who were undergoing mastectomy, neoadjuvant chemotherapy, or who had more than 2 metastatic lymph nodes.) The investigators found no difference in overall or disease-free survival or local-regional recurrence between the 2 treatment groups over 9.2 years of follow up.¹⁴

Based on this practice-changing trial result, guidelines of the National Comprehensive Cancer Network no longer recommend completion ALND for patients who meet the ACOSOG Z0011 criteria. For patients who do not meet ACOSOG Z0011 criteria, we do intraoperative pathologic lymph node assessment with either frozen section or imprint cytology, and we perform immediate ALND when results are positive.

Indications for SLN biopsy include:

• invasive breast cancer with clinically negative axillary nodes
• ductal carcinoma in situ (DCIS) with microinvasion or extensive enough to require mastectomy
• clinically negative axillary nodes after neoadjuvant chemotherapy.

Contraindications for SLN biopsy include:

• bulky palpable lymphadenopathy
• pregnancy, as the safety of radioactive isotope and blue dye is not well studied; in isotope mapping the radiation dose is small and within safety limits for pregnant patients
• inflammatory breast cancer.

Complications of any axillary surgery may include risk of lymphedema (5% with SLN biopsy and 30% to 40% with ALND).¹⁵ Other complications include neuropathy of the affected arm with chronic pain and numbness of the skin.

Positive trends: Improved patient outcomes, specialized clinician training

Management of breast cancer has changed dramatically over the past several decades. More women are surviving breast cancer thanks to improvements in early detection, an individualized treatment approach with less aggressive surgery, and more effective targeted systemic therapies. A multidisciplinary, team-oriented approach with emphasis on minimally invasive biopsy and better cosmetic outcomes has enhanced quality of care.

Complexity in breast disease management has led to the development of formal fellowship training in breast surgical oncology. Studies have demonstrated that patients treated by high-volume breast surgeons are more satisfied with their care and have improved cancer outcomes.^16,17 Women should be aware that they have different options for their breast cancer care, and surgeons with advanced specialization in this field may provide optimal results and better quality of care.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

It sometimes seems that the pace of life, and its stresses, have spiraled out of control: There just never seems to be enough time to deal with all the directions in which we are pulled. This easily can lead to the exhaustion of physical or emotional strength or motivation, otherwise known as “burnout.” Burnout is physical or mental collapse caused by overwork or stress and we are all at risk of suffering it. Conflicting demands on our time, loss of control (real or imagined), and a diminishing sense of worth grind at us from every direction.

In general, having some control over schedule and hours worked is associated with reductions in burnout and improved job satisfaction.¹ But this is not always the case. Well-intentioned efforts to reduce workload, such as the electronic medical records or physician order entry systems, have actually made the problem worse.² The seeming level of control that comes with being the chair of an obstetrics and gynecology department does not necessarily reduce burnout rates,³ and neither does the perceived resilience of mental health professionals, who still report burnout rates that approach 25%.⁴

This article continues the focus on recalibrating work/life balance that began last month with “ObGyn burnout: ACOG takes aim,” by Lucia DiVenere, MA, and the peer-to-peer audiocast with Ms. DiVenere and myself titled “Is burnout on the rise and what are the signs ObGyns should be on the lookout for?” Here, I identify the causes and symptoms of burnout and provide specific tools to help you develop resilience.

Why burnout occurs

Simply identifying ourselves as professionals and the same attributes that make us successful as physicians (type-A behavior, obsessive-compulsive commitment to our profession) put us at risk for professional burnout (see “Who is most at risk for burnout?”). Those predilections combine with the forces from the world in which we live and practice to increase this threat (TABLE 1). Conditions in which there are weak retention rates, high turnover, heavy workloads, and low staffing levels or staffing shortages increase the risk of burnout and, when burnout is present, are associated with a degraded quality of care.⁵

Does stress cause burnout?

Stress is often seen as the reason for burnout. Research shows that there is no single source of burnout,⁶ however, and a number of factors combine to cause this physical or mental collapse. Stress can be a positive or negative factor in our performance. Too little stress and we feel underutilized; too much stress and we collapse from the strain.

There is a middle ground where stress and expectations keep us focused and at peak productivity (FIGURE 1). The key is the balance between control and demand: When we have a greater level of control, we can handle high demands (FIGURE 2). It is when we lack that control that high demands result in what has been called “toxic stress,” and we collapse under the strain.

The impact of burnout

Burnout is associated with reduced performance and job satisfaction, increased rates of illness and absenteeism, accidents, premature retirement, and even premature death. Physically, stress induces the dry mouth, dilated pupils, and release of adrenalin and noradrenalin associated with the “fight-or-flight” reaction. The degree to which the physical, emotional, and professional symptoms are manifest depends on the depth or stage of burnout present (TABLE 2). Overall, burnout is associated with an increased risk for physical illness.⁷ Economically, the impact of physician burnout (for physicians practicing in Canada) has been estimated to be $213.1 million,⁸ which includes $185.2 million due to early retirement and $27.9 million due to reduced clinical hours.

“Do I have burnout?”

We all suffer from fatigue and have stress, but do we have burnout? With so many myths surrounding stress and burnout, it is sometimes hard to know where the truth lies. Some of those myths say that:

• you can leave your troubles at home
• mental stress does not affect physical performance
• stress is only for wimps
• stress and burnout are chemical imbalances that can be treated with medications
• stress is always bad
• burnout will get better if you just give it more time.

Maslach Burnout Inventory. The effective “gold standard” for diagnosing burnout is the Maslach Burnout Inventory,⁹ which operationalizes burnout as a 3-dimensional syndrome made up of exhaustion, cynicism, and inefficacy. Other diagnostic tools have been introduced¹⁰ but have not gained the wide acceptance of the Maslach Inventory. Some authors have argued that burnout and depression represent different, closely spaced points along a spectrum and that any effort to separate them may be artificial.^11,12

The Maslach Burnout Inventory consists of a survey of 22 items; it requires a fee to take and is interpreted by a qualified individual. A simpler screening test consists of 10 questions (TABLE 3). If you answer “yes” to 5 or more of the questions, you probably have burnout. An even quicker test is to see, when you go on vacation, if your symptoms disappear. If so, you are not depressed; you have burnout. (If you cannot even go on vacation, then it is almost certain.)

12 stages of burnout. Psychologists Herbert Freudenberger and Gail North have theorized that the burnout process can be divided into 12 phases (TABLE 4).¹³ These stages are not necessarily sequential—some may be absent and others may present simultaneously. It is easy to see how these can represent stages in a potentially spiraling series of behaviors and changes that result in complete dysfunction. It is also easy to understand that the characteristics that are associated with success in medical school, clinical training, and practice, such as high expectations, placing the needs of others above our own, and a desire to prove oneself, virtually define the first 3 stages.

Approaches for burnout control and prevention

There are some simple steps we can take to reduce the risk of burnout or to reverse its effects. Because fatigue and stress are 2 of the greatest risk factors, reducing these is a good place to start.

Prioritize sleep. When it comes to fatigue, that one is easy: get some sleep. Physicians tend to sleep fewer hours than the general population and what we get is often not the type that is restful and restorative.¹⁴ Just reducing the number of hours worked is not enough, as a number of studies have found.¹⁵ The rest must result in relaxation.

e Stress reduction may seem a more difficult goal than getting more sleep. In reality, there are several simple approaches to use to reduce stress:

• Even though we all have busy clinical schedules, take short breaks to rest, sing, laugh, and exercise. Even breaks as short as 10 minutes can be effective.¹⁶
• Separate work from private life by taking a short break to resolve issues before heading home. Avoiding “baggage” or homework will go a long way to giving you the perspective you need from your time off. This may also mean that you have to delegate tasks, share chores, or get carry-out for dinner.
• Set meaningful and realistic goals for yourself professionally and personally. Do not expect or demand more than is possible. This will mean setting priorities and recognizing that some tasks may have to wait.
• Finally, do not forget to pay yourself with hobbies and activities that you enjoy.

Take action

If you feel the effects of burnout tugging at your coattails, you can reduce the effects, deal with the sources, and improve your attitude (TABLE 5). Rest and relaxation will go a long way to helping, but do not forget to take care of your physical well-being with a healthy diet, exercise, and health checkups. Deal with the sources of burnout by identifying the stressors, setting realistic priorities, and practicing good time management.

You also should lobby for changes that will increase your control and reduce unnecessary obstacles to completing your goals. Be your own best advocate. Look for the good and try to identify at least one instance during the day where your presence or acts made a difference. In the end, it is like Smokey the Bear says, “Only you can prevent burnout.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

It sometimes seems that the pace of life, and its stresses, have spiraled out of control: There just never seems to be enough time to deal with all the directions in which we are pulled. This easily can lead to the exhaustion of physical or emotional strength or motivation, otherwise known as “burnout.” Burnout is physical or mental collapse caused by overwork or stress and we are all at risk of suffering it. Conflicting demands on our time, loss of control (real or imagined), and a diminishing sense of worth grind at us from every direction.

In general, having some control over schedule and hours worked is associated with reductions in burnout and improved job satisfaction.¹ But this is not always the case. Well-intentioned efforts to reduce workload, such as the electronic medical records or physician order entry systems, have actually made the problem worse.² The seeming level of control that comes with being the chair of an obstetrics and gynecology department does not necessarily reduce burnout rates,³ and neither does the perceived resilience of mental health professionals, who still report burnout rates that approach 25%.⁴

This article continues the focus on recalibrating work/life balance that began last month with “ObGyn burnout: ACOG takes aim,” by Lucia DiVenere, MA, and the peer-to-peer audiocast with Ms. DiVenere and myself titled “Is burnout on the rise and what are the signs ObGyns should be on the lookout for?” Here, I identify the causes and symptoms of burnout and provide specific tools to help you develop resilience.

Why burnout occurs

Simply identifying ourselves as professionals and the same attributes that make us successful as physicians (type-A behavior, obsessive-compulsive commitment to our profession) put us at risk for professional burnout (see “Who is most at risk for burnout?”). Those predilections combine with the forces from the world in which we live and practice to increase this threat (TABLE 1). Conditions in which there are weak retention rates, high turnover, heavy workloads, and low staffing levels or staffing shortages increase the risk of burnout and, when burnout is present, are associated with a degraded quality of care.⁵

Does stress cause burnout?

Stress is often seen as the reason for burnout. Research shows that there is no single source of burnout,⁶ however, and a number of factors combine to cause this physical or mental collapse. Stress can be a positive or negative factor in our performance. Too little stress and we feel underutilized; too much stress and we collapse from the strain.

There is a middle ground where stress and expectations keep us focused and at peak productivity (FIGURE 1). The key is the balance between control and demand: When we have a greater level of control, we can handle high demands (FIGURE 2). It is when we lack that control that high demands result in what has been called “toxic stress,” and we collapse under the strain.

The impact of burnout

Burnout is associated with reduced performance and job satisfaction, increased rates of illness and absenteeism, accidents, premature retirement, and even premature death. Physically, stress induces the dry mouth, dilated pupils, and release of adrenalin and noradrenalin associated with the “fight-or-flight” reaction. The degree to which the physical, emotional, and professional symptoms are manifest depends on the depth or stage of burnout present (TABLE 2). Overall, burnout is associated with an increased risk for physical illness.⁷ Economically, the impact of physician burnout (for physicians practicing in Canada) has been estimated to be $213.1 million,⁸ which includes $185.2 million due to early retirement and $27.9 million due to reduced clinical hours.

“Do I have burnout?”

We all suffer from fatigue and have stress, but do we have burnout? With so many myths surrounding stress and burnout, it is sometimes hard to know where the truth lies. Some of those myths say that:

• you can leave your troubles at home
• mental stress does not affect physical performance
• stress is only for wimps
• stress and burnout are chemical imbalances that can be treated with medications
• stress is always bad
• burnout will get better if you just give it more time.

Maslach Burnout Inventory. The effective “gold standard” for diagnosing burnout is the Maslach Burnout Inventory,⁹ which operationalizes burnout as a 3-dimensional syndrome made up of exhaustion, cynicism, and inefficacy. Other diagnostic tools have been introduced¹⁰ but have not gained the wide acceptance of the Maslach Inventory. Some authors have argued that burnout and depression represent different, closely spaced points along a spectrum and that any effort to separate them may be artificial.^11,12

The Maslach Burnout Inventory consists of a survey of 22 items; it requires a fee to take and is interpreted by a qualified individual. A simpler screening test consists of 10 questions (TABLE 3). If you answer “yes” to 5 or more of the questions, you probably have burnout. An even quicker test is to see, when you go on vacation, if your symptoms disappear. If so, you are not depressed; you have burnout. (If you cannot even go on vacation, then it is almost certain.)

12 stages of burnout. Psychologists Herbert Freudenberger and Gail North have theorized that the burnout process can be divided into 12 phases (TABLE 4).¹³ These stages are not necessarily sequential—some may be absent and others may present simultaneously. It is easy to see how these can represent stages in a potentially spiraling series of behaviors and changes that result in complete dysfunction. It is also easy to understand that the characteristics that are associated with success in medical school, clinical training, and practice, such as high expectations, placing the needs of others above our own, and a desire to prove oneself, virtually define the first 3 stages.

Approaches for burnout control and prevention

There are some simple steps we can take to reduce the risk of burnout or to reverse its effects. Because fatigue and stress are 2 of the greatest risk factors, reducing these is a good place to start.

Prioritize sleep. When it comes to fatigue, that one is easy: get some sleep. Physicians tend to sleep fewer hours than the general population and what we get is often not the type that is restful and restorative.¹⁴ Just reducing the number of hours worked is not enough, as a number of studies have found.¹⁵ The rest must result in relaxation.

e Stress reduction may seem a more difficult goal than getting more sleep. In reality, there are several simple approaches to use to reduce stress:

• Even though we all have busy clinical schedules, take short breaks to rest, sing, laugh, and exercise. Even breaks as short as 10 minutes can be effective.¹⁶
• Separate work from private life by taking a short break to resolve issues before heading home. Avoiding “baggage” or homework will go a long way to giving you the perspective you need from your time off. This may also mean that you have to delegate tasks, share chores, or get carry-out for dinner.
• Set meaningful and realistic goals for yourself professionally and personally. Do not expect or demand more than is possible. This will mean setting priorities and recognizing that some tasks may have to wait.
• Finally, do not forget to pay yourself with hobbies and activities that you enjoy.

Take action

If you feel the effects of burnout tugging at your coattails, you can reduce the effects, deal with the sources, and improve your attitude (TABLE 5). Rest and relaxation will go a long way to helping, but do not forget to take care of your physical well-being with a healthy diet, exercise, and health checkups. Deal with the sources of burnout by identifying the stressors, setting realistic priorities, and practicing good time management.

You also should lobby for changes that will increase your control and reduce unnecessary obstacles to completing your goals. Be your own best advocate. Look for the good and try to identify at least one instance during the day where your presence or acts made a difference. In the end, it is like Smokey the Bear says, “Only you can prevent burnout.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

It sometimes seems that the pace of life, and its stresses, have spiraled out of control: There just never seems to be enough time to deal with all the directions in which we are pulled. This easily can lead to the exhaustion of physical or emotional strength or motivation, otherwise known as “burnout.” Burnout is physical or mental collapse caused by overwork or stress and we are all at risk of suffering it. Conflicting demands on our time, loss of control (real or imagined), and a diminishing sense of worth grind at us from every direction.

In general, having some control over schedule and hours worked is associated with reductions in burnout and improved job satisfaction.¹ But this is not always the case. Well-intentioned efforts to reduce workload, such as the electronic medical records or physician order entry systems, have actually made the problem worse.² The seeming level of control that comes with being the chair of an obstetrics and gynecology department does not necessarily reduce burnout rates,³ and neither does the perceived resilience of mental health professionals, who still report burnout rates that approach 25%.⁴

This article continues the focus on recalibrating work/life balance that began last month with “ObGyn burnout: ACOG takes aim,” by Lucia DiVenere, MA, and the peer-to-peer audiocast with Ms. DiVenere and myself titled “Is burnout on the rise and what are the signs ObGyns should be on the lookout for?” Here, I identify the causes and symptoms of burnout and provide specific tools to help you develop resilience.

Why burnout occurs

Simply identifying ourselves as professionals and the same attributes that make us successful as physicians (type-A behavior, obsessive-compulsive commitment to our profession) put us at risk for professional burnout (see “Who is most at risk for burnout?”). Those predilections combine with the forces from the world in which we live and practice to increase this threat (TABLE 1). Conditions in which there are weak retention rates, high turnover, heavy workloads, and low staffing levels or staffing shortages increase the risk of burnout and, when burnout is present, are associated with a degraded quality of care.⁵

Does stress cause burnout?

Stress is often seen as the reason for burnout. Research shows that there is no single source of burnout,⁶ however, and a number of factors combine to cause this physical or mental collapse. Stress can be a positive or negative factor in our performance. Too little stress and we feel underutilized; too much stress and we collapse from the strain.

There is a middle ground where stress and expectations keep us focused and at peak productivity (FIGURE 1). The key is the balance between control and demand: When we have a greater level of control, we can handle high demands (FIGURE 2). It is when we lack that control that high demands result in what has been called “toxic stress,” and we collapse under the strain.

The impact of burnout

Burnout is associated with reduced performance and job satisfaction, increased rates of illness and absenteeism, accidents, premature retirement, and even premature death. Physically, stress induces the dry mouth, dilated pupils, and release of adrenalin and noradrenalin associated with the “fight-or-flight” reaction. The degree to which the physical, emotional, and professional symptoms are manifest depends on the depth or stage of burnout present (TABLE 2). Overall, burnout is associated with an increased risk for physical illness.⁷ Economically, the impact of physician burnout (for physicians practicing in Canada) has been estimated to be $213.1 million,⁸ which includes $185.2 million due to early retirement and $27.9 million due to reduced clinical hours.

“Do I have burnout?”

We all suffer from fatigue and have stress, but do we have burnout? With so many myths surrounding stress and burnout, it is sometimes hard to know where the truth lies. Some of those myths say that:

• you can leave your troubles at home
• mental stress does not affect physical performance
• stress is only for wimps
• stress and burnout are chemical imbalances that can be treated with medications
• stress is always bad
• burnout will get better if you just give it more time.

Maslach Burnout Inventory. The effective “gold standard” for diagnosing burnout is the Maslach Burnout Inventory,⁹ which operationalizes burnout as a 3-dimensional syndrome made up of exhaustion, cynicism, and inefficacy. Other diagnostic tools have been introduced¹⁰ but have not gained the wide acceptance of the Maslach Inventory. Some authors have argued that burnout and depression represent different, closely spaced points along a spectrum and that any effort to separate them may be artificial.^11,12

The Maslach Burnout Inventory consists of a survey of 22 items; it requires a fee to take and is interpreted by a qualified individual. A simpler screening test consists of 10 questions (TABLE 3). If you answer “yes” to 5 or more of the questions, you probably have burnout. An even quicker test is to see, when you go on vacation, if your symptoms disappear. If so, you are not depressed; you have burnout. (If you cannot even go on vacation, then it is almost certain.)

12 stages of burnout. Psychologists Herbert Freudenberger and Gail North have theorized that the burnout process can be divided into 12 phases (TABLE 4).¹³ These stages are not necessarily sequential—some may be absent and others may present simultaneously. It is easy to see how these can represent stages in a potentially spiraling series of behaviors and changes that result in complete dysfunction. It is also easy to understand that the characteristics that are associated with success in medical school, clinical training, and practice, such as high expectations, placing the needs of others above our own, and a desire to prove oneself, virtually define the first 3 stages.

Approaches for burnout control and prevention

There are some simple steps we can take to reduce the risk of burnout or to reverse its effects. Because fatigue and stress are 2 of the greatest risk factors, reducing these is a good place to start.

Prioritize sleep. When it comes to fatigue, that one is easy: get some sleep. Physicians tend to sleep fewer hours than the general population and what we get is often not the type that is restful and restorative.¹⁴ Just reducing the number of hours worked is not enough, as a number of studies have found.¹⁵ The rest must result in relaxation.

e Stress reduction may seem a more difficult goal than getting more sleep. In reality, there are several simple approaches to use to reduce stress:

• Even though we all have busy clinical schedules, take short breaks to rest, sing, laugh, and exercise. Even breaks as short as 10 minutes can be effective.¹⁶
• Separate work from private life by taking a short break to resolve issues before heading home. Avoiding “baggage” or homework will go a long way to giving you the perspective you need from your time off. This may also mean that you have to delegate tasks, share chores, or get carry-out for dinner.
• Set meaningful and realistic goals for yourself professionally and personally. Do not expect or demand more than is possible. This will mean setting priorities and recognizing that some tasks may have to wait.
• Finally, do not forget to pay yourself with hobbies and activities that you enjoy.

Take action

If you feel the effects of burnout tugging at your coattails, you can reduce the effects, deal with the sources, and improve your attitude (TABLE 5). Rest and relaxation will go a long way to helping, but do not forget to take care of your physical well-being with a healthy diet, exercise, and health checkups. Deal with the sources of burnout by identifying the stressors, setting realistic priorities, and practicing good time management.

You also should lobby for changes that will increase your control and reduce unnecessary obstacles to completing your goals. Be your own best advocate. Look for the good and try to identify at least one instance during the day where your presence or acts made a difference. In the end, it is like Smokey the Bear says, “Only you can prevent burnout.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Each year approximately 60,000 women are diagnosed with endometrial cancer. The majority of the identified tumors will be low grade—cancer found at an early stage that may be treated with surgery alone. Unfortunately, however, too many of the 60,000 patients will have poor prognostic features, such as serous or clear cell histology (high-grade cancer), lymphovascular space invasion, or positive lymph node status.

Advances in technology and the state of science have come a long way since the dichotomy of Type I (endometrioid) and Type II (serous and clear cell) tumors were described by Dr. J. Bokhman in the early 1980s.¹ Our previous Update from several years ago stressed the importance of further understanding of the molecular rationale of high-risk, Type II tumors.² To review, The Cancer Genome Atlas project (TCGA) performed a genomic and proteomic characterization in 373 endometrial carcinomas demonstrating the traditional p53 mutations of serous tumors and PTEN or KRAS genes of endometrioid tumors.³ Most interestingly, they identified numerous other mutations and proposed 4 new genomic categories:

1. polymerase (DNA-directed) epsilon catalytic subunit (POLE) ultramutated
2. microsatellite instability (MSI) hypermutated
3. somatic copy number alterations high (serous tumors)
4. somatic copy number alterations low (endometrioid cancer).

In 2016, we are now understanding the molecular basis of disease and how it affects survival; these 4 categories have different survival. But why? Perhaps the answer lies within the endogenous immune system. Tumor-infiltrating lymphocytes are associated with improved survival in multiple types of cancer, including endometrial. Whether these lymphocytes are regulatory or cytotoxic T-cells convolutes the matter further.⁴ To understand these intricacies we need to further categorize how a tumor’s genetic mutations affect antigen exposure to the immune system, quantitate the clinical impact of the findings, and selectively target patients with novel therapeutics.

In this Update, we look at data on POLE mutations, exploring 2 studies that help us to better understand why these types of mutations have uniquely positive prognostic implications (when they logically should not have good survival rates). In addition, we discuss 2 studies that examined mismatch repair defects, in endometrial cancer specifically, and the programmed death (PD)-1 pathway in both endometrial and other cancer types. Are these molecular entities of tumors associated with better or worse prognosis, and why?

Molecular profiling: Prognostic implications of POLE mutations

Church DN, Stelloo E, Nout RA, et al. Prognostic significance of POLE proofreading mutations in endometrial cancer. J Natl Cancer Inst. 2014;107(1):402.

van Gool IC, Eggink FA, Freeman-Mills L, et al. POLE Proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347 - 3355.

The TCGA identified a subgroup of endometrial carcinomas with mutations of the DNA polymerase POLE. These mutants have a high rate of proofreading error and frequent base pair substitutions. This POLE subgroup (6% to 12% of endometrial tumors) is associated with endometrioid histology and high-grade tumors. Patients with these tumors would be expected to have an aggressive course with poor survival, but often these patients survive without a recurrence. We need more understanding of why. 

POLE mutations and prognosis

In a secondary analysis by Church and colleagues of the PORTEC-1 and -2 studies (2 large, randomized controlled trials evaluating postoperative external beam radiation therapy [EBRT] or vaginal brachytherapy), tumors were tested for mutations in POLE (POLE-mutant and POLE wild-type). POLE mutations were detected in 6.1% of tumors overall. Despite their high grade, POLE-mutant tumors resulted in fewer recurrences (6.2% vs 14.1%) and fewer deaths (2.3% vs 9.7%) than POLE wild-type tumors. In grade 3 tumors, 0 of 15 POLE-mutant tumors recurred.

These results indicate that, even with having poor prognostic features, endometrial cancers with mutations in POLE have an excellent prognosis.⁵

POLE mutations and the immune response

To explain the discrepancy in the results by Church and colleagues, van Gool and colleagues analyzed endometrial cancer specimens from PORTEC-1, -2, and the TCGA studies. Endometrial cancers were categorized as POLE-mutants, POLE wild-type, or microsatellite stable (MSS) tumors. They found that POLE-mutant endometrial cancers have an increased lymphocytic infiltrate (present in 22 of 47 POLE-mutant specimens) as compared with POLE wild-type or MSS tumors. 

Also, POLE-mutants had an increased density of cytotoxic T-cells (CD8+) at the tumor center and margin that significantly exceeded that of POLE wild-type or MSS tumors. The proportion of tumors with CD8+ cells exceeding the median were also higher in POLE-mutant (60%) compared with POLE wild-type (31.3%) and MSS (7.2%) tumors. Markers LAG3, TIM-3, TIGI, as well as T-cell inhibitors PD1 and CTLA-4, confirmed evidence of T-cell exhaustion--all of which correlated with CD8 expression. 

These findings suggest that POLE mutations lead to hundreds of thousands of DNA fragments stimulating the immune system through prolonged antigenic exposure.⁶ This immune response is so powerful that even these tumors with poor prognostic features will have excellent clinical outcomes.

Mismatch repair and immunology: Targeted therapy for targeted patients

McMeekin DS, Tritchler DL, Cohn DE, et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: an NRG oncology/gynecologic oncology group study. J Clin Oncol. 2016;34(25):3062-3068.

Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520.

The most frequent genetic mutation in endometrial cancer is mismatch repair (MMR) deficiency. Loss of this pathway leads to a failure of repairing replication errors and gives rise to small repeated sequences of DNA, known as MSI. Germline mutations in MMR (Lynch syndrome) occur in only 3% to 5% of endometrial cancers. Somatic mutations in MMR give rise to 10% to 20% of colorectal cancers and upwards of 20% to 40% of endometrial cancers.

Given this high frequency, universal screening utilizing immunohistochemistry of proteins MLH1, MSH2, MSH6, and PMS2 has become the standard of care in tumors to identify MMR deficiency. MMR-deficient endometrial tumors are associated with higher grade and lymphovascular space invasion. The actual clinical prognosis of these tumors, however, has not been well described.⁷ McMeekin and colleagues set out to examine prognosis.

Details of the study by McMeekin and colleagues
In the collaborative study, researchers assessed 1,024 tumors for MMR and categorized them into 1 of 4 groups: normal(62.4%), epigenetic MMR-defective (25.78%),MMR-probable mutation (9.67%), or MSI-low (2.15%). The researchers found that the pathologic features were associatedwith MMR status. For instance, MMR-defective tumors were more likely thanMMR-normal tumors to be Grade 2 (50% vs 40.7%, respectively). Lymphovascular space invasion also occurred more frequently in MMR-defective than in MMR-normal tumors (32.7% vs 17.13%, respectively). Approximately 22% of patients with MMR-defective tumors had stage III or IV disease, while only 13% to 14% of the other groups presented with such advanced stage.

On univariate analysis, an MMR-defective tumor was associated with worsened progression-free survival (hazard ratio [HR], 1.37). On subsequent multivariate analysis, no difference in survival in MMR-defective vs MMR-normal tumors was found. The authors concluded that MMR status is predictive of response to adjuvant therapy.

An intriguing biologic explanation of how MMR status affects response to adjuvant therapy is that MMR-defective tumors contain lymphocytic infiltrates, consistent with an increased immunologic response.⁸ Similar to the previously discussed POLE mutations, MMR-defective tumors have a tremendous increase in somatic mutations that are on the order of 10 to 100 times that of MMR-proficient tumors. These MMR-defective tumors likely give rise to increased antigen exposure to the immune system.

These immune infiltrates will show signs of exhaustion and upregulate negative feedback systems, which is the point at which the PD-1 pathway becomes critically important. The PD-1 receptor is expressed predominately on T-cells and its ligands regulate the immune system by inhibition of self-reactive T-cells.⁹

MMR deficiency and anti-programmed death receptor 1

The study by McMeekin and colleagues shows MMR-defective tumors have poor prognostic features but the same survival as those with MMR proficiency or good prognostic features. Why is this the case? A recent study by Le and colleagues analyzed this question.  

Details of the study by Le and colleagues
The investigators performed a phase 2 trial evaluating pembrolizumab (10 mg/kg IV every 14 days), an anti-PD 1 immune checkpoint inhibitor in patients with tumors demonstrating MMR-deficiency. The 3 cohorts included: MMR-defective colorectal cancer (n = 10), MMR-proficient colorectal cancer (n = 18), and MMR-defective noncolorectal cancer (n = 7, including 2 endometrial cancers). Objective response rates were 40%, 0%, and 71% for each group, respectively. 

MMR-defective tumors had a striking HR of disease progression or death of 0.04 (95% confidence interval, 0.01-0.21; P<.001). Genomic analysis was performed and identified 578 potential mutation- associated neoantigens in the MMR-defective groups (compared with only 21 in the MMR-proficient tumors). These findings promote the concept of a mutation-associated antigen component to the endogenous immune response.¹⁰

Conclusion

The above-stated mutations of mismatch repair and POLE are changing our perspective of endometrial cancer and shedding light on the complexities of tumor biology. As future research increasingly incorporates genomic profiling, we anticipate clinical trials may build evidence that adjuvant therapy will be directed by molecular staging, as opposed to traditional surgical or even histologic staging, as these mutations are the root cause of the tumor phenotype.

Key for readers to take away from this Update is that genomic profiling and enrollment in clinical trials is critical to understanding the implications of these mutations and how to best treat our patients. In addition, we should encourage our patients with endometrial cancer to see genetic counselors and have appropriate screening of MMR-deficiency. This will continue to advance our understanding as well as to provide patients with valuable information regarding their diagnosis.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Each year approximately 60,000 women are diagnosed with endometrial cancer. The majority of the identified tumors will be low grade—cancer found at an early stage that may be treated with surgery alone. Unfortunately, however, too many of the 60,000 patients will have poor prognostic features, such as serous or clear cell histology (high-grade cancer), lymphovascular space invasion, or positive lymph node status.

Advances in technology and the state of science have come a long way since the dichotomy of Type I (endometrioid) and Type II (serous and clear cell) tumors were described by Dr. J. Bokhman in the early 1980s.¹ Our previous Update from several years ago stressed the importance of further understanding of the molecular rationale of high-risk, Type II tumors.² To review, The Cancer Genome Atlas project (TCGA) performed a genomic and proteomic characterization in 373 endometrial carcinomas demonstrating the traditional p53 mutations of serous tumors and PTEN or KRAS genes of endometrioid tumors.³ Most interestingly, they identified numerous other mutations and proposed 4 new genomic categories:

1. polymerase (DNA-directed) epsilon catalytic subunit (POLE) ultramutated
2. microsatellite instability (MSI) hypermutated
3. somatic copy number alterations high (serous tumors)
4. somatic copy number alterations low (endometrioid cancer).

In 2016, we are now understanding the molecular basis of disease and how it affects survival; these 4 categories have different survival. But why? Perhaps the answer lies within the endogenous immune system. Tumor-infiltrating lymphocytes are associated with improved survival in multiple types of cancer, including endometrial. Whether these lymphocytes are regulatory or cytotoxic T-cells convolutes the matter further.⁴ To understand these intricacies we need to further categorize how a tumor’s genetic mutations affect antigen exposure to the immune system, quantitate the clinical impact of the findings, and selectively target patients with novel therapeutics.

In this Update, we look at data on POLE mutations, exploring 2 studies that help us to better understand why these types of mutations have uniquely positive prognostic implications (when they logically should not have good survival rates). In addition, we discuss 2 studies that examined mismatch repair defects, in endometrial cancer specifically, and the programmed death (PD)-1 pathway in both endometrial and other cancer types. Are these molecular entities of tumors associated with better or worse prognosis, and why?

Molecular profiling: Prognostic implications of POLE mutations

Church DN, Stelloo E, Nout RA, et al. Prognostic significance of POLE proofreading mutations in endometrial cancer. J Natl Cancer Inst. 2014;107(1):402.

van Gool IC, Eggink FA, Freeman-Mills L, et al. POLE Proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347 - 3355.

The TCGA identified a subgroup of endometrial carcinomas with mutations of the DNA polymerase POLE. These mutants have a high rate of proofreading error and frequent base pair substitutions. This POLE subgroup (6% to 12% of endometrial tumors) is associated with endometrioid histology and high-grade tumors. Patients with these tumors would be expected to have an aggressive course with poor survival, but often these patients survive without a recurrence. We need more understanding of why. 

POLE mutations and prognosis

In a secondary analysis by Church and colleagues of the PORTEC-1 and -2 studies (2 large, randomized controlled trials evaluating postoperative external beam radiation therapy [EBRT] or vaginal brachytherapy), tumors were tested for mutations in POLE (POLE-mutant and POLE wild-type). POLE mutations were detected in 6.1% of tumors overall. Despite their high grade, POLE-mutant tumors resulted in fewer recurrences (6.2% vs 14.1%) and fewer deaths (2.3% vs 9.7%) than POLE wild-type tumors. In grade 3 tumors, 0 of 15 POLE-mutant tumors recurred.

These results indicate that, even with having poor prognostic features, endometrial cancers with mutations in POLE have an excellent prognosis.⁵

POLE mutations and the immune response

To explain the discrepancy in the results by Church and colleagues, van Gool and colleagues analyzed endometrial cancer specimens from PORTEC-1, -2, and the TCGA studies. Endometrial cancers were categorized as POLE-mutants, POLE wild-type, or microsatellite stable (MSS) tumors. They found that POLE-mutant endometrial cancers have an increased lymphocytic infiltrate (present in 22 of 47 POLE-mutant specimens) as compared with POLE wild-type or MSS tumors. 

Also, POLE-mutants had an increased density of cytotoxic T-cells (CD8+) at the tumor center and margin that significantly exceeded that of POLE wild-type or MSS tumors. The proportion of tumors with CD8+ cells exceeding the median were also higher in POLE-mutant (60%) compared with POLE wild-type (31.3%) and MSS (7.2%) tumors. Markers LAG3, TIM-3, TIGI, as well as T-cell inhibitors PD1 and CTLA-4, confirmed evidence of T-cell exhaustion--all of which correlated with CD8 expression. 

These findings suggest that POLE mutations lead to hundreds of thousands of DNA fragments stimulating the immune system through prolonged antigenic exposure.⁶ This immune response is so powerful that even these tumors with poor prognostic features will have excellent clinical outcomes.

Mismatch repair and immunology: Targeted therapy for targeted patients

McMeekin DS, Tritchler DL, Cohn DE, et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: an NRG oncology/gynecologic oncology group study. J Clin Oncol. 2016;34(25):3062-3068.

Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520.

The most frequent genetic mutation in endometrial cancer is mismatch repair (MMR) deficiency. Loss of this pathway leads to a failure of repairing replication errors and gives rise to small repeated sequences of DNA, known as MSI. Germline mutations in MMR (Lynch syndrome) occur in only 3% to 5% of endometrial cancers. Somatic mutations in MMR give rise to 10% to 20% of colorectal cancers and upwards of 20% to 40% of endometrial cancers.

Given this high frequency, universal screening utilizing immunohistochemistry of proteins MLH1, MSH2, MSH6, and PMS2 has become the standard of care in tumors to identify MMR deficiency. MMR-deficient endometrial tumors are associated with higher grade and lymphovascular space invasion. The actual clinical prognosis of these tumors, however, has not been well described.⁷ McMeekin and colleagues set out to examine prognosis.

Details of the study by McMeekin and colleagues
In the collaborative study, researchers assessed 1,024 tumors for MMR and categorized them into 1 of 4 groups: normal(62.4%), epigenetic MMR-defective (25.78%),MMR-probable mutation (9.67%), or MSI-low (2.15%). The researchers found that the pathologic features were associatedwith MMR status. For instance, MMR-defective tumors were more likely thanMMR-normal tumors to be Grade 2 (50% vs 40.7%, respectively). Lymphovascular space invasion also occurred more frequently in MMR-defective than in MMR-normal tumors (32.7% vs 17.13%, respectively). Approximately 22% of patients with MMR-defective tumors had stage III or IV disease, while only 13% to 14% of the other groups presented with such advanced stage.

On univariate analysis, an MMR-defective tumor was associated with worsened progression-free survival (hazard ratio [HR], 1.37). On subsequent multivariate analysis, no difference in survival in MMR-defective vs MMR-normal tumors was found. The authors concluded that MMR status is predictive of response to adjuvant therapy.

An intriguing biologic explanation of how MMR status affects response to adjuvant therapy is that MMR-defective tumors contain lymphocytic infiltrates, consistent with an increased immunologic response.⁸ Similar to the previously discussed POLE mutations, MMR-defective tumors have a tremendous increase in somatic mutations that are on the order of 10 to 100 times that of MMR-proficient tumors. These MMR-defective tumors likely give rise to increased antigen exposure to the immune system.

These immune infiltrates will show signs of exhaustion and upregulate negative feedback systems, which is the point at which the PD-1 pathway becomes critically important. The PD-1 receptor is expressed predominately on T-cells and its ligands regulate the immune system by inhibition of self-reactive T-cells.⁹

MMR deficiency and anti-programmed death receptor 1

The study by McMeekin and colleagues shows MMR-defective tumors have poor prognostic features but the same survival as those with MMR proficiency or good prognostic features. Why is this the case? A recent study by Le and colleagues analyzed this question.  

Details of the study by Le and colleagues
The investigators performed a phase 2 trial evaluating pembrolizumab (10 mg/kg IV every 14 days), an anti-PD 1 immune checkpoint inhibitor in patients with tumors demonstrating MMR-deficiency. The 3 cohorts included: MMR-defective colorectal cancer (n = 10), MMR-proficient colorectal cancer (n = 18), and MMR-defective noncolorectal cancer (n = 7, including 2 endometrial cancers). Objective response rates were 40%, 0%, and 71% for each group, respectively. 

MMR-defective tumors had a striking HR of disease progression or death of 0.04 (95% confidence interval, 0.01-0.21; P<.001). Genomic analysis was performed and identified 578 potential mutation- associated neoantigens in the MMR-defective groups (compared with only 21 in the MMR-proficient tumors). These findings promote the concept of a mutation-associated antigen component to the endogenous immune response.¹⁰

Conclusion

The above-stated mutations of mismatch repair and POLE are changing our perspective of endometrial cancer and shedding light on the complexities of tumor biology. As future research increasingly incorporates genomic profiling, we anticipate clinical trials may build evidence that adjuvant therapy will be directed by molecular staging, as opposed to traditional surgical or even histologic staging, as these mutations are the root cause of the tumor phenotype.

Key for readers to take away from this Update is that genomic profiling and enrollment in clinical trials is critical to understanding the implications of these mutations and how to best treat our patients. In addition, we should encourage our patients with endometrial cancer to see genetic counselors and have appropriate screening of MMR-deficiency. This will continue to advance our understanding as well as to provide patients with valuable information regarding their diagnosis.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Each year approximately 60,000 women are diagnosed with endometrial cancer. The majority of the identified tumors will be low grade—cancer found at an early stage that may be treated with surgery alone. Unfortunately, however, too many of the 60,000 patients will have poor prognostic features, such as serous or clear cell histology (high-grade cancer), lymphovascular space invasion, or positive lymph node status.

Advances in technology and the state of science have come a long way since the dichotomy of Type I (endometrioid) and Type II (serous and clear cell) tumors were described by Dr. J. Bokhman in the early 1980s.¹ Our previous Update from several years ago stressed the importance of further understanding of the molecular rationale of high-risk, Type II tumors.² To review, The Cancer Genome Atlas project (TCGA) performed a genomic and proteomic characterization in 373 endometrial carcinomas demonstrating the traditional p53 mutations of serous tumors and PTEN or KRAS genes of endometrioid tumors.³ Most interestingly, they identified numerous other mutations and proposed 4 new genomic categories:

1. polymerase (DNA-directed) epsilon catalytic subunit (POLE) ultramutated
2. microsatellite instability (MSI) hypermutated
3. somatic copy number alterations high (serous tumors)
4. somatic copy number alterations low (endometrioid cancer).

In 2016, we are now understanding the molecular basis of disease and how it affects survival; these 4 categories have different survival. But why? Perhaps the answer lies within the endogenous immune system. Tumor-infiltrating lymphocytes are associated with improved survival in multiple types of cancer, including endometrial. Whether these lymphocytes are regulatory or cytotoxic T-cells convolutes the matter further.⁴ To understand these intricacies we need to further categorize how a tumor’s genetic mutations affect antigen exposure to the immune system, quantitate the clinical impact of the findings, and selectively target patients with novel therapeutics.

In this Update, we look at data on POLE mutations, exploring 2 studies that help us to better understand why these types of mutations have uniquely positive prognostic implications (when they logically should not have good survival rates). In addition, we discuss 2 studies that examined mismatch repair defects, in endometrial cancer specifically, and the programmed death (PD)-1 pathway in both endometrial and other cancer types. Are these molecular entities of tumors associated with better or worse prognosis, and why?

Molecular profiling: Prognostic implications of POLE mutations

Church DN, Stelloo E, Nout RA, et al. Prognostic significance of POLE proofreading mutations in endometrial cancer. J Natl Cancer Inst. 2014;107(1):402.

van Gool IC, Eggink FA, Freeman-Mills L, et al. POLE Proofreading mutations elicit an antitumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347 - 3355.

The TCGA identified a subgroup of endometrial carcinomas with mutations of the DNA polymerase POLE. These mutants have a high rate of proofreading error and frequent base pair substitutions. This POLE subgroup (6% to 12% of endometrial tumors) is associated with endometrioid histology and high-grade tumors. Patients with these tumors would be expected to have an aggressive course with poor survival, but often these patients survive without a recurrence. We need more understanding of why. 

POLE mutations and prognosis

In a secondary analysis by Church and colleagues of the PORTEC-1 and -2 studies (2 large, randomized controlled trials evaluating postoperative external beam radiation therapy [EBRT] or vaginal brachytherapy), tumors were tested for mutations in POLE (POLE-mutant and POLE wild-type). POLE mutations were detected in 6.1% of tumors overall. Despite their high grade, POLE-mutant tumors resulted in fewer recurrences (6.2% vs 14.1%) and fewer deaths (2.3% vs 9.7%) than POLE wild-type tumors. In grade 3 tumors, 0 of 15 POLE-mutant tumors recurred.

These results indicate that, even with having poor prognostic features, endometrial cancers with mutations in POLE have an excellent prognosis.⁵

POLE mutations and the immune response

To explain the discrepancy in the results by Church and colleagues, van Gool and colleagues analyzed endometrial cancer specimens from PORTEC-1, -2, and the TCGA studies. Endometrial cancers were categorized as POLE-mutants, POLE wild-type, or microsatellite stable (MSS) tumors. They found that POLE-mutant endometrial cancers have an increased lymphocytic infiltrate (present in 22 of 47 POLE-mutant specimens) as compared with POLE wild-type or MSS tumors. 

Also, POLE-mutants had an increased density of cytotoxic T-cells (CD8+) at the tumor center and margin that significantly exceeded that of POLE wild-type or MSS tumors. The proportion of tumors with CD8+ cells exceeding the median were also higher in POLE-mutant (60%) compared with POLE wild-type (31.3%) and MSS (7.2%) tumors. Markers LAG3, TIM-3, TIGI, as well as T-cell inhibitors PD1 and CTLA-4, confirmed evidence of T-cell exhaustion--all of which correlated with CD8 expression. 

These findings suggest that POLE mutations lead to hundreds of thousands of DNA fragments stimulating the immune system through prolonged antigenic exposure.⁶ This immune response is so powerful that even these tumors with poor prognostic features will have excellent clinical outcomes.

Mismatch repair and immunology: Targeted therapy for targeted patients

McMeekin DS, Tritchler DL, Cohn DE, et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: an NRG oncology/gynecologic oncology group study. J Clin Oncol. 2016;34(25):3062-3068.

Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520.

The most frequent genetic mutation in endometrial cancer is mismatch repair (MMR) deficiency. Loss of this pathway leads to a failure of repairing replication errors and gives rise to small repeated sequences of DNA, known as MSI. Germline mutations in MMR (Lynch syndrome) occur in only 3% to 5% of endometrial cancers. Somatic mutations in MMR give rise to 10% to 20% of colorectal cancers and upwards of 20% to 40% of endometrial cancers.

Given this high frequency, universal screening utilizing immunohistochemistry of proteins MLH1, MSH2, MSH6, and PMS2 has become the standard of care in tumors to identify MMR deficiency. MMR-deficient endometrial tumors are associated with higher grade and lymphovascular space invasion. The actual clinical prognosis of these tumors, however, has not been well described.⁷ McMeekin and colleagues set out to examine prognosis.

Details of the study by McMeekin and colleagues
In the collaborative study, researchers assessed 1,024 tumors for MMR and categorized them into 1 of 4 groups: normal(62.4%), epigenetic MMR-defective (25.78%),MMR-probable mutation (9.67%), or MSI-low (2.15%). The researchers found that the pathologic features were associatedwith MMR status. For instance, MMR-defective tumors were more likely thanMMR-normal tumors to be Grade 2 (50% vs 40.7%, respectively). Lymphovascular space invasion also occurred more frequently in MMR-defective than in MMR-normal tumors (32.7% vs 17.13%, respectively). Approximately 22% of patients with MMR-defective tumors had stage III or IV disease, while only 13% to 14% of the other groups presented with such advanced stage.

On univariate analysis, an MMR-defective tumor was associated with worsened progression-free survival (hazard ratio [HR], 1.37). On subsequent multivariate analysis, no difference in survival in MMR-defective vs MMR-normal tumors was found. The authors concluded that MMR status is predictive of response to adjuvant therapy.

An intriguing biologic explanation of how MMR status affects response to adjuvant therapy is that MMR-defective tumors contain lymphocytic infiltrates, consistent with an increased immunologic response.⁸ Similar to the previously discussed POLE mutations, MMR-defective tumors have a tremendous increase in somatic mutations that are on the order of 10 to 100 times that of MMR-proficient tumors. These MMR-defective tumors likely give rise to increased antigen exposure to the immune system.

These immune infiltrates will show signs of exhaustion and upregulate negative feedback systems, which is the point at which the PD-1 pathway becomes critically important. The PD-1 receptor is expressed predominately on T-cells and its ligands regulate the immune system by inhibition of self-reactive T-cells.⁹

MMR deficiency and anti-programmed death receptor 1

The study by McMeekin and colleagues shows MMR-defective tumors have poor prognostic features but the same survival as those with MMR proficiency or good prognostic features. Why is this the case? A recent study by Le and colleagues analyzed this question.  

Details of the study by Le and colleagues
The investigators performed a phase 2 trial evaluating pembrolizumab (10 mg/kg IV every 14 days), an anti-PD 1 immune checkpoint inhibitor in patients with tumors demonstrating MMR-deficiency. The 3 cohorts included: MMR-defective colorectal cancer (n = 10), MMR-proficient colorectal cancer (n = 18), and MMR-defective noncolorectal cancer (n = 7, including 2 endometrial cancers). Objective response rates were 40%, 0%, and 71% for each group, respectively. 

MMR-defective tumors had a striking HR of disease progression or death of 0.04 (95% confidence interval, 0.01-0.21; P<.001). Genomic analysis was performed and identified 578 potential mutation- associated neoantigens in the MMR-defective groups (compared with only 21 in the MMR-proficient tumors). These findings promote the concept of a mutation-associated antigen component to the endogenous immune response.¹⁰

Conclusion

The above-stated mutations of mismatch repair and POLE are changing our perspective of endometrial cancer and shedding light on the complexities of tumor biology. As future research increasingly incorporates genomic profiling, we anticipate clinical trials may build evidence that adjuvant therapy will be directed by molecular staging, as opposed to traditional surgical or even histologic staging, as these mutations are the root cause of the tumor phenotype.

Key for readers to take away from this Update is that genomic profiling and enrollment in clinical trials is critical to understanding the implications of these mutations and how to best treat our patients. In addition, we should encourage our patients with endometrial cancer to see genetic counselors and have appropriate screening of MMR-deficiency. This will continue to advance our understanding as well as to provide patients with valuable information regarding their diagnosis.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Each year, the decisions of the Supreme Court have a significant impact on ObGyn practice. During the 2015–2016 term, which ended in June, the Court issued important rulings on abortion facilities, Affordable Care Act (ACA) contraception coverage, health care False Claims Act (FCA) liability, and state health care data collection. The American Medical Association (AMA), the Association of American Medical Colleges (AAMC), the American College of Obstetricians and Gynecologists (ACOG), and other organizations that represent health care professionals play an important role in health-related Supreme Court cases. For example, amicus curiae (“friend of the Court”) briefs are filed not by parties to a case but by organizations that have a special insight into or interest in a case. Although the extent to which amicus briefs influence cases is often unclear, organization representatives think their briefs make a difference, and briefs undoubtedly do in some cases.

The 2016 presidential election will determine the Supreme Court make-up for the next term, but in this article we consider recent cases that affect ObGyns’ practice in particular. We start with the cases in which professional organizations filed amicus briefs and then turn to other notable cases.

1. Abortion access in Texas and other states

The most important ObGyn case of the 2015–2016 term was Whole Woman’s Health v Hellerstedt.¹

At stake. Texas adopted a statute requiring 1) that physicians who perform abortions have admitting privileges at a hospital within 30 miles of the clinic and 2) that abortion clinics meet the state’s standards for ambulatory surgical centers. The current law, upheld by the Court some years ago, is that state laws affecting abortion are unconstitutional if they “unduly burden” the right to abortion. By undue burden, the Court meant, “Regulations that have the purpose or effect of presenting a substantial obstacle to a woman seeking an abortion impose an undue burden on the right.” The question in the Texas case was whether the statute’s 2 requirements were undue.

ACOG, AMA, and other groups filed a brief stating that the Texas law did not promote the welfare of women but instead was unnecessary and not “supported by accepted medical practice or scientific evidence.”² In another brief the Society of Hospital Medicine and the Society of ObGyn Hospitalists also indicated that having admitting privileges is appropriate only for physicians who regularly admit patients to a hospital.³

A brief filed by the American Association of Pro-Life Obstetricians and Gynecologists and several other organizations argued the other side: “The surgical center and admitting privileges requirements imposed by the Act reflect the professional standard of practice for outpatient gynecological and similar surgery.”⁴

Final ruling. In a 5−3 decision, the Court struck down the Texas law for providing little or no health benefits while significantly burdening abortion facility access. Many clinics had closed or were in plans to because of the difficulty and expense of complying with the law. This case has national implications. Similar laws, either in place or being considered in other states, will almost certainly be ruled unconstitutional.

2. Contraceptive coverage

The case of Zubik v Burwell was closely watched this past year.

At stake. Under the ACA, a nonprofit religious organization may certify its objection to its insurance plan’s contraception coverage, at which point other arrangements are made to provide contraceptive coverage through the same plan. Religious organizations objected to the certification requirement.

A brief filed by ACOG, Physicians for Reproductive Health, and other groups emphasized the importance of providing contraceptives and contraceptive counseling as part of regular health care and suggested that the current accommodation for religious organizations is appropriate.⁵

After hearing the formal oral arguments, the Court asked for additional briefs on “whether contraceptive coverage could be provided to petitioners’ employees, through petitioners’ insurance companies, without any such notice from petitioners.”⁶

Final ruling. The parties agreed such a system would resolve the issue, so the Court sent the case back to the lower court to work out the details. In effect, the case was mediated—an unusual if not unique action for the Court. The resolution probably will achieve what the briefs sought—access to contraceptives and continuity of care.

3. Fraud and abuse litigation

The FCA, which provides for triple damages (3 times actual damages) and stiff civil penalties for anyone who presents the federal government (Medicare, Medicaid) with false claims for goods or services, is a major means of uncovering and punishing health care fraud and abuse. In health care, this law has been used to prosecute cases involving services paid for but not provided, unnecessary services, and off-label pharmaceutical promotion.

An important part of the FCA is that it allows a private intervenor (whistleblower) to initiate an action against a health care provider. The government may then take up the case. If not, the intervenor may pursue it; the incentive is 15% to 30% of the damages the government is awarded.

At stake. The Court was asked if “implied certification” applies to FCA cases.⁷ Implied certification means that requesting a payment from Medicare or Medicaid implies that the provider is not knowingly withholding information material to the government’s decision to pay the claim. In separately filed briefs, AMA et al⁸ and American Hospital Association (AHA) et al⁹ argued that applying implied certification to FCA cases would expand FCA litigation (particularly by intervenors), which is already expensive for health care institutions.

Final ruling. The Court unanimously adopted implied certification but noted that nondisclosure of information must be shown to be a material misrepresentation rather than a trivial regulatory or contractual violation. Furthermore, the Court emphasized that the basis for a claim must be an allegation of fraud, not of malpractice. These findings, which certainly are not what the health care organizations had hoped for, likely will lead to an increase in FCA cases.

4. Collection of state health care data

In Vermont, and about 20 other states that collect data on health care utilization and costs, health insurers and other entities are required to submit detailed reports about health care claims.¹⁰ Some insurers objected to this requirement.

At stake. An AHA–AAMC brief noted the importance of health care data and of Vermont’s collecting these data as contributing to better, more efficient health care delivery.¹¹ Another brief, filed by AMA and the Vermont Medical Society, presented more legal or statutory arguments.¹²

Final ruling. The Court held that the Vermont plan and similar plans violate the federal Employee Retirement Income Security Act of 1974. As health insurance companies and other entities already provide detailed utilization and cost data to the federal government, producing up to 50 additional reports for state governments would be burdensome. Any state that wants the information, the Court said, should obtain it from the federal government.

What’s to come

The Court’s recent decisions on access to abortion services and contraceptives were good for patients of ObGyns, but its decisions on health care FCA liability and state health care data collection were, arguably, not as good for ObGyn business practices.

The Court itself had an unusual year. Justice Scalia died in February, and Congress’s inaction on seating a replacement meant that most of the term’s cases were decided by an 8-member Court. Nevertheless, the Court was deadlocked 4−4 on only 4 of the 80 cases it heard. In addition, it was relatively agreed on outcomes; in only about one-third of cases were there more than 2 justices disagreeing with the outcome.

It is unlikely that a replacement for Justice Scalia will be confirmed before the Court begins its new term in October. The need to replace Justice Scalia and the potential turnover of other Court members—Justice Ginsburg is 83, Justice Kennedy is 80, and Justice Breyer is 78—are reminders of the importance of this year’s presidential election. In the meantime, the Court is accepting the cases that will make up the coming term’s docket, and ObGyns undoubtedly will play a role in cases that involve health care.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Each year, the decisions of the Supreme Court have a significant impact on ObGyn practice. During the 2015–2016 term, which ended in June, the Court issued important rulings on abortion facilities, Affordable Care Act (ACA) contraception coverage, health care False Claims Act (FCA) liability, and state health care data collection. The American Medical Association (AMA), the Association of American Medical Colleges (AAMC), the American College of Obstetricians and Gynecologists (ACOG), and other organizations that represent health care professionals play an important role in health-related Supreme Court cases. For example, amicus curiae (“friend of the Court”) briefs are filed not by parties to a case but by organizations that have a special insight into or interest in a case. Although the extent to which amicus briefs influence cases is often unclear, organization representatives think their briefs make a difference, and briefs undoubtedly do in some cases.

The 2016 presidential election will determine the Supreme Court make-up for the next term, but in this article we consider recent cases that affect ObGyns’ practice in particular. We start with the cases in which professional organizations filed amicus briefs and then turn to other notable cases.

1. Abortion access in Texas and other states

The most important ObGyn case of the 2015–2016 term was Whole Woman’s Health v Hellerstedt.¹

At stake. Texas adopted a statute requiring 1) that physicians who perform abortions have admitting privileges at a hospital within 30 miles of the clinic and 2) that abortion clinics meet the state’s standards for ambulatory surgical centers. The current law, upheld by the Court some years ago, is that state laws affecting abortion are unconstitutional if they “unduly burden” the right to abortion. By undue burden, the Court meant, “Regulations that have the purpose or effect of presenting a substantial obstacle to a woman seeking an abortion impose an undue burden on the right.” The question in the Texas case was whether the statute’s 2 requirements were undue.

ACOG, AMA, and other groups filed a brief stating that the Texas law did not promote the welfare of women but instead was unnecessary and not “supported by accepted medical practice or scientific evidence.”² In another brief the Society of Hospital Medicine and the Society of ObGyn Hospitalists also indicated that having admitting privileges is appropriate only for physicians who regularly admit patients to a hospital.³

A brief filed by the American Association of Pro-Life Obstetricians and Gynecologists and several other organizations argued the other side: “The surgical center and admitting privileges requirements imposed by the Act reflect the professional standard of practice for outpatient gynecological and similar surgery.”⁴

Final ruling. In a 5−3 decision, the Court struck down the Texas law for providing little or no health benefits while significantly burdening abortion facility access. Many clinics had closed or were in plans to because of the difficulty and expense of complying with the law. This case has national implications. Similar laws, either in place or being considered in other states, will almost certainly be ruled unconstitutional.

2. Contraceptive coverage

The case of Zubik v Burwell was closely watched this past year.

At stake. Under the ACA, a nonprofit religious organization may certify its objection to its insurance plan’s contraception coverage, at which point other arrangements are made to provide contraceptive coverage through the same plan. Religious organizations objected to the certification requirement.

A brief filed by ACOG, Physicians for Reproductive Health, and other groups emphasized the importance of providing contraceptives and contraceptive counseling as part of regular health care and suggested that the current accommodation for religious organizations is appropriate.⁵

After hearing the formal oral arguments, the Court asked for additional briefs on “whether contraceptive coverage could be provided to petitioners’ employees, through petitioners’ insurance companies, without any such notice from petitioners.”⁶

Final ruling. The parties agreed such a system would resolve the issue, so the Court sent the case back to the lower court to work out the details. In effect, the case was mediated—an unusual if not unique action for the Court. The resolution probably will achieve what the briefs sought—access to contraceptives and continuity of care.

3. Fraud and abuse litigation

The FCA, which provides for triple damages (3 times actual damages) and stiff civil penalties for anyone who presents the federal government (Medicare, Medicaid) with false claims for goods or services, is a major means of uncovering and punishing health care fraud and abuse. In health care, this law has been used to prosecute cases involving services paid for but not provided, unnecessary services, and off-label pharmaceutical promotion.

An important part of the FCA is that it allows a private intervenor (whistleblower) to initiate an action against a health care provider. The government may then take up the case. If not, the intervenor may pursue it; the incentive is 15% to 30% of the damages the government is awarded.

At stake. The Court was asked if “implied certification” applies to FCA cases.⁷ Implied certification means that requesting a payment from Medicare or Medicaid implies that the provider is not knowingly withholding information material to the government’s decision to pay the claim. In separately filed briefs, AMA et al⁸ and American Hospital Association (AHA) et al⁹ argued that applying implied certification to FCA cases would expand FCA litigation (particularly by intervenors), which is already expensive for health care institutions.

Final ruling. The Court unanimously adopted implied certification but noted that nondisclosure of information must be shown to be a material misrepresentation rather than a trivial regulatory or contractual violation. Furthermore, the Court emphasized that the basis for a claim must be an allegation of fraud, not of malpractice. These findings, which certainly are not what the health care organizations had hoped for, likely will lead to an increase in FCA cases.

4. Collection of state health care data

In Vermont, and about 20 other states that collect data on health care utilization and costs, health insurers and other entities are required to submit detailed reports about health care claims.¹⁰ Some insurers objected to this requirement.

At stake. An AHA–AAMC brief noted the importance of health care data and of Vermont’s collecting these data as contributing to better, more efficient health care delivery.¹¹ Another brief, filed by AMA and the Vermont Medical Society, presented more legal or statutory arguments.¹²

Final ruling. The Court held that the Vermont plan and similar plans violate the federal Employee Retirement Income Security Act of 1974. As health insurance companies and other entities already provide detailed utilization and cost data to the federal government, producing up to 50 additional reports for state governments would be burdensome. Any state that wants the information, the Court said, should obtain it from the federal government.