Kerri Wachter

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

It may be time to reevaluate the use of standard cardiopulmonary resuscitation for out-of-hospital cardiac arrest, now that results from a large prospective, randomized trial show better outcomes with a more advanced form of CPR.

Treatment with active compression-decompression CPR with enhanced negative intrathoracic pressure during the decompression phase significantly increased survival to hospital discharge with favorable neurologic function, compared with standard CPR, after an out-of-hospital cardiac arrest of presumed cardiac cause. The findings come from a study of 1,653 patients treated for cardiac arrest by emergency medical service professionals in seven geographic regions; patients were randomized to receive standard or enhanced CPR (Lancet 2011;377:301-11).

Treatment with the enhanced CPR method led to a 53% relative increase in survival to hospital discharge with a modified Rankin Scale score of no more than 3 – the study’s primary end point – compared with standard CPR. Consistent survival differences between study groups were noted throughout the study, independent of age, study site, sex, and date of treatment.

In addition, overall survival increased by nearly 50% at 1 year in the intervention group, compared with those who received standard CPR. Neurologic function was similar between the two groups at 90 days and 365 days after the out-of-hospital cardiac arrest, reported Dr. Tom P. Aufderheide, professor of emergency medicine at the Medical College of Wisconsin in Milwaukee, and his coinvestigators.

The study was sponsored by Advanced Circulatory Systems, which makes two of the devices used in the intervention arm of the study. The company helped investigators to obtain government funding, design the study, interpret the data, and write the report for publication.

Improvements in out-of-hospital CPR are needed given the poor overall survival rates, which average about 5% in North America and Europe. "Poor survival rates persist, in part, because manual chest compression and ventilation ... is inherently inefficient, providing less than 25% of healthy blood flow to the heart and brain," they wrote.

Research has shown that decreased intrathoracic pressure is associated with a simultaneous decrease in intracranial pressure and increased blood flow to the heart and brain. Clinical studies have also shown substantial improvement in 24-hour survival with the use of increased negative intrathoracic pressure during the decompression phase of CPR. Active compression-decompression CPR increases ventilation to 13.5 L/min, compared with 7.8 L/min with standard CPR, the researchers noted.

Adults with out-of-hospital cardiac arrest were eligible for the study. Patients were initially excluded for obvious or likely traumatic injuries causing cardiac arrest, a preexisting do-not-resuscitate order, signs of obvious clinical death, conditions that precluded the use of CPR, an in-hospital cardiac arrest, or recent sternotomy. The final exclusion criteria included all initial criteria plus receiving less than 1 minute of CPR by EMS personnel and a complete airway obstruction; intubation with a leaky or uncuffed advanced airway device; noncardiac cause of arrest; and presence of a stoma, tracheotomy, or tracheostomy.

Rescuers performed active compression-decompression CPR with a handheld CPR device (ResQPump/CardioPump) that consists of a suction cup attached to the chest, a handle, an audible metronome set to 80 beats per minute, and a force gauge to guide compression depth and chest wall recoil. This technique requires compression to the same depth as standard CPR and then upward lifting to fully decompress the chest. In addition, an impedance-threshold device (ResQPOD), with an inspiratory resistance of 16 cm H2O and less than 5 cm H2O expiratory impedance, was connected to a face mask or advanced airway.

The first EMS provider to arrive at the site started chest compressions as soon as possible for patients in both study groups. Standard CPR, defibrillation, and advanced life support treatment were performed in accordance with local policy and the American Heart Association guidelines. A compression-to-ventilation ratio of 30:2 was used during basic life support for both techniques; however, for the intervention protocol, rescuers provided CPR at 80 compressions per minute as soon as possible. The active compression-decompression device force gauge was used to help achieve the recommended compression depth and complete chest recoil.

The seven study sites had 46 EMS agencies in urban, suburban, and rural areas, and served 2.3 million people. In all, 4,940 EMS personnel underwent didactic and hands-on training before the study started and every 6 months thereafter.

Nearly all survivors had no or mild long-term neurologic deficits, which did not differ between groups. Disabilities rating scale scores, which are a key functional assessment of patients with severe disability, did not differ between groups.

"We suggest that improved cerebral perfusion during CPR in the intervention group resulted in reduced cerebral ischemia but that recovery and restoration of brain function might take more time than does the recovery of cardiac function," the investigators wrote.

"These findings also support the idea that improved perfusion outside the hospital in the intervention group could result in more stable candidates for cardiac catheterization than were found in the standard CPR group, resulting in more patients in the intervention group being provided cardiac catheterization," they added.

While there were no differences in overall major adverse event rates between groups, the "occurrence of pulmonary edema was increased by 50% in the device group, which was coexistent with the increase in survival with favorable neurologic function. The clinical relevance of this finding is unclear: the percentage increase in pulmonary edema (46%) was proportional to the increase in survival in the intervention group (53%)," the researchers observed.

Dr. Aufderheide has been a consultant to Jolife Medical and Medtronic Foundation. One of the listed authors is coinventor of the two devices used in the study and founded Advanced Circulatory Systems. Another author has received lecture fees from Advanced Circulatory Systems, and another has significant financial relationships with Baxter, Vita Care Medical Products, and Cook Medical.

Patients with type 1 diabetes are almost 10 times more likely to be infected with enterovirus than are individuals without diabetes, based on the first meta-analysis of studies using molecular diagnosis of the virus. The findings were reported online Feb. 3 in BMJ (2011;342:d35 [doi:10.1136/bmj.d35]).

Although it has been suggested in the literature that enterovirus might play a role in the development of type 1 diabetes, to date there has been no systematic review of molecular studies. Researchers in Australia performed such a review of 25 controlled studies that used molecular methods to investigate such an association. They found a summary odds ratio of 9.8 (P less than .001) for identifying enterovirus in patients with type 1 diabetes, compared with patients without it.

"While the findings from this meta-analysis of observational studies cannot prove that enterovirus infection has a causal role in pathogenesis of diabetes, the results provide additional support to the direct evidence of enterovirus infection in pancreatic tissue of individuals with type 1 diabetes," wrote authors Wing-Chi Yeung, Dr. William D. Rawlinson, and Dr. Maria E. Craig of the University of New South Wales.

For this meta-analysis, two reviewers independently conducted systematic searches for controlled observational studies of enterovirus and type 1 diabetes. They searched the PubMed (from 1965 to May 2010) and Embase (from 1974 to May 2010) databases.

They included only case-control or cohort studies that used molecular methods for viral detection (such as reverse transcription-polymerase chain reaction [RT-PCR], in situ hybridization, or immunostaining for detection of viral capsid protein) to identify current or recent infection in blood, stool, or tissue of patients with prediabetes and diabetes. "Molecular testing is now standard for diagnosis of acute enterovirus infection," they noted.

They classified the studies into two groups – prediabetes and diabetes – depending on whether autoimmunity or type 1 diabetes (newly diagnosed, established type and eventual type 1 diabetes) was the outcome. This systematic review of 33 prevalence studies, involved 1,931 patients and 2,517 nondiabetic individuals.

They identified 34 studies – 9 involving patients with prediabetes (198 cases and 733 controls) and 25 studies of diabetes patients (1,733 cases and 1,784 controls). Thirty studies used RT-PCR or in situ hybridization to detect enterovirus RNA; immunostaining for the enterovirus capsid protein vp1 on autopsy pancreas specimens was used on four studies. Most studies investigated children and adolescents up to age 16 years, though some included adults up to age 53.

The summary odds ratio of identifying enterovirus in patients with prediabetes, compared with patients without diabetes was 3.7 (P less than .001). All but one of the 25 studies of patients with type 1 diabetes had odds ratios greater than one for patients with diabetes testing positive for enterovirus, with a summary odds ratio of 9.8 (P less than .001).

They used sensitivity analyses to test the robustness of the results by country and study quality. In all, 19 studies were conducted in Europe. "There was some evidence for geographical differences; in non-European studies the odds ratio was 13.5, compared with 8.6 in European studies, though there was considerably overlap in the confidence intervals," they wrote.

In addition, "the odds of having an enterovirus infection in people with established diabetes (OR, 11) suggest that persistent enterovirus infection is also common among patients with type 1 diabetes."

The investigators reported that they have no relevant financial relationships.

Patients with type 1 diabetes are almost 10 times more likely to be infected with enterovirus than are individuals without diabetes, based on the first meta-analysis of studies using molecular diagnosis of the virus. The findings were reported online Feb. 3 in BMJ (2011;342:d35 [doi:10.1136/bmj.d35]).

Although it has been suggested in the literature that enterovirus might play a role in the development of type 1 diabetes, to date there has been no systematic review of molecular studies. Researchers in Australia performed such a review of 25 controlled studies that used molecular methods to investigate such an association. They found a summary odds ratio of 9.8 (P less than .001) for identifying enterovirus in patients with type 1 diabetes, compared with patients without it.

"While the findings from this meta-analysis of observational studies cannot prove that enterovirus infection has a causal role in pathogenesis of diabetes, the results provide additional support to the direct evidence of enterovirus infection in pancreatic tissue of individuals with type 1 diabetes," wrote authors Wing-Chi Yeung, Dr. William D. Rawlinson, and Dr. Maria E. Craig of the University of New South Wales.

For this meta-analysis, two reviewers independently conducted systematic searches for controlled observational studies of enterovirus and type 1 diabetes. They searched the PubMed (from 1965 to May 2010) and Embase (from 1974 to May 2010) databases.

They included only case-control or cohort studies that used molecular methods for viral detection (such as reverse transcription-polymerase chain reaction [RT-PCR], in situ hybridization, or immunostaining for detection of viral capsid protein) to identify current or recent infection in blood, stool, or tissue of patients with prediabetes and diabetes. "Molecular testing is now standard for diagnosis of acute enterovirus infection," they noted.

They classified the studies into two groups – prediabetes and diabetes – depending on whether autoimmunity or type 1 diabetes (newly diagnosed, established type and eventual type 1 diabetes) was the outcome. This systematic review of 33 prevalence studies, involved 1,931 patients and 2,517 nondiabetic individuals.

They identified 34 studies – 9 involving patients with prediabetes (198 cases and 733 controls) and 25 studies of diabetes patients (1,733 cases and 1,784 controls). Thirty studies used RT-PCR or in situ hybridization to detect enterovirus RNA; immunostaining for the enterovirus capsid protein vp1 on autopsy pancreas specimens was used on four studies. Most studies investigated children and adolescents up to age 16 years, though some included adults up to age 53.

The summary odds ratio of identifying enterovirus in patients with prediabetes, compared with patients without diabetes was 3.7 (P less than .001). All but one of the 25 studies of patients with type 1 diabetes had odds ratios greater than one for patients with diabetes testing positive for enterovirus, with a summary odds ratio of 9.8 (P less than .001).

They used sensitivity analyses to test the robustness of the results by country and study quality. In all, 19 studies were conducted in Europe. "There was some evidence for geographical differences; in non-European studies the odds ratio was 13.5, compared with 8.6 in European studies, though there was considerably overlap in the confidence intervals," they wrote.

In addition, "the odds of having an enterovirus infection in people with established diabetes (OR, 11) suggest that persistent enterovirus infection is also common among patients with type 1 diabetes."

The investigators reported that they have no relevant financial relationships.

Patients with type 1 diabetes are almost 10 times more likely to be infected with enterovirus than are individuals without diabetes, based on the first meta-analysis of studies using molecular diagnosis of the virus. The findings were reported online Feb. 3 in BMJ (2011;342:d35 [doi:10.1136/bmj.d35]).

Although it has been suggested in the literature that enterovirus might play a role in the development of type 1 diabetes, to date there has been no systematic review of molecular studies. Researchers in Australia performed such a review of 25 controlled studies that used molecular methods to investigate such an association. They found a summary odds ratio of 9.8 (P less than .001) for identifying enterovirus in patients with type 1 diabetes, compared with patients without it.

"While the findings from this meta-analysis of observational studies cannot prove that enterovirus infection has a causal role in pathogenesis of diabetes, the results provide additional support to the direct evidence of enterovirus infection in pancreatic tissue of individuals with type 1 diabetes," wrote authors Wing-Chi Yeung, Dr. William D. Rawlinson, and Dr. Maria E. Craig of the University of New South Wales.

For this meta-analysis, two reviewers independently conducted systematic searches for controlled observational studies of enterovirus and type 1 diabetes. They searched the PubMed (from 1965 to May 2010) and Embase (from 1974 to May 2010) databases.

They included only case-control or cohort studies that used molecular methods for viral detection (such as reverse transcription-polymerase chain reaction [RT-PCR], in situ hybridization, or immunostaining for detection of viral capsid protein) to identify current or recent infection in blood, stool, or tissue of patients with prediabetes and diabetes. "Molecular testing is now standard for diagnosis of acute enterovirus infection," they noted.

They classified the studies into two groups – prediabetes and diabetes – depending on whether autoimmunity or type 1 diabetes (newly diagnosed, established type and eventual type 1 diabetes) was the outcome. This systematic review of 33 prevalence studies, involved 1,931 patients and 2,517 nondiabetic individuals.

They identified 34 studies – 9 involving patients with prediabetes (198 cases and 733 controls) and 25 studies of diabetes patients (1,733 cases and 1,784 controls). Thirty studies used RT-PCR or in situ hybridization to detect enterovirus RNA; immunostaining for the enterovirus capsid protein vp1 on autopsy pancreas specimens was used on four studies. Most studies investigated children and adolescents up to age 16 years, though some included adults up to age 53.

The summary odds ratio of identifying enterovirus in patients with prediabetes, compared with patients without diabetes was 3.7 (P less than .001). All but one of the 25 studies of patients with type 1 diabetes had odds ratios greater than one for patients with diabetes testing positive for enterovirus, with a summary odds ratio of 9.8 (P less than .001).

They used sensitivity analyses to test the robustness of the results by country and study quality. In all, 19 studies were conducted in Europe. "There was some evidence for geographical differences; in non-European studies the odds ratio was 13.5, compared with 8.6 in European studies, though there was considerably overlap in the confidence intervals," they wrote.

In addition, "the odds of having an enterovirus infection in people with established diabetes (OR, 11) suggest that persistent enterovirus infection is also common among patients with type 1 diabetes."

The investigators reported that they have no relevant financial relationships.

The Food and Drug Administration is asking health care professionals to report any confirmed cases of anaplastic large cell lymphoma (ALCL) in women with silicone gel- or saline-filled breast implants, citing concerns about a possible association.

The agency’s announcement during a teleconference on Jan. 26 is based on a review of scientific literature published between 1997 and 2010, along with information from other international regulators, scientists, and breast implant manufacturers.

"ALCL is rare and has occurred in a very small number of women when compared to the millions who have breast implants," said Dr. William Maisel, chief scientist and deputy director for science in FDA’s Center for Devices and Radiological Health. The literature review identified 34 unique cases of this rare cancer in women with both saline and silicone breast implants. There have been roughly 60 cases of ALCL in women with breast implants worldwide, according to the FDA. It’s estimated that 5-10 million women have breast implants worldwide.

"Data reviewed by the FDA suggest that patients with breast implants may have a very small but significant risk of ALCL in the scar capsule adjacent to the implant," the agency noted in a press release. Most of the cases reviewed by the agency were diagnosed when patients sought treatment for implant-related symptoms such as pain, lumps, swelling, or asymmetry.

The FDA recommends that health care professionals consider the possibility of ALCL if a patient has late onset, persistent fluid around the implant (peri-implant seroma). When implant seroma is found, fresh seroma fluid should be sent for pathology tests to rule out ALCL. Patient information about breast implants and ALCL can be found in the FDA’s Consumer Updates.

Health care providers should discuss the risks and benefits with women who are considering breast implant surgery. The FDA published its literature review in a document posted on its Web site today titled "Anaplastic Large Cell Lymphoma (ALCL) in Women with Breast Implants: Preliminary FDA Findings and Analyses." The FDA also plans to provide an update on its review of silicone gel–filled breast implants in the spring of 2011.

Health care professionals should report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program, either online or by calling 800-332-1088.

The FDA also provides general information about breast implants to share with patients.

The Food and Drug Administration is asking health care professionals to report any confirmed cases of anaplastic large cell lymphoma (ALCL) in women with silicone gel- or saline-filled breast implants, citing concerns about a possible association.

The agency’s announcement during a teleconference on Jan. 26 is based on a review of scientific literature published between 1997 and 2010, along with information from other international regulators, scientists, and breast implant manufacturers.

"ALCL is rare and has occurred in a very small number of women when compared to the millions who have breast implants," said Dr. William Maisel, chief scientist and deputy director for science in FDA’s Center for Devices and Radiological Health. The literature review identified 34 unique cases of this rare cancer in women with both saline and silicone breast implants. There have been roughly 60 cases of ALCL in women with breast implants worldwide, according to the FDA. It’s estimated that 5-10 million women have breast implants worldwide.

"Data reviewed by the FDA suggest that patients with breast implants may have a very small but significant risk of ALCL in the scar capsule adjacent to the implant," the agency noted in a press release. Most of the cases reviewed by the agency were diagnosed when patients sought treatment for implant-related symptoms such as pain, lumps, swelling, or asymmetry.

The FDA recommends that health care professionals consider the possibility of ALCL if a patient has late onset, persistent fluid around the implant (peri-implant seroma). When implant seroma is found, fresh seroma fluid should be sent for pathology tests to rule out ALCL. Patient information about breast implants and ALCL can be found in the FDA’s Consumer Updates.

Health care providers should discuss the risks and benefits with women who are considering breast implant surgery. The FDA published its literature review in a document posted on its Web site today titled "Anaplastic Large Cell Lymphoma (ALCL) in Women with Breast Implants: Preliminary FDA Findings and Analyses." The FDA also plans to provide an update on its review of silicone gel–filled breast implants in the spring of 2011.

Health care professionals should report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program, either online or by calling 800-332-1088.

The FDA also provides general information about breast implants to share with patients.

The Food and Drug Administration is asking health care professionals to report any confirmed cases of anaplastic large cell lymphoma (ALCL) in women with silicone gel- or saline-filled breast implants, citing concerns about a possible association.

The agency’s announcement during a teleconference on Jan. 26 is based on a review of scientific literature published between 1997 and 2010, along with information from other international regulators, scientists, and breast implant manufacturers.

"ALCL is rare and has occurred in a very small number of women when compared to the millions who have breast implants," said Dr. William Maisel, chief scientist and deputy director for science in FDA’s Center for Devices and Radiological Health. The literature review identified 34 unique cases of this rare cancer in women with both saline and silicone breast implants. There have been roughly 60 cases of ALCL in women with breast implants worldwide, according to the FDA. It’s estimated that 5-10 million women have breast implants worldwide.

"Data reviewed by the FDA suggest that patients with breast implants may have a very small but significant risk of ALCL in the scar capsule adjacent to the implant," the agency noted in a press release. Most of the cases reviewed by the agency were diagnosed when patients sought treatment for implant-related symptoms such as pain, lumps, swelling, or asymmetry.

The FDA recommends that health care professionals consider the possibility of ALCL if a patient has late onset, persistent fluid around the implant (peri-implant seroma). When implant seroma is found, fresh seroma fluid should be sent for pathology tests to rule out ALCL. Patient information about breast implants and ALCL can be found in the FDA’s Consumer Updates.

Health care providers should discuss the risks and benefits with women who are considering breast implant surgery. The FDA published its literature review in a document posted on its Web site today titled "Anaplastic Large Cell Lymphoma (ALCL) in Women with Breast Implants: Preliminary FDA Findings and Analyses." The FDA also plans to provide an update on its review of silicone gel–filled breast implants in the spring of 2011.

Health care professionals should report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program, either online or by calling 800-332-1088.

The FDA also provides general information about breast implants to share with patients.

Lynn B. Jorde, Ph.D., discusses problems with direct-to-consumer genomic testing and the potential of whole-genome sequencing.

Lynn B. Jorde, Ph.D., discusses problems with direct-to-consumer genomic testing and the potential of whole-genome sequencing.

Lynn B. Jorde, Ph.D., discusses problems with direct-to-consumer genomic testing and the potential of whole-genome sequencing.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine's (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM's review of the scientific evidence about vitamin D supports the Academy's long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine's (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM's review of the scientific evidence about vitamin D supports the Academy's long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine's (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM's review of the scientific evidence about vitamin D supports the Academy's long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine’s (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM’s review of the scientific evidence about vitamin D supports the Academy’s long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine’s (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM’s review of the scientific evidence about vitamin D supports the Academy’s long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

The American Academy of Dermatology still recommends vitamin D come from a healthy diet and supplements, not from unprotected skin exposure to ultraviolet radiation, according to their newly updated position statement.

The update comes in response to the Institute of Medicine’s (IOM) recent review of existing data on possible roles for vitamin D status in certain types of cancers, and neurologic, infectious, autoimmune, and cardiovascular diseases. In the report, the IOM called existing evidence "inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirement." However, the organization found that the evidence does support a role for vitamin D in bone health.

"The IOM’s review of the scientific evidence about vitamin D supports the Academy’s long-standing recommendation on safe ways to get this important vitamin – through a healthy diet which incorporates foods naturally rich in vitamin D, vitamin D–fortified foods and beverages, and vitamin D supplements," AAD president Dr. William D. James noted in a statement.

In particular, the statement reinforces the idea that unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.

The Academy recommends a comprehensive photoprotective regimen, including the regular and proper use of a broad-spectrum sunscreen to protect against skin cancer.

The statement also includes new IOM Recommended Dietary Allowances (RDA) for calcium and vitamin D intake. Of note, these age-based values were derived assuming minimal or no sun exposure, given inconsistent contributions of sunlight to vitamin D in the population and also because of the risk of cancer associated with sun exposure.

Adequate vitamin D was defined by the IOM as blood levels of at least 20 ng/mL as measured in the United States (50 nmol/L as measured in Canada).

Physicians should discuss options for obtaining sufficient dietary or supplementary sources of vitamin D with patients having concerned about their vitamin D levels.

Attempting to identify breast cancer micrometastases and isolated tumor-cell clusters through further analysis of initially negative sentinel lymph nodes does not appear to add any clinical benefit, according to a report published online in the New England Journal of Medicine.

Researchers from the National Surgical Adjuvant Breast and Bowel Project (NSABP) determined that the presence of small occult metastases in sentinel nodes was an independent predictor of survival, but the magnitude of differences in outcome at 5 years between patients with and without occult metastases was small.

Occult metastases were detected in 15.9% of the 3,887 patients included in this analysis: 11.1% had isolated tumor-cell clusters, 4.4% had micrometastases, and 0.4% had macrometastases. There were statistically significant decreases in overall survival (P = .03), disease-free survival (P = .02), and distant-disease-free interval (P = .04) when patients with occult metastases were compared with those in whom occult metastases were not found, wrote Dr. Donald L. Weaver, professor of pathology at the University of Vermont in Burlington, and his coinvestigators.

The magnitude of differences in 5-year Kaplan-Meier estimates was just 1-3 percentage points. Comparison of patients with and without occult metastases showed rates to be 95% and 96%, respectively, for overall survival; 86% and 89%, respectively, for disease-free survival; and 90% and 93%, respectively, for distant-disease-free interval.

"Our findings argue against analysis of additional tissue levels or routine immunohistochemical analysis for sentinel-lymph-node evaluation," Dr. Weaver and his coinvestigators wrote in the study released on Jan. 19 (doi: 10.1056/NEJMa1008108).

Increased use of serial sectioning of the sentinel lymph node (SLN) for pathologic assessment using hematoxylin and eosin (H&E) stain or immunohistochemistry has increased identification of SLNs with minimal involvement in recent years. However, the clinical significance of minimal SLN involvement – the presence of micrometastases and/or isolated tumor-cell clusters – and the optimal management of these patients have been unclear, the investigators said.

The primary aim of the phase-III NSABP trial B-32 was to evaluate equivalence of SLN biopsy alone to biopsy with complete axillary dissection. It included 5,611 women who had confirmed resectable invasive adenocarcinoma of the breast. They had to have clinically negative lymph nodes, with no positive ipsilateral axillary lymph nodes or prior removal of ipsilateral axillary lymph nodes.

In all, 2,807 women were randomized to undergo sentinel node resection immediately followed by conventional axillary dissection (arm I) and 2,804 were randomized to sentinel node biopsy with axillary lymph node dissection (ALND) only if the sentinel node was positive (arm II). SLNs from both groups were assessed postoperatively using 2-mm slices from paraffin tissue blocks and H&E staining. Routine immunohistochemistry was not permitted, but it could be done for confirmation of suspicious findings from H&E staining.

As reported at the 2010 annual meeting of the American Society for Clinical Oncology and later published (Lancet Oncology 2010;11:927-33), the investigators found no difference in disease-free or overall survival between the two groups.

This new analysis was aimed at determining the clinical significance of occult metastatic disease in selected axillary lymph nodes (sentinel nodes). It included 3,887 tissue blocks of sentinel nodes obtained from all patients with negative nodes at the initial evaluation. These were sent to a central laboratory for further evaluation. Follow-up data were available for 3,884 women. The median time in the study was 95 months.

Additional and deeper samples were evaluated for occult metastases using H&E and immunohistochemical staining. The protocol was designed "to detect virtually all occult metastases larger than 1.0 mm in the greatest dimension and to randomly detect a proportion of occult metastases smaller than 1.0 mm," the investigators noted.

Patients were classified based on whether occult metastases were detected in the SNL. A subgroup analysis used American Joint Committee on Cancer definitions of isolated tumor-cell clusters (no larger than 0.2 mm in the greatest dimension), micrometastases (greater than 0.2 mm but no larger than 2.0 mm), and macrometastases (larger than 2.0 mm), Dr. Weaver and his coinvestigators reported.

Models were adjusted for patient age (older than 49 years or not), tumor size (no larger than 2.0 cm, 2.1 cm to 4.0 cm, or at least 4.1 cm), surgical treatment plan (lumpectomy or mastectomy), type of systemic chemotherapy, use of radiation therapy, and study group. The adjusted hazard ratios were 1.40 for death, 1.31 for any outcome event, and 1.30 for distant disease.

"Our findings are consistent with the hypothesis that nodal tumor burden is a continuous variable and indicate that occult metastases are an independent prognostic factor," they wrote.

The differences observed between patients with and without occult metastases with respect to 5-year Kaplan-Meier estimates of overall survival (between-group difference, 1.2%), disease-free survival (2.8%), and distant-disease-free interval (2.8%) were statistically significant but relatively small, the researchers pointed out.

These findings are not surprising after a more limited presentation by NSABP investigator Thomas B. Julian at the San Antonio Breast Cancer Symposium in December. Dr. Julian reported findings only for micrometastases detected in the SLN by H&E staining alone.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

The disease-free survival outcome for patients who had micrometastatic sentinel nodes by H&E stain were the same as for those who had positive sentinel nodes. "Macrometastatic patients, on the other hand, had a higher hazard rate of 1.8, which was significantly important," Dr. Julian said.

As for overall survival, "patients who had sentinel nodes with micrometastatic disease had a hazard rate of 0.8 – very similar to those patients who were sentinel-node negative. The P value was insignificant. For those patients who had macrometastases, the hazard rate was 2.4. That was found to be significant," said Dr. Julian, associate director of the breast care center at Allegheny General Hospital in Pittsburgh.

In the published analysis, Dr. Weaver and his associates found that occult metastases were not discriminatory predictors of cancer recurrence. Just 3.6% of the node-negative patients had regional or distant recurrences as first events, and only 30 of these events (in 0.8% of all patients) occurred in patients with occult metastases. All told, 80.5% of patients with occult metastases were alive and free of disease.

"Identification of occult metastases does not appear to be clinically useful for patients with newly diagnosed disease in whom systemic therapy can be recommended on the basis of the characteristics of the primary tumor," the investigators wrote.

The prevalence of occult metastases was significantly associated with age younger than 50 years, clinical tumor size greater than 2.0 cm in the greatest dimension, and planned mastectomy. The authors noted that these findings are not surprising.

"Perhaps the most interesting interaction was with endocrine therapy, indicating that occult metastases are associated with estrogen receptor–positive tumors, a favorable prognostic factor, and that endocrine therapy markedly reduces the risk of a poor outcome," Dr. Weaver and his associates wrote.

They also found that isolated tumor-cell clusters had a smaller effect on outcome than micrometastases for every outcome evaluated, regardless of whether occult macrometastases were included or excluded. The magnitude of difference in 5-year Kaplan-Meier estimates for death from breast cancer was small for detection of isolated tumor-cell clusters vs. no detection (0.6%) and for the detection of micrometastases vs. no detection (2.4%).

The B-32 trial was sponsored by the National Cancer Institute. All of the study authors reported that they have no relevant financial relationships.

Attempting to identify breast cancer micrometastases and isolated tumor-cell clusters through further analysis of initially negative sentinel lymph nodes does not appear to add any clinical benefit, according to a report published online in the New England Journal of Medicine.

Researchers from the National Surgical Adjuvant Breast and Bowel Project (NSABP) determined that the presence of small occult metastases in sentinel nodes was an independent predictor of survival, but the magnitude of differences in outcome at 5 years between patients with and without occult metastases was small.

Occult metastases were detected in 15.9% of the 3,887 patients included in this analysis: 11.1% had isolated tumor-cell clusters, 4.4% had micrometastases, and 0.4% had macrometastases. There were statistically significant decreases in overall survival (P = .03), disease-free survival (P = .02), and distant-disease-free interval (P = .04) when patients with occult metastases were compared with those in whom occult metastases were not found, wrote Dr. Donald L. Weaver, professor of pathology at the University of Vermont in Burlington, and his coinvestigators.

The magnitude of differences in 5-year Kaplan-Meier estimates was just 1-3 percentage points. Comparison of patients with and without occult metastases showed rates to be 95% and 96%, respectively, for overall survival; 86% and 89%, respectively, for disease-free survival; and 90% and 93%, respectively, for distant-disease-free interval.

"Our findings argue against analysis of additional tissue levels or routine immunohistochemical analysis for sentinel-lymph-node evaluation," Dr. Weaver and his coinvestigators wrote in the study released on Jan. 19 (doi: 10.1056/NEJMa1008108).

Increased use of serial sectioning of the sentinel lymph node (SLN) for pathologic assessment using hematoxylin and eosin (H&E) stain or immunohistochemistry has increased identification of SLNs with minimal involvement in recent years. However, the clinical significance of minimal SLN involvement – the presence of micrometastases and/or isolated tumor-cell clusters – and the optimal management of these patients have been unclear, the investigators said.

The primary aim of the phase-III NSABP trial B-32 was to evaluate equivalence of SLN biopsy alone to biopsy with complete axillary dissection. It included 5,611 women who had confirmed resectable invasive adenocarcinoma of the breast. They had to have clinically negative lymph nodes, with no positive ipsilateral axillary lymph nodes or prior removal of ipsilateral axillary lymph nodes.

In all, 2,807 women were randomized to undergo sentinel node resection immediately followed by conventional axillary dissection (arm I) and 2,804 were randomized to sentinel node biopsy with axillary lymph node dissection (ALND) only if the sentinel node was positive (arm II). SLNs from both groups were assessed postoperatively using 2-mm slices from paraffin tissue blocks and H&E staining. Routine immunohistochemistry was not permitted, but it could be done for confirmation of suspicious findings from H&E staining.

As reported at the 2010 annual meeting of the American Society for Clinical Oncology and later published (Lancet Oncology 2010;11:927-33), the investigators found no difference in disease-free or overall survival between the two groups.

This new analysis was aimed at determining the clinical significance of occult metastatic disease in selected axillary lymph nodes (sentinel nodes). It included 3,887 tissue blocks of sentinel nodes obtained from all patients with negative nodes at the initial evaluation. These were sent to a central laboratory for further evaluation. Follow-up data were available for 3,884 women. The median time in the study was 95 months.

Additional and deeper samples were evaluated for occult metastases using H&E and immunohistochemical staining. The protocol was designed "to detect virtually all occult metastases larger than 1.0 mm in the greatest dimension and to randomly detect a proportion of occult metastases smaller than 1.0 mm," the investigators noted.

Patients were classified based on whether occult metastases were detected in the SNL. A subgroup analysis used American Joint Committee on Cancer definitions of isolated tumor-cell clusters (no larger than 0.2 mm in the greatest dimension), micrometastases (greater than 0.2 mm but no larger than 2.0 mm), and macrometastases (larger than 2.0 mm), Dr. Weaver and his coinvestigators reported.

Models were adjusted for patient age (older than 49 years or not), tumor size (no larger than 2.0 cm, 2.1 cm to 4.0 cm, or at least 4.1 cm), surgical treatment plan (lumpectomy or mastectomy), type of systemic chemotherapy, use of radiation therapy, and study group. The adjusted hazard ratios were 1.40 for death, 1.31 for any outcome event, and 1.30 for distant disease.

"Our findings are consistent with the hypothesis that nodal tumor burden is a continuous variable and indicate that occult metastases are an independent prognostic factor," they wrote.

The differences observed between patients with and without occult metastases with respect to 5-year Kaplan-Meier estimates of overall survival (between-group difference, 1.2%), disease-free survival (2.8%), and distant-disease-free interval (2.8%) were statistically significant but relatively small, the researchers pointed out.

These findings are not surprising after a more limited presentation by NSABP investigator Thomas B. Julian at the San Antonio Breast Cancer Symposium in December. Dr. Julian reported findings only for micrometastases detected in the SLN by H&E staining alone.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

The disease-free survival outcome for patients who had micrometastatic sentinel nodes by H&E stain were the same as for those who had positive sentinel nodes. "Macrometastatic patients, on the other hand, had a higher hazard rate of 1.8, which was significantly important," Dr. Julian said.

As for overall survival, "patients who had sentinel nodes with micrometastatic disease had a hazard rate of 0.8 – very similar to those patients who were sentinel-node negative. The P value was insignificant. For those patients who had macrometastases, the hazard rate was 2.4. That was found to be significant," said Dr. Julian, associate director of the breast care center at Allegheny General Hospital in Pittsburgh.

In the published analysis, Dr. Weaver and his associates found that occult metastases were not discriminatory predictors of cancer recurrence. Just 3.6% of the node-negative patients had regional or distant recurrences as first events, and only 30 of these events (in 0.8% of all patients) occurred in patients with occult metastases. All told, 80.5% of patients with occult metastases were alive and free of disease.

"Identification of occult metastases does not appear to be clinically useful for patients with newly diagnosed disease in whom systemic therapy can be recommended on the basis of the characteristics of the primary tumor," the investigators wrote.

The prevalence of occult metastases was significantly associated with age younger than 50 years, clinical tumor size greater than 2.0 cm in the greatest dimension, and planned mastectomy. The authors noted that these findings are not surprising.

"Perhaps the most interesting interaction was with endocrine therapy, indicating that occult metastases are associated with estrogen receptor–positive tumors, a favorable prognostic factor, and that endocrine therapy markedly reduces the risk of a poor outcome," Dr. Weaver and his associates wrote.

They also found that isolated tumor-cell clusters had a smaller effect on outcome than micrometastases for every outcome evaluated, regardless of whether occult macrometastases were included or excluded. The magnitude of difference in 5-year Kaplan-Meier estimates for death from breast cancer was small for detection of isolated tumor-cell clusters vs. no detection (0.6%) and for the detection of micrometastases vs. no detection (2.4%).

The B-32 trial was sponsored by the National Cancer Institute. All of the study authors reported that they have no relevant financial relationships.

Attempting to identify breast cancer micrometastases and isolated tumor-cell clusters through further analysis of initially negative sentinel lymph nodes does not appear to add any clinical benefit, according to a report published online in the New England Journal of Medicine.

Researchers from the National Surgical Adjuvant Breast and Bowel Project (NSABP) determined that the presence of small occult metastases in sentinel nodes was an independent predictor of survival, but the magnitude of differences in outcome at 5 years between patients with and without occult metastases was small.

Occult metastases were detected in 15.9% of the 3,887 patients included in this analysis: 11.1% had isolated tumor-cell clusters, 4.4% had micrometastases, and 0.4% had macrometastases. There were statistically significant decreases in overall survival (P = .03), disease-free survival (P = .02), and distant-disease-free interval (P = .04) when patients with occult metastases were compared with those in whom occult metastases were not found, wrote Dr. Donald L. Weaver, professor of pathology at the University of Vermont in Burlington, and his coinvestigators.

The magnitude of differences in 5-year Kaplan-Meier estimates was just 1-3 percentage points. Comparison of patients with and without occult metastases showed rates to be 95% and 96%, respectively, for overall survival; 86% and 89%, respectively, for disease-free survival; and 90% and 93%, respectively, for distant-disease-free interval.

"Our findings argue against analysis of additional tissue levels or routine immunohistochemical analysis for sentinel-lymph-node evaluation," Dr. Weaver and his coinvestigators wrote in the study released on Jan. 19 (doi: 10.1056/NEJMa1008108).

Increased use of serial sectioning of the sentinel lymph node (SLN) for pathologic assessment using hematoxylin and eosin (H&E) stain or immunohistochemistry has increased identification of SLNs with minimal involvement in recent years. However, the clinical significance of minimal SLN involvement – the presence of micrometastases and/or isolated tumor-cell clusters – and the optimal management of these patients have been unclear, the investigators said.

The primary aim of the phase-III NSABP trial B-32 was to evaluate equivalence of SLN biopsy alone to biopsy with complete axillary dissection. It included 5,611 women who had confirmed resectable invasive adenocarcinoma of the breast. They had to have clinically negative lymph nodes, with no positive ipsilateral axillary lymph nodes or prior removal of ipsilateral axillary lymph nodes.

In all, 2,807 women were randomized to undergo sentinel node resection immediately followed by conventional axillary dissection (arm I) and 2,804 were randomized to sentinel node biopsy with axillary lymph node dissection (ALND) only if the sentinel node was positive (arm II). SLNs from both groups were assessed postoperatively using 2-mm slices from paraffin tissue blocks and H&E staining. Routine immunohistochemistry was not permitted, but it could be done for confirmation of suspicious findings from H&E staining.

As reported at the 2010 annual meeting of the American Society for Clinical Oncology and later published (Lancet Oncology 2010;11:927-33), the investigators found no difference in disease-free or overall survival between the two groups.

This new analysis was aimed at determining the clinical significance of occult metastatic disease in selected axillary lymph nodes (sentinel nodes). It included 3,887 tissue blocks of sentinel nodes obtained from all patients with negative nodes at the initial evaluation. These were sent to a central laboratory for further evaluation. Follow-up data were available for 3,884 women. The median time in the study was 95 months.

Additional and deeper samples were evaluated for occult metastases using H&E and immunohistochemical staining. The protocol was designed "to detect virtually all occult metastases larger than 1.0 mm in the greatest dimension and to randomly detect a proportion of occult metastases smaller than 1.0 mm," the investigators noted.

Patients were classified based on whether occult metastases were detected in the SNL. A subgroup analysis used American Joint Committee on Cancer definitions of isolated tumor-cell clusters (no larger than 0.2 mm in the greatest dimension), micrometastases (greater than 0.2 mm but no larger than 2.0 mm), and macrometastases (larger than 2.0 mm), Dr. Weaver and his coinvestigators reported.

Models were adjusted for patient age (older than 49 years or not), tumor size (no larger than 2.0 cm, 2.1 cm to 4.0 cm, or at least 4.1 cm), surgical treatment plan (lumpectomy or mastectomy), type of systemic chemotherapy, use of radiation therapy, and study group. The adjusted hazard ratios were 1.40 for death, 1.31 for any outcome event, and 1.30 for distant disease.

"Our findings are consistent with the hypothesis that nodal tumor burden is a continuous variable and indicate that occult metastases are an independent prognostic factor," they wrote.

The differences observed between patients with and without occult metastases with respect to 5-year Kaplan-Meier estimates of overall survival (between-group difference, 1.2%), disease-free survival (2.8%), and distant-disease-free interval (2.8%) were statistically significant but relatively small, the researchers pointed out.

These findings are not surprising after a more limited presentation by NSABP investigator Thomas B. Julian at the San Antonio Breast Cancer Symposium in December. Dr. Julian reported findings only for micrometastases detected in the SLN by H&E staining alone.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

The disease-free survival outcome for patients who had micrometastatic sentinel nodes by H&E stain were the same as for those who had positive sentinel nodes. "Macrometastatic patients, on the other hand, had a higher hazard rate of 1.8, which was significantly important," Dr. Julian said.

As for overall survival, "patients who had sentinel nodes with micrometastatic disease had a hazard rate of 0.8 – very similar to those patients who were sentinel-node negative. The P value was insignificant. For those patients who had macrometastases, the hazard rate was 2.4. That was found to be significant," said Dr. Julian, associate director of the breast care center at Allegheny General Hospital in Pittsburgh.

In the published analysis, Dr. Weaver and his associates found that occult metastases were not discriminatory predictors of cancer recurrence. Just 3.6% of the node-negative patients had regional or distant recurrences as first events, and only 30 of these events (in 0.8% of all patients) occurred in patients with occult metastases. All told, 80.5% of patients with occult metastases were alive and free of disease.

"Identification of occult metastases does not appear to be clinically useful for patients with newly diagnosed disease in whom systemic therapy can be recommended on the basis of the characteristics of the primary tumor," the investigators wrote.

The prevalence of occult metastases was significantly associated with age younger than 50 years, clinical tumor size greater than 2.0 cm in the greatest dimension, and planned mastectomy. The authors noted that these findings are not surprising.

"Perhaps the most interesting interaction was with endocrine therapy, indicating that occult metastases are associated with estrogen receptor–positive tumors, a favorable prognostic factor, and that endocrine therapy markedly reduces the risk of a poor outcome," Dr. Weaver and his associates wrote.

They also found that isolated tumor-cell clusters had a smaller effect on outcome than micrometastases for every outcome evaluated, regardless of whether occult macrometastases were included or excluded. The magnitude of difference in 5-year Kaplan-Meier estimates for death from breast cancer was small for detection of isolated tumor-cell clusters vs. no detection (0.6%) and for the detection of micrometastases vs. no detection (2.4%).

The B-32 trial was sponsored by the National Cancer Institute. All of the study authors reported that they have no relevant financial relationships.

SAN ANTONIO – Exemestane was as effective as anastrozole – but no better – in the first large trial to compare nonsteroidal and steroidal aromatase inhibitors as adjuvant therapy in postmenopausal women with hormone receptor–positive early breast cancer.

At a median follow-up of 4 years, event-free survival was not significantly different between women receiving adjuvant exemestane (Aromasin) and those given anastrozole (Arimedex) (hazard ratio, 1.02; P = .85) in the randomized, phase III study.

Event rates were low in both arms, with 91% of patients in each arm disease free. Investigators reported no significant differences in overall survival (HR, 0.93; P = .64), distant disease-free survival (HR, 0.95; P =.46), or disease-specific survival (HR, 0.93; P = .62), either. Subgroup analyses by lymph-node status and prior chemotherapy did not alter the event-free survival results.

"We believe that exemestane is comparable to anastrozole, and provides a new option for 5 years of up-front adjuvant endocrine therapy," Dr. Paul E. Goss said, presenting results at the annual San Antonio Breast Cancer Symposium.

Researchers had hoped that a steroidal aromatase inhibitor (AI), such as exemestane, would exhibit additional antitumor effect beyond those seen with nonsteroidal AIs, such as anastrazole.

Anastrozole, a nonsteroidal reversible competitive AI, can "profoundly and specifically suppress circulating and intra- and peritumoral estrogens," noted Dr. Goss, director of breast cancer research at the Massachusetts General Hospital in Boston. It is approved for use as frontline adjuvant therapy in postmenopausal patients with hormone receptor–positive early breast cancer.

Exemestane, a steroidal irreversible suicide AI, is not approved for up-front adjuvant endocrine therapy, but rather for use after 2-3 years of initial tamoxifen. The study rationale was that exemestane may exert more potent estrogen suppression than would anastrozole. Exemestane has mild androgenic activity that suppresses sex hormone–binding globulin, and therefore could induce a secondary antitumor effect, the investigators reasoned. The androgenic/anabolic effects of exemestane might counteract bone loss, reduce cholesterol and triglyceride levels, and cause fewer menopausal symptoms.

The open-label, randomized, phase III NCIC-CTG (National Cancer Institute of Canada–Clinical Trials Group) MA 27 trial enrolled postmenopausal women with estrogen receptor–positive early primary breast cancer. Women could also be eligible if they were 55 years of age or younger without menses in 12 months but with postmenopausal FSH, or if they had undergone bilateral oophorectomy.

Patients were excluded if they had local or metastatic breast cancer, previous AI therapy, concurrent hormone therapy, concurrent selective estrogen receptor modulator therapy, or raloxifene treatment within 3 weeks of randomization.

In all, 7,576 women were recruited in 2003-2006 and randomized to either anastrozole 1 mg/day for 5 years or exemestane 25 mg/day for 5 years. Patients were stratified by lymph-node status, adjuvant chemotherapy use, and trastuzumab use.

In the original 2x2 design, patients in each treatment arm were randomly assigned to receive 400-mg celecoxib twice daily or placebo for 3 years, but this was abandoned after concerns about cardiovascular toxicities were raised. By then, 1,622 women had been randomized to celecoxib.

"In a meta-analysis of NCI celecoxib-containing trials, it was found that about 58% randomized to date in MA27 ... had moderate- to high-risk cardiac risk factors. Hence, the celecoxib/placebo randomization was discontinued," Dr. Goss said. "For the purposes of these results, the question of dual COX-2/aromatase inhibition remains unanswered."

He reported that roughly 70% of adverse events in the trial were grade 1-2. There was no significant difference between anastrazole and exemestane in menopausal-type adverse events (hot flashes, arthritis/arthralgia, and muscle pain), although vaginal bleeding was slightly less common with exemestane, said Dr. Goss. Abnormal results on liver function tests were more common in the exemestane arm.

"Importantly, cardiovascular effects were nonsignificant; there was no difference in the two arms," Dr. Goss noted. However, hypertriglyceridemia and hypercholesterolemia were less common with exemestane. Self-reported new diagnoses of osteoporosis were slightly more frequent with anastrozole. Clinical fractures (all fractures and fragility fractures) were the same for both groups.

By 3 years, about a quarter of patients in each group had discontinued treatment.

The trial was supported in part by Pfizer Inc., which makes Aromasin. Dr. Goss reported that he has received honoraria from Novartis, Pfizer, and AstraZeneca.

SAN ANTONIO – Exemestane was as effective as anastrozole – but no better – in the first large trial to compare nonsteroidal and steroidal aromatase inhibitors as adjuvant therapy in postmenopausal women with hormone receptor–positive early breast cancer.

At a median follow-up of 4 years, event-free survival was not significantly different between women receiving adjuvant exemestane (Aromasin) and those given anastrozole (Arimedex) (hazard ratio, 1.02; P = .85) in the randomized, phase III study.

Event rates were low in both arms, with 91% of patients in each arm disease free. Investigators reported no significant differences in overall survival (HR, 0.93; P = .64), distant disease-free survival (HR, 0.95; P =.46), or disease-specific survival (HR, 0.93; P = .62), either. Subgroup analyses by lymph-node status and prior chemotherapy did not alter the event-free survival results.

"We believe that exemestane is comparable to anastrozole, and provides a new option for 5 years of up-front adjuvant endocrine therapy," Dr. Paul E. Goss said, presenting results at the annual San Antonio Breast Cancer Symposium.

Researchers had hoped that a steroidal aromatase inhibitor (AI), such as exemestane, would exhibit additional antitumor effect beyond those seen with nonsteroidal AIs, such as anastrazole.

Anastrozole, a nonsteroidal reversible competitive AI, can "profoundly and specifically suppress circulating and intra- and peritumoral estrogens," noted Dr. Goss, director of breast cancer research at the Massachusetts General Hospital in Boston. It is approved for use as frontline adjuvant therapy in postmenopausal patients with hormone receptor–positive early breast cancer.

Exemestane, a steroidal irreversible suicide AI, is not approved for up-front adjuvant endocrine therapy, but rather for use after 2-3 years of initial tamoxifen. The study rationale was that exemestane may exert more potent estrogen suppression than would anastrozole. Exemestane has mild androgenic activity that suppresses sex hormone–binding globulin, and therefore could induce a secondary antitumor effect, the investigators reasoned. The androgenic/anabolic effects of exemestane might counteract bone loss, reduce cholesterol and triglyceride levels, and cause fewer menopausal symptoms.

The open-label, randomized, phase III NCIC-CTG (National Cancer Institute of Canada–Clinical Trials Group) MA 27 trial enrolled postmenopausal women with estrogen receptor–positive early primary breast cancer. Women could also be eligible if they were 55 years of age or younger without menses in 12 months but with postmenopausal FSH, or if they had undergone bilateral oophorectomy.

Patients were excluded if they had local or metastatic breast cancer, previous AI therapy, concurrent hormone therapy, concurrent selective estrogen receptor modulator therapy, or raloxifene treatment within 3 weeks of randomization.

In all, 7,576 women were recruited in 2003-2006 and randomized to either anastrozole 1 mg/day for 5 years or exemestane 25 mg/day for 5 years. Patients were stratified by lymph-node status, adjuvant chemotherapy use, and trastuzumab use.

In the original 2x2 design, patients in each treatment arm were randomly assigned to receive 400-mg celecoxib twice daily or placebo for 3 years, but this was abandoned after concerns about cardiovascular toxicities were raised. By then, 1,622 women had been randomized to celecoxib.

"In a meta-analysis of NCI celecoxib-containing trials, it was found that about 58% randomized to date in MA27 ... had moderate- to high-risk cardiac risk factors. Hence, the celecoxib/placebo randomization was discontinued," Dr. Goss said. "For the purposes of these results, the question of dual COX-2/aromatase inhibition remains unanswered."

He reported that roughly 70% of adverse events in the trial were grade 1-2. There was no significant difference between anastrazole and exemestane in menopausal-type adverse events (hot flashes, arthritis/arthralgia, and muscle pain), although vaginal bleeding was slightly less common with exemestane, said Dr. Goss. Abnormal results on liver function tests were more common in the exemestane arm.

"Importantly, cardiovascular effects were nonsignificant; there was no difference in the two arms," Dr. Goss noted. However, hypertriglyceridemia and hypercholesterolemia were less common with exemestane. Self-reported new diagnoses of osteoporosis were slightly more frequent with anastrozole. Clinical fractures (all fractures and fragility fractures) were the same for both groups.

By 3 years, about a quarter of patients in each group had discontinued treatment.

The trial was supported in part by Pfizer Inc., which makes Aromasin. Dr. Goss reported that he has received honoraria from Novartis, Pfizer, and AstraZeneca.

SAN ANTONIO – Exemestane was as effective as anastrozole – but no better – in the first large trial to compare nonsteroidal and steroidal aromatase inhibitors as adjuvant therapy in postmenopausal women with hormone receptor–positive early breast cancer.

At a median follow-up of 4 years, event-free survival was not significantly different between women receiving adjuvant exemestane (Aromasin) and those given anastrozole (Arimedex) (hazard ratio, 1.02; P = .85) in the randomized, phase III study.

Event rates were low in both arms, with 91% of patients in each arm disease free. Investigators reported no significant differences in overall survival (HR, 0.93; P = .64), distant disease-free survival (HR, 0.95; P =.46), or disease-specific survival (HR, 0.93; P = .62), either. Subgroup analyses by lymph-node status and prior chemotherapy did not alter the event-free survival results.

"We believe that exemestane is comparable to anastrozole, and provides a new option for 5 years of up-front adjuvant endocrine therapy," Dr. Paul E. Goss said, presenting results at the annual San Antonio Breast Cancer Symposium.

Researchers had hoped that a steroidal aromatase inhibitor (AI), such as exemestane, would exhibit additional antitumor effect beyond those seen with nonsteroidal AIs, such as anastrazole.

Anastrozole, a nonsteroidal reversible competitive AI, can "profoundly and specifically suppress circulating and intra- and peritumoral estrogens," noted Dr. Goss, director of breast cancer research at the Massachusetts General Hospital in Boston. It is approved for use as frontline adjuvant therapy in postmenopausal patients with hormone receptor–positive early breast cancer.

Exemestane, a steroidal irreversible suicide AI, is not approved for up-front adjuvant endocrine therapy, but rather for use after 2-3 years of initial tamoxifen. The study rationale was that exemestane may exert more potent estrogen suppression than would anastrozole. Exemestane has mild androgenic activity that suppresses sex hormone–binding globulin, and therefore could induce a secondary antitumor effect, the investigators reasoned. The androgenic/anabolic effects of exemestane might counteract bone loss, reduce cholesterol and triglyceride levels, and cause fewer menopausal symptoms.

The open-label, randomized, phase III NCIC-CTG (National Cancer Institute of Canada–Clinical Trials Group) MA 27 trial enrolled postmenopausal women with estrogen receptor–positive early primary breast cancer. Women could also be eligible if they were 55 years of age or younger without menses in 12 months but with postmenopausal FSH, or if they had undergone bilateral oophorectomy.

Patients were excluded if they had local or metastatic breast cancer, previous AI therapy, concurrent hormone therapy, concurrent selective estrogen receptor modulator therapy, or raloxifene treatment within 3 weeks of randomization.

In all, 7,576 women were recruited in 2003-2006 and randomized to either anastrozole 1 mg/day for 5 years or exemestane 25 mg/day for 5 years. Patients were stratified by lymph-node status, adjuvant chemotherapy use, and trastuzumab use.

In the original 2x2 design, patients in each treatment arm were randomly assigned to receive 400-mg celecoxib twice daily or placebo for 3 years, but this was abandoned after concerns about cardiovascular toxicities were raised. By then, 1,622 women had been randomized to celecoxib.

"In a meta-analysis of NCI celecoxib-containing trials, it was found that about 58% randomized to date in MA27 ... had moderate- to high-risk cardiac risk factors. Hence, the celecoxib/placebo randomization was discontinued," Dr. Goss said. "For the purposes of these results, the question of dual COX-2/aromatase inhibition remains unanswered."

He reported that roughly 70% of adverse events in the trial were grade 1-2. There was no significant difference between anastrazole and exemestane in menopausal-type adverse events (hot flashes, arthritis/arthralgia, and muscle pain), although vaginal bleeding was slightly less common with exemestane, said Dr. Goss. Abnormal results on liver function tests were more common in the exemestane arm.

"Importantly, cardiovascular effects were nonsignificant; there was no difference in the two arms," Dr. Goss noted. However, hypertriglyceridemia and hypercholesterolemia were less common with exemestane. Self-reported new diagnoses of osteoporosis were slightly more frequent with anastrozole. Clinical fractures (all fractures and fragility fractures) were the same for both groups.

By 3 years, about a quarter of patients in each group had discontinued treatment.

The trial was supported in part by Pfizer Inc., which makes Aromasin. Dr. Goss reported that he has received honoraria from Novartis, Pfizer, and AstraZeneca.

SAN ANTONIO – Adding manual lymph drainage to exercise therapy did not prevent lymphedema in a study of 160 breast cancer patients who underwent axillary lymph node dissection.

Researchers reported that the incidence of lymphedema following axillary lymph node dissection (ALND) was similar whether or not women had manual drainage in a randomized trial presented at the annual San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Based on these findings and previous data, "breast cancer patients have to perform exercise therapy immediately started after the axillary dissection to prevent arm lymphedema," said Nele Devoogdt, a physical therapist at University Hospitals Leuven in Belgium.

Manual lymph drainage involves stretching/massaging the skin around lymph nodes to improve resorption by the lymph capillaries, increase lymph transport (by stimulating lymph collectors), and to create collateral pathways of lymph transport, Ms. Devoogdt said. Although manual lymph drainage is used in several countries, including Belgium, to prevent lymphedema, the preventive effect has not been previously demonstrated in a peer-reviewed randomized trial.

For this study, the researchers recruited 160 breast cancer patients, who underwent ALND in one arm. Both arms were assessed prior to the procedure to assess the natural difference in size.

A total of 79 patients were randomized to exercise therapy and manual lymph drainage, while 81 patients had only exercise therapy. Both groups were given lifestyle guidelines for minimizing lymphedema.

Patients in both groups attended 1-2 sessions per week (29 exercise therapy sessions on average). In the treatment group, manual lymph drainage was performed 1-3 times per week (34 sessions on average).

At 1 month post-ALND, patients started treatment and an arm assessment was performed. Arm assessments followed at 3 months, 6 months (at which point treatment was stopped), and 12 months.

The primary outcome measure was the incidence of arm lymphedema – defined as a circumference increase of at least 2 cm at two successive measurements. The researchers found no significant difference in lymphedema incidence between the two groups at any time point. At 3 months, the incidence was 7% in the drainage group, compared with 5% in the exercise-only group; at 6 months, the incidence was 12% and 10%, respectively; and at 12 months, it was 23% and 18%.

Secondary outcomes also showed no significant differences in time to lymphedema, increase in arm volume, mental and physical health-related quality of life, and functional problems related to arm lymphedema.

The investigators reported that they have no relevant financial relationships.

SAN ANTONIO – Adding manual lymph drainage to exercise therapy did not prevent lymphedema in a study of 160 breast cancer patients who underwent axillary lymph node dissection.

Researchers reported that the incidence of lymphedema following axillary lymph node dissection (ALND) was similar whether or not women had manual drainage in a randomized trial presented at the annual San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Based on these findings and previous data, "breast cancer patients have to perform exercise therapy immediately started after the axillary dissection to prevent arm lymphedema," said Nele Devoogdt, a physical therapist at University Hospitals Leuven in Belgium.

Manual lymph drainage involves stretching/massaging the skin around lymph nodes to improve resorption by the lymph capillaries, increase lymph transport (by stimulating lymph collectors), and to create collateral pathways of lymph transport, Ms. Devoogdt said. Although manual lymph drainage is used in several countries, including Belgium, to prevent lymphedema, the preventive effect has not been previously demonstrated in a peer-reviewed randomized trial.

For this study, the researchers recruited 160 breast cancer patients, who underwent ALND in one arm. Both arms were assessed prior to the procedure to assess the natural difference in size.

A total of 79 patients were randomized to exercise therapy and manual lymph drainage, while 81 patients had only exercise therapy. Both groups were given lifestyle guidelines for minimizing lymphedema.

Patients in both groups attended 1-2 sessions per week (29 exercise therapy sessions on average). In the treatment group, manual lymph drainage was performed 1-3 times per week (34 sessions on average).

At 1 month post-ALND, patients started treatment and an arm assessment was performed. Arm assessments followed at 3 months, 6 months (at which point treatment was stopped), and 12 months.

The primary outcome measure was the incidence of arm lymphedema – defined as a circumference increase of at least 2 cm at two successive measurements. The researchers found no significant difference in lymphedema incidence between the two groups at any time point. At 3 months, the incidence was 7% in the drainage group, compared with 5% in the exercise-only group; at 6 months, the incidence was 12% and 10%, respectively; and at 12 months, it was 23% and 18%.

Secondary outcomes also showed no significant differences in time to lymphedema, increase in arm volume, mental and physical health-related quality of life, and functional problems related to arm lymphedema.

The investigators reported that they have no relevant financial relationships.

SAN ANTONIO – Adding manual lymph drainage to exercise therapy did not prevent lymphedema in a study of 160 breast cancer patients who underwent axillary lymph node dissection.

Researchers reported that the incidence of lymphedema following axillary lymph node dissection (ALND) was similar whether or not women had manual drainage in a randomized trial presented at the annual San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Based on these findings and previous data, "breast cancer patients have to perform exercise therapy immediately started after the axillary dissection to prevent arm lymphedema," said Nele Devoogdt, a physical therapist at University Hospitals Leuven in Belgium.

Manual lymph drainage involves stretching/massaging the skin around lymph nodes to improve resorption by the lymph capillaries, increase lymph transport (by stimulating lymph collectors), and to create collateral pathways of lymph transport, Ms. Devoogdt said. Although manual lymph drainage is used in several countries, including Belgium, to prevent lymphedema, the preventive effect has not been previously demonstrated in a peer-reviewed randomized trial.

For this study, the researchers recruited 160 breast cancer patients, who underwent ALND in one arm. Both arms were assessed prior to the procedure to assess the natural difference in size.

A total of 79 patients were randomized to exercise therapy and manual lymph drainage, while 81 patients had only exercise therapy. Both groups were given lifestyle guidelines for minimizing lymphedema.

Patients in both groups attended 1-2 sessions per week (29 exercise therapy sessions on average). In the treatment group, manual lymph drainage was performed 1-3 times per week (34 sessions on average).

At 1 month post-ALND, patients started treatment and an arm assessment was performed. Arm assessments followed at 3 months, 6 months (at which point treatment was stopped), and 12 months.

The primary outcome measure was the incidence of arm lymphedema – defined as a circumference increase of at least 2 cm at two successive measurements. The researchers found no significant difference in lymphedema incidence between the two groups at any time point. At 3 months, the incidence was 7% in the drainage group, compared with 5% in the exercise-only group; at 6 months, the incidence was 12% and 10%, respectively; and at 12 months, it was 23% and 18%.

Secondary outcomes also showed no significant differences in time to lymphedema, increase in arm volume, mental and physical health-related quality of life, and functional problems related to arm lymphedema.

The investigators reported that they have no relevant financial relationships.