Robert Finn

SCOTTSDALE, ARIZ. — Patients undergoing carotid endarterectomy or carotid angioplasty and stenting are more likely to experience microemboli if they have comorbid coronary artery disease, Dr. Maureen Tedesco said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

Dr. Tedesco and her colleagues at Stanford (Calif.) University had previously shown a greater risk of microemboli with carotid angioplasty and stenting (CAS) than with carotid endarterectomy (CEA).

That link emerged again in her retrospective study of 64 consecutive carotid patients. Based on diffusion-weighted MRI images read by two blinded neuroradiologists, 24 (71%) of 34 CAS patients experienced new microemboli compared with 1 (3%) of 30 CEA patients, a significant difference.

Most of the patients with microemboli had no neurologic symptoms. In those who did experience symptoms, most resolved within 36 hours. No patient died or had a stroke within 30 days of the procedure

Dr. Tedesco looked at a large number of patient and procedural characteristics in a search of risk factors for the development of microemboli. The only significant association was the presence of CAD. There was no link between microemboli and a host of other factors including age, a history of symptomatic disease, stroke, transient ischemic attacks, smoking, diabetes mellitus, hypertension, hyperlipidemia, obesity, peripheral vascular disease, or atrial fibrillation. Nor was there any association between microemboli and total fluoroscopy time or the performance of an arch angiogram.

Since 80% of the patients who had new microemboli after intervention had a history of CAD, Dr. Tedesco said, “This finding should be considered when recommending CAS for patients who are deemed high risk due solely to cardiac comorbidity.”

SCOTTSDALE, ARIZ. — Patients undergoing carotid endarterectomy or carotid angioplasty and stenting are more likely to experience microemboli if they have comorbid coronary artery disease, Dr. Maureen Tedesco said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

Dr. Tedesco and her colleagues at Stanford (Calif.) University had previously shown a greater risk of microemboli with carotid angioplasty and stenting (CAS) than with carotid endarterectomy (CEA).

That link emerged again in her retrospective study of 64 consecutive carotid patients. Based on diffusion-weighted MRI images read by two blinded neuroradiologists, 24 (71%) of 34 CAS patients experienced new microemboli compared with 1 (3%) of 30 CEA patients, a significant difference.

Most of the patients with microemboli had no neurologic symptoms. In those who did experience symptoms, most resolved within 36 hours. No patient died or had a stroke within 30 days of the procedure

Dr. Tedesco looked at a large number of patient and procedural characteristics in a search of risk factors for the development of microemboli. The only significant association was the presence of CAD. There was no link between microemboli and a host of other factors including age, a history of symptomatic disease, stroke, transient ischemic attacks, smoking, diabetes mellitus, hypertension, hyperlipidemia, obesity, peripheral vascular disease, or atrial fibrillation. Nor was there any association between microemboli and total fluoroscopy time or the performance of an arch angiogram.

Since 80% of the patients who had new microemboli after intervention had a history of CAD, Dr. Tedesco said, “This finding should be considered when recommending CAS for patients who are deemed high risk due solely to cardiac comorbidity.”

SCOTTSDALE, ARIZ. — Patients undergoing carotid endarterectomy or carotid angioplasty and stenting are more likely to experience microemboli if they have comorbid coronary artery disease, Dr. Maureen Tedesco said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

Dr. Tedesco and her colleagues at Stanford (Calif.) University had previously shown a greater risk of microemboli with carotid angioplasty and stenting (CAS) than with carotid endarterectomy (CEA).

That link emerged again in her retrospective study of 64 consecutive carotid patients. Based on diffusion-weighted MRI images read by two blinded neuroradiologists, 24 (71%) of 34 CAS patients experienced new microemboli compared with 1 (3%) of 30 CEA patients, a significant difference.

Most of the patients with microemboli had no neurologic symptoms. In those who did experience symptoms, most resolved within 36 hours. No patient died or had a stroke within 30 days of the procedure

Dr. Tedesco looked at a large number of patient and procedural characteristics in a search of risk factors for the development of microemboli. The only significant association was the presence of CAD. There was no link between microemboli and a host of other factors including age, a history of symptomatic disease, stroke, transient ischemic attacks, smoking, diabetes mellitus, hypertension, hyperlipidemia, obesity, peripheral vascular disease, or atrial fibrillation. Nor was there any association between microemboli and total fluoroscopy time or the performance of an arch angiogram.

Since 80% of the patients who had new microemboli after intervention had a history of CAD, Dr. Tedesco said, “This finding should be considered when recommending CAS for patients who are deemed high risk due solely to cardiac comorbidity.”

SCOTTSDALE, ARIZ. — Duplex ultrasound with contrast enhancement delivered by continuous infusion shows promise in the detection of endoleaks following endovascular aneurysm repair, Dr. Ruth L. Bush said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

“Our early results strongly suggest that contrast enhancement with a continuous infusion technique could be used as a primary diagnostic imaging modality for follow-up endograft surveillance,” possibly replacing CT as the standard for graft surveillance, said Dr. Bush of the Baylor College of Medicine, Houston.

Following endovascular aneurysm repair (EVAR), patients must be assessed periodically for sac size, stent-graft integrity, and endoleaks. CT is a fine imaging modality for this surveillance, but at the cost of substantial doses of ionizing radiation and exposure to iodinated contrast media, which can be nephrotoxic. Furthermore, CT scanning is expensive. According to some reports, more than 65% of postoperative costs following EVAR are related to CT scanning.

Unfortunately, color duplex ultrasound has been shown to have a lower sensitivity and a lower positive predictive value than CT has in this surveillance. Delivery of contrast enhancement in a bolus improves echogenicity and can even detect slow endoleaks that are not visible in CT. But the disadvantage of this technique is that bolus injection of the contrast medium allows for only a short scanning time—less than 10 minutes—so multiple injections are usually necessary. The contrast is provided by microbubbles, which must be small enough to pass through the pulmonary capillaries. The various gas microbubble contrast media are generally considered safe and to have low toxicity. However, it has proven difficult to maintain these microbubbles in the systemic circulation.

Some of these problems are avoided by continuous infusion of the contrast medium. Dr. Bush uses a syringe filled with contrast medium and normal saline and infuses the mixture at the rate of 4 cc/min to extend the scanning time to 20 minutes or more.

In a preliminary study in 20 patients, contrast-enhanced ultrasound found one type 1 endoleak and nine type 2 endoleaks. In those same patients, color duplex ultrasound found one type 1 endoleak and only four type 2 endoleaks, and CT found one type 1 endoleak and six type 2 endoleaks.

The patients' body type affected scanning time. The investigators noted a direct relationship between scanning time and body mass index.

And it's important to control scanning parameters carefully. For one thing, the syringe holding the contrast medium needs to be agitated continually to avoid breakdown of the microbubbles.

And it's necessary to optimize the harmonic imaging on the ultrasound machines, decrease the mechanical index and the compression, and adjust the focal zone to be below the aorta.

“All of this was done in an attempt to maintain the integrity of the microbubbles,” Dr. Bush said. “If you have a mechanical index turned up too high or the compression and the focal zone adjusted [imperfectly], the microbubbles would shatter and you won't get a good result.”

The learning curve for this technique is about 10–15 patients, she said.

Delivery of contrast enhancement in a bolus can even detect slow endoleaks that are not visible in CT. DR. BUSH

SCOTTSDALE, ARIZ. — Duplex ultrasound with contrast enhancement delivered by continuous infusion shows promise in the detection of endoleaks following endovascular aneurysm repair, Dr. Ruth L. Bush said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

“Our early results strongly suggest that contrast enhancement with a continuous infusion technique could be used as a primary diagnostic imaging modality for follow-up endograft surveillance,” possibly replacing CT as the standard for graft surveillance, said Dr. Bush of the Baylor College of Medicine, Houston.

Following endovascular aneurysm repair (EVAR), patients must be assessed periodically for sac size, stent-graft integrity, and endoleaks. CT is a fine imaging modality for this surveillance, but at the cost of substantial doses of ionizing radiation and exposure to iodinated contrast media, which can be nephrotoxic. Furthermore, CT scanning is expensive. According to some reports, more than 65% of postoperative costs following EVAR are related to CT scanning.

Unfortunately, color duplex ultrasound has been shown to have a lower sensitivity and a lower positive predictive value than CT has in this surveillance. Delivery of contrast enhancement in a bolus improves echogenicity and can even detect slow endoleaks that are not visible in CT. But the disadvantage of this technique is that bolus injection of the contrast medium allows for only a short scanning time—less than 10 minutes—so multiple injections are usually necessary. The contrast is provided by microbubbles, which must be small enough to pass through the pulmonary capillaries. The various gas microbubble contrast media are generally considered safe and to have low toxicity. However, it has proven difficult to maintain these microbubbles in the systemic circulation.

Some of these problems are avoided by continuous infusion of the contrast medium. Dr. Bush uses a syringe filled with contrast medium and normal saline and infuses the mixture at the rate of 4 cc/min to extend the scanning time to 20 minutes or more.

In a preliminary study in 20 patients, contrast-enhanced ultrasound found one type 1 endoleak and nine type 2 endoleaks. In those same patients, color duplex ultrasound found one type 1 endoleak and only four type 2 endoleaks, and CT found one type 1 endoleak and six type 2 endoleaks.

The patients' body type affected scanning time. The investigators noted a direct relationship between scanning time and body mass index.

And it's important to control scanning parameters carefully. For one thing, the syringe holding the contrast medium needs to be agitated continually to avoid breakdown of the microbubbles.

And it's necessary to optimize the harmonic imaging on the ultrasound machines, decrease the mechanical index and the compression, and adjust the focal zone to be below the aorta.

“All of this was done in an attempt to maintain the integrity of the microbubbles,” Dr. Bush said. “If you have a mechanical index turned up too high or the compression and the focal zone adjusted [imperfectly], the microbubbles would shatter and you won't get a good result.”

The learning curve for this technique is about 10–15 patients, she said.

Delivery of contrast enhancement in a bolus can even detect slow endoleaks that are not visible in CT. DR. BUSH

SCOTTSDALE, ARIZ. — Duplex ultrasound with contrast enhancement delivered by continuous infusion shows promise in the detection of endoleaks following endovascular aneurysm repair, Dr. Ruth L. Bush said at an international congress on endovascular interventions sponsored by the Arizona Heart Institute.

“Our early results strongly suggest that contrast enhancement with a continuous infusion technique could be used as a primary diagnostic imaging modality for follow-up endograft surveillance,” possibly replacing CT as the standard for graft surveillance, said Dr. Bush of the Baylor College of Medicine, Houston.

Following endovascular aneurysm repair (EVAR), patients must be assessed periodically for sac size, stent-graft integrity, and endoleaks. CT is a fine imaging modality for this surveillance, but at the cost of substantial doses of ionizing radiation and exposure to iodinated contrast media, which can be nephrotoxic. Furthermore, CT scanning is expensive. According to some reports, more than 65% of postoperative costs following EVAR are related to CT scanning.

Unfortunately, color duplex ultrasound has been shown to have a lower sensitivity and a lower positive predictive value than CT has in this surveillance. Delivery of contrast enhancement in a bolus improves echogenicity and can even detect slow endoleaks that are not visible in CT. But the disadvantage of this technique is that bolus injection of the contrast medium allows for only a short scanning time—less than 10 minutes—so multiple injections are usually necessary. The contrast is provided by microbubbles, which must be small enough to pass through the pulmonary capillaries. The various gas microbubble contrast media are generally considered safe and to have low toxicity. However, it has proven difficult to maintain these microbubbles in the systemic circulation.

Some of these problems are avoided by continuous infusion of the contrast medium. Dr. Bush uses a syringe filled with contrast medium and normal saline and infuses the mixture at the rate of 4 cc/min to extend the scanning time to 20 minutes or more.

In a preliminary study in 20 patients, contrast-enhanced ultrasound found one type 1 endoleak and nine type 2 endoleaks. In those same patients, color duplex ultrasound found one type 1 endoleak and only four type 2 endoleaks, and CT found one type 1 endoleak and six type 2 endoleaks.

The patients' body type affected scanning time. The investigators noted a direct relationship between scanning time and body mass index.

And it's important to control scanning parameters carefully. For one thing, the syringe holding the contrast medium needs to be agitated continually to avoid breakdown of the microbubbles.

And it's necessary to optimize the harmonic imaging on the ultrasound machines, decrease the mechanical index and the compression, and adjust the focal zone to be below the aorta.

“All of this was done in an attempt to maintain the integrity of the microbubbles,” Dr. Bush said. “If you have a mechanical index turned up too high or the compression and the focal zone adjusted [imperfectly], the microbubbles would shatter and you won't get a good result.”

The learning curve for this technique is about 10–15 patients, she said.

Delivery of contrast enhancement in a bolus can even detect slow endoleaks that are not visible in CT. DR. BUSH

RANCHO MIRAGE, CALIF. – Behavioral treatments should be the first line of defense when treating children with hypersomnia, Dr. Raphael Pelayo said at a meeting on sleep disorders in infants and childhood.

Dr. Pelayo developed the mnemonic S.E.L.F. to help children, parents, and physicians remember some of the best ways to regulate sleep: with Social interactions, Exercise, Light, and Food.

“This really works,” said Dr. Pelayo of Stanford (Calif.) University. “It sounds too simple, and you may not believe it, but this really, really works.”

When children exhibit excessive daytime sleepiness, the first impulse of many parents is to put them to bed earlier.

This is often exactly the wrong thing to do, in part because the children fall to sleep with light and wake up with darkness, the reverse of what nature intended.

Similarly, many teenagers skip breakfast but snack just before bedtime, have trouble sleeping, and are sleepy the following day. Before prescribing modafinil, have the parents restrict the teen's access to food in the evening.

Dr. Pelayo recently treated one teenager whose daily schedule involved a full day of classes, several hours of tutoring, and then time in the gym for exercise and socializing. “So I asked, 'Is it okay to put the gym after school but before the tutoring?' Simple switches like that can be effective,” he said.

Often parents will drag a hypersomnolent child to the doctor, and point out during the visit that he or she spends the entire evening watching television or playing computer games. “The parents want you to be the heavy and take away their computer time, their TV time,” Dr. Pelayo said. “Instead I flip things around with them a little. I say, 'You can watch TV all you like–first thing in the morning. You can play computer games–first thing in the morning.'”

“Behavior before drugs” is the slogan Dr. Pelayo uses even with children with narcolepsy.

“With narcoleptics, it cannot be overemphasized that it's got to be naps before drugs,” he said at the meeting sponsored by the Annenberg Center for Health Sciences. “For the rest of your life you've got to be conscious of your sleep hours.”

RANCHO MIRAGE, CALIF. – Behavioral treatments should be the first line of defense when treating children with hypersomnia, Dr. Raphael Pelayo said at a meeting on sleep disorders in infants and childhood.

Dr. Pelayo developed the mnemonic S.E.L.F. to help children, parents, and physicians remember some of the best ways to regulate sleep: with Social interactions, Exercise, Light, and Food.

“This really works,” said Dr. Pelayo of Stanford (Calif.) University. “It sounds too simple, and you may not believe it, but this really, really works.”

When children exhibit excessive daytime sleepiness, the first impulse of many parents is to put them to bed earlier.

This is often exactly the wrong thing to do, in part because the children fall to sleep with light and wake up with darkness, the reverse of what nature intended.

Similarly, many teenagers skip breakfast but snack just before bedtime, have trouble sleeping, and are sleepy the following day. Before prescribing modafinil, have the parents restrict the teen's access to food in the evening.

Dr. Pelayo recently treated one teenager whose daily schedule involved a full day of classes, several hours of tutoring, and then time in the gym for exercise and socializing. “So I asked, 'Is it okay to put the gym after school but before the tutoring?' Simple switches like that can be effective,” he said.

Often parents will drag a hypersomnolent child to the doctor, and point out during the visit that he or she spends the entire evening watching television or playing computer games. “The parents want you to be the heavy and take away their computer time, their TV time,” Dr. Pelayo said. “Instead I flip things around with them a little. I say, 'You can watch TV all you like–first thing in the morning. You can play computer games–first thing in the morning.'”

“Behavior before drugs” is the slogan Dr. Pelayo uses even with children with narcolepsy.

“With narcoleptics, it cannot be overemphasized that it's got to be naps before drugs,” he said at the meeting sponsored by the Annenberg Center for Health Sciences. “For the rest of your life you've got to be conscious of your sleep hours.”

RANCHO MIRAGE, CALIF. – Behavioral treatments should be the first line of defense when treating children with hypersomnia, Dr. Raphael Pelayo said at a meeting on sleep disorders in infants and childhood.

Dr. Pelayo developed the mnemonic S.E.L.F. to help children, parents, and physicians remember some of the best ways to regulate sleep: with Social interactions, Exercise, Light, and Food.

“This really works,” said Dr. Pelayo of Stanford (Calif.) University. “It sounds too simple, and you may not believe it, but this really, really works.”

When children exhibit excessive daytime sleepiness, the first impulse of many parents is to put them to bed earlier.

This is often exactly the wrong thing to do, in part because the children fall to sleep with light and wake up with darkness, the reverse of what nature intended.

Similarly, many teenagers skip breakfast but snack just before bedtime, have trouble sleeping, and are sleepy the following day. Before prescribing modafinil, have the parents restrict the teen's access to food in the evening.

Dr. Pelayo recently treated one teenager whose daily schedule involved a full day of classes, several hours of tutoring, and then time in the gym for exercise and socializing. “So I asked, 'Is it okay to put the gym after school but before the tutoring?' Simple switches like that can be effective,” he said.

Often parents will drag a hypersomnolent child to the doctor, and point out during the visit that he or she spends the entire evening watching television or playing computer games. “The parents want you to be the heavy and take away their computer time, their TV time,” Dr. Pelayo said. “Instead I flip things around with them a little. I say, 'You can watch TV all you like–first thing in the morning. You can play computer games–first thing in the morning.'”

“Behavior before drugs” is the slogan Dr. Pelayo uses even with children with narcolepsy.

“With narcoleptics, it cannot be overemphasized that it's got to be naps before drugs,” he said at the meeting sponsored by the Annenberg Center for Health Sciences. “For the rest of your life you've got to be conscious of your sleep hours.”

HOLLYWOOD, CALIF. – The more complex a child's victimization history, the more likely he or she is to experience multiple negative outcomes, including posttraumatic stress disorder, depression, and substance use, Benjamin E. Saunders, Ph.D., reported at the annual meeting of the International Society for Traumatic Stress Studies.

In a longitudinal study of 530 families reported to the U.S. Navy's Family Advocacy Program for child sexual abuse, child physical abuse, or partner violence, more than two-thirds of the children interviewed reported experiencing several different types of trauma. The average child experienced 2.26 different types of trauma, and 18% of the children experienced four or five different types, said Dr. Saunders of the Medical University of South Carolina, Charleston.

He emphasized that, for the purposes of the study, a child who experienced many instances of physical abuse but no other forms of victimization would be classified as having experienced only a single type of trauma. Data were collected from 12 major naval installations.

Of the 195 children between the ages of 7 and 18 years (mean age, 12.2), 67% were victims of personal assault, including 29% who were victims of sexual assault, 34% who were victims of physical assault, and 48% who were victims of physical abuse. In addition, 80% of the children had witnessed violence, including 70% who had witnessed community violence and 44% who had witnessed domestic violence.

Girls were significantly more likely than boys were to be victims of sexual assault (46% vs. 1%) and to witness domestic violence (49% vs. 34%), but otherwise there were no significant gender differences in the subcategories of violent exposure, Dr. Saunders reported at the meeting, which was also sponsored by Boston University.

The children were assessed at four time points–the first at 2–6 weeks after the initial report and the fourth, 36–40 months after the report. At the first time point, and after researchers controlled for gender and age, the number of victimization types significantly predicted all five measured outcomes–diagnosis of posttraumatic stress disorder, diagnosis of depression, problems with alcohol, problems with other drugs, and participation in a delinquent act, he said.

After 3 years, significant associations were found between the number of victimization types and all but one of those outcomes. Only problems with alcohol failed to show a significant relationship with the number of victimization types, after controlling for gender and age.

In view of the high prevalence of multiple victimizations, one message is that therapists would be wrong to focus on only a single type of victimization in a child, Dr. Saunders said.

HOLLYWOOD, CALIF. – The more complex a child's victimization history, the more likely he or she is to experience multiple negative outcomes, including posttraumatic stress disorder, depression, and substance use, Benjamin E. Saunders, Ph.D., reported at the annual meeting of the International Society for Traumatic Stress Studies.

In a longitudinal study of 530 families reported to the U.S. Navy's Family Advocacy Program for child sexual abuse, child physical abuse, or partner violence, more than two-thirds of the children interviewed reported experiencing several different types of trauma. The average child experienced 2.26 different types of trauma, and 18% of the children experienced four or five different types, said Dr. Saunders of the Medical University of South Carolina, Charleston.

He emphasized that, for the purposes of the study, a child who experienced many instances of physical abuse but no other forms of victimization would be classified as having experienced only a single type of trauma. Data were collected from 12 major naval installations.

Of the 195 children between the ages of 7 and 18 years (mean age, 12.2), 67% were victims of personal assault, including 29% who were victims of sexual assault, 34% who were victims of physical assault, and 48% who were victims of physical abuse. In addition, 80% of the children had witnessed violence, including 70% who had witnessed community violence and 44% who had witnessed domestic violence.

Girls were significantly more likely than boys were to be victims of sexual assault (46% vs. 1%) and to witness domestic violence (49% vs. 34%), but otherwise there were no significant gender differences in the subcategories of violent exposure, Dr. Saunders reported at the meeting, which was also sponsored by Boston University.

The children were assessed at four time points–the first at 2–6 weeks after the initial report and the fourth, 36–40 months after the report. At the first time point, and after researchers controlled for gender and age, the number of victimization types significantly predicted all five measured outcomes–diagnosis of posttraumatic stress disorder, diagnosis of depression, problems with alcohol, problems with other drugs, and participation in a delinquent act, he said.

After 3 years, significant associations were found between the number of victimization types and all but one of those outcomes. Only problems with alcohol failed to show a significant relationship with the number of victimization types, after controlling for gender and age.

In view of the high prevalence of multiple victimizations, one message is that therapists would be wrong to focus on only a single type of victimization in a child, Dr. Saunders said.

HOLLYWOOD, CALIF. – The more complex a child's victimization history, the more likely he or she is to experience multiple negative outcomes, including posttraumatic stress disorder, depression, and substance use, Benjamin E. Saunders, Ph.D., reported at the annual meeting of the International Society for Traumatic Stress Studies.

In a longitudinal study of 530 families reported to the U.S. Navy's Family Advocacy Program for child sexual abuse, child physical abuse, or partner violence, more than two-thirds of the children interviewed reported experiencing several different types of trauma. The average child experienced 2.26 different types of trauma, and 18% of the children experienced four or five different types, said Dr. Saunders of the Medical University of South Carolina, Charleston.

He emphasized that, for the purposes of the study, a child who experienced many instances of physical abuse but no other forms of victimization would be classified as having experienced only a single type of trauma. Data were collected from 12 major naval installations.

Of the 195 children between the ages of 7 and 18 years (mean age, 12.2), 67% were victims of personal assault, including 29% who were victims of sexual assault, 34% who were victims of physical assault, and 48% who were victims of physical abuse. In addition, 80% of the children had witnessed violence, including 70% who had witnessed community violence and 44% who had witnessed domestic violence.

Girls were significantly more likely than boys were to be victims of sexual assault (46% vs. 1%) and to witness domestic violence (49% vs. 34%), but otherwise there were no significant gender differences in the subcategories of violent exposure, Dr. Saunders reported at the meeting, which was also sponsored by Boston University.

The children were assessed at four time points–the first at 2–6 weeks after the initial report and the fourth, 36–40 months after the report. At the first time point, and after researchers controlled for gender and age, the number of victimization types significantly predicted all five measured outcomes–diagnosis of posttraumatic stress disorder, diagnosis of depression, problems with alcohol, problems with other drugs, and participation in a delinquent act, he said.

After 3 years, significant associations were found between the number of victimization types and all but one of those outcomes. Only problems with alcohol failed to show a significant relationship with the number of victimization types, after controlling for gender and age.

In view of the high prevalence of multiple victimizations, one message is that therapists would be wrong to focus on only a single type of victimization in a child, Dr. Saunders said.

LOS ANGELES — A combination of three biomarkers may reliably predict which patients with Barrett's esophagus will progress to esophageal adenocarcinoma, Dr. Patricia L. Blount reported at the annual meeting of the American Association for Cancer Research.

In a study involving 243 patients with Barrett's esophagus, 79.1% of patients who had all three genetic abnormalities on baseline endoscopic biopsy progressed to esophageal adenocarcinoma within 6 years. Conversely, among patients who had none of the abnormalities, there was not a single progression to cancer in almost 8 years. Progression rates for patients with one and two abnormalities were 5.7% and 28.4%, respectively, at 6 years.

Compared with patients with no abnormalities, patients with any two of the abnormalities were 9 times more likely to progress to esophageal adenocarcinoma, and those with all three of the abnormalities were 39 times more likely to progress during an average follow-up of 71 months; these differences were statistically significant. Patients with one abnormality were 1.8 times more likely to progress than those with no abnormalities, but this was not a significant difference.

In general, only about 10% of patients with Barrett's esophagus progress to esophageal adenocarcinoma, noted Dr. Blount, of the Fred Hutchinson Cancer Research Center, Seattle. Even frequent endoscopic surveillance can miss the small, focal lesions signaling progression to cancer. Thus, a reliable method of predicting progression could have far-reaching clinical effects. The investigators are working to translate this research into a practical test that does not require the facilities of a research laboratory, he said.

The investigators focused on DNA aneuploidy and tetraploidy and on alterations in the genes for the tumor-suppressor proteins TP53 and CDKN2A accompanied by a loss of heterozygosity (LOH) for those genes. Patients who had either aneuploidy or tetraploidy, 17p LOH (loss of heterozygosity on the short arm of chromosome 17), or 9p LOH (similarly, on chromosome 9) were more likely to progress to cancer.

As in other studies, the results of this study suggested that the use of NSAIDs may be protective against progression to esophageal adenocarcinoma.

The study was funded by the National Institutes of Health. Dr. Blount said that she had no conflicts of interest to disclose regarding the study.

LOS ANGELES — A combination of three biomarkers may reliably predict which patients with Barrett's esophagus will progress to esophageal adenocarcinoma, Dr. Patricia L. Blount reported at the annual meeting of the American Association for Cancer Research.

In a study involving 243 patients with Barrett's esophagus, 79.1% of patients who had all three genetic abnormalities on baseline endoscopic biopsy progressed to esophageal adenocarcinoma within 6 years. Conversely, among patients who had none of the abnormalities, there was not a single progression to cancer in almost 8 years. Progression rates for patients with one and two abnormalities were 5.7% and 28.4%, respectively, at 6 years.

Compared with patients with no abnormalities, patients with any two of the abnormalities were 9 times more likely to progress to esophageal adenocarcinoma, and those with all three of the abnormalities were 39 times more likely to progress during an average follow-up of 71 months; these differences were statistically significant. Patients with one abnormality were 1.8 times more likely to progress than those with no abnormalities, but this was not a significant difference.

In general, only about 10% of patients with Barrett's esophagus progress to esophageal adenocarcinoma, noted Dr. Blount, of the Fred Hutchinson Cancer Research Center, Seattle. Even frequent endoscopic surveillance can miss the small, focal lesions signaling progression to cancer. Thus, a reliable method of predicting progression could have far-reaching clinical effects. The investigators are working to translate this research into a practical test that does not require the facilities of a research laboratory, he said.

The investigators focused on DNA aneuploidy and tetraploidy and on alterations in the genes for the tumor-suppressor proteins TP53 and CDKN2A accompanied by a loss of heterozygosity (LOH) for those genes. Patients who had either aneuploidy or tetraploidy, 17p LOH (loss of heterozygosity on the short arm of chromosome 17), or 9p LOH (similarly, on chromosome 9) were more likely to progress to cancer.

As in other studies, the results of this study suggested that the use of NSAIDs may be protective against progression to esophageal adenocarcinoma.

The study was funded by the National Institutes of Health. Dr. Blount said that she had no conflicts of interest to disclose regarding the study.

LOS ANGELES — A combination of three biomarkers may reliably predict which patients with Barrett's esophagus will progress to esophageal adenocarcinoma, Dr. Patricia L. Blount reported at the annual meeting of the American Association for Cancer Research.

In a study involving 243 patients with Barrett's esophagus, 79.1% of patients who had all three genetic abnormalities on baseline endoscopic biopsy progressed to esophageal adenocarcinoma within 6 years. Conversely, among patients who had none of the abnormalities, there was not a single progression to cancer in almost 8 years. Progression rates for patients with one and two abnormalities were 5.7% and 28.4%, respectively, at 6 years.

Compared with patients with no abnormalities, patients with any two of the abnormalities were 9 times more likely to progress to esophageal adenocarcinoma, and those with all three of the abnormalities were 39 times more likely to progress during an average follow-up of 71 months; these differences were statistically significant. Patients with one abnormality were 1.8 times more likely to progress than those with no abnormalities, but this was not a significant difference.

In general, only about 10% of patients with Barrett's esophagus progress to esophageal adenocarcinoma, noted Dr. Blount, of the Fred Hutchinson Cancer Research Center, Seattle. Even frequent endoscopic surveillance can miss the small, focal lesions signaling progression to cancer. Thus, a reliable method of predicting progression could have far-reaching clinical effects. The investigators are working to translate this research into a practical test that does not require the facilities of a research laboratory, he said.

The investigators focused on DNA aneuploidy and tetraploidy and on alterations in the genes for the tumor-suppressor proteins TP53 and CDKN2A accompanied by a loss of heterozygosity (LOH) for those genes. Patients who had either aneuploidy or tetraploidy, 17p LOH (loss of heterozygosity on the short arm of chromosome 17), or 9p LOH (similarly, on chromosome 9) were more likely to progress to cancer.

As in other studies, the results of this study suggested that the use of NSAIDs may be protective against progression to esophageal adenocarcinoma.

The study was funded by the National Institutes of Health. Dr. Blount said that she had no conflicts of interest to disclose regarding the study.

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and her colleagues.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis following a dose of this antibiotic?”

The patients completed a questionnaire on health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio, 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR, 8.8). After controlling for age, they found a statistically significant association between penicillin allergy and atopy (OR, 3.5).

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and her colleagues.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis following a dose of this antibiotic?”

The patients completed a questionnaire on health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio, 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR, 8.8). After controlling for age, they found a statistically significant association between penicillin allergy and atopy (OR, 3.5).

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and her colleagues.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis following a dose of this antibiotic?”

The patients completed a questionnaire on health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio, 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR, 8.8). After controlling for age, they found a statistically significant association between penicillin allergy and atopy (OR, 3.5).

SAN DIEGO — Women who experience symptoms of allergic rhinitis during early pregnancy are more than six times as likely to have children with allergic rhinitis than are women who have no such symptoms, Dr. Miwa Shinohara said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results suggest that women should be aggressive in controlling allergic rhinitis symptoms during early pregnancy, with avoidance of allergens providing the best means of control, said Dr. Shinohara, of department of pediatrics at Kochi (Japan) University.

The retrospective cohort study involved 400 women with physician-diagnosed allergic rhinitis and their offspring. When the children were an average of 9.9 months old (range 1.7–18.7 months), the mothers completed a questionnaire about their allergic rhinitis symptoms during pregnancy. The study's primary outcome measure was whether the children themselves had physician-diagnosed allergic rhinitis.

Of the 400 women, 150 recalled having no allergic rhinitis symptoms during pregnancy, 219 recalled having symptoms early in pregnancy, and 173 recalled having symptoms late in pregnancy. (These figures total more than 400 because some women had symptoms both early and late in pregnancy.)

After adjustment for age, gender, month of birth, and the father's history of allergic rhinitis, women who had symptoms early in pregnancy were 6.3 times as likely to have children with allergic rhinitis as women who had no such symptoms. There was no statistically significant increase in the odds ratio for women who had symptoms late in pregnancy.

Additionally, there was no statistically significant association between the mother's symptoms and a diagnosis of bronchial asthma, food allergy, or atopic dermatitis in their children. And there was no statistically significant association between the father's symptoms of allergic rhinitis during pregnancy and the child's allergic rhinitis.

Dr. Shinohara said that the results imply the presence of an epigenetic mechanism for transmitting allergic rhinitis from mother to child, presumably through organ-specific hypersensitivity.

SAN DIEGO — Women who experience symptoms of allergic rhinitis during early pregnancy are more than six times as likely to have children with allergic rhinitis than are women who have no such symptoms, Dr. Miwa Shinohara said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results suggest that women should be aggressive in controlling allergic rhinitis symptoms during early pregnancy, with avoidance of allergens providing the best means of control, said Dr. Shinohara, of department of pediatrics at Kochi (Japan) University.

The retrospective cohort study involved 400 women with physician-diagnosed allergic rhinitis and their offspring. When the children were an average of 9.9 months old (range 1.7–18.7 months), the mothers completed a questionnaire about their allergic rhinitis symptoms during pregnancy. The study's primary outcome measure was whether the children themselves had physician-diagnosed allergic rhinitis.

Of the 400 women, 150 recalled having no allergic rhinitis symptoms during pregnancy, 219 recalled having symptoms early in pregnancy, and 173 recalled having symptoms late in pregnancy. (These figures total more than 400 because some women had symptoms both early and late in pregnancy.)

After adjustment for age, gender, month of birth, and the father's history of allergic rhinitis, women who had symptoms early in pregnancy were 6.3 times as likely to have children with allergic rhinitis as women who had no such symptoms. There was no statistically significant increase in the odds ratio for women who had symptoms late in pregnancy.

Additionally, there was no statistically significant association between the mother's symptoms and a diagnosis of bronchial asthma, food allergy, or atopic dermatitis in their children. And there was no statistically significant association between the father's symptoms of allergic rhinitis during pregnancy and the child's allergic rhinitis.

Dr. Shinohara said that the results imply the presence of an epigenetic mechanism for transmitting allergic rhinitis from mother to child, presumably through organ-specific hypersensitivity.

SAN DIEGO — Women who experience symptoms of allergic rhinitis during early pregnancy are more than six times as likely to have children with allergic rhinitis than are women who have no such symptoms, Dr. Miwa Shinohara said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results suggest that women should be aggressive in controlling allergic rhinitis symptoms during early pregnancy, with avoidance of allergens providing the best means of control, said Dr. Shinohara, of department of pediatrics at Kochi (Japan) University.

The retrospective cohort study involved 400 women with physician-diagnosed allergic rhinitis and their offspring. When the children were an average of 9.9 months old (range 1.7–18.7 months), the mothers completed a questionnaire about their allergic rhinitis symptoms during pregnancy. The study's primary outcome measure was whether the children themselves had physician-diagnosed allergic rhinitis.

Of the 400 women, 150 recalled having no allergic rhinitis symptoms during pregnancy, 219 recalled having symptoms early in pregnancy, and 173 recalled having symptoms late in pregnancy. (These figures total more than 400 because some women had symptoms both early and late in pregnancy.)

After adjustment for age, gender, month of birth, and the father's history of allergic rhinitis, women who had symptoms early in pregnancy were 6.3 times as likely to have children with allergic rhinitis as women who had no such symptoms. There was no statistically significant increase in the odds ratio for women who had symptoms late in pregnancy.

Additionally, there was no statistically significant association between the mother's symptoms and a diagnosis of bronchial asthma, food allergy, or atopic dermatitis in their children. And there was no statistically significant association between the father's symptoms of allergic rhinitis during pregnancy and the child's allergic rhinitis.

Dr. Shinohara said that the results imply the presence of an epigenetic mechanism for transmitting allergic rhinitis from mother to child, presumably through organ-specific hypersensitivity.

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and associates.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin. All were recruited from the offices of allergists.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, penicillin, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis after a dose of this antibiotic?”

The patients completed a questionnaire inquiring about several health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and a personal history of atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR 8.8). After controlling for age, they found a statistically significant association between a personal history of penicillin allergy and a personal history of atopy (OR 3.5). No other associations were statistically significant.

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and associates.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin. All were recruited from the offices of allergists.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, penicillin, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis after a dose of this antibiotic?”

The patients completed a questionnaire inquiring about several health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and a personal history of atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR 8.8). After controlling for age, they found a statistically significant association between a personal history of penicillin allergy and a personal history of atopy (OR 3.5). No other associations were statistically significant.

SAN DIEGO — People who report allergies to other drugs were more than 27 times as likely to report a penicillin allergy as people who reported no other drug allergies, Dr. Andrea J. Apter reported in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Other statistically significant predictors of penicillin allergy were a family history of penicillin allergy and a personal history of asthma, allergic rhinitis, or atopic dermatitis, wrote Dr. Apter of the University of Pennsylvania, Philadelphia, and associates.

The study involved 24 adults with penicillin allergies and 39 age-matched controls with no allergies to penicillin. All were recruited from the offices of allergists.

Patients were judged to have a penicillin allergy if they responded positively to the questions, “Are you allergic to penicillin or its derivatives (for example, penicillin, amoxicillin, Augmentin, ampicillin, dicloxacillin, piperacillin, ticarcillin)? By allergic reaction, did you have hives, angioedema, wheeze, hypotension, or anaphylaxis after a dose of this antibiotic?”

The patients completed a questionnaire inquiring about several health-related matters, such as whether they had asthma, allergic rhinitis, or eczema; were currently taking more than two medications; or had more than two current medical diagnoses.

After controlling for age and a personal history of atopy, the researchers found statistically significant associations between penicillin allergy and allergies to other drugs (odds ratio 27.4) and between a personal history of penicillin allergy and a family history of penicillin allergy (OR 8.8). After controlling for age, they found a statistically significant association between a personal history of penicillin allergy and a personal history of atopy (OR 3.5). No other associations were statistically significant.

LOS ANGELES — Cetuximab (Erbitux) prolonged overall survival of patients with metastatic colorectal cancer in one large clinical study and extended progression-free survival for patients in another investigation, according to the results of two large phase III trials presented for the first time at the annual meeting of the American Association for Cancer Research.

In a study conducted by the National Cancer Institute of Canada (NCIC) and the Australasian Gastro-Intestinal Trials Group, 572 patients who had failed two previous rounds of chemotherapy were randomized to receive either best supportive care alone or best supportive care plus cetuximab.

According to Dr. Derek J. Jonker of the University of Ottawa, overall survival increased from a median of 4.6 months to 6.1 months with cetuximab, a monoclonal antibody that inhibits cell growth by binding to the epidermal growth factor receptor. Among patients on cetuximab, 19 (6.6%) had complete or partial responses; none of the patients on best supportive care alone had such improvements. Cetuximab also was associated with a 32% decrease in the risk of progression. These results were statistically significant.

In the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) trial, 1,298 patients who had failed one previous round of chemotherapy were randomized to receive either irinotecan alone or irinotecan plus cetuximab. According to Dr. Alberto F. Sobrero of Hospital San Marino in Genoa, Italy, the combination resulted in an increase in progression-free survival from 2.6 months to 4.0 months and an increase in the response rate from 4% to 16%, with both differences being statistically significant. There was no statistically significant increase in overall survival, but Dr. Sobrero said this might be because half of the patients in the irinotecan-alone arm crossed over and received cetuximab following the end of the trial.

These studies “give us the preponderance of evidence that we need to conclude that cetuximab is a real drug of use in patients with colorectal cancer,” said Dr. Richard M. Goldberg, of the University of North Carolina at Chapel Hill, at a press briefing. Dr. Goldberg was not directly involved in either trial.

He noted that although these trials present evidence for the use of cetuximab as a second-line or third-line therapy, the drug might also find a use as a first-line therapy. He expects some results from one of the two trials of cetuximab as first-line therapy to be presented at the meeting of the American Society for Clinical Oncology in June. And two additional trials are investigating cetuximab as adjuvant therapy for colorectal cancer.

In the NCIC and EPIC trials, patients received cetuximab at an initial dose of 400 mg/m

Cetuximab is not without side effects. The most common are diarrhea, fatigue, and an acneiform rash, and severe infusion reactions are also possible. The rash, which can be quite troublesome, appears to correlate with treatment effectiveness. Patients who did not experience a skin reaction had a response rate of 4%–5%, while those with severe skin reactions had a 55% response rate, Dr. Sobrero said.

Describing the results of the NCIC trial as “clear and unambiguous,” Dr. Jonker said, “The study is significant because it is the first time that a biologically targeted therapy given on its own has improved survival in colorectal cancer. … There are now five effective types of therapy for the treatment of colorectal cancer. … It's going to be a complex issue to sort out how to best give these drugs in an appropriate sequence.”

In considering the clinical impact of these trials, Dr. Sobrero said, “One thing is running scientific experiments; the other is taking this into the battleground of everyday patient management. That is really tough. … If the patient has indolent disease, he's not heavily symptomatic, why should I bother in going for a combination? I have data showing that if I give [cetuximab] later in the course, I will attain the same survival. So that would be the condition for going for sequential treatment. If I have an aggressive disease, a symptomatic condition, as we very often encounter in our practice, I will be very much tempted to go with the combination.”

Dr. Goldberg noted that “a minority of patients responds to these drugs, but those patients who respond have a very meaningful response in most cases.”

Cetuximab has already received Food and Drug Administration approval for use in colorectal cancer and head and neck cancer. The NCIC trial was supported by ImClone and Bristol-Myers Squibb, which manufacture and distribute the drug. The EPIC trial was supported in part by Bristol-Myers Squibb and Merck.

Overall survival increased from a median of 4.6 months to 6.1 months with cetuximab. DR. JONKER

LOS ANGELES — Cetuximab (Erbitux) prolonged overall survival of patients with metastatic colorectal cancer in one large clinical study and extended progression-free survival for patients in another investigation, according to the results of two large phase III trials presented for the first time at the annual meeting of the American Association for Cancer Research.

In a study conducted by the National Cancer Institute of Canada (NCIC) and the Australasian Gastro-Intestinal Trials Group, 572 patients who had failed two previous rounds of chemotherapy were randomized to receive either best supportive care alone or best supportive care plus cetuximab.

According to Dr. Derek J. Jonker of the University of Ottawa, overall survival increased from a median of 4.6 months to 6.1 months with cetuximab, a monoclonal antibody that inhibits cell growth by binding to the epidermal growth factor receptor. Among patients on cetuximab, 19 (6.6%) had complete or partial responses; none of the patients on best supportive care alone had such improvements. Cetuximab also was associated with a 32% decrease in the risk of progression. These results were statistically significant.

In the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) trial, 1,298 patients who had failed one previous round of chemotherapy were randomized to receive either irinotecan alone or irinotecan plus cetuximab. According to Dr. Alberto F. Sobrero of Hospital San Marino in Genoa, Italy, the combination resulted in an increase in progression-free survival from 2.6 months to 4.0 months and an increase in the response rate from 4% to 16%, with both differences being statistically significant. There was no statistically significant increase in overall survival, but Dr. Sobrero said this might be because half of the patients in the irinotecan-alone arm crossed over and received cetuximab following the end of the trial.

These studies “give us the preponderance of evidence that we need to conclude that cetuximab is a real drug of use in patients with colorectal cancer,” said Dr. Richard M. Goldberg, of the University of North Carolina at Chapel Hill, at a press briefing. Dr. Goldberg was not directly involved in either trial.

He noted that although these trials present evidence for the use of cetuximab as a second-line or third-line therapy, the drug might also find a use as a first-line therapy. He expects some results from one of the two trials of cetuximab as first-line therapy to be presented at the meeting of the American Society for Clinical Oncology in June. And two additional trials are investigating cetuximab as adjuvant therapy for colorectal cancer.

In the NCIC and EPIC trials, patients received cetuximab at an initial dose of 400 mg/m

Cetuximab is not without side effects. The most common are diarrhea, fatigue, and an acneiform rash, and severe infusion reactions are also possible. The rash, which can be quite troublesome, appears to correlate with treatment effectiveness. Patients who did not experience a skin reaction had a response rate of 4%–5%, while those with severe skin reactions had a 55% response rate, Dr. Sobrero said.

Describing the results of the NCIC trial as “clear and unambiguous,” Dr. Jonker said, “The study is significant because it is the first time that a biologically targeted therapy given on its own has improved survival in colorectal cancer. … There are now five effective types of therapy for the treatment of colorectal cancer. … It's going to be a complex issue to sort out how to best give these drugs in an appropriate sequence.”

In considering the clinical impact of these trials, Dr. Sobrero said, “One thing is running scientific experiments; the other is taking this into the battleground of everyday patient management. That is really tough. … If the patient has indolent disease, he's not heavily symptomatic, why should I bother in going for a combination? I have data showing that if I give [cetuximab] later in the course, I will attain the same survival. So that would be the condition for going for sequential treatment. If I have an aggressive disease, a symptomatic condition, as we very often encounter in our practice, I will be very much tempted to go with the combination.”

Dr. Goldberg noted that “a minority of patients responds to these drugs, but those patients who respond have a very meaningful response in most cases.”

Cetuximab has already received Food and Drug Administration approval for use in colorectal cancer and head and neck cancer. The NCIC trial was supported by ImClone and Bristol-Myers Squibb, which manufacture and distribute the drug. The EPIC trial was supported in part by Bristol-Myers Squibb and Merck.

Overall survival increased from a median of 4.6 months to 6.1 months with cetuximab. DR. JONKER

LOS ANGELES — Cetuximab (Erbitux) prolonged overall survival of patients with metastatic colorectal cancer in one large clinical study and extended progression-free survival for patients in another investigation, according to the results of two large phase III trials presented for the first time at the annual meeting of the American Association for Cancer Research.

In a study conducted by the National Cancer Institute of Canada (NCIC) and the Australasian Gastro-Intestinal Trials Group, 572 patients who had failed two previous rounds of chemotherapy were randomized to receive either best supportive care alone or best supportive care plus cetuximab.

According to Dr. Derek J. Jonker of the University of Ottawa, overall survival increased from a median of 4.6 months to 6.1 months with cetuximab, a monoclonal antibody that inhibits cell growth by binding to the epidermal growth factor receptor. Among patients on cetuximab, 19 (6.6%) had complete or partial responses; none of the patients on best supportive care alone had such improvements. Cetuximab also was associated with a 32% decrease in the risk of progression. These results were statistically significant.

In the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) trial, 1,298 patients who had failed one previous round of chemotherapy were randomized to receive either irinotecan alone or irinotecan plus cetuximab. According to Dr. Alberto F. Sobrero of Hospital San Marino in Genoa, Italy, the combination resulted in an increase in progression-free survival from 2.6 months to 4.0 months and an increase in the response rate from 4% to 16%, with both differences being statistically significant. There was no statistically significant increase in overall survival, but Dr. Sobrero said this might be because half of the patients in the irinotecan-alone arm crossed over and received cetuximab following the end of the trial.

These studies “give us the preponderance of evidence that we need to conclude that cetuximab is a real drug of use in patients with colorectal cancer,” said Dr. Richard M. Goldberg, of the University of North Carolina at Chapel Hill, at a press briefing. Dr. Goldberg was not directly involved in either trial.

He noted that although these trials present evidence for the use of cetuximab as a second-line or third-line therapy, the drug might also find a use as a first-line therapy. He expects some results from one of the two trials of cetuximab as first-line therapy to be presented at the meeting of the American Society for Clinical Oncology in June. And two additional trials are investigating cetuximab as adjuvant therapy for colorectal cancer.

In the NCIC and EPIC trials, patients received cetuximab at an initial dose of 400 mg/m

Cetuximab is not without side effects. The most common are diarrhea, fatigue, and an acneiform rash, and severe infusion reactions are also possible. The rash, which can be quite troublesome, appears to correlate with treatment effectiveness. Patients who did not experience a skin reaction had a response rate of 4%–5%, while those with severe skin reactions had a 55% response rate, Dr. Sobrero said.

Describing the results of the NCIC trial as “clear and unambiguous,” Dr. Jonker said, “The study is significant because it is the first time that a biologically targeted therapy given on its own has improved survival in colorectal cancer. … There are now five effective types of therapy for the treatment of colorectal cancer. … It's going to be a complex issue to sort out how to best give these drugs in an appropriate sequence.”

In considering the clinical impact of these trials, Dr. Sobrero said, “One thing is running scientific experiments; the other is taking this into the battleground of everyday patient management. That is really tough. … If the patient has indolent disease, he's not heavily symptomatic, why should I bother in going for a combination? I have data showing that if I give [cetuximab] later in the course, I will attain the same survival. So that would be the condition for going for sequential treatment. If I have an aggressive disease, a symptomatic condition, as we very often encounter in our practice, I will be very much tempted to go with the combination.”

Dr. Goldberg noted that “a minority of patients responds to these drugs, but those patients who respond have a very meaningful response in most cases.”

Cetuximab has already received Food and Drug Administration approval for use in colorectal cancer and head and neck cancer. The NCIC trial was supported by ImClone and Bristol-Myers Squibb, which manufacture and distribute the drug. The EPIC trial was supported in part by Bristol-Myers Squibb and Merck.

Overall survival increased from a median of 4.6 months to 6.1 months with cetuximab. DR. JONKER

SCOTTSDALE, ARIZ. — Endovascular repair of abdominal aortic aneurysms was associated with fewer perioperative complications than was open repair in a large study based on Medicare data.

At an international congress on endovascular interventions sponsored by the Arizona Heart Institute, Dr. James F. McKinsey reported on 174,974 patients who had open repair and 38,629 patients who underwent endovascular repair. In the open surgery group, 30-day mortality was over 2.5 times greater than in the endovascular group, a significant difference. (See box.)

Also, endovascular repair was associated with fewer peripheral vascular complications (1.6% vs. 3.3%), a lower incidence of postoperative shock (0.1% vs. 0.4%), and fewer infections (0.7% vs. 2.9%).

Endovascular repair was associated with significantly fewer gastrointestinal, pulmonary, renal, neurologic, cardiac, and surgical complications.

The mean length of hospital stay (3 days vs. 9 days) also strongly favored the endovascular group.

Device malfunction was the only complication that was significantly greater in the endovascular group, compared with the open surgery group (3.0% vs. 1.1%).

“The people undergoing endovascular repair were a sicker group to start with,” said Dr. McKinsey, of Columbia University Medical Center, New York. They tended to have elevated lipid levels as well as a higher incidence of diabetes, hypertension, coronary artery disease, and cerebrovascular disease.

In recent years, several controlled clinical trials arrived at the same conclusion: that endovascular repair of abdominal aortic aneurysms (AAA) is superior to open repair. “The difficulty with these trials is that they were generally done in centers of excellence that are really geared toward endovascular repair, and may not reflect the average common-day experience in the United States,” Dr. McKinsey said.

Using the full Medicare database has several advantages. Information from 41 million patients is included, and this allows detailed subgroup analysis to be conducted while retaining statistical power. Furthermore, the use of unique patient identifiers makes longitudinal studies possible, even when patients are seen at more than one hospital.

On the other hand, patients in this database are not randomly assigned to a treatment, diagnostic codes are not uniformly consistent, and some desirable data—such as test results—are absent.

The study included patients with diagnostic codes indicating primary or secondary diagnoses of AAA with or without rupture.

There were several exclusion criteria, including ruptured thoracic aneurysm, ruptured thoracoabdominal abdominal aneurysm, and complications resulting from other vascular devices, implants, or grafts.

ELSEVIER GLOBAL MEDICAL NEWS

SCOTTSDALE, ARIZ. — Endovascular repair of abdominal aortic aneurysms was associated with fewer perioperative complications than was open repair in a large study based on Medicare data.

At an international congress on endovascular interventions sponsored by the Arizona Heart Institute, Dr. James F. McKinsey reported on 174,974 patients who had open repair and 38,629 patients who underwent endovascular repair. In the open surgery group, 30-day mortality was over 2.5 times greater than in the endovascular group, a significant difference. (See box.)

Also, endovascular repair was associated with fewer peripheral vascular complications (1.6% vs. 3.3%), a lower incidence of postoperative shock (0.1% vs. 0.4%), and fewer infections (0.7% vs. 2.9%).

Endovascular repair was associated with significantly fewer gastrointestinal, pulmonary, renal, neurologic, cardiac, and surgical complications.

The mean length of hospital stay (3 days vs. 9 days) also strongly favored the endovascular group.

Device malfunction was the only complication that was significantly greater in the endovascular group, compared with the open surgery group (3.0% vs. 1.1%).

“The people undergoing endovascular repair were a sicker group to start with,” said Dr. McKinsey, of Columbia University Medical Center, New York. They tended to have elevated lipid levels as well as a higher incidence of diabetes, hypertension, coronary artery disease, and cerebrovascular disease.

In recent years, several controlled clinical trials arrived at the same conclusion: that endovascular repair of abdominal aortic aneurysms (AAA) is superior to open repair. “The difficulty with these trials is that they were generally done in centers of excellence that are really geared toward endovascular repair, and may not reflect the average common-day experience in the United States,” Dr. McKinsey said.

Using the full Medicare database has several advantages. Information from 41 million patients is included, and this allows detailed subgroup analysis to be conducted while retaining statistical power. Furthermore, the use of unique patient identifiers makes longitudinal studies possible, even when patients are seen at more than one hospital.

On the other hand, patients in this database are not randomly assigned to a treatment, diagnostic codes are not uniformly consistent, and some desirable data—such as test results—are absent.

The study included patients with diagnostic codes indicating primary or secondary diagnoses of AAA with or without rupture.

There were several exclusion criteria, including ruptured thoracic aneurysm, ruptured thoracoabdominal abdominal aneurysm, and complications resulting from other vascular devices, implants, or grafts.

ELSEVIER GLOBAL MEDICAL NEWS

SCOTTSDALE, ARIZ. — Endovascular repair of abdominal aortic aneurysms was associated with fewer perioperative complications than was open repair in a large study based on Medicare data.

At an international congress on endovascular interventions sponsored by the Arizona Heart Institute, Dr. James F. McKinsey reported on 174,974 patients who had open repair and 38,629 patients who underwent endovascular repair. In the open surgery group, 30-day mortality was over 2.5 times greater than in the endovascular group, a significant difference. (See box.)

Also, endovascular repair was associated with fewer peripheral vascular complications (1.6% vs. 3.3%), a lower incidence of postoperative shock (0.1% vs. 0.4%), and fewer infections (0.7% vs. 2.9%).

Endovascular repair was associated with significantly fewer gastrointestinal, pulmonary, renal, neurologic, cardiac, and surgical complications.

The mean length of hospital stay (3 days vs. 9 days) also strongly favored the endovascular group.

Device malfunction was the only complication that was significantly greater in the endovascular group, compared with the open surgery group (3.0% vs. 1.1%).

“The people undergoing endovascular repair were a sicker group to start with,” said Dr. McKinsey, of Columbia University Medical Center, New York. They tended to have elevated lipid levels as well as a higher incidence of diabetes, hypertension, coronary artery disease, and cerebrovascular disease.

In recent years, several controlled clinical trials arrived at the same conclusion: that endovascular repair of abdominal aortic aneurysms (AAA) is superior to open repair. “The difficulty with these trials is that they were generally done in centers of excellence that are really geared toward endovascular repair, and may not reflect the average common-day experience in the United States,” Dr. McKinsey said.

Using the full Medicare database has several advantages. Information from 41 million patients is included, and this allows detailed subgroup analysis to be conducted while retaining statistical power. Furthermore, the use of unique patient identifiers makes longitudinal studies possible, even when patients are seen at more than one hospital.

On the other hand, patients in this database are not randomly assigned to a treatment, diagnostic codes are not uniformly consistent, and some desirable data—such as test results—are absent.

The study included patients with diagnostic codes indicating primary or secondary diagnoses of AAA with or without rupture.

There were several exclusion criteria, including ruptured thoracic aneurysm, ruptured thoracoabdominal abdominal aneurysm, and complications resulting from other vascular devices, implants, or grafts.

ELSEVIER GLOBAL MEDICAL NEWS