Kerri Wachter

TAMPA — Ninety percent of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids reported symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

“This is an effective noninvasive treatment option for patients, with an alternative treatment rate and reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MR-guided focused ultrasound ablation (MRgFUS), high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms.

The women in the study were premenopausal and had no desire to have children in the future, noted Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn. They had to have at least one uterine fibroid of at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 8 underwent alternative treatments: 6 patients had hysterectomies, and 2 had myomectomies.

A total of 11 patients did not provide any information about symptomatic improvement, leaving 89 patients available for a phone interview at 12-months' follow-up. Of these, 97% reported overall symptom improvement (by responding “yes” to a question about improvement).

A total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Disclosures: Dr. Hesley has received grant support for other studies from InSightec, which makes the ExAblate system, but this study was not funded by outside sources.

The improvement was 'very comparable to the literature for myomectomy and uterine artery embolization.'

Source DR. HESLEY

TAMPA — Ninety percent of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids reported symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

“This is an effective noninvasive treatment option for patients, with an alternative treatment rate and reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MR-guided focused ultrasound ablation (MRgFUS), high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms.

The women in the study were premenopausal and had no desire to have children in the future, noted Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn. They had to have at least one uterine fibroid of at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 8 underwent alternative treatments: 6 patients had hysterectomies, and 2 had myomectomies.

A total of 11 patients did not provide any information about symptomatic improvement, leaving 89 patients available for a phone interview at 12-months' follow-up. Of these, 97% reported overall symptom improvement (by responding “yes” to a question about improvement).

A total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Disclosures: Dr. Hesley has received grant support for other studies from InSightec, which makes the ExAblate system, but this study was not funded by outside sources.

The improvement was 'very comparable to the literature for myomectomy and uterine artery embolization.'

Source DR. HESLEY

TAMPA — Ninety percent of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids reported symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

“This is an effective noninvasive treatment option for patients, with an alternative treatment rate and reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MR-guided focused ultrasound ablation (MRgFUS), high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms.

The women in the study were premenopausal and had no desire to have children in the future, noted Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn. They had to have at least one uterine fibroid of at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 8 underwent alternative treatments: 6 patients had hysterectomies, and 2 had myomectomies.

A total of 11 patients did not provide any information about symptomatic improvement, leaving 89 patients available for a phone interview at 12-months' follow-up. Of these, 97% reported overall symptom improvement (by responding “yes” to a question about improvement).

A total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Disclosures: Dr. Hesley has received grant support for other studies from InSightec, which makes the ExAblate system, but this study was not funded by outside sources.

The improvement was 'very comparable to the literature for myomectomy and uterine artery embolization.'

Source DR. HESLEY

The early stopping of a clinical trial because of clear benefit from a new drug or regimen is usually good news. In the long run, however, researchers may find that they lack clear answers about the ethics and validity—and sometimes the benefit itself—of doing so.

The controversy over early stopping and early release of data stems from the desire to speed patient access to what appears to be a superior treatment, and the question of whether this will end up being done at the cost of scientific validity.

Trials involving sunitinib (Sutent) for pancreatic neuroendocrine tumors and lenalidomide (Revlimid) for multiple myeloma are two recent examples.

In February, researchers announced that a data-monitoring committee stopped the 171-patient sunitinib study after an analysis revealed that progression-free survival, the primary end point, was much longer in the active treatment arm.

In December 2009, a 568-patient study was not stopped, but early release of initial data showed that progression-free survival was longer in patients who received maintenance therapy with the oral drug lenalidomide after stem cell transplant than in patients who got a placebo.

“On the one hand, if the trial really is positive, then that's important information to get out there to the medical community and patients,” said Dr. Richard Schilsky, chairman of Cancer and Leukemia Group B (CALGB), which conducted the multiple myeloma trial. “On the other hand, there's this risk that you put the data out there early, and it doesn't hold up over time.”

When trials are stopped early for benefit, “typically the experimental arm is so much better than the standard arm that it is felt that it is medically and ethically necessary to announce the results before the trial is actually completed,” said Dr. Schilsky, former president of the American Society of Clinical Oncology and chief of hematology and oncology at the University of Chicago Medical Center.

One area of contention is the choice of end point that's used in a study's predefined early-stopping rules. Presumably, the primary end point of the study is used in the early stopping criteria, Dr. Schilsky said. In oncology trials, that often means progression-free survival.

But progression-free survival often is used as a surrogate for overall survival, said Dr. Jennifer Obel, a member of ASCO's cancer communications committee and an oncologist with NorthShore University HealthSystem in Illinois. Progression-free survival is quicker to measure, but whether it's clinically meaningful is unclear. Both the sunitinib and lenalidomide studies were stopped for benefits in disease progression.

“The real, meaningful end point is overall survival,” Dr. Obel said. Usually, patients who live longer do so without progression, but in some instances, drugs have prolonged progression-free survival but not overall survival.

Smaller P Values, Fewer Events

Another argument against early stopping is that it can overestimate the treatment benefit. In a systematic review of trials stopped early for benefit, researchers found that trials that accrued fewer events (that is, with end points that drove early stopping) estimated larger treatment effects (JAMA 2005;294:2203-9).

“The whole problem with this is that the effect size that we're looking for is relatively small,” said Dr. Jeffrey Crawford, chief of medical oncology at Duke University in Durham, N.C. “We're looking for a very small difference in survival in an unselected population. When you look for these small differences, the only way to really know is to have a large enough sample size that you have confidence in the result.”

Dr. Schilsky noted that “the stringency of the statistical analysis plan is important.” Early stopping often requires a much smaller P value to show significance. “It's a much higher threshold for stopping early because there are so many fewer events. You don't want to declare a trial to be positive unless the events are so unbalanced that you think it's extremely unlikely to be due to chance,” he said.

Weighing Drug Availability

Patients in the control arm pose yet another complication. If the experimental arm is better, patients who receive the control drug or regimen often gain access to the experimental drug or regimen. “Does that then potentially confound the final interpretation of the study results, because then you have a potentially significant number of patients who cross over?” Dr. Schilsky asked.

Early stopping because of efficacy is even more complicated when the experimental drug is not yet available. In that event, it's up to the manufacturer to develop a compassionate-use protocol specifying the patient population and how to administer the drug, he noted. Compassionate use allows the drug to be available to patients, even as the company is following the usual regulatory procedure for approval.

The effects of early stopping because of efficacy go far beyond the trial itself, with implications for ongoing and future studies of the same disease. “If you stop early and declare that you have a [new] standard of care, does that impact other ongoing studies that are not using that [new standard] of care arm, or does that impact the planning for the next generation of studies?” Dr. Schilsky asked. “You may find that the accrual to other ongoing trials screeches to a halt because everyone says 'this trial design is no longer relevant in light of this new information.'”

Making the Decision

Ultimately, the decision to stop a trial early is in the hands of the safety data–monitoring committee (DMC). “This sort of data release is almost always undertaken only after a very thorough review by an independent data-monitoring committee,” Dr. Schilsky said. “DMCs are in the best position to make these decisions and they do it only after lots of careful deliberation.”

Ideally, the DMC should weigh in and make a recommendation on what should be done for the patients who are in the control arm of the study, at the very least, he said.

In the case of lenalidomide for multiple myeloma, “the study was markedly positive in favor of the Revlimid maintenance, and led our data- and safety-monitoring board to recommend early release of the results,” Dr. Schilsky noted. Accrual had been completed and all patients were in follow-up, but “the study crossed a statistical boundary for early release of the data before the protocol-specified number of events for the final analysis was available.”

This process involved notifying the Food and Drug Administration, the National Cancer Institute, and the drug manufacturer, as well as developing letters for physicians and patients involved in the study, and sending out a press release. In this case, because lenalidomide is already available, oncologists could start prescribing the drug for this patient group immediately.

Advancing technology and the development of more personalized medicine may help resolve some of the issues concerning the early stopping of trials, Dr. Crawford suggested.

“What will solve this will be biomarker-directed treatment subgroups. … We can look at a much smaller sample of patients because we're looking at a much bigger effect,” he said. “In the long run, that's going to be a much better approach to oncology than continuing to treat thousands of patients with treatment A vs. B.”

Disclosures: Both Dr. Schilsky and Dr. Obel said that they have no significant financial relationships. Dr. Crawford has received research support from and been an adviser, speaker, or consultant for several pharmaceutical companies.

'There's this risk that you put the data out there early, and it doesn't hold up over time.'

Source Dr. Schilsky

The early stopping of a clinical trial because of clear benefit from a new drug or regimen is usually good news. In the long run, however, researchers may find that they lack clear answers about the ethics and validity—and sometimes the benefit itself—of doing so.

The controversy over early stopping and early release of data stems from the desire to speed patient access to what appears to be a superior treatment, and the question of whether this will end up being done at the cost of scientific validity.

Trials involving sunitinib (Sutent) for pancreatic neuroendocrine tumors and lenalidomide (Revlimid) for multiple myeloma are two recent examples.

In February, researchers announced that a data-monitoring committee stopped the 171-patient sunitinib study after an analysis revealed that progression-free survival, the primary end point, was much longer in the active treatment arm.

In December 2009, a 568-patient study was not stopped, but early release of initial data showed that progression-free survival was longer in patients who received maintenance therapy with the oral drug lenalidomide after stem cell transplant than in patients who got a placebo.

“On the one hand, if the trial really is positive, then that's important information to get out there to the medical community and patients,” said Dr. Richard Schilsky, chairman of Cancer and Leukemia Group B (CALGB), which conducted the multiple myeloma trial. “On the other hand, there's this risk that you put the data out there early, and it doesn't hold up over time.”

When trials are stopped early for benefit, “typically the experimental arm is so much better than the standard arm that it is felt that it is medically and ethically necessary to announce the results before the trial is actually completed,” said Dr. Schilsky, former president of the American Society of Clinical Oncology and chief of hematology and oncology at the University of Chicago Medical Center.

One area of contention is the choice of end point that's used in a study's predefined early-stopping rules. Presumably, the primary end point of the study is used in the early stopping criteria, Dr. Schilsky said. In oncology trials, that often means progression-free survival.

But progression-free survival often is used as a surrogate for overall survival, said Dr. Jennifer Obel, a member of ASCO's cancer communications committee and an oncologist with NorthShore University HealthSystem in Illinois. Progression-free survival is quicker to measure, but whether it's clinically meaningful is unclear. Both the sunitinib and lenalidomide studies were stopped for benefits in disease progression.

“The real, meaningful end point is overall survival,” Dr. Obel said. Usually, patients who live longer do so without progression, but in some instances, drugs have prolonged progression-free survival but not overall survival.

Smaller P Values, Fewer Events

Another argument against early stopping is that it can overestimate the treatment benefit. In a systematic review of trials stopped early for benefit, researchers found that trials that accrued fewer events (that is, with end points that drove early stopping) estimated larger treatment effects (JAMA 2005;294:2203-9).

“The whole problem with this is that the effect size that we're looking for is relatively small,” said Dr. Jeffrey Crawford, chief of medical oncology at Duke University in Durham, N.C. “We're looking for a very small difference in survival in an unselected population. When you look for these small differences, the only way to really know is to have a large enough sample size that you have confidence in the result.”

Dr. Schilsky noted that “the stringency of the statistical analysis plan is important.” Early stopping often requires a much smaller P value to show significance. “It's a much higher threshold for stopping early because there are so many fewer events. You don't want to declare a trial to be positive unless the events are so unbalanced that you think it's extremely unlikely to be due to chance,” he said.

Weighing Drug Availability

Patients in the control arm pose yet another complication. If the experimental arm is better, patients who receive the control drug or regimen often gain access to the experimental drug or regimen. “Does that then potentially confound the final interpretation of the study results, because then you have a potentially significant number of patients who cross over?” Dr. Schilsky asked.

Early stopping because of efficacy is even more complicated when the experimental drug is not yet available. In that event, it's up to the manufacturer to develop a compassionate-use protocol specifying the patient population and how to administer the drug, he noted. Compassionate use allows the drug to be available to patients, even as the company is following the usual regulatory procedure for approval.

The effects of early stopping because of efficacy go far beyond the trial itself, with implications for ongoing and future studies of the same disease. “If you stop early and declare that you have a [new] standard of care, does that impact other ongoing studies that are not using that [new standard] of care arm, or does that impact the planning for the next generation of studies?” Dr. Schilsky asked. “You may find that the accrual to other ongoing trials screeches to a halt because everyone says 'this trial design is no longer relevant in light of this new information.'”

Making the Decision

Ultimately, the decision to stop a trial early is in the hands of the safety data–monitoring committee (DMC). “This sort of data release is almost always undertaken only after a very thorough review by an independent data-monitoring committee,” Dr. Schilsky said. “DMCs are in the best position to make these decisions and they do it only after lots of careful deliberation.”

Ideally, the DMC should weigh in and make a recommendation on what should be done for the patients who are in the control arm of the study, at the very least, he said.

In the case of lenalidomide for multiple myeloma, “the study was markedly positive in favor of the Revlimid maintenance, and led our data- and safety-monitoring board to recommend early release of the results,” Dr. Schilsky noted. Accrual had been completed and all patients were in follow-up, but “the study crossed a statistical boundary for early release of the data before the protocol-specified number of events for the final analysis was available.”

This process involved notifying the Food and Drug Administration, the National Cancer Institute, and the drug manufacturer, as well as developing letters for physicians and patients involved in the study, and sending out a press release. In this case, because lenalidomide is already available, oncologists could start prescribing the drug for this patient group immediately.

Advancing technology and the development of more personalized medicine may help resolve some of the issues concerning the early stopping of trials, Dr. Crawford suggested.

“What will solve this will be biomarker-directed treatment subgroups. … We can look at a much smaller sample of patients because we're looking at a much bigger effect,” he said. “In the long run, that's going to be a much better approach to oncology than continuing to treat thousands of patients with treatment A vs. B.”

Disclosures: Both Dr. Schilsky and Dr. Obel said that they have no significant financial relationships. Dr. Crawford has received research support from and been an adviser, speaker, or consultant for several pharmaceutical companies.

'There's this risk that you put the data out there early, and it doesn't hold up over time.'

Source Dr. Schilsky

The early stopping of a clinical trial because of clear benefit from a new drug or regimen is usually good news. In the long run, however, researchers may find that they lack clear answers about the ethics and validity—and sometimes the benefit itself—of doing so.

The controversy over early stopping and early release of data stems from the desire to speed patient access to what appears to be a superior treatment, and the question of whether this will end up being done at the cost of scientific validity.

Trials involving sunitinib (Sutent) for pancreatic neuroendocrine tumors and lenalidomide (Revlimid) for multiple myeloma are two recent examples.

In February, researchers announced that a data-monitoring committee stopped the 171-patient sunitinib study after an analysis revealed that progression-free survival, the primary end point, was much longer in the active treatment arm.

In December 2009, a 568-patient study was not stopped, but early release of initial data showed that progression-free survival was longer in patients who received maintenance therapy with the oral drug lenalidomide after stem cell transplant than in patients who got a placebo.

“On the one hand, if the trial really is positive, then that's important information to get out there to the medical community and patients,” said Dr. Richard Schilsky, chairman of Cancer and Leukemia Group B (CALGB), which conducted the multiple myeloma trial. “On the other hand, there's this risk that you put the data out there early, and it doesn't hold up over time.”

When trials are stopped early for benefit, “typically the experimental arm is so much better than the standard arm that it is felt that it is medically and ethically necessary to announce the results before the trial is actually completed,” said Dr. Schilsky, former president of the American Society of Clinical Oncology and chief of hematology and oncology at the University of Chicago Medical Center.

One area of contention is the choice of end point that's used in a study's predefined early-stopping rules. Presumably, the primary end point of the study is used in the early stopping criteria, Dr. Schilsky said. In oncology trials, that often means progression-free survival.

But progression-free survival often is used as a surrogate for overall survival, said Dr. Jennifer Obel, a member of ASCO's cancer communications committee and an oncologist with NorthShore University HealthSystem in Illinois. Progression-free survival is quicker to measure, but whether it's clinically meaningful is unclear. Both the sunitinib and lenalidomide studies were stopped for benefits in disease progression.

“The real, meaningful end point is overall survival,” Dr. Obel said. Usually, patients who live longer do so without progression, but in some instances, drugs have prolonged progression-free survival but not overall survival.

Smaller P Values, Fewer Events

Another argument against early stopping is that it can overestimate the treatment benefit. In a systematic review of trials stopped early for benefit, researchers found that trials that accrued fewer events (that is, with end points that drove early stopping) estimated larger treatment effects (JAMA 2005;294:2203-9).

“The whole problem with this is that the effect size that we're looking for is relatively small,” said Dr. Jeffrey Crawford, chief of medical oncology at Duke University in Durham, N.C. “We're looking for a very small difference in survival in an unselected population. When you look for these small differences, the only way to really know is to have a large enough sample size that you have confidence in the result.”

Dr. Schilsky noted that “the stringency of the statistical analysis plan is important.” Early stopping often requires a much smaller P value to show significance. “It's a much higher threshold for stopping early because there are so many fewer events. You don't want to declare a trial to be positive unless the events are so unbalanced that you think it's extremely unlikely to be due to chance,” he said.

Weighing Drug Availability

Patients in the control arm pose yet another complication. If the experimental arm is better, patients who receive the control drug or regimen often gain access to the experimental drug or regimen. “Does that then potentially confound the final interpretation of the study results, because then you have a potentially significant number of patients who cross over?” Dr. Schilsky asked.

Early stopping because of efficacy is even more complicated when the experimental drug is not yet available. In that event, it's up to the manufacturer to develop a compassionate-use protocol specifying the patient population and how to administer the drug, he noted. Compassionate use allows the drug to be available to patients, even as the company is following the usual regulatory procedure for approval.

The effects of early stopping because of efficacy go far beyond the trial itself, with implications for ongoing and future studies of the same disease. “If you stop early and declare that you have a [new] standard of care, does that impact other ongoing studies that are not using that [new standard] of care arm, or does that impact the planning for the next generation of studies?” Dr. Schilsky asked. “You may find that the accrual to other ongoing trials screeches to a halt because everyone says 'this trial design is no longer relevant in light of this new information.'”

Making the Decision

Ultimately, the decision to stop a trial early is in the hands of the safety data–monitoring committee (DMC). “This sort of data release is almost always undertaken only after a very thorough review by an independent data-monitoring committee,” Dr. Schilsky said. “DMCs are in the best position to make these decisions and they do it only after lots of careful deliberation.”

Ideally, the DMC should weigh in and make a recommendation on what should be done for the patients who are in the control arm of the study, at the very least, he said.

In the case of lenalidomide for multiple myeloma, “the study was markedly positive in favor of the Revlimid maintenance, and led our data- and safety-monitoring board to recommend early release of the results,” Dr. Schilsky noted. Accrual had been completed and all patients were in follow-up, but “the study crossed a statistical boundary for early release of the data before the protocol-specified number of events for the final analysis was available.”

This process involved notifying the Food and Drug Administration, the National Cancer Institute, and the drug manufacturer, as well as developing letters for physicians and patients involved in the study, and sending out a press release. In this case, because lenalidomide is already available, oncologists could start prescribing the drug for this patient group immediately.

Advancing technology and the development of more personalized medicine may help resolve some of the issues concerning the early stopping of trials, Dr. Crawford suggested.

“What will solve this will be biomarker-directed treatment subgroups. … We can look at a much smaller sample of patients because we're looking at a much bigger effect,” he said. “In the long run, that's going to be a much better approach to oncology than continuing to treat thousands of patients with treatment A vs. B.”

Disclosures: Both Dr. Schilsky and Dr. Obel said that they have no significant financial relationships. Dr. Crawford has received research support from and been an adviser, speaker, or consultant for several pharmaceutical companies.

'There's this risk that you put the data out there early, and it doesn't hold up over time.'

Source Dr. Schilsky

Major Finding: Of all patients, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

Data Source: A study of 69 women with fibroids who underwent MRgFUS and rated their improvement.

Disclosures: Dr. Hesley reported that she has received research grant support for other studies from InSightec, which makes the ExAblate system. However, this study was not funded by outside sources.

TAMPA — Of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids, 90% reported their symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

MR-guided focused ultrasound ablation (MRgFUS) has a “reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MRgFUS, high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case, fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms, including uterine embolization, myomectomy, hysterectomy, and gonadotropin-releasing hormone agonist treatment.

The women in the study were premenopausal, had no desire to have children in the future, and had at least one uterine fibroid at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS, said Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 6 patients had hysterectomies, and 2 had myomectomies.

At 12-months' follow-up,a total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Symptom improvement with MRgFUS was comparable to myomectomy and uterine artery embolization.

Source Dr. Hesley

Major Finding: Of all patients, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

Data Source: A study of 69 women with fibroids who underwent MRgFUS and rated their improvement.

Disclosures: Dr. Hesley reported that she has received research grant support for other studies from InSightec, which makes the ExAblate system. However, this study was not funded by outside sources.

TAMPA — Of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids, 90% reported their symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

MR-guided focused ultrasound ablation (MRgFUS) has a “reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MRgFUS, high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case, fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms, including uterine embolization, myomectomy, hysterectomy, and gonadotropin-releasing hormone agonist treatment.

The women in the study were premenopausal, had no desire to have children in the future, and had at least one uterine fibroid at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS, said Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 6 patients had hysterectomies, and 2 had myomectomies.

At 12-months' follow-up,a total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Symptom improvement with MRgFUS was comparable to myomectomy and uterine artery embolization.

Source Dr. Hesley

Major Finding: Of all patients, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

Data Source: A study of 69 women with fibroids who underwent MRgFUS and rated their improvement.

Disclosures: Dr. Hesley reported that she has received research grant support for other studies from InSightec, which makes the ExAblate system. However, this study was not funded by outside sources.

TAMPA — Of women who underwent magnetic resonance–guided focused ultrasound ablation for uterine fibroids, 90% reported their symptom improvement as excellent or considerable at 12 months' follow-up, in a small study of the noninvasive treatment.

MR-guided focused ultrasound ablation (MRgFUS) has a “reported symptom improvement in patients that is very comparable to the literature for myomectomy and uterine artery embolization,” Dr. Gina K. Hesley said at the annual meeting of the Society of Interventional Radiology.

In MRgFUS, high-intensity focused ultrasound is used during an MR scan to thermally destroy pathogenic tissue—in this case, fibroids. The main advantage of MRgFUS is that the procedure is noninvasive. The concomitant use of MRI allows precise targeting of the fibroid and monitoring of the temperature increase in the fibroid tissue.

A total of 125 patients were scheduled for MRgFUS at the Mayo Clinic between March 2005 and September 2008. The researchers followed 119 patients who completed MRgFUS treatment for 12 months using phone interviews to assess symptomatic relief and any additional procedures for fibroid-related symptoms, including uterine embolization, myomectomy, hysterectomy, and gonadotropin-releasing hormone agonist treatment.

The women in the study were premenopausal, had no desire to have children in the future, and had at least one uterine fibroid at least 3 cm in diameter. Women with many uterine fibroids were counseled to have uterine embolization instead of MRgFUS, said Dr. Hesley of the department of radiology at the Mayo Clinic in Rochester, Minn.

Symptomatic improvement was self-reported based on percent improvement. The researchers considered 0%–10% improvement as insignificant, 11%–40% improvement as moderate, 41%–70% improvement as considerable, and 71%–100% as excellent.

Following treatment, 15 patients were lost to follow-up and 4 patients had their fibroids removed during surgeries performed for reasons unrelated to fibroid symptoms. Of the remaining 100 patients, 6 patients had hysterectomies, and 2 had myomectomies.

At 12-months' follow-up,a total of 69 patients rated their percent improvement. In all, 74% rated their symptom improvement as excellent, 16% as considerable, 9% as moderate, and 1% as insignificant.

The researchers have received initial approval for National Institutes of Health funding of a randomized controlled trial comparing MRgFUS and uterine embolization.

Symptom improvement with MRgFUS was comparable to myomectomy and uterine artery embolization.

Source Dr. Hesley

Major Finding: The mean age of stroke patients significantly dropped, from 71.3 years in 1993–1994 to 68.4 years in 2005.

Data Source: Population-based study of 1.3 million people in the Cincinnati/Northern Kentucky region.

Disclosures: The study is funded by the National Institute for Neurological Disorders and Stroke. The authors reported that they have no relevant financial relationships.

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993–1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993–1994 to 5.5% in 1999 and to 7.3% in 2005. (See graph for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, to identify the subtype of stroke, and to review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The linear function of the at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000. All rates were standardized to the U.S. 2000 population.

There were 1,907 strokes in 1993–1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference sponsored by the American Heart Association.

They looked at the prevalence of risk factors using data from population-based telephone surveys. Among those aged 20–44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45–54 years.

Elsevier Global Medical News

Major Finding: The mean age of stroke patients significantly dropped, from 71.3 years in 1993–1994 to 68.4 years in 2005.

Data Source: Population-based study of 1.3 million people in the Cincinnati/Northern Kentucky region.

Disclosures: The study is funded by the National Institute for Neurological Disorders and Stroke. The authors reported that they have no relevant financial relationships.

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993–1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993–1994 to 5.5% in 1999 and to 7.3% in 2005. (See graph for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, to identify the subtype of stroke, and to review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The linear function of the at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000. All rates were standardized to the U.S. 2000 population.

There were 1,907 strokes in 1993–1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference sponsored by the American Heart Association.

They looked at the prevalence of risk factors using data from population-based telephone surveys. Among those aged 20–44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45–54 years.

Elsevier Global Medical News

Major Finding: The mean age of stroke patients significantly dropped, from 71.3 years in 1993–1994 to 68.4 years in 2005.

Data Source: Population-based study of 1.3 million people in the Cincinnati/Northern Kentucky region.

Disclosures: The study is funded by the National Institute for Neurological Disorders and Stroke. The authors reported that they have no relevant financial relationships.

SAN ANTONIO — Not only is the average age of stroke patients getting significantly younger, but the proportion of young stroke patients—those younger than 45 years—is going up significantly, according to a population-based study of more than 1 million people over a 12-year period.

The average age at the time of stroke dropped from 71.3 years in 1993–1994 to 70.9 years in 1999 to 68.4 years in 2005, Dr. Brett Kissela reported at the annual International Stroke Conference. Over the same period, the percentage of stroke patients younger than 45 years went up, from 4.5% in 1993–1994 to 5.5% in 1999 and to 7.3% in 2005. (See graph for rates.)

“In the converse, in the oldest age groups … there were statistically significant declines in incidence rates,” said Dr. Kissela, professor of neurology at the University of Cincinnati.

Dr. Kissela and his coinvestigators examined data from the Greater Cincinnati/Northern Kentucky stroke study, which includes 1.3 million people in a five-county region. The region is representative of the United States in terms of age, median income, educational level, and percentage of blacks in the population.

The investigators identified patients retrospectively by using ICD-9 discharge diagnosis codes and symptom-based screening of admission logs. Potential stroke cases were identified in local hospitals, hospital-based clinics, or coroner's offices. In addition, there was a sampling of nursing homes and physician offices.

The medical record abstract for each potential case was reviewed by a study physician to determine whether to include it as a stroke, to identify the subtype of stroke, and to review imaging if necessary and available.

The same clinical case definition was used for comparisons across study periods. For the incidence rates, the numerator was the number of incident cases and the denominator was the at-risk population. The linear function of the at-risk population was calculated using U.S. Census population data for 1980, 1990, and 2000. All rates were standardized to the U.S. 2000 population.

There were 1,907 strokes in 1993–1994, 1,955 in 1999, and 1,888 in 2005. In each period, more than half (55%-58%) of the individuals who had a stroke were women. Blacks accounted for 18%-20% of the population, Dr. Kissela reported at the conference sponsored by the American Heart Association.

They looked at the prevalence of risk factors using data from population-based telephone surveys. Among those aged 20–44, both diabetes and coronary heart disease significantly increased between 1995 and 2005. The prevalence of diabetes increased from 0% to 5% and CHD increased from 0.4% to 7%. There were similar trends for hypertension and high cholesterol, although these were not significant. In contrast, there were no significant changes in these risk factors among those aged 45–54 years.

Elsevier Global Medical News

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 19 healthy controls. The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 19 healthy controls. The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

An investigational monoclonal antibody can be used to identify early-stage pancreatic cancer, researchers reported.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference in advance of presentation of the findings at the American Society of Clinical Oncology's annual gastrointestinal cancer symposium. The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said.

The researchers analyzed data on about 68 patients who had undergone surgery for pancreatic cancer, and 19 healthy controls. The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting pancreatic cancer.

The PAM4 antibody also has the potential to be part of an effective therapy. “Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, N.J.

Researchers have begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

Dr. Gold estimated that the assay and related therapies are 2-3 years from clinical use.

Disclosures: Senior author Dr. David Goldenberg is the chief scientific officer and chairman of the board of directors for Immunomedics, which develops monoclonal antibody–based treatments. Dr. Gold did not provide a disclosure statement.

My Take

Hope for Earlier Diagnosis

Early diagnosis of pancreatic cancer can lead to a 10-fold improvement of survival (about 20% 5-year surgical survival for stage I disease versus 2% for stage IV disease). The problem has always been how to identify the patient with early disease.

The recent discovery that circulating blood levels of PAM4 (quantified through use of the monoclonal antibody clivatuzumab) are “relatively unique to pancreatic cancer” and positive in 68% of those with stage I pancreatic cancer raises hopes that we will have a tool for earlier diagnosis.

We need to know more about the protein and the false-positive rates, to ensure that it is not prevalent in noncancer patients with chronic pancreatitis, diabetes mellitus, cigarette smoking, and other conditions that predispose to pancreatic cancer. That information and the development of an algorithm for assessing circulating levels of PAM4 as a screening test will be important to determining its future clinical use.

GAITHERSBURG, MD. — Black box warnings added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none in the last year, according to Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees. Event dates are either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006 when 194 event dates were reported.

This “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine), Omniscan (gadodiamide), OptiMARK (gadoversetamide), MultiHance (gadobenate dimeglumine) and ProHance (gadoteridol).

As of September 2009, 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics).

The FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out agents that increase NSF risk.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority recommended the use of Omniscan and OptiMARK be contraindicated in patients with severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language.

GAITHERSBURG, MD. — Black box warnings added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none in the last year, according to Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees. Event dates are either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006 when 194 event dates were reported.

This “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine), Omniscan (gadodiamide), OptiMARK (gadoversetamide), MultiHance (gadobenate dimeglumine) and ProHance (gadoteridol).

As of September 2009, 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics).

The FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out agents that increase NSF risk.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority recommended the use of Omniscan and OptiMARK be contraindicated in patients with severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language.

GAITHERSBURG, MD. — Black box warnings added to the labels of all gadolinium-based MRI contrast agents have reduced the number of reported nephrogenic systemic fibrosis events to almost none in the last year, according to Dr. James Kaiser.

“The numbers of new events have tapered dramatically, probably due to public awareness of the association of NSF [nephrogenic systemic fibrosis] with GBCA [gadolinium-based contrast agent] administration,” he said at a joint meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs and Drug Safety and Risk Management advisory committees. Event dates are either the date of administration of contrast or the date of diagnosis of NSF.

The FDA began receiving reports of NSF possibly being linked to gadolinium-based contrast agents in 2006 when 194 event dates were reported.

This “probably reflects awareness of the medical community of the potential connection between GBCA administration and NSF and changes in radiologic practice,” said Dr. Kaiser of the FDA's office of surveillance and epidemiology. There were 128 reported events in 2007, 55 in 2008, and 6 in 2009 (through September).

In 2007, the FDA asked manufacturers to include a boxed warning on the product labels of all gadolinium-based contrast agents.

Five gadolinium-based contrast agents have been approved for use in the United States: Magnevist (gadopentetate dimeglumine), Omniscan (gadodiamide), OptiMARK (gadoversetamide), MultiHance (gadobenate dimeglumine) and ProHance (gadoteridol).

As of September 2009, 382 reports of NSF had been associated with Omniscan (GE HealthCare), 195 with Magnevist (Bayer HealthCare), 35 with OptiMARK (Covidien), 1 with MultiHance (Bracco Diagnostics), and 0 with ProHance (Bracco Diagnostics).

The FDA asked the committees to consider whether warning labels should continue to be grouped together as a class or if there was adequate evidence to single out agents that increase NSF risk.

“The majority of the group feels that at least two of the agents appear to be different from the other agents,” said Dr. Robert A. Harrington, who chairs the Cardiovascular and Renal Drugs Advisory Committee. The majority recommended the use of Omniscan and OptiMARK be contraindicated in patients with severe kidney dysfunction. However, there was uncertainty as to how to define severe kidney dysfunction.

There was less consensus on whether a third agent, Magnevist, might also warrant contraindication language.

Physicians now have another meningococcal vaccine option, with the approval of Menveo (meningococcal [groups A, C, Y, and W-135] oligosaccharide diphtheria CRM197 conjugate vaccine) for patients aged 11-55 years.

The vaccine is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitides serogroups A, C, Y, and W-135.

The incidence of meningitis is estimated to range between 1,000 and 2,000 cases per year in the United States, according to the Centers for Disease Control and Prevention.

Meningococcal disease is a leading cause of bacterial meningitis and sepsis. Even with early treatment, the disease may be fatal.

Menveo, made by Novartis, will be supplied in packages containing five single-dose vials of the MenCYW-135 liquid conjugate component to be used to reconstitute five single-dose vials of the MenA lyophilized conjugate component.

Two meningococcal vaccines are already available in the United States. Those two vaccines are the polysaccharide vaccine MPSV4 (Menomune, Sanofi Pasteur) and the conjugate vaccine MCV4 (Menactra, Sanofi Pasteur).

The CDC's Advisory Committee on Immunization Practices recommends routine immunization with a quadravalent meningococcal conjugate vaccine for all adolescents aged 11-18 years, college freshmen living in dormitories, and those aged 2-10 and 19-55 years who are in high-risk groups.

Physicians now have another meningococcal vaccine option, with the approval of Menveo (meningococcal [groups A, C, Y, and W-135] oligosaccharide diphtheria CRM197 conjugate vaccine) for patients aged 11-55 years.

The vaccine is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitides serogroups A, C, Y, and W-135.

The incidence of meningitis is estimated to range between 1,000 and 2,000 cases per year in the United States, according to the Centers for Disease Control and Prevention.

Meningococcal disease is a leading cause of bacterial meningitis and sepsis. Even with early treatment, the disease may be fatal.

Menveo, made by Novartis, will be supplied in packages containing five single-dose vials of the MenCYW-135 liquid conjugate component to be used to reconstitute five single-dose vials of the MenA lyophilized conjugate component.

Two meningococcal vaccines are already available in the United States. Those two vaccines are the polysaccharide vaccine MPSV4 (Menomune, Sanofi Pasteur) and the conjugate vaccine MCV4 (Menactra, Sanofi Pasteur).

The CDC's Advisory Committee on Immunization Practices recommends routine immunization with a quadravalent meningococcal conjugate vaccine for all adolescents aged 11-18 years, college freshmen living in dormitories, and those aged 2-10 and 19-55 years who are in high-risk groups.

Physicians now have another meningococcal vaccine option, with the approval of Menveo (meningococcal [groups A, C, Y, and W-135] oligosaccharide diphtheria CRM197 conjugate vaccine) for patients aged 11-55 years.

The vaccine is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitides serogroups A, C, Y, and W-135.

The incidence of meningitis is estimated to range between 1,000 and 2,000 cases per year in the United States, according to the Centers for Disease Control and Prevention.

Meningococcal disease is a leading cause of bacterial meningitis and sepsis. Even with early treatment, the disease may be fatal.

Menveo, made by Novartis, will be supplied in packages containing five single-dose vials of the MenCYW-135 liquid conjugate component to be used to reconstitute five single-dose vials of the MenA lyophilized conjugate component.

Two meningococcal vaccines are already available in the United States. Those two vaccines are the polysaccharide vaccine MPSV4 (Menomune, Sanofi Pasteur) and the conjugate vaccine MCV4 (Menactra, Sanofi Pasteur).

The CDC's Advisory Committee on Immunization Practices recommends routine immunization with a quadravalent meningococcal conjugate vaccine for all adolescents aged 11-18 years, college freshmen living in dormitories, and those aged 2-10 and 19-55 years who are in high-risk groups.

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved the misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. As a way to ensure that a malignant melanoma will eventually be found, periodic total body examinations by a physician, and regular patient self-examinations, are key. He stressed that physician examinations and self–skin exams are complementary.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception. Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist; a partial biopsy not capturing the most diagnostically relevant part of the lesion; malignant melanoma being misdiagnosed as a dysplastic or spitz nevus; unrecognized desmoplastic malignant melanoma; and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed each of the following cases in detail:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, noted Dr. Marghoob.

In order to track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. In addition, dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. In addition, a partial biopsy may not be representative of the rest of the lesion. If a partial biopsy was performed, re-excise the lesion.

Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” said Dr. Marghoob. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion, which was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, said Dr. Marghoob.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised—at least in adults, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For “banal”-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, are associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, said Dr. Marghoob.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier

As can be seen from the histology, this lesion was a melanoma, but depending on the location of a partial biopsy the results can range from a Clark's nevus to melanoma in situ to microinvasive to deeply invasive melanoma.

Source Images Courtesy Dr. Ashfaq A. Marghoob

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved the misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. As a way to ensure that a malignant melanoma will eventually be found, periodic total body examinations by a physician, and regular patient self-examinations, are key. He stressed that physician examinations and self–skin exams are complementary.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception. Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist; a partial biopsy not capturing the most diagnostically relevant part of the lesion; malignant melanoma being misdiagnosed as a dysplastic or spitz nevus; unrecognized desmoplastic malignant melanoma; and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed each of the following cases in detail:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, noted Dr. Marghoob.

In order to track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. In addition, dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. In addition, a partial biopsy may not be representative of the rest of the lesion. If a partial biopsy was performed, re-excise the lesion.

Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” said Dr. Marghoob. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion, which was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, said Dr. Marghoob.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised—at least in adults, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For “banal”-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, are associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, said Dr. Marghoob.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier

As can be seen from the histology, this lesion was a melanoma, but depending on the location of a partial biopsy the results can range from a Clark's nevus to melanoma in situ to microinvasive to deeply invasive melanoma.

Source Images Courtesy Dr. Ashfaq A. Marghoob

Misdiagnosis of melanoma is a major cause of litigation against both physicians and dermatopathologists.

Of all claims between 1985 and 2001, 14% involved the misdiagnosis of melanoma, Dr. Ashfaq A. Marghoob reported at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

Furthermore, the majority of claims involving the misdiagnosis of melanoma were because of a false negative diagnosis, which may translate to a reduced chance of survival for some patients, said Dr. Marghoob, who is a dermatologist at Memorial Sloan-Kettering Cancer Center in New York.

Two important strategies can help minimize missing melanoma, he said.

First, remain vigilant and remember that many melanomas lack the classic ABCD features. “Questioning yourself and your pathologist regarding the diagnosis will help towards identifying many of these melanomas. In other words, remain skeptical of lesions lacking clinical-dermoscopy correlation or lesions lacking dermoscopy-histopathology correlation.

“Second, engage patients in their own care by having them share the responsibility of detecting early melanoma by encouraging them to examine their own skin on a regular basis,” he said.

Some melanomas may not manifest concerning features, and can mimic benign lesions. As a way to ensure that a malignant melanoma will eventually be found, periodic total body examinations by a physician, and regular patient self-examinations, are key. He stressed that physician examinations and self–skin exams are complementary.

Although it is widely accepted that early detection means better prognosis, modest delays of up to 6 months have not been shown to affect ultimate outcomes. However, there is one exception. Nodular melanoma can grow rapidly, and even small delays in diagnosis can have serious consequences.

The most common scenarios in melanoma litigation cases include nodular melanoma being misdiagnosed by a clinician or pathologist; a partial biopsy not capturing the most diagnostically relevant part of the lesion; malignant melanoma being misdiagnosed as a dysplastic or spitz nevus; unrecognized desmoplastic malignant melanoma; and metastatic malignant melanoma with an unknown primary or recurrence of melanoma (Am. J. Surg. Pathol. 2003;27:1278-83).

Dr. Marghoob discussed each of the following cases in detail:

▸ Misdiagnosis of nodular melanoma as nevus by a clinician or pathologist. Many nodular melanomas lack helpful diagnostic features, such as those in the ABCD criteria for malignant melanoma, which can lead to a misdiagnosis. However, the ABCDE criteria that take lesion evolution into account may be of some help, noted Dr. Marghoob.

In order to track lesion evolution, ask patients about the history of changes and symptoms. Total body photography may help on rare occasions to detect new lesions, some of which may be subtle. In addition, dermoscopy results may persuade the clinician to obtain a biopsy of a clinically banal–appearing lesion that is in fact a nodular melanoma.

▸ Partial biopsy issues. If a biopsy is performed of a lesion that clinically looks like melanoma and the pathology diagnosis is nevus, it is imperative that the clinician and pathologist reconcile the difference. In cases where there is discordance, consider asking for step-sectioning, special stains, or—in very rare instances—fluorescence in situ hybridization to look for signature chromosomal aberrations. In addition, a partial biopsy may not be representative of the rest of the lesion. If a partial biopsy was performed, re-excise the lesion.

Excisional biopsy is the preferred method for melanocytic lesions, when possible, because partial biopsy may sample nondiagnostic areas or miss the prognostically worse portion of the lesion.

“Partial biopsy assumes that a clinician can consistently predict the portion of a suspicious pigmented lesion that will have the worst representative histology,” said Dr. Marghoob. In one study, 40% of excised melanomas had worse pathology, compared with initial punch biopsy, and 20% of melanomas revealed invasion, which was not seen in initial punch biopsy (Arch. Dermatol. 1996;132:1297-302).

The ideal biopsy is excisional with a 2- to 3-mm margin, is oriented along the lines of lymphatic drainage, and is step sectioned. This limits sampling error, removes dysplastic nevus completely (preventing recurrence), and better predicts the Breslow depth if the lesion proves to be a melanoma, said Dr. Marghoob.

▸ Misdiagnosis of a melanoma as dysplastic or spitz nevus. When a partial biopsy reveals dysplastic or spitz nevus, it is important to completely excise the lesion. Malignant melanoma can sometimes masquerade as a spitz nevus, and focus of malignant melanoma may have been missed on the biopsy. Many dermatologists are of the opinion that spitz nevi should be completely excised—at least in adults, he said.

▸ Unrecognized desmoplastic malignant melanoma. Desmoplastic melanoma can be banal in appearance, with 70% appearing amelanotic, he said. These lesions may only present as firmness in the subcutaneous tissue. For “banal”-appearing firm lesions on chronically sun-damaged skin, suspicion should be raised if the lesions are symptomatic, growing, are associated with a lentigo maligna, or reveal irregular vessels with dermoscopy, said Dr. Marghoob.

▸ Metastatic melanoma with unknown primary or recurrence of melanoma. Whenever possible, do not remove seemingly benign lesions and discard them, he said. Also, be careful and selective about the use of liquid nitrogen or a laser on lesions that have not been confirmed to be benign through biopsy.

He noted that cases of assumed benign lesions that recur after ablation (via liquid nitrogen, curettage, or laser) may ultimately prove to be melanoma on histopathology. Furthermore, in the unlikely event that a patient develops metastatic melanoma with an unknown primary, it may be presumed that one of the ablated lesions was the primary.

Dr. Marghoob disclosed having no conflicts of interest. SDEF and this news organization are owned by Elsevier

As can be seen from the histology, this lesion was a melanoma, but depending on the location of a partial biopsy the results can range from a Clark's nevus to melanoma in situ to microinvasive to deeply invasive melanoma.

Source Images Courtesy Dr. Ashfaq A. Marghoob

PITTSBURGH — Treatment at trauma centers was associated with 70 additional life-years per 100 patients, compared with care at nontrauma centers in a large, multistate study.

Although care at a trauma center was found to be more expensive than care at a nontrauma hospital, trauma center costs were well within widely accepted benchmarks used to judge cost-effectiveness, Ellen MacKenzie, Ph.D., said at the annual meeting of the American Association for the Surgery of Trauma.

The cohort of 5,043 severely injured adult trauma patients received care in 69 hospitals in 14 states. In all, 1,085 patients died. All patients who were discharged were contacted by phone at 3 and 12 months to determine their use of health services and assess their functional status. Medical records, claims data from the Centers for Medicare and Medicaid Services, hospital bills, and patient interviews were used to calculate costs.

The researchers estimated cost-effectiveness using three standard methods: cost per life saved, cost per life-year gained, and cost per quality-adjusted life-year (QALY) gained. Using data from the National Study for Cost and Outcomes in Trauma database, they included patients who died or who sustained an injury with an Abbreviated Injury Score of at least 3.

To estimate incremental life years gained, the researchers assumed that a survivor benefit from trauma center care does not extend beyond 1 year post injury. They also discounted future life-years by the standard value of 3%. This analysis found 70 additional life-years per 100 patients in trauma versus nontrauma centers.

QALYs were calculated using adjusted values on the Short Form-16 at 3 and 12 months, together with assumptions about how function declines with age. To estimate costs, the researchers derived estimates of 1-year treatment costs using previous data, then projected lifetime costs, making some assumptions about life expectancy and ongoing medical expenditures for survivors.

The added cost of treatment in a trauma center versus a non–trauma center was found to be $36,319 per life-year gained ($790,931 per life saved) and $36,961 per QALY gained—well within the cost-effectiveness ratios of $50,000 to $100,000 per life-year gain deemed acceptable in the literature. The higher price tag associated with treatment at a trauma center is attributable largely to costs incurred during initial hospitalization.

The difference between the two types of facilities in per-lifetime patient costs was estimated to be $20,000, said Dr. MacKenzie, chair of the department of health policy and management at the Johns Hopkins University's Bloomberg School of Public Health.

The study “provides data that is likely to be critical in our efforts to persuade legislators and the public to invest in trauma systems infrastructure,” said the invited discussant for the paper, Dr. Robert C. Mackersie, professor of surgery and director of trauma services at San Francisco General Hospital.

Disclosures: Dr. MacKenzie reported that she has no relevant financial relationships.

PITTSBURGH — Treatment at trauma centers was associated with 70 additional life-years per 100 patients, compared with care at nontrauma centers in a large, multistate study.

Although care at a trauma center was found to be more expensive than care at a nontrauma hospital, trauma center costs were well within widely accepted benchmarks used to judge cost-effectiveness, Ellen MacKenzie, Ph.D., said at the annual meeting of the American Association for the Surgery of Trauma.

The cohort of 5,043 severely injured adult trauma patients received care in 69 hospitals in 14 states. In all, 1,085 patients died. All patients who were discharged were contacted by phone at 3 and 12 months to determine their use of health services and assess their functional status. Medical records, claims data from the Centers for Medicare and Medicaid Services, hospital bills, and patient interviews were used to calculate costs.

The researchers estimated cost-effectiveness using three standard methods: cost per life saved, cost per life-year gained, and cost per quality-adjusted life-year (QALY) gained. Using data from the National Study for Cost and Outcomes in Trauma database, they included patients who died or who sustained an injury with an Abbreviated Injury Score of at least 3.

To estimate incremental life years gained, the researchers assumed that a survivor benefit from trauma center care does not extend beyond 1 year post injury. They also discounted future life-years by the standard value of 3%. This analysis found 70 additional life-years per 100 patients in trauma versus nontrauma centers.

QALYs were calculated using adjusted values on the Short Form-16 at 3 and 12 months, together with assumptions about how function declines with age. To estimate costs, the researchers derived estimates of 1-year treatment costs using previous data, then projected lifetime costs, making some assumptions about life expectancy and ongoing medical expenditures for survivors.

The added cost of treatment in a trauma center versus a non–trauma center was found to be $36,319 per life-year gained ($790,931 per life saved) and $36,961 per QALY gained—well within the cost-effectiveness ratios of $50,000 to $100,000 per life-year gain deemed acceptable in the literature. The higher price tag associated with treatment at a trauma center is attributable largely to costs incurred during initial hospitalization.

The difference between the two types of facilities in per-lifetime patient costs was estimated to be $20,000, said Dr. MacKenzie, chair of the department of health policy and management at the Johns Hopkins University's Bloomberg School of Public Health.

The study “provides data that is likely to be critical in our efforts to persuade legislators and the public to invest in trauma systems infrastructure,” said the invited discussant for the paper, Dr. Robert C. Mackersie, professor of surgery and director of trauma services at San Francisco General Hospital.

Disclosures: Dr. MacKenzie reported that she has no relevant financial relationships.

PITTSBURGH — Treatment at trauma centers was associated with 70 additional life-years per 100 patients, compared with care at nontrauma centers in a large, multistate study.

Although care at a trauma center was found to be more expensive than care at a nontrauma hospital, trauma center costs were well within widely accepted benchmarks used to judge cost-effectiveness, Ellen MacKenzie, Ph.D., said at the annual meeting of the American Association for the Surgery of Trauma.

The cohort of 5,043 severely injured adult trauma patients received care in 69 hospitals in 14 states. In all, 1,085 patients died. All patients who were discharged were contacted by phone at 3 and 12 months to determine their use of health services and assess their functional status. Medical records, claims data from the Centers for Medicare and Medicaid Services, hospital bills, and patient interviews were used to calculate costs.

The researchers estimated cost-effectiveness using three standard methods: cost per life saved, cost per life-year gained, and cost per quality-adjusted life-year (QALY) gained. Using data from the National Study for Cost and Outcomes in Trauma database, they included patients who died or who sustained an injury with an Abbreviated Injury Score of at least 3.

To estimate incremental life years gained, the researchers assumed that a survivor benefit from trauma center care does not extend beyond 1 year post injury. They also discounted future life-years by the standard value of 3%. This analysis found 70 additional life-years per 100 patients in trauma versus nontrauma centers.

QALYs were calculated using adjusted values on the Short Form-16 at 3 and 12 months, together with assumptions about how function declines with age. To estimate costs, the researchers derived estimates of 1-year treatment costs using previous data, then projected lifetime costs, making some assumptions about life expectancy and ongoing medical expenditures for survivors.

The added cost of treatment in a trauma center versus a non–trauma center was found to be $36,319 per life-year gained ($790,931 per life saved) and $36,961 per QALY gained—well within the cost-effectiveness ratios of $50,000 to $100,000 per life-year gain deemed acceptable in the literature. The higher price tag associated with treatment at a trauma center is attributable largely to costs incurred during initial hospitalization.

The difference between the two types of facilities in per-lifetime patient costs was estimated to be $20,000, said Dr. MacKenzie, chair of the department of health policy and management at the Johns Hopkins University's Bloomberg School of Public Health.

The study “provides data that is likely to be critical in our efforts to persuade legislators and the public to invest in trauma systems infrastructure,” said the invited discussant for the paper, Dr. Robert C. Mackersie, professor of surgery and director of trauma services at San Francisco General Hospital.

Disclosures: Dr. MacKenzie reported that she has no relevant financial relationships.

PITTSBURGH — A simple bedside swallowing evaluation can be used to safely clear patients for oral food and drink after they have been on mechanical ventilation, and it can identify those who need additional evaluation, based on results of a prospective study of almost 300 trauma patients.

The five-step evaluation consists of the following criteria: mental status (alert or not alert), presence or absence of facial symmetry, testing for the swallowing reflex, a trial of ice chips, and a trial sip of water.

A total of 291 adult trauma patients who required intubation and mechanical ventilation were enrolled in the study between January and December 2008 at a level I trauma center. Each patient was assessed at bedside within 48 hours of separation from the ventilator, said Dr. Carlos Brown, a surgeon at the University Medical Center Brackenridge in Austin, Tex.

Patients had to meet all five requirements to pass the bedside swallowing evaluation, which led to diet advance per physician order. A patient who failed any one component remained NPO (nothing by mouth), and a repeat evaluation was performed within 48 hours. For example, a patient who could not initiate swallowing within 10 seconds after the therapist pressed gently on the anterior larynx would fail the swallowing reflex test. Three failures would result in a barium swallow test for additional evaluation, Dr. Brown said at the annual meeting of the American Association for the Surgery of Trauma.

The evaluation is was based on the Massey bedside swallowing screen used in stroke patients (J. Neurosci. Nurs. 2002;34:252–3;257–60).

The mean patient age was 38 years. The group was largely male (78%), and almost all (86%) had blunt trauma. Most of the patients (80%) were intubated because of a neurologic problem. In all, 76% were extubated and 24% had received a tracheostomy. At the first evaluation, about half (49%) passed. All patients who passed the bedside swallowing evaluation were discharged from the hospital without any aspiration events.

The researchers identified the following independent risk factors for failing the bedside swallowing evaluation: tracheostomy (21-fold increased risk), age greater than 70 years (12-fold increased risk), and ventilation longer than 72 hours (8-fold increased risk).

The failures that occurred in 148 patients were associated with mental status (24% of patients), lack of facial symmetry (2%), absence of a swallowing reflex (64%), and inability to swallow ice chips or a sip of water without obvious aspiration (8%).

Patients who failed the evaluation were older, had a lower Glasgow Coma Scale score upon admission, and had a higher Injury Severity Score—29 vs. 18 in those who passed. Brain injury, thoracic injuries, and spine and/or skull fractures were more prevalent in the failure group, but they had fewer abdominal injuries than did their counterparts. The failure group also had more craniotomies (28% vs. 8%) and more tracheostomies (45% vs. 1%).

The failure group was ventilated longer—14 days vs. 5 days. Just 23% of patients intubated for less than 72 hours failed the bedside evaluation, whereas almost 78% of those intubated for at least 72 hours failed. In addition, those who failed had more pulmonary infections during ventilation (41% vs. 8%), delirium tremens (13% vs. 3%), and cardiovascular failure (7% vs. 1%). ICU length of stay also was longer for those in the failure group (13 days vs. 4 days) as was hospital length of stay (24 days vs. 9 days).

Disclosures: Dr. Brown reported that he has no relevant financial relationships.

PITTSBURGH — A simple bedside swallowing evaluation can be used to safely clear patients for oral food and drink after they have been on mechanical ventilation, and it can identify those who need additional evaluation, based on results of a prospective study of almost 300 trauma patients.

The five-step evaluation consists of the following criteria: mental status (alert or not alert), presence or absence of facial symmetry, testing for the swallowing reflex, a trial of ice chips, and a trial sip of water.

A total of 291 adult trauma patients who required intubation and mechanical ventilation were enrolled in the study between January and December 2008 at a level I trauma center. Each patient was assessed at bedside within 48 hours of separation from the ventilator, said Dr. Carlos Brown, a surgeon at the University Medical Center Brackenridge in Austin, Tex.

Patients had to meet all five requirements to pass the bedside swallowing evaluation, which led to diet advance per physician order. A patient who failed any one component remained NPO (nothing by mouth), and a repeat evaluation was performed within 48 hours. For example, a patient who could not initiate swallowing within 10 seconds after the therapist pressed gently on the anterior larynx would fail the swallowing reflex test. Three failures would result in a barium swallow test for additional evaluation, Dr. Brown said at the annual meeting of the American Association for the Surgery of Trauma.

The evaluation is was based on the Massey bedside swallowing screen used in stroke patients (J. Neurosci. Nurs. 2002;34:252–3;257–60).

The mean patient age was 38 years. The group was largely male (78%), and almost all (86%) had blunt trauma. Most of the patients (80%) were intubated because of a neurologic problem. In all, 76% were extubated and 24% had received a tracheostomy. At the first evaluation, about half (49%) passed. All patients who passed the bedside swallowing evaluation were discharged from the hospital without any aspiration events.

The researchers identified the following independent risk factors for failing the bedside swallowing evaluation: tracheostomy (21-fold increased risk), age greater than 70 years (12-fold increased risk), and ventilation longer than 72 hours (8-fold increased risk).

The failures that occurred in 148 patients were associated with mental status (24% of patients), lack of facial symmetry (2%), absence of a swallowing reflex (64%), and inability to swallow ice chips or a sip of water without obvious aspiration (8%).

Patients who failed the evaluation were older, had a lower Glasgow Coma Scale score upon admission, and had a higher Injury Severity Score—29 vs. 18 in those who passed. Brain injury, thoracic injuries, and spine and/or skull fractures were more prevalent in the failure group, but they had fewer abdominal injuries than did their counterparts. The failure group also had more craniotomies (28% vs. 8%) and more tracheostomies (45% vs. 1%).

The failure group was ventilated longer—14 days vs. 5 days. Just 23% of patients intubated for less than 72 hours failed the bedside evaluation, whereas almost 78% of those intubated for at least 72 hours failed. In addition, those who failed had more pulmonary infections during ventilation (41% vs. 8%), delirium tremens (13% vs. 3%), and cardiovascular failure (7% vs. 1%). ICU length of stay also was longer for those in the failure group (13 days vs. 4 days) as was hospital length of stay (24 days vs. 9 days).

Disclosures: Dr. Brown reported that he has no relevant financial relationships.

PITTSBURGH — A simple bedside swallowing evaluation can be used to safely clear patients for oral food and drink after they have been on mechanical ventilation, and it can identify those who need additional evaluation, based on results of a prospective study of almost 300 trauma patients.

The five-step evaluation consists of the following criteria: mental status (alert or not alert), presence or absence of facial symmetry, testing for the swallowing reflex, a trial of ice chips, and a trial sip of water.

A total of 291 adult trauma patients who required intubation and mechanical ventilation were enrolled in the study between January and December 2008 at a level I trauma center. Each patient was assessed at bedside within 48 hours of separation from the ventilator, said Dr. Carlos Brown, a surgeon at the University Medical Center Brackenridge in Austin, Tex.

Patients had to meet all five requirements to pass the bedside swallowing evaluation, which led to diet advance per physician order. A patient who failed any one component remained NPO (nothing by mouth), and a repeat evaluation was performed within 48 hours. For example, a patient who could not initiate swallowing within 10 seconds after the therapist pressed gently on the anterior larynx would fail the swallowing reflex test. Three failures would result in a barium swallow test for additional evaluation, Dr. Brown said at the annual meeting of the American Association for the Surgery of Trauma.

The evaluation is was based on the Massey bedside swallowing screen used in stroke patients (J. Neurosci. Nurs. 2002;34:252–3;257–60).

The mean patient age was 38 years. The group was largely male (78%), and almost all (86%) had blunt trauma. Most of the patients (80%) were intubated because of a neurologic problem. In all, 76% were extubated and 24% had received a tracheostomy. At the first evaluation, about half (49%) passed. All patients who passed the bedside swallowing evaluation were discharged from the hospital without any aspiration events.

The researchers identified the following independent risk factors for failing the bedside swallowing evaluation: tracheostomy (21-fold increased risk), age greater than 70 years (12-fold increased risk), and ventilation longer than 72 hours (8-fold increased risk).

The failures that occurred in 148 patients were associated with mental status (24% of patients), lack of facial symmetry (2%), absence of a swallowing reflex (64%), and inability to swallow ice chips or a sip of water without obvious aspiration (8%).

Patients who failed the evaluation were older, had a lower Glasgow Coma Scale score upon admission, and had a higher Injury Severity Score—29 vs. 18 in those who passed. Brain injury, thoracic injuries, and spine and/or skull fractures were more prevalent in the failure group, but they had fewer abdominal injuries than did their counterparts. The failure group also had more craniotomies (28% vs. 8%) and more tracheostomies (45% vs. 1%).

The failure group was ventilated longer—14 days vs. 5 days. Just 23% of patients intubated for less than 72 hours failed the bedside evaluation, whereas almost 78% of those intubated for at least 72 hours failed. In addition, those who failed had more pulmonary infections during ventilation (41% vs. 8%), delirium tremens (13% vs. 3%), and cardiovascular failure (7% vs. 1%). ICU length of stay also was longer for those in the failure group (13 days vs. 4 days) as was hospital length of stay (24 days vs. 9 days).

Disclosures: Dr. Brown reported that he has no relevant financial relationships.