Michele G. Sullivan

RIVIERA MAYA, MEXICO — Aspirate or biopsy any breast mass discovered in a pregnant or lactating woman, because breast cancer in these patients is associated with higher mortality—probably because of delay in diagnosis, Dr. Carol Scott-Conner said at a meeting on medical negligence and risk management.

Studies show that women who are pregnant within 2 years of a breast cancer diagnosis are at a much higher risk of poor outcomes, with 50% having locally advanced or regional disease at diagnosis, compared with 39% of nonpregnant patients, said Dr. Scott-Conner, professor of surgery at the University of Iowa, Iowa City.

Reasons for diagnostic delay may include the fact that masses are more difficult to detect in engorged breasts; patient denial and physician procrastination also probably play a role. “These masses also may be confused with mastitis or other benign entities, like fibroadenoma, lactating adenoma, galactocele, or breast abscess,” she said.

Although it has not been proven, there are concerns that pregnancy-associated breast cancer may be a more aggressive form of the disease. “Many patients I see have experienced no delay in diagnosis but still have a fairly advanced tumor. We just don't know,” she said.

Most patients come in with a self-identified palpable mass. Fine-needle aspiration cytology will give valuable information for these lesions. “I'm a great believer in liberal use of FNAC,” said Dr. Scott-Conner, previous chair of surgery at the university.

“It's a benign test that's easy to do and is very helpful.” Make sure to inform the lab that the patient is pregnant or lactating, though, because normal proliferative changes can mimic neoplastic changes, she noted at the meeting, which was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Aspirate or biopsy any breast mass discovered in a pregnant or lactating woman, because breast cancer in these patients is associated with higher mortality—probably because of delay in diagnosis, Dr. Carol Scott-Conner said at a meeting on medical negligence and risk management.

Studies show that women who are pregnant within 2 years of a breast cancer diagnosis are at a much higher risk of poor outcomes, with 50% having locally advanced or regional disease at diagnosis, compared with 39% of nonpregnant patients, said Dr. Scott-Conner, professor of surgery at the University of Iowa, Iowa City.

Reasons for diagnostic delay may include the fact that masses are more difficult to detect in engorged breasts; patient denial and physician procrastination also probably play a role. “These masses also may be confused with mastitis or other benign entities, like fibroadenoma, lactating adenoma, galactocele, or breast abscess,” she said.

Although it has not been proven, there are concerns that pregnancy-associated breast cancer may be a more aggressive form of the disease. “Many patients I see have experienced no delay in diagnosis but still have a fairly advanced tumor. We just don't know,” she said.

Most patients come in with a self-identified palpable mass. Fine-needle aspiration cytology will give valuable information for these lesions. “I'm a great believer in liberal use of FNAC,” said Dr. Scott-Conner, previous chair of surgery at the university.

“It's a benign test that's easy to do and is very helpful.” Make sure to inform the lab that the patient is pregnant or lactating, though, because normal proliferative changes can mimic neoplastic changes, she noted at the meeting, which was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Aspirate or biopsy any breast mass discovered in a pregnant or lactating woman, because breast cancer in these patients is associated with higher mortality—probably because of delay in diagnosis, Dr. Carol Scott-Conner said at a meeting on medical negligence and risk management.

Studies show that women who are pregnant within 2 years of a breast cancer diagnosis are at a much higher risk of poor outcomes, with 50% having locally advanced or regional disease at diagnosis, compared with 39% of nonpregnant patients, said Dr. Scott-Conner, professor of surgery at the University of Iowa, Iowa City.

Reasons for diagnostic delay may include the fact that masses are more difficult to detect in engorged breasts; patient denial and physician procrastination also probably play a role. “These masses also may be confused with mastitis or other benign entities, like fibroadenoma, lactating adenoma, galactocele, or breast abscess,” she said.

Although it has not been proven, there are concerns that pregnancy-associated breast cancer may be a more aggressive form of the disease. “Many patients I see have experienced no delay in diagnosis but still have a fairly advanced tumor. We just don't know,” she said.

Most patients come in with a self-identified palpable mass. Fine-needle aspiration cytology will give valuable information for these lesions. “I'm a great believer in liberal use of FNAC,” said Dr. Scott-Conner, previous chair of surgery at the university.

“It's a benign test that's easy to do and is very helpful.” Make sure to inform the lab that the patient is pregnant or lactating, though, because normal proliferative changes can mimic neoplastic changes, she noted at the meeting, which was sponsored by Boston University.

RIVIERA MAYA, MEXICO — For patients with low-risk injuries, three plain-film x-rays are probably sufficient to diagnose clinically significant cervical spine injuries—but for those who have higher-risk injuries or multiple blunt traumas, a computed axial tomographic scan is often a better option.

CTs are “vastly superior” to plain radiographs in identifying cervical injuries, Dr. John Marx said at a meeting on medical negligence and risk management. “While most missed injuries are stable, it only takes one missed unstable injury” to set the stage for a serious problem, he said.

Several key studies have confirmed the usefulness of CT in this setting. One of the best was a subanalysis of the National Emergency X-Radiography Utilization Study, which included 818 patients with cervical spine injuries. About 36% of these patients, all of whom underwent radiographic studies, had a least one additional finding on the cervical spine CT, and 27% of those were not contiguous with the index injury, Dr. Marx said. Plain film also missed 33% of the cervical spine injuries that CT picked up; 74% of those missed injuries were clinically significant. (Ann. Emerg. Med. 2006;47:129–33)

“This is a real argument to go to CT if you see anything on plain film,” he said.

A 2005 study confirmed CT's usefulness in 437 unconscious, intubated blunt trauma patients, including 61 with cervical spine injuries. CT scanning had a sensitivity of 98%, a specificity of 99%, and a negative predictive value of 99.7%.

There were no missed unstable injuries. In contrast, adequate lateral cervical spine films detected only 24 injuries (14 unstable), with a sensitivity of 53.3% (J. Trauma 2005;58:897–901)

Another 2005 study retrospectively examined the effectiveness of CT scans in identifying fractures in the thoracic, lumbar, and cervical regions of 236 patients. The CT scans missed fractures in only two patients, and neither of those fractures was clinically significant (J. Trauma 2005;58:890–6).

Although CT is not an inexpensive study, it can easily prove its worth not only in cervical spine, but also in thoracolumbar injuries, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center in Charlotte, N.C.

For patients with multiple injuries, a cervical spine CT is not only better diagnostically, but “faster and probably more cost effective than trying to get the three plain film views,” Dr. Marx said.

“We have also gotten into the habit of pan-scanning the neck, head, chest, and pelvis of our very sick patients who are going to need a lot of studies. This isn't cheap—it costs about $15,000—but it's a wonderful study and seems to make sense for selected patients,” he said at the meeting sponsored by Boston University.

RIVIERA MAYA, MEXICO — For patients with low-risk injuries, three plain-film x-rays are probably sufficient to diagnose clinically significant cervical spine injuries—but for those who have higher-risk injuries or multiple blunt traumas, a computed axial tomographic scan is often a better option.

CTs are “vastly superior” to plain radiographs in identifying cervical injuries, Dr. John Marx said at a meeting on medical negligence and risk management. “While most missed injuries are stable, it only takes one missed unstable injury” to set the stage for a serious problem, he said.

Several key studies have confirmed the usefulness of CT in this setting. One of the best was a subanalysis of the National Emergency X-Radiography Utilization Study, which included 818 patients with cervical spine injuries. About 36% of these patients, all of whom underwent radiographic studies, had a least one additional finding on the cervical spine CT, and 27% of those were not contiguous with the index injury, Dr. Marx said. Plain film also missed 33% of the cervical spine injuries that CT picked up; 74% of those missed injuries were clinically significant. (Ann. Emerg. Med. 2006;47:129–33)

“This is a real argument to go to CT if you see anything on plain film,” he said.

A 2005 study confirmed CT's usefulness in 437 unconscious, intubated blunt trauma patients, including 61 with cervical spine injuries. CT scanning had a sensitivity of 98%, a specificity of 99%, and a negative predictive value of 99.7%.

There were no missed unstable injuries. In contrast, adequate lateral cervical spine films detected only 24 injuries (14 unstable), with a sensitivity of 53.3% (J. Trauma 2005;58:897–901)

Another 2005 study retrospectively examined the effectiveness of CT scans in identifying fractures in the thoracic, lumbar, and cervical regions of 236 patients. The CT scans missed fractures in only two patients, and neither of those fractures was clinically significant (J. Trauma 2005;58:890–6).

Although CT is not an inexpensive study, it can easily prove its worth not only in cervical spine, but also in thoracolumbar injuries, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center in Charlotte, N.C.

For patients with multiple injuries, a cervical spine CT is not only better diagnostically, but “faster and probably more cost effective than trying to get the three plain film views,” Dr. Marx said.

“We have also gotten into the habit of pan-scanning the neck, head, chest, and pelvis of our very sick patients who are going to need a lot of studies. This isn't cheap—it costs about $15,000—but it's a wonderful study and seems to make sense for selected patients,” he said at the meeting sponsored by Boston University.

RIVIERA MAYA, MEXICO — For patients with low-risk injuries, three plain-film x-rays are probably sufficient to diagnose clinically significant cervical spine injuries—but for those who have higher-risk injuries or multiple blunt traumas, a computed axial tomographic scan is often a better option.

CTs are “vastly superior” to plain radiographs in identifying cervical injuries, Dr. John Marx said at a meeting on medical negligence and risk management. “While most missed injuries are stable, it only takes one missed unstable injury” to set the stage for a serious problem, he said.

Several key studies have confirmed the usefulness of CT in this setting. One of the best was a subanalysis of the National Emergency X-Radiography Utilization Study, which included 818 patients with cervical spine injuries. About 36% of these patients, all of whom underwent radiographic studies, had a least one additional finding on the cervical spine CT, and 27% of those were not contiguous with the index injury, Dr. Marx said. Plain film also missed 33% of the cervical spine injuries that CT picked up; 74% of those missed injuries were clinically significant. (Ann. Emerg. Med. 2006;47:129–33)

“This is a real argument to go to CT if you see anything on plain film,” he said.

A 2005 study confirmed CT's usefulness in 437 unconscious, intubated blunt trauma patients, including 61 with cervical spine injuries. CT scanning had a sensitivity of 98%, a specificity of 99%, and a negative predictive value of 99.7%.

There were no missed unstable injuries. In contrast, adequate lateral cervical spine films detected only 24 injuries (14 unstable), with a sensitivity of 53.3% (J. Trauma 2005;58:897–901)

Another 2005 study retrospectively examined the effectiveness of CT scans in identifying fractures in the thoracic, lumbar, and cervical regions of 236 patients. The CT scans missed fractures in only two patients, and neither of those fractures was clinically significant (J. Trauma 2005;58:890–6).

Although CT is not an inexpensive study, it can easily prove its worth not only in cervical spine, but also in thoracolumbar injuries, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center in Charlotte, N.C.

For patients with multiple injuries, a cervical spine CT is not only better diagnostically, but “faster and probably more cost effective than trying to get the three plain film views,” Dr. Marx said.

“We have also gotten into the habit of pan-scanning the neck, head, chest, and pelvis of our very sick patients who are going to need a lot of studies. This isn't cheap—it costs about $15,000—but it's a wonderful study and seems to make sense for selected patients,” he said at the meeting sponsored by Boston University.

RIVIERA MAYA, MEXICO — To avoid missing an acute myocardial infarction, look beyond the elephant in the emergency department.

“The old 'elephant on my chest' story of the classic … is the one that we love,” Dr. John Marx said at a meeting on medical negligence and risk management.

But up to 40% of patients with acute myocardial infarction come to the ED with atypical presentations, including a normal or nondiagnostic electrocardiogram or with a complete absence of chest pain.

In fact, many patients complain only of anginal equivalents—nonspecific symptoms that may go unrecognized as red flags for a heart attack, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center and professor of emergency medicine at the University of North Carolina at Chapel Hill.

“Perhaps they may just be short of breath, weak, nauseated, and sweaty, which is very typical [of MI] in those with long-standing diabetes. These are extraordinarily general symptoms and very problematic for us,” he said.

Atypical presentations, along with ECG misses, make heady opportunities for plaintiffs' lawyers, Dr. Marx said at the meeting, which was sponsored by Boston University. “Three to five percent of acute MIs are sent home from the emergency department, and these account for 26% of malpractice losses in emergency medicine. The average award in these cases is about $981,000.”

Anginal equivalents are most common in elderly patients (up to 70% of those over age 85); those with long-standing insulin-dependent diabetes (40% vs. 25% of those without diabetes); women (up to 60% in some series); nonwhite patients; and those with no risk factors for heart attack.

These patients require risk stratification, multiple sets of enzyme studies performed at least 6 hours apart, and continuous ST-T monitoring, Dr. Marx said.

“Never rely on a single set of enzyme studies,” he warned. “If you do, you are harming yourself two ways: First, you have established on the chart that you're worried [about an MI], and second, you've failed to exclude that possibility by ordering only one set of tests.”

If both sets of enzymes are normal and the continuous ST-T monitoring is negative, you can safely submit that patient to provocative testing, either immediately or, if the patient is very low risk, within 5 days.

Don't overrely on the ECG, Dr. Marx stressed. “A normal or unchanged [ECG] does not rule out a diagnosis of MI or unstable angina. It may be helpful if you can get a look at some previous [ECGs] for comparison.”

RIVIERA MAYA, MEXICO — To avoid missing an acute myocardial infarction, look beyond the elephant in the emergency department.

“The old 'elephant on my chest' story of the classic … is the one that we love,” Dr. John Marx said at a meeting on medical negligence and risk management.

But up to 40% of patients with acute myocardial infarction come to the ED with atypical presentations, including a normal or nondiagnostic electrocardiogram or with a complete absence of chest pain.

In fact, many patients complain only of anginal equivalents—nonspecific symptoms that may go unrecognized as red flags for a heart attack, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center and professor of emergency medicine at the University of North Carolina at Chapel Hill.

“Perhaps they may just be short of breath, weak, nauseated, and sweaty, which is very typical [of MI] in those with long-standing diabetes. These are extraordinarily general symptoms and very problematic for us,” he said.

Atypical presentations, along with ECG misses, make heady opportunities for plaintiffs' lawyers, Dr. Marx said at the meeting, which was sponsored by Boston University. “Three to five percent of acute MIs are sent home from the emergency department, and these account for 26% of malpractice losses in emergency medicine. The average award in these cases is about $981,000.”

Anginal equivalents are most common in elderly patients (up to 70% of those over age 85); those with long-standing insulin-dependent diabetes (40% vs. 25% of those without diabetes); women (up to 60% in some series); nonwhite patients; and those with no risk factors for heart attack.

These patients require risk stratification, multiple sets of enzyme studies performed at least 6 hours apart, and continuous ST-T monitoring, Dr. Marx said.

“Never rely on a single set of enzyme studies,” he warned. “If you do, you are harming yourself two ways: First, you have established on the chart that you're worried [about an MI], and second, you've failed to exclude that possibility by ordering only one set of tests.”

If both sets of enzymes are normal and the continuous ST-T monitoring is negative, you can safely submit that patient to provocative testing, either immediately or, if the patient is very low risk, within 5 days.

Don't overrely on the ECG, Dr. Marx stressed. “A normal or unchanged [ECG] does not rule out a diagnosis of MI or unstable angina. It may be helpful if you can get a look at some previous [ECGs] for comparison.”

RIVIERA MAYA, MEXICO — To avoid missing an acute myocardial infarction, look beyond the elephant in the emergency department.

“The old 'elephant on my chest' story of the classic … is the one that we love,” Dr. John Marx said at a meeting on medical negligence and risk management.

But up to 40% of patients with acute myocardial infarction come to the ED with atypical presentations, including a normal or nondiagnostic electrocardiogram or with a complete absence of chest pain.

In fact, many patients complain only of anginal equivalents—nonspecific symptoms that may go unrecognized as red flags for a heart attack, said Dr. Marx, chair of emergency medicine at the Carolinas Medical Center and professor of emergency medicine at the University of North Carolina at Chapel Hill.

“Perhaps they may just be short of breath, weak, nauseated, and sweaty, which is very typical [of MI] in those with long-standing diabetes. These are extraordinarily general symptoms and very problematic for us,” he said.

Atypical presentations, along with ECG misses, make heady opportunities for plaintiffs' lawyers, Dr. Marx said at the meeting, which was sponsored by Boston University. “Three to five percent of acute MIs are sent home from the emergency department, and these account for 26% of malpractice losses in emergency medicine. The average award in these cases is about $981,000.”

Anginal equivalents are most common in elderly patients (up to 70% of those over age 85); those with long-standing insulin-dependent diabetes (40% vs. 25% of those without diabetes); women (up to 60% in some series); nonwhite patients; and those with no risk factors for heart attack.

These patients require risk stratification, multiple sets of enzyme studies performed at least 6 hours apart, and continuous ST-T monitoring, Dr. Marx said.

“Never rely on a single set of enzyme studies,” he warned. “If you do, you are harming yourself two ways: First, you have established on the chart that you're worried [about an MI], and second, you've failed to exclude that possibility by ordering only one set of tests.”

If both sets of enzymes are normal and the continuous ST-T monitoring is negative, you can safely submit that patient to provocative testing, either immediately or, if the patient is very low risk, within 5 days.

Don't overrely on the ECG, Dr. Marx stressed. “A normal or unchanged [ECG] does not rule out a diagnosis of MI or unstable angina. It may be helpful if you can get a look at some previous [ECGs] for comparison.”

The continued decline in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

A concentrated push to increase screening to 80%—the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

National surveys show that each year, about half of U.S. citizens eligible for screening undergo the test. But despite the steady decreases in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

Dr. Sidney Winawer, a gastroenterologist who holds the Paul Sherlock Chair at Memorial Sloan Kettering Cancer Center, New York, agreed.

“We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month].”

The American Cancer Society's latest report on U.S. trends says about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decline since 1985. But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, the report says.

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers—gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

He envisions a message with three components: family history, gender equality, and minimizing fear. “We have to emphasize that the risks are equal for men and women. … It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

But advances in treatment also play a very strong role here, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York.

“Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Screening and treatment are undoubtedly the biggest contributors to the steady decrease in colorectal cancer, the physicians said. But other factors are at work, exerting a smaller effect or one that is difficult to extrapolate. “Lifestyle changes have probably played a part,” he said. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. Advances in the comfort and accuracy of screening will combine to make it a more acceptable option for more people, they predicted.

“We are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography (CTC) will make imaging studies much more acceptable to a wider pool of patients.

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care.”

Education of patients and physicians is key, he said. It's unreasonable to expect every primary care physician to spend 5 minutes discussing screening with every eligible patient, but “it's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

GI Cancer Trends Detailed in Report

The American Cancer Society's 2007 report highlighted trends not only in colorectal cancer but also in other gastrointestinal cancers.

Gastric cancer fell slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

There have been no significant improvements at all in pancreatic cancer incidence or mortality, the report noted. The report predicts 33,000 deaths, equally divided between the genders, for 2007. The small declines that have occurred are probably related to a general decrease in smoking, said Dr. Neugut.

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the vast majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, said Dr. Neugut.

The continued decline in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

A concentrated push to increase screening to 80%—the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

National surveys show that each year, about half of U.S. citizens eligible for screening undergo the test. But despite the steady decreases in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

Dr. Sidney Winawer, a gastroenterologist who holds the Paul Sherlock Chair at Memorial Sloan Kettering Cancer Center, New York, agreed.

“We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month].”

The American Cancer Society's latest report on U.S. trends says about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decline since 1985. But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, the report says.

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers—gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

He envisions a message with three components: family history, gender equality, and minimizing fear. “We have to emphasize that the risks are equal for men and women. … It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

But advances in treatment also play a very strong role here, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York.

“Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Screening and treatment are undoubtedly the biggest contributors to the steady decrease in colorectal cancer, the physicians said. But other factors are at work, exerting a smaller effect or one that is difficult to extrapolate. “Lifestyle changes have probably played a part,” he said. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. Advances in the comfort and accuracy of screening will combine to make it a more acceptable option for more people, they predicted.

“We are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography (CTC) will make imaging studies much more acceptable to a wider pool of patients.

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care.”

Education of patients and physicians is key, he said. It's unreasonable to expect every primary care physician to spend 5 minutes discussing screening with every eligible patient, but “it's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

GI Cancer Trends Detailed in Report

The American Cancer Society's 2007 report highlighted trends not only in colorectal cancer but also in other gastrointestinal cancers.

Gastric cancer fell slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

There have been no significant improvements at all in pancreatic cancer incidence or mortality, the report noted. The report predicts 33,000 deaths, equally divided between the genders, for 2007. The small declines that have occurred are probably related to a general decrease in smoking, said Dr. Neugut.

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the vast majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, said Dr. Neugut.

The continued decline in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

A concentrated push to increase screening to 80%—the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

National surveys show that each year, about half of U.S. citizens eligible for screening undergo the test. But despite the steady decreases in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

Dr. Sidney Winawer, a gastroenterologist who holds the Paul Sherlock Chair at Memorial Sloan Kettering Cancer Center, New York, agreed.

“We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month].”

The American Cancer Society's latest report on U.S. trends says about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decline since 1985. But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, the report says.

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers—gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

He envisions a message with three components: family history, gender equality, and minimizing fear. “We have to emphasize that the risks are equal for men and women. … It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

But advances in treatment also play a very strong role here, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York.

“Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Screening and treatment are undoubtedly the biggest contributors to the steady decrease in colorectal cancer, the physicians said. But other factors are at work, exerting a smaller effect or one that is difficult to extrapolate. “Lifestyle changes have probably played a part,” he said. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. Advances in the comfort and accuracy of screening will combine to make it a more acceptable option for more people, they predicted.

“We are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography (CTC) will make imaging studies much more acceptable to a wider pool of patients.

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care.”

Education of patients and physicians is key, he said. It's unreasonable to expect every primary care physician to spend 5 minutes discussing screening with every eligible patient, but “it's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

GI Cancer Trends Detailed in Report

The American Cancer Society's 2007 report highlighted trends not only in colorectal cancer but also in other gastrointestinal cancers.

Gastric cancer fell slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

There have been no significant improvements at all in pancreatic cancer incidence or mortality, the report noted. The report predicts 33,000 deaths, equally divided between the genders, for 2007. The small declines that have occurred are probably related to a general decrease in smoking, said Dr. Neugut.

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the vast majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, said Dr. Neugut.

SAN ANTONIO — Ibandronate seems to be easier on the kidneys than are other bisphosphonates in cancer patients who take the drugs for bone metastases, and may even help normalize renal function in patients whose kidneys declined with zoledronic acid treatment.

The studies, presented at the Sixth International Meeting on Cancer-Induced Bone Disease, suggest that the drug may be living up to its clinical trial promises, Dr. Jörg Seraphin said.

“These data suggest that the renal safety profile of ibandronate in phase III trials transfers to actual clinical practice,” he wrote in a poster at the meeting, which was sponsored by the Cancer and Bone Society.

Dr. Seraphin presented initial results from a 24-week observational study conducted in 157 centers in Germany. The analysis included 913 patients with breast cancer that had spread to bone; the study is expected to enroll 1,500 patients.

All of the women received ibandronate, with 88% receiving standard intravenous therapy (6 mg every 2 weeks), 10% receiving oral therapy (50 mg per day), and 2% receiving both IV and oral ibandronate. Most of the patients (549) had not taken any previous bisphosphonates, 93 had previously taken ibandronate, and 271 had previously received other drugs in the class.

Patients had serum creatinine measures taken at baseline and at 24 weeks. Patients and physicians also rated tolerability for both forms of ibandronate.

At baseline, patients who had previously received other bisphosphonates had slightly—but not significantly—higher serum creatinine levels. During treatment, the mean values remained stable among all three groups. However, the maximum creatinine increase in the group previously treated with other bisphosphonates was four times higher (4.2 mg/dL) than the maximum increase in the bisphosphonate-naive or prior-ibandronate groups (1.2 mg/dL and 1 mg/dL, respectively).

“This effect is likely due to the renal toxicity of other bisphosphonates, which have been confirmed in other studies,” wrote Dr. Seraphin, a hematologic oncologist in a joint practice in Northeim, Germany.

Almost all physicians (98%) and patients (96%) rated ibandronate's tolerability as good or very good. The drug was also effective in maintaining bone: 90% of patients did not have a fracture during the study.

A retrospective study hinted that switching to ibandronate could help normalize impaired kidney function associated with zoledronic acid treatment in cancer patients with bone metastases. The study—by Dr. Ingo Diel of the Institute for Gynecological Oncology, Mannheim, Germany—included 106 patients. Of these, 72 received ibandronate monotherapy, and 34 were switched to ibandronate from zoledronic acid, most (65%) because of impaired renal function.

The patients' average age was 65 years; 61 had breast cancer, 38 had multiple myeloma, 3 had non-small cell lung carcinoma, and 4 had prostate cancer. In both treatment groups, the mean baseline serum creatinine level was 1 mg/dL and the mean glomerular filtration rate was 75 mL/min per 1.73 m

Compared with ibandronate-only patients, patients in the switch group were more than seven times as likely to have an increased serum creatinine level, and more than four times as likely to have an impaired glomerular filtration rate.

However, the incidence of these markers of impaired renal function tended to decrease with longer ibandronate treatment, Dr. Diel said. Switching patients showed a significant increase in serum creatinine levels during their zoledronic acid treatment period (1 mg/dL to 1.4 mg/dL), which declined linearly to just over 1 mg/dL by 24 months of ibandronate treatment.

There was a potential survival bias in this evaluation, Dr. Diel noted. “Patients who survived for longer periods were more likely to have better renal function attributable to their overall condition, and not due to bisphosphonate treatment.”

Serum creatinine levels remained stable over 24 months in the ibandronate-only patients, he added.

“These results suggest that treatment with zoledronic acid may be associated with renal deterioration, which may recover over time when the patient is switched to ibandronate. It warrants future investigation whether initiating treatment with ibandronate rather than zoledronic acid limits renal deterioration.”

SAN ANTONIO — Ibandronate seems to be easier on the kidneys than are other bisphosphonates in cancer patients who take the drugs for bone metastases, and may even help normalize renal function in patients whose kidneys declined with zoledronic acid treatment.

The studies, presented at the Sixth International Meeting on Cancer-Induced Bone Disease, suggest that the drug may be living up to its clinical trial promises, Dr. Jörg Seraphin said.

“These data suggest that the renal safety profile of ibandronate in phase III trials transfers to actual clinical practice,” he wrote in a poster at the meeting, which was sponsored by the Cancer and Bone Society.

Dr. Seraphin presented initial results from a 24-week observational study conducted in 157 centers in Germany. The analysis included 913 patients with breast cancer that had spread to bone; the study is expected to enroll 1,500 patients.

All of the women received ibandronate, with 88% receiving standard intravenous therapy (6 mg every 2 weeks), 10% receiving oral therapy (50 mg per day), and 2% receiving both IV and oral ibandronate. Most of the patients (549) had not taken any previous bisphosphonates, 93 had previously taken ibandronate, and 271 had previously received other drugs in the class.

Patients had serum creatinine measures taken at baseline and at 24 weeks. Patients and physicians also rated tolerability for both forms of ibandronate.

At baseline, patients who had previously received other bisphosphonates had slightly—but not significantly—higher serum creatinine levels. During treatment, the mean values remained stable among all three groups. However, the maximum creatinine increase in the group previously treated with other bisphosphonates was four times higher (4.2 mg/dL) than the maximum increase in the bisphosphonate-naive or prior-ibandronate groups (1.2 mg/dL and 1 mg/dL, respectively).

“This effect is likely due to the renal toxicity of other bisphosphonates, which have been confirmed in other studies,” wrote Dr. Seraphin, a hematologic oncologist in a joint practice in Northeim, Germany.

Almost all physicians (98%) and patients (96%) rated ibandronate's tolerability as good or very good. The drug was also effective in maintaining bone: 90% of patients did not have a fracture during the study.

A retrospective study hinted that switching to ibandronate could help normalize impaired kidney function associated with zoledronic acid treatment in cancer patients with bone metastases. The study—by Dr. Ingo Diel of the Institute for Gynecological Oncology, Mannheim, Germany—included 106 patients. Of these, 72 received ibandronate monotherapy, and 34 were switched to ibandronate from zoledronic acid, most (65%) because of impaired renal function.

The patients' average age was 65 years; 61 had breast cancer, 38 had multiple myeloma, 3 had non-small cell lung carcinoma, and 4 had prostate cancer. In both treatment groups, the mean baseline serum creatinine level was 1 mg/dL and the mean glomerular filtration rate was 75 mL/min per 1.73 m

Compared with ibandronate-only patients, patients in the switch group were more than seven times as likely to have an increased serum creatinine level, and more than four times as likely to have an impaired glomerular filtration rate.

However, the incidence of these markers of impaired renal function tended to decrease with longer ibandronate treatment, Dr. Diel said. Switching patients showed a significant increase in serum creatinine levels during their zoledronic acid treatment period (1 mg/dL to 1.4 mg/dL), which declined linearly to just over 1 mg/dL by 24 months of ibandronate treatment.

There was a potential survival bias in this evaluation, Dr. Diel noted. “Patients who survived for longer periods were more likely to have better renal function attributable to their overall condition, and not due to bisphosphonate treatment.”

Serum creatinine levels remained stable over 24 months in the ibandronate-only patients, he added.

“These results suggest that treatment with zoledronic acid may be associated with renal deterioration, which may recover over time when the patient is switched to ibandronate. It warrants future investigation whether initiating treatment with ibandronate rather than zoledronic acid limits renal deterioration.”

SAN ANTONIO — Ibandronate seems to be easier on the kidneys than are other bisphosphonates in cancer patients who take the drugs for bone metastases, and may even help normalize renal function in patients whose kidneys declined with zoledronic acid treatment.

The studies, presented at the Sixth International Meeting on Cancer-Induced Bone Disease, suggest that the drug may be living up to its clinical trial promises, Dr. Jörg Seraphin said.

“These data suggest that the renal safety profile of ibandronate in phase III trials transfers to actual clinical practice,” he wrote in a poster at the meeting, which was sponsored by the Cancer and Bone Society.

Dr. Seraphin presented initial results from a 24-week observational study conducted in 157 centers in Germany. The analysis included 913 patients with breast cancer that had spread to bone; the study is expected to enroll 1,500 patients.

All of the women received ibandronate, with 88% receiving standard intravenous therapy (6 mg every 2 weeks), 10% receiving oral therapy (50 mg per day), and 2% receiving both IV and oral ibandronate. Most of the patients (549) had not taken any previous bisphosphonates, 93 had previously taken ibandronate, and 271 had previously received other drugs in the class.

Patients had serum creatinine measures taken at baseline and at 24 weeks. Patients and physicians also rated tolerability for both forms of ibandronate.

At baseline, patients who had previously received other bisphosphonates had slightly—but not significantly—higher serum creatinine levels. During treatment, the mean values remained stable among all three groups. However, the maximum creatinine increase in the group previously treated with other bisphosphonates was four times higher (4.2 mg/dL) than the maximum increase in the bisphosphonate-naive or prior-ibandronate groups (1.2 mg/dL and 1 mg/dL, respectively).

“This effect is likely due to the renal toxicity of other bisphosphonates, which have been confirmed in other studies,” wrote Dr. Seraphin, a hematologic oncologist in a joint practice in Northeim, Germany.

Almost all physicians (98%) and patients (96%) rated ibandronate's tolerability as good or very good. The drug was also effective in maintaining bone: 90% of patients did not have a fracture during the study.

A retrospective study hinted that switching to ibandronate could help normalize impaired kidney function associated with zoledronic acid treatment in cancer patients with bone metastases. The study—by Dr. Ingo Diel of the Institute for Gynecological Oncology, Mannheim, Germany—included 106 patients. Of these, 72 received ibandronate monotherapy, and 34 were switched to ibandronate from zoledronic acid, most (65%) because of impaired renal function.

The patients' average age was 65 years; 61 had breast cancer, 38 had multiple myeloma, 3 had non-small cell lung carcinoma, and 4 had prostate cancer. In both treatment groups, the mean baseline serum creatinine level was 1 mg/dL and the mean glomerular filtration rate was 75 mL/min per 1.73 m

Compared with ibandronate-only patients, patients in the switch group were more than seven times as likely to have an increased serum creatinine level, and more than four times as likely to have an impaired glomerular filtration rate.

However, the incidence of these markers of impaired renal function tended to decrease with longer ibandronate treatment, Dr. Diel said. Switching patients showed a significant increase in serum creatinine levels during their zoledronic acid treatment period (1 mg/dL to 1.4 mg/dL), which declined linearly to just over 1 mg/dL by 24 months of ibandronate treatment.

There was a potential survival bias in this evaluation, Dr. Diel noted. “Patients who survived for longer periods were more likely to have better renal function attributable to their overall condition, and not due to bisphosphonate treatment.”

Serum creatinine levels remained stable over 24 months in the ibandronate-only patients, he added.

“These results suggest that treatment with zoledronic acid may be associated with renal deterioration, which may recover over time when the patient is switched to ibandronate. It warrants future investigation whether initiating treatment with ibandronate rather than zoledronic acid limits renal deterioration.”

RIVIERA MAYA, MEXICO — Women whose ejection fraction remains less than 50% after a diagnosis of peripartum cardiomyopathy face a significantly increased risk of cardiac deterioration and death with any subsequent pregnancies, Dr. Bernard Gonik said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“We know that the patient whose echocardiogram has not normalized within 6 months has a very poor prognosis in terms of future pregnancy,” said Dr. Gonik, the Fann Srere Endowed Chair in Perinatal Medicine at Wayne State University, Detroit.

“Of these women, 50% will have symptoms during a subsequent pregnancy, 33% will experience deterioration of cardiac function, 42% will have persistent cardiomyopathy, and 25% will die.”

These numbers are based on a 2001 review published in the New England Journal of Medicine. That article discussed outcomes in 92 women with the disorder who had a subsequent pregnancy. The article also identified the very poor prognosis for the 20% of women whose cardiac function does not normalize within a period of 6 months postpartum (N. Engl. J. Med. 2001;344:1567–71).

“The prognosis for these women is really bad, with up to 85% dying by 5 years,” Dr. Gonik said at the meeting, sponsored by Boston University. “Almost half of these deaths will occur within the first 6 months post partum.”

Conversely, among women with ejection fractions of more than 50%, only 6% had symptoms with a subsequent pregnancy, 17% deteriorated, 9% had persistent cardiomyopathy, and none died.

Peripartum cardiomyopathy is defined as the development of heart failure during the last month of pregnancy or within 3 months of delivery, in the absence of preexisting heart disease and with no other known cause, Dr. Gonik said.

The condition occurs in about 1 in 5,000 pregnancies. The etiology is unknown.

Risk factors include multiparity, advanced maternal age, twins, preeclampsia, hypertension, and black race.

RIVIERA MAYA, MEXICO — Women whose ejection fraction remains less than 50% after a diagnosis of peripartum cardiomyopathy face a significantly increased risk of cardiac deterioration and death with any subsequent pregnancies, Dr. Bernard Gonik said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“We know that the patient whose echocardiogram has not normalized within 6 months has a very poor prognosis in terms of future pregnancy,” said Dr. Gonik, the Fann Srere Endowed Chair in Perinatal Medicine at Wayne State University, Detroit.

“Of these women, 50% will have symptoms during a subsequent pregnancy, 33% will experience deterioration of cardiac function, 42% will have persistent cardiomyopathy, and 25% will die.”

These numbers are based on a 2001 review published in the New England Journal of Medicine. That article discussed outcomes in 92 women with the disorder who had a subsequent pregnancy. The article also identified the very poor prognosis for the 20% of women whose cardiac function does not normalize within a period of 6 months postpartum (N. Engl. J. Med. 2001;344:1567–71).

“The prognosis for these women is really bad, with up to 85% dying by 5 years,” Dr. Gonik said at the meeting, sponsored by Boston University. “Almost half of these deaths will occur within the first 6 months post partum.”

Conversely, among women with ejection fractions of more than 50%, only 6% had symptoms with a subsequent pregnancy, 17% deteriorated, 9% had persistent cardiomyopathy, and none died.

Peripartum cardiomyopathy is defined as the development of heart failure during the last month of pregnancy or within 3 months of delivery, in the absence of preexisting heart disease and with no other known cause, Dr. Gonik said.

The condition occurs in about 1 in 5,000 pregnancies. The etiology is unknown.

Risk factors include multiparity, advanced maternal age, twins, preeclampsia, hypertension, and black race.

RIVIERA MAYA, MEXICO — Women whose ejection fraction remains less than 50% after a diagnosis of peripartum cardiomyopathy face a significantly increased risk of cardiac deterioration and death with any subsequent pregnancies, Dr. Bernard Gonik said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“We know that the patient whose echocardiogram has not normalized within 6 months has a very poor prognosis in terms of future pregnancy,” said Dr. Gonik, the Fann Srere Endowed Chair in Perinatal Medicine at Wayne State University, Detroit.

“Of these women, 50% will have symptoms during a subsequent pregnancy, 33% will experience deterioration of cardiac function, 42% will have persistent cardiomyopathy, and 25% will die.”

These numbers are based on a 2001 review published in the New England Journal of Medicine. That article discussed outcomes in 92 women with the disorder who had a subsequent pregnancy. The article also identified the very poor prognosis for the 20% of women whose cardiac function does not normalize within a period of 6 months postpartum (N. Engl. J. Med. 2001;344:1567–71).

“The prognosis for these women is really bad, with up to 85% dying by 5 years,” Dr. Gonik said at the meeting, sponsored by Boston University. “Almost half of these deaths will occur within the first 6 months post partum.”

Conversely, among women with ejection fractions of more than 50%, only 6% had symptoms with a subsequent pregnancy, 17% deteriorated, 9% had persistent cardiomyopathy, and none died.

Peripartum cardiomyopathy is defined as the development of heart failure during the last month of pregnancy or within 3 months of delivery, in the absence of preexisting heart disease and with no other known cause, Dr. Gonik said.

The condition occurs in about 1 in 5,000 pregnancies. The etiology is unknown.

Risk factors include multiparity, advanced maternal age, twins, preeclampsia, hypertension, and black race.

PITTSBURGH — Preoperative neurologic and genetic work-ups may detect a previously unsuspected cause of cardiac disease in children about to receive a heart transplant, Dr. Debabrata Ghosh reported in a poster at the annual meeting of the Child Neurology Society.

“The presence of neurologic or genetic diseases should never be an absolute contraindication to heart transplant for these children,” Dr. Ghosh said in an interview. “In our study, all 10 of the children with neurologic or genetic etiologies were alive and well at 4 years' follow-up.”

His retrospective study examined 4-year outcomes in 40 children who underwent 41 heart transplants at a mean age of 9 years. All received pretransplant and posttransplant neurologic evaluations; those with idiopathic cardiomyopathies were evaluated before surgery for possible neurologic, neuromuscular, metabolic, or genetic cardiac etiologies.

Structural heart disease was present in 13 children. Of those with nonstructural congenital heart disease, 23 had cardiomyopathy, and of those, 10 (43%) had a definitive etiology, with neuromuscular and neurometabolic conditions accounting for most causes.

Neuromuscular disease was found in five: Two (twins) had dilated cardiomyopathy secondary to Emery-Dreifuss muscular dystrophy, one had Friedreich's ataxia with dilated cardiomyopathy, one had myofibrillar (desmin) myopathy with hypertrophic cardiomyopathy and arrhythmia, and one had an autosomal recessive form of limb-girdle muscular dystrophy.

Neurometabolic disease was found in two children: One had mitochondrial cytopathy (complex III deficiency), and one had a suspected fatty acid oxidation defect with dilated cardiomyopathy.

The other three children had genetic cardiac disorders, including arrhythmogenic right ventricular dysplasia, X-linked dilated cardiomyopathy, and autosomal dominant cardiomyopathy.

Of the entire group, 93% were alive at 1 year after surgery and 90% were still alive 4 years later, including all 10 children with neurologic or genetic causes of their heart disease, said Dr. Ghosh of the Cleveland Clinic Foundation.

PITTSBURGH — Preoperative neurologic and genetic work-ups may detect a previously unsuspected cause of cardiac disease in children about to receive a heart transplant, Dr. Debabrata Ghosh reported in a poster at the annual meeting of the Child Neurology Society.

“The presence of neurologic or genetic diseases should never be an absolute contraindication to heart transplant for these children,” Dr. Ghosh said in an interview. “In our study, all 10 of the children with neurologic or genetic etiologies were alive and well at 4 years' follow-up.”

His retrospective study examined 4-year outcomes in 40 children who underwent 41 heart transplants at a mean age of 9 years. All received pretransplant and posttransplant neurologic evaluations; those with idiopathic cardiomyopathies were evaluated before surgery for possible neurologic, neuromuscular, metabolic, or genetic cardiac etiologies.

Structural heart disease was present in 13 children. Of those with nonstructural congenital heart disease, 23 had cardiomyopathy, and of those, 10 (43%) had a definitive etiology, with neuromuscular and neurometabolic conditions accounting for most causes.

Neuromuscular disease was found in five: Two (twins) had dilated cardiomyopathy secondary to Emery-Dreifuss muscular dystrophy, one had Friedreich's ataxia with dilated cardiomyopathy, one had myofibrillar (desmin) myopathy with hypertrophic cardiomyopathy and arrhythmia, and one had an autosomal recessive form of limb-girdle muscular dystrophy.

Neurometabolic disease was found in two children: One had mitochondrial cytopathy (complex III deficiency), and one had a suspected fatty acid oxidation defect with dilated cardiomyopathy.

The other three children had genetic cardiac disorders, including arrhythmogenic right ventricular dysplasia, X-linked dilated cardiomyopathy, and autosomal dominant cardiomyopathy.

Of the entire group, 93% were alive at 1 year after surgery and 90% were still alive 4 years later, including all 10 children with neurologic or genetic causes of their heart disease, said Dr. Ghosh of the Cleveland Clinic Foundation.

PITTSBURGH — Preoperative neurologic and genetic work-ups may detect a previously unsuspected cause of cardiac disease in children about to receive a heart transplant, Dr. Debabrata Ghosh reported in a poster at the annual meeting of the Child Neurology Society.

“The presence of neurologic or genetic diseases should never be an absolute contraindication to heart transplant for these children,” Dr. Ghosh said in an interview. “In our study, all 10 of the children with neurologic or genetic etiologies were alive and well at 4 years' follow-up.”

His retrospective study examined 4-year outcomes in 40 children who underwent 41 heart transplants at a mean age of 9 years. All received pretransplant and posttransplant neurologic evaluations; those with idiopathic cardiomyopathies were evaluated before surgery for possible neurologic, neuromuscular, metabolic, or genetic cardiac etiologies.

Structural heart disease was present in 13 children. Of those with nonstructural congenital heart disease, 23 had cardiomyopathy, and of those, 10 (43%) had a definitive etiology, with neuromuscular and neurometabolic conditions accounting for most causes.

Neuromuscular disease was found in five: Two (twins) had dilated cardiomyopathy secondary to Emery-Dreifuss muscular dystrophy, one had Friedreich's ataxia with dilated cardiomyopathy, one had myofibrillar (desmin) myopathy with hypertrophic cardiomyopathy and arrhythmia, and one had an autosomal recessive form of limb-girdle muscular dystrophy.

Neurometabolic disease was found in two children: One had mitochondrial cytopathy (complex III deficiency), and one had a suspected fatty acid oxidation defect with dilated cardiomyopathy.

The other three children had genetic cardiac disorders, including arrhythmogenic right ventricular dysplasia, X-linked dilated cardiomyopathy, and autosomal dominant cardiomyopathy.

Of the entire group, 93% were alive at 1 year after surgery and 90% were still alive 4 years later, including all 10 children with neurologic or genetic causes of their heart disease, said Dr. Ghosh of the Cleveland Clinic Foundation.

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection appears to be triggered by the fetus's inflammatory response, as a way to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.”

In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-a, interleukin-1 b, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-a, a myelinotoxic factor, perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. “The jury comes in with a preconceived notion that all CP is due to birth injury, and could have been avoided if a C-section was performed early enough. It's very difficult to convince them that in 90% of the cases, the cause is simply not known.”

The conference was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection appears to be triggered by the fetus's inflammatory response, as a way to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.”

In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-a, interleukin-1 b, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-a, a myelinotoxic factor, perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. “The jury comes in with a preconceived notion that all CP is due to birth injury, and could have been avoided if a C-section was performed early enough. It's very difficult to convince them that in 90% of the cases, the cause is simply not known.”

The conference was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection appears to be triggered by the fetus's inflammatory response, as a way to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.”

In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-a, interleukin-1 b, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-a, a myelinotoxic factor, perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. “The jury comes in with a preconceived notion that all CP is due to birth injury, and could have been avoided if a C-section was performed early enough. It's very difficult to convince them that in 90% of the cases, the cause is simply not known.”

The conference was sponsored by Boston University.

PHILADELPHIA — Some patients with severe or difficult-to-control asthma are still failing to achieve control, despite taking high doses of both inhaled corticosteroids and long-acting β-agonists as recommended by current practice guidelines.

“These findings highlight the unmet need in severe or difficult-to-treat asthma and the need for an alternative therapeutic approach,” Dr. Larry Borish said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Borish, of the University of Virginia, Charlottesville, presented a subgroup analysis of the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, the largest investigation to date of patients with severe or hard-to-control asthma.

Although there have been many clinical trials involving the salmeterol/fluticasone combination (SFC), most have been in patients with mild or moderate disease. TENOR is the first study in which researchers are examining the drugs' effects in patients with severe or hard-to-control disease, Dr. Borish said in an interview.

TENOR had patients with mild and moderate asthma (3% and 48%, respectively), but the disease was classified as difficult to treat in 98% of the group.

Dr. Borish's analysis described 24-month treatment outcomes in 1,253 adults: 205 on low-dose salmeterol/fluticasone (SFC with 100 mcg or 250 mcg fluticasone), 271 on high-dose SFC (500/50), and 777 on other medications and naive to SFC.

All of the patients were assessed at baseline and at 24 months with multiple measures, including the Asthma Therapy Assessment Questionnaire (ATAQ), the Asthma-Related Quality of Life (AQoL), and forced expiratory lung volume in 1 second (FEV1). An important statistical point, Dr. Borish said, was that propensity scores were used to adjust for selection bias and confounding between the groups. “This is extremely robust and may approximate a randomized controlled experiment,” he said in an interview.

Before adjustment, the low-dose SFC group had significantly higher quality of life scores, compared with the control group. However, although the difference persisted after adjusting for confounders, it was not clinically significant, Dr. Borish said. The high-dose SFC group had significantly lower quality of life scores, compared with the control group, a difference that was lost after adjustment.

ATAQ scores after adjustment were lower in the low-dose SFC group than in the control group, indicating better control. However, in the high-dose SFC group, the scores were not significantly different from those in the control group.

The high-dose SFC group had significantly higher FEV1 after adjustment than did the control group, whereas FEV1 values in the low-dose group were only marginally higher than they were in controls.

After 24 months of treatment, patients on low-dose SFC were significantly less likely than controls to be classified as having severe asthma, whereas patients on high-dose SFC were significantly more likely than controls to have severe asthma. However, asthma exacerbation rates were similar between controls and both treatment groups.

The results paint a picture of a group of asthma patients failing to respond well to therapy, despite receiving the high doses of SFC suggested by current guidelines, Dr. Borish said. “[Perhaps those] who were started on low-dose SFC and did well enough for their physicians to keep them on that low dose, by our outcome parameters, are doing better than the patients who were either started on or… moved to higher-dose SFC. Patients on the higher dose probably look worse because they are more likely to have a disease that is resistant to corticosteroids and either resistant to long-acting β-agonists or conceivably even exacerbated by them.”

Many patients don't respond to the low-dose SFC but do well on the higher dose. Because their asthma is controlled, they were not included in the study, supported by a grant from Genentech Inc.

PHILADELPHIA — Some patients with severe or difficult-to-control asthma are still failing to achieve control, despite taking high doses of both inhaled corticosteroids and long-acting β-agonists as recommended by current practice guidelines.

“These findings highlight the unmet need in severe or difficult-to-treat asthma and the need for an alternative therapeutic approach,” Dr. Larry Borish said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Borish, of the University of Virginia, Charlottesville, presented a subgroup analysis of the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, the largest investigation to date of patients with severe or hard-to-control asthma.

Although there have been many clinical trials involving the salmeterol/fluticasone combination (SFC), most have been in patients with mild or moderate disease. TENOR is the first study in which researchers are examining the drugs' effects in patients with severe or hard-to-control disease, Dr. Borish said in an interview.

TENOR had patients with mild and moderate asthma (3% and 48%, respectively), but the disease was classified as difficult to treat in 98% of the group.

Dr. Borish's analysis described 24-month treatment outcomes in 1,253 adults: 205 on low-dose salmeterol/fluticasone (SFC with 100 mcg or 250 mcg fluticasone), 271 on high-dose SFC (500/50), and 777 on other medications and naive to SFC.

All of the patients were assessed at baseline and at 24 months with multiple measures, including the Asthma Therapy Assessment Questionnaire (ATAQ), the Asthma-Related Quality of Life (AQoL), and forced expiratory lung volume in 1 second (FEV1). An important statistical point, Dr. Borish said, was that propensity scores were used to adjust for selection bias and confounding between the groups. “This is extremely robust and may approximate a randomized controlled experiment,” he said in an interview.

Before adjustment, the low-dose SFC group had significantly higher quality of life scores, compared with the control group. However, although the difference persisted after adjusting for confounders, it was not clinically significant, Dr. Borish said. The high-dose SFC group had significantly lower quality of life scores, compared with the control group, a difference that was lost after adjustment.

ATAQ scores after adjustment were lower in the low-dose SFC group than in the control group, indicating better control. However, in the high-dose SFC group, the scores were not significantly different from those in the control group.

The high-dose SFC group had significantly higher FEV1 after adjustment than did the control group, whereas FEV1 values in the low-dose group were only marginally higher than they were in controls.

After 24 months of treatment, patients on low-dose SFC were significantly less likely than controls to be classified as having severe asthma, whereas patients on high-dose SFC were significantly more likely than controls to have severe asthma. However, asthma exacerbation rates were similar between controls and both treatment groups.

The results paint a picture of a group of asthma patients failing to respond well to therapy, despite receiving the high doses of SFC suggested by current guidelines, Dr. Borish said. “[Perhaps those] who were started on low-dose SFC and did well enough for their physicians to keep them on that low dose, by our outcome parameters, are doing better than the patients who were either started on or… moved to higher-dose SFC. Patients on the higher dose probably look worse because they are more likely to have a disease that is resistant to corticosteroids and either resistant to long-acting β-agonists or conceivably even exacerbated by them.”

Many patients don't respond to the low-dose SFC but do well on the higher dose. Because their asthma is controlled, they were not included in the study, supported by a grant from Genentech Inc.

PHILADELPHIA — Some patients with severe or difficult-to-control asthma are still failing to achieve control, despite taking high doses of both inhaled corticosteroids and long-acting β-agonists as recommended by current practice guidelines.

“These findings highlight the unmet need in severe or difficult-to-treat asthma and the need for an alternative therapeutic approach,” Dr. Larry Borish said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Borish, of the University of Virginia, Charlottesville, presented a subgroup analysis of the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, the largest investigation to date of patients with severe or hard-to-control asthma.

Although there have been many clinical trials involving the salmeterol/fluticasone combination (SFC), most have been in patients with mild or moderate disease. TENOR is the first study in which researchers are examining the drugs' effects in patients with severe or hard-to-control disease, Dr. Borish said in an interview.

TENOR had patients with mild and moderate asthma (3% and 48%, respectively), but the disease was classified as difficult to treat in 98% of the group.

Dr. Borish's analysis described 24-month treatment outcomes in 1,253 adults: 205 on low-dose salmeterol/fluticasone (SFC with 100 mcg or 250 mcg fluticasone), 271 on high-dose SFC (500/50), and 777 on other medications and naive to SFC.

All of the patients were assessed at baseline and at 24 months with multiple measures, including the Asthma Therapy Assessment Questionnaire (ATAQ), the Asthma-Related Quality of Life (AQoL), and forced expiratory lung volume in 1 second (FEV1). An important statistical point, Dr. Borish said, was that propensity scores were used to adjust for selection bias and confounding between the groups. “This is extremely robust and may approximate a randomized controlled experiment,” he said in an interview.

Before adjustment, the low-dose SFC group had significantly higher quality of life scores, compared with the control group. However, although the difference persisted after adjusting for confounders, it was not clinically significant, Dr. Borish said. The high-dose SFC group had significantly lower quality of life scores, compared with the control group, a difference that was lost after adjustment.

ATAQ scores after adjustment were lower in the low-dose SFC group than in the control group, indicating better control. However, in the high-dose SFC group, the scores were not significantly different from those in the control group.

The high-dose SFC group had significantly higher FEV1 after adjustment than did the control group, whereas FEV1 values in the low-dose group were only marginally higher than they were in controls.

After 24 months of treatment, patients on low-dose SFC were significantly less likely than controls to be classified as having severe asthma, whereas patients on high-dose SFC were significantly more likely than controls to have severe asthma. However, asthma exacerbation rates were similar between controls and both treatment groups.

The results paint a picture of a group of asthma patients failing to respond well to therapy, despite receiving the high doses of SFC suggested by current guidelines, Dr. Borish said. “[Perhaps those] who were started on low-dose SFC and did well enough for their physicians to keep them on that low dose, by our outcome parameters, are doing better than the patients who were either started on or… moved to higher-dose SFC. Patients on the higher dose probably look worse because they are more likely to have a disease that is resistant to corticosteroids and either resistant to long-acting β-agonists or conceivably even exacerbated by them.”

Many patients don't respond to the low-dose SFC but do well on the higher dose. Because their asthma is controlled, they were not included in the study, supported by a grant from Genentech Inc.

RIVIERA MAYA, MEXICO — All babies born by vacuum extraction should have an umbilical cord hematocrit drawn, and be closely monitored for changes that could signify a subgaleal bleed—an unusual injury in these deliveries, but the most devastating one possible, Dr. Michael G. Ross said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I suggest that all vacuum deliveries have an umbilical cord hematocrit. … It's easy, it's inexpensive and it gives you a benchmark as to where this baby started, so that if it starts behaving abnormally you can easily see what's happening [with regard to bleeding],” said Dr. Ross, chairman of obstetrics and gynecology at the University of California, Los Angeles.

Intensive monitoring in the first few hours after birth, including noting blood pressure, heart rate, and cephalic swelling, can also help identify these babies, who can easily lose half their blood volume into the subgaleal space before being diagnosed.

All too often, these devastating bleeds escape notice until the baby is in serious danger. “Pediatricians are usually first concerned about anoxia, so they ventilate the baby, and then infection, so they give antibiotics. The initial hematocrit that's drawn in the nursery may come back as 45%, which can be read as a low normal, but which in reality may already be showing a loss of one-third of the baby's blood volume.” The umbilical hematocrit provides a true baseline for the baby's red blood cells; a significant neonatal blood loss may be detected by decreasing hematocrit, greatly increasing the likelihood of catching a potentially fatal bleed, he said.

A subgaleal hemorrhage is a large collection of blood in the soft tissue space between the galea aponeurotica and the skull's periosteum. Unlike a cephalohematoma, this bleed crosses suture lines. The space in which it occurs can hold up to 250 cc of blood—equal to a baby's entire blood volume.

Most physicians first became aware of this complication after a 1998 FDA advisory described it in 12 unsolicited deaths and nine serious injuries after vacuum deliveries. After the FDA advisory, which asked physicians and hospitals to report vacuum-related neonatal injuries, 55 injuries came to light in just 6 months; 23 of these were subgaleal hemorrhages.

The American College of Obstetricians and Gynecologists has estimated the incidence as up to 4.5% in vacuum births, though this figure is greater than that of life-threatening subgaleal bleeds, which is likely closer to 1 in 1000 vacuum births. “We do feel that it is vastly, vastly under reported,” said Dr. Ross, “The reported cases are probably just the tip of the iceberg.”

Babies with this type of bleed usually begin acting abnormally about 1 hour after birth. The swelling on the head is soft to firm, fluctuant, and diffuse. In minor bleeds, the baby may be pale and show anemia. In major bleeds, there can be hypotonia, hypotension, seizures, and permanent brain injury.

Aside from restoring blood volume and administering coagulation factors and vitamin K, the best method of treatment remains unknown, Dr. Ross said. Surgery, drains, and wrapping the head have all been proposed, but there are no good data to support any of these options.

There are no firmly established risk factors for subgaleal bleeds. Preexisting hypoxia or coagulopathy have been proposed, but most proposals focus on vacuum extraction technique: difficult extraction, prolonged vacuum use, incorrect cup placement, rocking motions during extraction, and incorrect direction of traction.

“There are no good data to suggest that any of these factors really cause it, though,” Dr. Ross said at the meeting sponsored by Boston University. “I have seen many cases [in legal settings] where there was one pull in the normal direction and the baby came right out, and there was a subgaleal bleed. Nevertheless the liability is such that we have to have good indications for a vacuum delivery and use the right methods, have the right number of pop-offs and the correct duration, because you will be held responsible for it if you don't follow the rules.”

Attorney commentators at the meeting concurred that defending such cases is “extraordinarily difficult.”

“It's almost as if the burden of proof is on the defendant to prove that there was an indication for the delivery and it was done correctly,” said Brian McKeen, a plaintiff's attorney from Northville, Mich.

John Scully, a defendant's attorney from Dallas, Texas, agreed. “These are exceptionally difficult cases to defend in a courtroom. They evoke enormous sympathy from a juror. The defendant must walk a fine line by demonstrating that he did everything possible to deliver the baby safely and did it intensely and according to the standards of care, yet still persuade the jury that he did not use excessive force while doing it. And that can be a tough sell,” he said.

RIVIERA MAYA, MEXICO — All babies born by vacuum extraction should have an umbilical cord hematocrit drawn, and be closely monitored for changes that could signify a subgaleal bleed—an unusual injury in these deliveries, but the most devastating one possible, Dr. Michael G. Ross said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I suggest that all vacuum deliveries have an umbilical cord hematocrit. … It's easy, it's inexpensive and it gives you a benchmark as to where this baby started, so that if it starts behaving abnormally you can easily see what's happening [with regard to bleeding],” said Dr. Ross, chairman of obstetrics and gynecology at the University of California, Los Angeles.

Intensive monitoring in the first few hours after birth, including noting blood pressure, heart rate, and cephalic swelling, can also help identify these babies, who can easily lose half their blood volume into the subgaleal space before being diagnosed.

All too often, these devastating bleeds escape notice until the baby is in serious danger. “Pediatricians are usually first concerned about anoxia, so they ventilate the baby, and then infection, so they give antibiotics. The initial hematocrit that's drawn in the nursery may come back as 45%, which can be read as a low normal, but which in reality may already be showing a loss of one-third of the baby's blood volume.” The umbilical hematocrit provides a true baseline for the baby's red blood cells; a significant neonatal blood loss may be detected by decreasing hematocrit, greatly increasing the likelihood of catching a potentially fatal bleed, he said.

A subgaleal hemorrhage is a large collection of blood in the soft tissue space between the galea aponeurotica and the skull's periosteum. Unlike a cephalohematoma, this bleed crosses suture lines. The space in which it occurs can hold up to 250 cc of blood—equal to a baby's entire blood volume.

Most physicians first became aware of this complication after a 1998 FDA advisory described it in 12 unsolicited deaths and nine serious injuries after vacuum deliveries. After the FDA advisory, which asked physicians and hospitals to report vacuum-related neonatal injuries, 55 injuries came to light in just 6 months; 23 of these were subgaleal hemorrhages.

The American College of Obstetricians and Gynecologists has estimated the incidence as up to 4.5% in vacuum births, though this figure is greater than that of life-threatening subgaleal bleeds, which is likely closer to 1 in 1000 vacuum births. “We do feel that it is vastly, vastly under reported,” said Dr. Ross, “The reported cases are probably just the tip of the iceberg.”

Babies with this type of bleed usually begin acting abnormally about 1 hour after birth. The swelling on the head is soft to firm, fluctuant, and diffuse. In minor bleeds, the baby may be pale and show anemia. In major bleeds, there can be hypotonia, hypotension, seizures, and permanent brain injury.

Aside from restoring blood volume and administering coagulation factors and vitamin K, the best method of treatment remains unknown, Dr. Ross said. Surgery, drains, and wrapping the head have all been proposed, but there are no good data to support any of these options.

There are no firmly established risk factors for subgaleal bleeds. Preexisting hypoxia or coagulopathy have been proposed, but most proposals focus on vacuum extraction technique: difficult extraction, prolonged vacuum use, incorrect cup placement, rocking motions during extraction, and incorrect direction of traction.

“There are no good data to suggest that any of these factors really cause it, though,” Dr. Ross said at the meeting sponsored by Boston University. “I have seen many cases [in legal settings] where there was one pull in the normal direction and the baby came right out, and there was a subgaleal bleed. Nevertheless the liability is such that we have to have good indications for a vacuum delivery and use the right methods, have the right number of pop-offs and the correct duration, because you will be held responsible for it if you don't follow the rules.”

Attorney commentators at the meeting concurred that defending such cases is “extraordinarily difficult.”

“It's almost as if the burden of proof is on the defendant to prove that there was an indication for the delivery and it was done correctly,” said Brian McKeen, a plaintiff's attorney from Northville, Mich.

John Scully, a defendant's attorney from Dallas, Texas, agreed. “These are exceptionally difficult cases to defend in a courtroom. They evoke enormous sympathy from a juror. The defendant must walk a fine line by demonstrating that he did everything possible to deliver the baby safely and did it intensely and according to the standards of care, yet still persuade the jury that he did not use excessive force while doing it. And that can be a tough sell,” he said.

RIVIERA MAYA, MEXICO — All babies born by vacuum extraction should have an umbilical cord hematocrit drawn, and be closely monitored for changes that could signify a subgaleal bleed—an unusual injury in these deliveries, but the most devastating one possible, Dr. Michael G. Ross said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I suggest that all vacuum deliveries have an umbilical cord hematocrit. … It's easy, it's inexpensive and it gives you a benchmark as to where this baby started, so that if it starts behaving abnormally you can easily see what's happening [with regard to bleeding],” said Dr. Ross, chairman of obstetrics and gynecology at the University of California, Los Angeles.

Intensive monitoring in the first few hours after birth, including noting blood pressure, heart rate, and cephalic swelling, can also help identify these babies, who can easily lose half their blood volume into the subgaleal space before being diagnosed.

All too often, these devastating bleeds escape notice until the baby is in serious danger. “Pediatricians are usually first concerned about anoxia, so they ventilate the baby, and then infection, so they give antibiotics. The initial hematocrit that's drawn in the nursery may come back as 45%, which can be read as a low normal, but which in reality may already be showing a loss of one-third of the baby's blood volume.” The umbilical hematocrit provides a true baseline for the baby's red blood cells; a significant neonatal blood loss may be detected by decreasing hematocrit, greatly increasing the likelihood of catching a potentially fatal bleed, he said.

A subgaleal hemorrhage is a large collection of blood in the soft tissue space between the galea aponeurotica and the skull's periosteum. Unlike a cephalohematoma, this bleed crosses suture lines. The space in which it occurs can hold up to 250 cc of blood—equal to a baby's entire blood volume.

Most physicians first became aware of this complication after a 1998 FDA advisory described it in 12 unsolicited deaths and nine serious injuries after vacuum deliveries. After the FDA advisory, which asked physicians and hospitals to report vacuum-related neonatal injuries, 55 injuries came to light in just 6 months; 23 of these were subgaleal hemorrhages.

The American College of Obstetricians and Gynecologists has estimated the incidence as up to 4.5% in vacuum births, though this figure is greater than that of life-threatening subgaleal bleeds, which is likely closer to 1 in 1000 vacuum births. “We do feel that it is vastly, vastly under reported,” said Dr. Ross, “The reported cases are probably just the tip of the iceberg.”

Babies with this type of bleed usually begin acting abnormally about 1 hour after birth. The swelling on the head is soft to firm, fluctuant, and diffuse. In minor bleeds, the baby may be pale and show anemia. In major bleeds, there can be hypotonia, hypotension, seizures, and permanent brain injury.

Aside from restoring blood volume and administering coagulation factors and vitamin K, the best method of treatment remains unknown, Dr. Ross said. Surgery, drains, and wrapping the head have all been proposed, but there are no good data to support any of these options.

There are no firmly established risk factors for subgaleal bleeds. Preexisting hypoxia or coagulopathy have been proposed, but most proposals focus on vacuum extraction technique: difficult extraction, prolonged vacuum use, incorrect cup placement, rocking motions during extraction, and incorrect direction of traction.

“There are no good data to suggest that any of these factors really cause it, though,” Dr. Ross said at the meeting sponsored by Boston University. “I have seen many cases [in legal settings] where there was one pull in the normal direction and the baby came right out, and there was a subgaleal bleed. Nevertheless the liability is such that we have to have good indications for a vacuum delivery and use the right methods, have the right number of pop-offs and the correct duration, because you will be held responsible for it if you don't follow the rules.”

Attorney commentators at the meeting concurred that defending such cases is “extraordinarily difficult.”

“It's almost as if the burden of proof is on the defendant to prove that there was an indication for the delivery and it was done correctly,” said Brian McKeen, a plaintiff's attorney from Northville, Mich.

John Scully, a defendant's attorney from Dallas, Texas, agreed. “These are exceptionally difficult cases to defend in a courtroom. They evoke enormous sympathy from a juror. The defendant must walk a fine line by demonstrating that he did everything possible to deliver the baby safely and did it intensely and according to the standards of care, yet still persuade the jury that he did not use excessive force while doing it. And that can be a tough sell,” he said.