Kerri Wachter

Genentech Inc. has changed the labeling information for Avastin (bevacizumab) to warn physicians about reported cases of a rare brain-capillary leak syndrome and nasal septum deviation.

Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum.

Cases of confirmed and possible reversible posterior leukoencephalopathy syndrome have been reported in patients receiving Avastin at a rate of less than 0.1% in clinical trials. The rare disorder is associated with hypertension, fluid retention, and the cytotoxic effects of immunosuppressive drugs on vascular endothelium.

The syndrome can present as headache, seizures, visual disturbance, and altered mental function. If patients develop the disorder, discontinue Avastin and initiate treatment of hypertension.

Resolution of improvement usually occurs in a few days. It is unknown whether it is safe to reinitiate Avastin therapy in patients who have experienced this disorder.

Prescribing information has also been changed to reflect seven cases of nasal septum deviation, reported as postmarketing events.

For more information, contact Genentech Inc. by calling 800-821-8590. To report any serious adverse events suspected to be associated with the use of Avastin, contact the company by calling 888-835-2555 or contact the Food and Drug Administration's MedWatch reporting system by visiting www.accessdata.fda.gov/scripts/medwatch

Genentech Inc. has changed the labeling information for Avastin (bevacizumab) to warn physicians about reported cases of a rare brain-capillary leak syndrome and nasal septum deviation.

Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum.

Cases of confirmed and possible reversible posterior leukoencephalopathy syndrome have been reported in patients receiving Avastin at a rate of less than 0.1% in clinical trials. The rare disorder is associated with hypertension, fluid retention, and the cytotoxic effects of immunosuppressive drugs on vascular endothelium.

The syndrome can present as headache, seizures, visual disturbance, and altered mental function. If patients develop the disorder, discontinue Avastin and initiate treatment of hypertension.

Resolution of improvement usually occurs in a few days. It is unknown whether it is safe to reinitiate Avastin therapy in patients who have experienced this disorder.

Prescribing information has also been changed to reflect seven cases of nasal septum deviation, reported as postmarketing events.

For more information, contact Genentech Inc. by calling 800-821-8590. To report any serious adverse events suspected to be associated with the use of Avastin, contact the company by calling 888-835-2555 or contact the Food and Drug Administration's MedWatch reporting system by visiting www.accessdata.fda.gov/scripts/medwatch

Genentech Inc. has changed the labeling information for Avastin (bevacizumab) to warn physicians about reported cases of a rare brain-capillary leak syndrome and nasal septum deviation.

Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum.

Cases of confirmed and possible reversible posterior leukoencephalopathy syndrome have been reported in patients receiving Avastin at a rate of less than 0.1% in clinical trials. The rare disorder is associated with hypertension, fluid retention, and the cytotoxic effects of immunosuppressive drugs on vascular endothelium.

The syndrome can present as headache, seizures, visual disturbance, and altered mental function. If patients develop the disorder, discontinue Avastin and initiate treatment of hypertension.

Resolution of improvement usually occurs in a few days. It is unknown whether it is safe to reinitiate Avastin therapy in patients who have experienced this disorder.

Prescribing information has also been changed to reflect seven cases of nasal septum deviation, reported as postmarketing events.

For more information, contact Genentech Inc. by calling 800-821-8590. To report any serious adverse events suspected to be associated with the use of Avastin, contact the company by calling 888-835-2555 or contact the Food and Drug Administration's MedWatch reporting system by visiting www.accessdata.fda.gov/scripts/medwatch

Certain lots of Comfort Shield Perineal Care Washcloths have been recalled because of contamination with Burkholderia cepacia.

The bacteria can cause serious infections including pneumonia and bacterial sepsis in immunocompromised individuals, those with cystic fibrosis, and hospitalized patients in general, as well as certain other patient groups.

The product was distributed to hospitals, medical centers, and long-term care facilities in the United States and Canada. The affected codes/lots include: 7403/1301, 7403/1312, 7403/1457, 7403/1677, 7408/1848, 7503/1999, 7524/2070, 7524/2086, 7905/1766, 7503-M/1702, and 7503-M/1995. There have been no reports of patient injury to date.

Customers with affected lots of the product should stop usage and contact Sage Products Inc. to return and replace the items. For more information or to arrange return and replacement, contact the company at 800-323-2220.

Certain lots of Comfort Shield Perineal Care Washcloths have been recalled because of contamination with Burkholderia cepacia.

The bacteria can cause serious infections including pneumonia and bacterial sepsis in immunocompromised individuals, those with cystic fibrosis, and hospitalized patients in general, as well as certain other patient groups.

The product was distributed to hospitals, medical centers, and long-term care facilities in the United States and Canada. The affected codes/lots include: 7403/1301, 7403/1312, 7403/1457, 7403/1677, 7408/1848, 7503/1999, 7524/2070, 7524/2086, 7905/1766, 7503-M/1702, and 7503-M/1995. There have been no reports of patient injury to date.

Customers with affected lots of the product should stop usage and contact Sage Products Inc. to return and replace the items. For more information or to arrange return and replacement, contact the company at 800-323-2220.

Certain lots of Comfort Shield Perineal Care Washcloths have been recalled because of contamination with Burkholderia cepacia.

The bacteria can cause serious infections including pneumonia and bacterial sepsis in immunocompromised individuals, those with cystic fibrosis, and hospitalized patients in general, as well as certain other patient groups.

The product was distributed to hospitals, medical centers, and long-term care facilities in the United States and Canada. The affected codes/lots include: 7403/1301, 7403/1312, 7403/1457, 7403/1677, 7408/1848, 7503/1999, 7524/2070, 7524/2086, 7905/1766, 7503-M/1702, and 7503-M/1995. There have been no reports of patient injury to date.

Customers with affected lots of the product should stop usage and contact Sage Products Inc. to return and replace the items. For more information or to arrange return and replacement, contact the company at 800-323-2220.

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have primary care physicians and cardiologists alike looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group (J. Am. Coll. Cardiol. 2006;48:1475–97).

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, who is a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released in October 2005, was for SPECT myocardial perfusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (i.e., radiation or contrast exposure) and the downstream effects of poor test performance (i.e., delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate. For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” Dr. Rubin said.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

Who should be performing cardiac imaging in general has been a matter of heated contention among cardiologists, radiologists, and interventionalists.

However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” Dr. Hendel said. The group hopes that these criteria serve as an endorsement for a more collaborative approach to cardiac imaging, he added.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have primary care physicians and cardiologists alike looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group (J. Am. Coll. Cardiol. 2006;48:1475–97).

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, who is a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released in October 2005, was for SPECT myocardial perfusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (i.e., radiation or contrast exposure) and the downstream effects of poor test performance (i.e., delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate. For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” Dr. Rubin said.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

Who should be performing cardiac imaging in general has been a matter of heated contention among cardiologists, radiologists, and interventionalists.

However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” Dr. Hendel said. The group hopes that these criteria serve as an endorsement for a more collaborative approach to cardiac imaging, he added.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have primary care physicians and cardiologists alike looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group (J. Am. Coll. Cardiol. 2006;48:1475–97).

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, who is a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released in October 2005, was for SPECT myocardial perfusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (i.e., radiation or contrast exposure) and the downstream effects of poor test performance (i.e., delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate. For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” Dr. Rubin said.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

Who should be performing cardiac imaging in general has been a matter of heated contention among cardiologists, radiologists, and interventionalists.

However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” Dr. Hendel said. The group hopes that these criteria serve as an endorsement for a more collaborative approach to cardiac imaging, he added.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

PHILADELPHIA — Newly diagnosed diabetes seems to confer a protective effect against fracture that disappears with increased disease duration, ultimately leading to an increased fracture risk in patients with long-term disease, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients with newly diagnosed diabetes had an 11% lower risk of osteoporotic fracture and an 18% lower risk of hip fracture, compared with controls, in a retrospective study of 82,094 diabetic patients and 236,682 control subjects. Individuals who have had diabetes for less than 5 years had the same risk as controls for an osteoporotic fracture. People with diabetes of longer duration had a significantly greater risk of osteoporotic fractures in general (9% greater) and hip fractures in particular (36% greater).

The data provide “compelling evidence that long-term diabetes is associated with increased fracture risk and that newly diagnosed diabetes shows some protective effect,” said Dr. William D. Leslie, professor of endocrinology and metabolism at the University of Manitoba, Winnipeg.

A number of population-based studies have shown that bone density is increased in patients with type 2 diabetes. “Paradoxically, fracture risk [in diabetic patients] is much greater than can be explained on the basis of bone density,” said Dr. Leslie. Diabetic complications leading to falls and possibly altered bone quality are thought to mediate these effects, but the exact relationship between diabetes and fracture risk has not been determined.

For this study, the researchers used fracture data from the Population Health Information System for the Province of Manitoba from 1984 to 2004. Each diabetic adult in the database who was at least 20 years old (as of Jan. 1, 1994) was matched with three nondiabetic control subjects based on gender, birth year, area of residence, and aboriginal or nonaboriginal ethnicity.

Diabetic patients were defined as those with at least one hospitalization or two physician claims for diabetes or a diagnosis of diabetes within a 3-year period. Diabetic patients were further classified by the duration of their disease. Long-term diabetics had the disease for more than 5 years (before 1994). Short-term diabetics had the disease for less than 5 years (prior to 1994). Newly diagnosed diabetics were those who were diagnosed between 1994 and 2004. To be considered nondiabetic, controls had to be continuously nondiabetic between 1984 and 2004. Fractures were determined from ICD-9 codes. Combined osteoporotic fractures included vertebral, wrist, or hip breaks. Hip fractures were also analyzed as a predefined subgroup.

A total of 16,457 osteoporotic fractures were identified among controls and 5,591 among diabetic patients. A total of 5,224 hip fractures were identified among controls and 1,901 among diabetic patients. Overall, there was no statistical difference between diabetics and controls in terms of osteoporotic or hip fracture rates. Both types of fracture risk increased exponentially with age. In addition, longer duration of diabetes was associated with a greater fracture risk for both types of fractures.

The researchers also tried to account for comorbidity by using the number of ambulatory diagnostic groups (ADGs), developed at Johns Hopkins University. In this tool, ICD codes are grouped into 32 different ADGs, based on clinical and expected utilization criteria. Increasing number of ADGs corresponds with increasing comorbidity. The researchers used a regression model including age and comorbidity (represented by ADG number).

For diabetic patients within each age group (younger than 50, 50–59, 60–69, 70–79, and 80 years and older), fracture risk increased with increasing duration of diabetes. Interestingly, the highest fracture rates for each diabetes subgroup were among the youngest age group. In fact, there was a fourfold increase in hip fracture risk for long-term diabetics younger than 50 years, compared with nondiabetic controls. The strongest protective effect of being newly diagnosed was seen among the oldest patients.

The researchers hypothesize that the opposing effects of overweight or obesity provide short-term protection from fractures, but with time, this effect is overcome by diabetes-associated complications.

PHILADELPHIA — Newly diagnosed diabetes seems to confer a protective effect against fracture that disappears with increased disease duration, ultimately leading to an increased fracture risk in patients with long-term disease, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients with newly diagnosed diabetes had an 11% lower risk of osteoporotic fracture and an 18% lower risk of hip fracture, compared with controls, in a retrospective study of 82,094 diabetic patients and 236,682 control subjects. Individuals who have had diabetes for less than 5 years had the same risk as controls for an osteoporotic fracture. People with diabetes of longer duration had a significantly greater risk of osteoporotic fractures in general (9% greater) and hip fractures in particular (36% greater).

The data provide “compelling evidence that long-term diabetes is associated with increased fracture risk and that newly diagnosed diabetes shows some protective effect,” said Dr. William D. Leslie, professor of endocrinology and metabolism at the University of Manitoba, Winnipeg.

A number of population-based studies have shown that bone density is increased in patients with type 2 diabetes. “Paradoxically, fracture risk [in diabetic patients] is much greater than can be explained on the basis of bone density,” said Dr. Leslie. Diabetic complications leading to falls and possibly altered bone quality are thought to mediate these effects, but the exact relationship between diabetes and fracture risk has not been determined.

For this study, the researchers used fracture data from the Population Health Information System for the Province of Manitoba from 1984 to 2004. Each diabetic adult in the database who was at least 20 years old (as of Jan. 1, 1994) was matched with three nondiabetic control subjects based on gender, birth year, area of residence, and aboriginal or nonaboriginal ethnicity.

Diabetic patients were defined as those with at least one hospitalization or two physician claims for diabetes or a diagnosis of diabetes within a 3-year period. Diabetic patients were further classified by the duration of their disease. Long-term diabetics had the disease for more than 5 years (before 1994). Short-term diabetics had the disease for less than 5 years (prior to 1994). Newly diagnosed diabetics were those who were diagnosed between 1994 and 2004. To be considered nondiabetic, controls had to be continuously nondiabetic between 1984 and 2004. Fractures were determined from ICD-9 codes. Combined osteoporotic fractures included vertebral, wrist, or hip breaks. Hip fractures were also analyzed as a predefined subgroup.

A total of 16,457 osteoporotic fractures were identified among controls and 5,591 among diabetic patients. A total of 5,224 hip fractures were identified among controls and 1,901 among diabetic patients. Overall, there was no statistical difference between diabetics and controls in terms of osteoporotic or hip fracture rates. Both types of fracture risk increased exponentially with age. In addition, longer duration of diabetes was associated with a greater fracture risk for both types of fractures.

The researchers also tried to account for comorbidity by using the number of ambulatory diagnostic groups (ADGs), developed at Johns Hopkins University. In this tool, ICD codes are grouped into 32 different ADGs, based on clinical and expected utilization criteria. Increasing number of ADGs corresponds with increasing comorbidity. The researchers used a regression model including age and comorbidity (represented by ADG number).

For diabetic patients within each age group (younger than 50, 50–59, 60–69, 70–79, and 80 years and older), fracture risk increased with increasing duration of diabetes. Interestingly, the highest fracture rates for each diabetes subgroup were among the youngest age group. In fact, there was a fourfold increase in hip fracture risk for long-term diabetics younger than 50 years, compared with nondiabetic controls. The strongest protective effect of being newly diagnosed was seen among the oldest patients.

The researchers hypothesize that the opposing effects of overweight or obesity provide short-term protection from fractures, but with time, this effect is overcome by diabetes-associated complications.

PHILADELPHIA — Newly diagnosed diabetes seems to confer a protective effect against fracture that disappears with increased disease duration, ultimately leading to an increased fracture risk in patients with long-term disease, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients with newly diagnosed diabetes had an 11% lower risk of osteoporotic fracture and an 18% lower risk of hip fracture, compared with controls, in a retrospective study of 82,094 diabetic patients and 236,682 control subjects. Individuals who have had diabetes for less than 5 years had the same risk as controls for an osteoporotic fracture. People with diabetes of longer duration had a significantly greater risk of osteoporotic fractures in general (9% greater) and hip fractures in particular (36% greater).

The data provide “compelling evidence that long-term diabetes is associated with increased fracture risk and that newly diagnosed diabetes shows some protective effect,” said Dr. William D. Leslie, professor of endocrinology and metabolism at the University of Manitoba, Winnipeg.

A number of population-based studies have shown that bone density is increased in patients with type 2 diabetes. “Paradoxically, fracture risk [in diabetic patients] is much greater than can be explained on the basis of bone density,” said Dr. Leslie. Diabetic complications leading to falls and possibly altered bone quality are thought to mediate these effects, but the exact relationship between diabetes and fracture risk has not been determined.

For this study, the researchers used fracture data from the Population Health Information System for the Province of Manitoba from 1984 to 2004. Each diabetic adult in the database who was at least 20 years old (as of Jan. 1, 1994) was matched with three nondiabetic control subjects based on gender, birth year, area of residence, and aboriginal or nonaboriginal ethnicity.

Diabetic patients were defined as those with at least one hospitalization or two physician claims for diabetes or a diagnosis of diabetes within a 3-year period. Diabetic patients were further classified by the duration of their disease. Long-term diabetics had the disease for more than 5 years (before 1994). Short-term diabetics had the disease for less than 5 years (prior to 1994). Newly diagnosed diabetics were those who were diagnosed between 1994 and 2004. To be considered nondiabetic, controls had to be continuously nondiabetic between 1984 and 2004. Fractures were determined from ICD-9 codes. Combined osteoporotic fractures included vertebral, wrist, or hip breaks. Hip fractures were also analyzed as a predefined subgroup.

A total of 16,457 osteoporotic fractures were identified among controls and 5,591 among diabetic patients. A total of 5,224 hip fractures were identified among controls and 1,901 among diabetic patients. Overall, there was no statistical difference between diabetics and controls in terms of osteoporotic or hip fracture rates. Both types of fracture risk increased exponentially with age. In addition, longer duration of diabetes was associated with a greater fracture risk for both types of fractures.

The researchers also tried to account for comorbidity by using the number of ambulatory diagnostic groups (ADGs), developed at Johns Hopkins University. In this tool, ICD codes are grouped into 32 different ADGs, based on clinical and expected utilization criteria. Increasing number of ADGs corresponds with increasing comorbidity. The researchers used a regression model including age and comorbidity (represented by ADG number).

For diabetic patients within each age group (younger than 50, 50–59, 60–69, 70–79, and 80 years and older), fracture risk increased with increasing duration of diabetes. Interestingly, the highest fracture rates for each diabetes subgroup were among the youngest age group. In fact, there was a fourfold increase in hip fracture risk for long-term diabetics younger than 50 years, compared with nondiabetic controls. The strongest protective effect of being newly diagnosed was seen among the oldest patients.

The researchers hypothesize that the opposing effects of overweight or obesity provide short-term protection from fractures, but with time, this effect is overcome by diabetes-associated complications.

Researchers are recruiting patients with severe and active systemic lupus erythematosus to participate in a pilot study involving hemapoietic stem cell transplant.

Potential participants with systemic lupus erythematosus (SLE) should be 15-40 years of age and have acceptable organ function. Participants should have 4 of the 11 American College of Rheumatology criteria for SLE but no other significant medical conditions. Patients may have active and refractory lupus affecting the kidneys, CNS, lungs, or blood. Participants also should have no evidence of malignancy, active hepatitis B virus or hepatitus C virus, or HIV infections. Written consent is required.

The treatment protocol includes priming and conditioning regimens. The priming regimen involves treatment with methylprednisolone, rituximab, cyclophosphamide, and mesna. At the end of this regimen, patients will receive a granulocyte colony-stimulating factor to mobilize stem cells for collection for transplant. Patients will undergo the conditioning regimen immediately prior to stem cell transplant.

Following transplantation, patients will be followed for 6 months and then at 9, 12, 18, and 24 months. After 2 years, patients will be followed yearly for 5 years.

The trial is being conducted at the National Institutes of Health campus in Bethesda, Md. The principal investigator is Dr. Steven Pavletic of the National Institute for Arthritis and Musculoskeletal and Skin Diseases. Physicians who know of interested patients may contact Cheryl Yarboro, R.N., by calling 301-402-6409.

Researchers are recruiting patients with severe and active systemic lupus erythematosus to participate in a pilot study involving hemapoietic stem cell transplant.

Potential participants with systemic lupus erythematosus (SLE) should be 15-40 years of age and have acceptable organ function. Participants should have 4 of the 11 American College of Rheumatology criteria for SLE but no other significant medical conditions. Patients may have active and refractory lupus affecting the kidneys, CNS, lungs, or blood. Participants also should have no evidence of malignancy, active hepatitis B virus or hepatitus C virus, or HIV infections. Written consent is required.

The treatment protocol includes priming and conditioning regimens. The priming regimen involves treatment with methylprednisolone, rituximab, cyclophosphamide, and mesna. At the end of this regimen, patients will receive a granulocyte colony-stimulating factor to mobilize stem cells for collection for transplant. Patients will undergo the conditioning regimen immediately prior to stem cell transplant.

Following transplantation, patients will be followed for 6 months and then at 9, 12, 18, and 24 months. After 2 years, patients will be followed yearly for 5 years.

The trial is being conducted at the National Institutes of Health campus in Bethesda, Md. The principal investigator is Dr. Steven Pavletic of the National Institute for Arthritis and Musculoskeletal and Skin Diseases. Physicians who know of interested patients may contact Cheryl Yarboro, R.N., by calling 301-402-6409.

Researchers are recruiting patients with severe and active systemic lupus erythematosus to participate in a pilot study involving hemapoietic stem cell transplant.

Potential participants with systemic lupus erythematosus (SLE) should be 15-40 years of age and have acceptable organ function. Participants should have 4 of the 11 American College of Rheumatology criteria for SLE but no other significant medical conditions. Patients may have active and refractory lupus affecting the kidneys, CNS, lungs, or blood. Participants also should have no evidence of malignancy, active hepatitis B virus or hepatitus C virus, or HIV infections. Written consent is required.

The treatment protocol includes priming and conditioning regimens. The priming regimen involves treatment with methylprednisolone, rituximab, cyclophosphamide, and mesna. At the end of this regimen, patients will receive a granulocyte colony-stimulating factor to mobilize stem cells for collection for transplant. Patients will undergo the conditioning regimen immediately prior to stem cell transplant.

Following transplantation, patients will be followed for 6 months and then at 9, 12, 18, and 24 months. After 2 years, patients will be followed yearly for 5 years.

The trial is being conducted at the National Institutes of Health campus in Bethesda, Md. The principal investigator is Dr. Steven Pavletic of the National Institute for Arthritis and Musculoskeletal and Skin Diseases. Physicians who know of interested patients may contact Cheryl Yarboro, R.N., by calling 301-402-6409.

OTTAWA — As age, degree of disease burden, and number of comorbidities rise among cardiac surgery patients, multimodality neuromonitoring is becoming increasingly important, Dr. John M. Murkin said at a meeting of the World Society of Cardio-Thoracic Surgeons.

Multimodality neuromonitoring includes epiaortic scanning of the aortic arch and ascending aorta to guide the canula and clamp placement, jugular venous pressure monitoring for cerebral perfusion pressure, use of transcranial Doppler to monitor cerebral blood flow velocity and detect emboli, near-infrared spectroscopy to detect cerebral malperfusion, and nasopharyngeal/tympanic temperature monitoring to avoid hyperthermia.

“It's clear that many of the patients that we operate on for coronary revascularization also have significant systemic atherosclerosis,” said Dr. Murkin, a professor of anesthesiology at the University of Western Ontario in London, Canada. Studies have associated cerebrovascular disease with postoperative neurologic abnormalities.

Most surgeons use mean arterial pressure as a surrogate for cerebral perfusion pressure but this is not necessarily appropriate. Venous outflow obstruction and cardiac dislocation can compromise cerebral perfusion pressure. For example, dislocation of the heart increases pressure in the superior vena cava but decreases cerebral perfusion pressure. Such drops in cerebral perfusion pressure can occur without a change in mean arterial pressure or mixed venous saturation but can result in profound cerebral desaturation, said Dr. Murkin, who disclosed that he has been supported by a number of equipment manufacturers. In particular he has received research support from Somanetics Corporation and is a consultant for Impulse Monitoring Inc., both of which produce neurophysiologic monitors.

“One of the things we've been advocating is to display the pressure in the proximal superior vena cava, by monitoring cerebral venous outflow using the introducer port of a pulmonary artery canula or a central venous pressure canula and using cerebral oximetry to detect critical perfusion pressure,” Dr. Murkin said.

It's also been demonstrated that there is significantly more jugular venous oxygen desaturation during beating heart procedures involving heart verticalization, compared with conventional bypass procedures. This could help explain why some studies have found no difference in the incidence of neurologic complications between beating heart procedures and conventional CABG. It was assumed that beating heart procedures would lead to fewer neurologic complications because of fewer emboli.

Patients at high risk—those undergoing deep hypothermia circulatory arrest or those with a high stroke risk, for example—can benefit from transcranial Doppler (TCD) and cerebral oximetry.

Most commonly performed on the middle cerebral artery, TCD provides a qualitative measure of cerebral blood flow velocity. TCD also uses the change in the return of sound waves to detect emboli, allowing surgeons to change technique to minimize emboli. Multigating—a technique that focuses signals at two different depths—allows physicians to differentiate artifacts or background noise from emboli. A signal that is picked up at both depths simultaneously strongly suggests an artifact.

Another TCD technique uses two frequencies of sound waves to distinguish between particulate and air emboli, which can have very different clinical significance. The technique is still under investigation but results so far have been promising.

TCD is not without problems though. Placing the transducer can require a great deal of skill. In as many as 20% of adults it is very difficult to find the temporal window along the zygomatic arch—the area of the skull which is thin enough to allow adequate penetration of sound waves.

Spatially resolved near-infrared spectroscopy (NIRS) detects changes in cerebral cortical oxygen saturation by measuring the changes in absorption of infrared light by hemoglobin—indicating the changing amount of oxygen present in the brain. In comparison with TCD, cerebral oximetry is easy to apply using non-invasive sticky pads placed bilaterally over the forehead and can be monitored in any patient. It allows clinicians to detect and correct decreases in cerebral oxygenation that may be otherwise undetected.

Studies have shown that during rewarming, bladder temperature rises slowly to 37° C but tympanic temperature (as a surrogate for brain temperature) rises more rapidly and may even significantly exceed 37° C. “We know that hyperthermia can exacerbate cerebral ischemic injury,” Dr. Murkin said.

Measuring nasopharyngeal, tympanic, or jugular bulb temperature is much more reflective of cerebral temperature. “The current recommendation is that the aortic inflow temperature should not exceed 37° C,” Dr. Murkin said.

OTTAWA — As age, degree of disease burden, and number of comorbidities rise among cardiac surgery patients, multimodality neuromonitoring is becoming increasingly important, Dr. John M. Murkin said at a meeting of the World Society of Cardio-Thoracic Surgeons.

Multimodality neuromonitoring includes epiaortic scanning of the aortic arch and ascending aorta to guide the canula and clamp placement, jugular venous pressure monitoring for cerebral perfusion pressure, use of transcranial Doppler to monitor cerebral blood flow velocity and detect emboli, near-infrared spectroscopy to detect cerebral malperfusion, and nasopharyngeal/tympanic temperature monitoring to avoid hyperthermia.

“It's clear that many of the patients that we operate on for coronary revascularization also have significant systemic atherosclerosis,” said Dr. Murkin, a professor of anesthesiology at the University of Western Ontario in London, Canada. Studies have associated cerebrovascular disease with postoperative neurologic abnormalities.

Most surgeons use mean arterial pressure as a surrogate for cerebral perfusion pressure but this is not necessarily appropriate. Venous outflow obstruction and cardiac dislocation can compromise cerebral perfusion pressure. For example, dislocation of the heart increases pressure in the superior vena cava but decreases cerebral perfusion pressure. Such drops in cerebral perfusion pressure can occur without a change in mean arterial pressure or mixed venous saturation but can result in profound cerebral desaturation, said Dr. Murkin, who disclosed that he has been supported by a number of equipment manufacturers. In particular he has received research support from Somanetics Corporation and is a consultant for Impulse Monitoring Inc., both of which produce neurophysiologic monitors.

“One of the things we've been advocating is to display the pressure in the proximal superior vena cava, by monitoring cerebral venous outflow using the introducer port of a pulmonary artery canula or a central venous pressure canula and using cerebral oximetry to detect critical perfusion pressure,” Dr. Murkin said.

It's also been demonstrated that there is significantly more jugular venous oxygen desaturation during beating heart procedures involving heart verticalization, compared with conventional bypass procedures. This could help explain why some studies have found no difference in the incidence of neurologic complications between beating heart procedures and conventional CABG. It was assumed that beating heart procedures would lead to fewer neurologic complications because of fewer emboli.

Patients at high risk—those undergoing deep hypothermia circulatory arrest or those with a high stroke risk, for example—can benefit from transcranial Doppler (TCD) and cerebral oximetry.

Most commonly performed on the middle cerebral artery, TCD provides a qualitative measure of cerebral blood flow velocity. TCD also uses the change in the return of sound waves to detect emboli, allowing surgeons to change technique to minimize emboli. Multigating—a technique that focuses signals at two different depths—allows physicians to differentiate artifacts or background noise from emboli. A signal that is picked up at both depths simultaneously strongly suggests an artifact.

Another TCD technique uses two frequencies of sound waves to distinguish between particulate and air emboli, which can have very different clinical significance. The technique is still under investigation but results so far have been promising.

TCD is not without problems though. Placing the transducer can require a great deal of skill. In as many as 20% of adults it is very difficult to find the temporal window along the zygomatic arch—the area of the skull which is thin enough to allow adequate penetration of sound waves.

Spatially resolved near-infrared spectroscopy (NIRS) detects changes in cerebral cortical oxygen saturation by measuring the changes in absorption of infrared light by hemoglobin—indicating the changing amount of oxygen present in the brain. In comparison with TCD, cerebral oximetry is easy to apply using non-invasive sticky pads placed bilaterally over the forehead and can be monitored in any patient. It allows clinicians to detect and correct decreases in cerebral oxygenation that may be otherwise undetected.

Studies have shown that during rewarming, bladder temperature rises slowly to 37° C but tympanic temperature (as a surrogate for brain temperature) rises more rapidly and may even significantly exceed 37° C. “We know that hyperthermia can exacerbate cerebral ischemic injury,” Dr. Murkin said.

Measuring nasopharyngeal, tympanic, or jugular bulb temperature is much more reflective of cerebral temperature. “The current recommendation is that the aortic inflow temperature should not exceed 37° C,” Dr. Murkin said.

OTTAWA — As age, degree of disease burden, and number of comorbidities rise among cardiac surgery patients, multimodality neuromonitoring is becoming increasingly important, Dr. John M. Murkin said at a meeting of the World Society of Cardio-Thoracic Surgeons.

Multimodality neuromonitoring includes epiaortic scanning of the aortic arch and ascending aorta to guide the canula and clamp placement, jugular venous pressure monitoring for cerebral perfusion pressure, use of transcranial Doppler to monitor cerebral blood flow velocity and detect emboli, near-infrared spectroscopy to detect cerebral malperfusion, and nasopharyngeal/tympanic temperature monitoring to avoid hyperthermia.

“It's clear that many of the patients that we operate on for coronary revascularization also have significant systemic atherosclerosis,” said Dr. Murkin, a professor of anesthesiology at the University of Western Ontario in London, Canada. Studies have associated cerebrovascular disease with postoperative neurologic abnormalities.

Most surgeons use mean arterial pressure as a surrogate for cerebral perfusion pressure but this is not necessarily appropriate. Venous outflow obstruction and cardiac dislocation can compromise cerebral perfusion pressure. For example, dislocation of the heart increases pressure in the superior vena cava but decreases cerebral perfusion pressure. Such drops in cerebral perfusion pressure can occur without a change in mean arterial pressure or mixed venous saturation but can result in profound cerebral desaturation, said Dr. Murkin, who disclosed that he has been supported by a number of equipment manufacturers. In particular he has received research support from Somanetics Corporation and is a consultant for Impulse Monitoring Inc., both of which produce neurophysiologic monitors.

“One of the things we've been advocating is to display the pressure in the proximal superior vena cava, by monitoring cerebral venous outflow using the introducer port of a pulmonary artery canula or a central venous pressure canula and using cerebral oximetry to detect critical perfusion pressure,” Dr. Murkin said.

It's also been demonstrated that there is significantly more jugular venous oxygen desaturation during beating heart procedures involving heart verticalization, compared with conventional bypass procedures. This could help explain why some studies have found no difference in the incidence of neurologic complications between beating heart procedures and conventional CABG. It was assumed that beating heart procedures would lead to fewer neurologic complications because of fewer emboli.

Patients at high risk—those undergoing deep hypothermia circulatory arrest or those with a high stroke risk, for example—can benefit from transcranial Doppler (TCD) and cerebral oximetry.

Most commonly performed on the middle cerebral artery, TCD provides a qualitative measure of cerebral blood flow velocity. TCD also uses the change in the return of sound waves to detect emboli, allowing surgeons to change technique to minimize emboli. Multigating—a technique that focuses signals at two different depths—allows physicians to differentiate artifacts or background noise from emboli. A signal that is picked up at both depths simultaneously strongly suggests an artifact.

Another TCD technique uses two frequencies of sound waves to distinguish between particulate and air emboli, which can have very different clinical significance. The technique is still under investigation but results so far have been promising.

TCD is not without problems though. Placing the transducer can require a great deal of skill. In as many as 20% of adults it is very difficult to find the temporal window along the zygomatic arch—the area of the skull which is thin enough to allow adequate penetration of sound waves.

Spatially resolved near-infrared spectroscopy (NIRS) detects changes in cerebral cortical oxygen saturation by measuring the changes in absorption of infrared light by hemoglobin—indicating the changing amount of oxygen present in the brain. In comparison with TCD, cerebral oximetry is easy to apply using non-invasive sticky pads placed bilaterally over the forehead and can be monitored in any patient. It allows clinicians to detect and correct decreases in cerebral oxygenation that may be otherwise undetected.

Studies have shown that during rewarming, bladder temperature rises slowly to 37° C but tympanic temperature (as a surrogate for brain temperature) rises more rapidly and may even significantly exceed 37° C. “We know that hyperthermia can exacerbate cerebral ischemic injury,” Dr. Murkin said.

Measuring nasopharyngeal, tympanic, or jugular bulb temperature is much more reflective of cerebral temperature. “The current recommendation is that the aortic inflow temperature should not exceed 37° C,” Dr. Murkin said.

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have both primary care physicians and cardiologists looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group.

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released last October, was for SPECT myocardial profusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of on factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (that is, radiation or contrast exposure) and the downstream effects of poor test performance (that is, delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate.

For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” said Dr. Rubin.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

It has been a matter of heated contention among cardiologists, radiologists, and interventionalists as to whom should be performing cardiac imaging in general. However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” said Dr. Hendel, adding that the group hopes the criteria serve as an endorsement for a more collaborative approach to cardiac imaging.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of the cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently, cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully, this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have both primary care physicians and cardiologists looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group.

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released last October, was for SPECT myocardial profusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of on factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (that is, radiation or contrast exposure) and the downstream effects of poor test performance (that is, delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate.

For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” said Dr. Rubin.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

It has been a matter of heated contention among cardiologists, radiologists, and interventionalists as to whom should be performing cardiac imaging in general. However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” said Dr. Hendel, adding that the group hopes the criteria serve as an endorsement for a more collaborative approach to cardiac imaging.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of the cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently, cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully, this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

To help physicians keep up with ever-changing imaging technology, the American College of Cardiology Foundation and key specialty societies have released appropriateness criteria for the use of cardiac CT and MR.

These are rapidly emerging technologies that have both primary care physicians and cardiologists looking for guidance on how to fit these tools into their practices, said Dr. Robert C. Hendel, who chaired the Appropriateness Criteria for Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging writing group.

In light of this need, the writing group is taking a somewhat novel approach, planning to revise the criteria every 12–18 months to keep up with new technology and evidence, said Dr. Hendel, a nuclear cardiologist with Midwest Heart Specialists in Fox River Grove, Ill. The first set of appropriateness criteria for imaging, released last October, was for SPECT myocardial profusion imaging.

The criteria aren't intended as hard and fast guidelines but instead represent the current expert thinking on when cardiac CT and MR should and should not be used. “Appropriateness criteria, in other words, are not substitutes for sound clinical judgment and practice experience with each patient and clinical presentation,” the authors said.

Imaging technology changes rapidly, meaning that there can be a big lag between peer-reviewed research and clinical practice. “I think that's one of the things that this document is intended to address because if you wait for the literature to catch up, it's never going to happen,” said Dr. Geoffrey D. Rubin, the American College of Radiology's representative on the technical panel.

The technical panel rated 39 cardiac computed tomography (CCT) and 33 cardiac magnetic resonance (CMR) indications representing common patient presentations such as symptoms suggestive of ischemia, multiple cardiac risk factors in an asymptomatic individual, and specific scenarios with high clinical suspicion that are further stratified on the basis of on factors such as clinical risk, prior test results, and the interval since prior testing.

Indications were scored 1–9, with appropriate indications scored 7–9, uncertain indications scored 4–6, and inappropriate indications scored 1–3. An imaging study was considered to be appropriate for an indication if the additional information, in combination with clinical judgment, exceeded negative consequences. Negative consequences include the risks of the procedure (that is, radiation or contrast exposure) and the downstream effects of poor test performance (that is, delays in diagnosis or inappropriate diagnosis).

In all, 13 CCT and 17 CMR indications were found to be appropriate and 14 CCT and 9 CMR indications were found to be inappropriate.

For example, CMR was deemed inappropriate (score of 1) for detection of coronary artery disease patients with chest pain with a high pretest probability of CAD.

Although CCT was considered appropriate for several scenarios beyond assessments of structure and function, more than 40% of the indications were in this area. Two-thirds of the appropriate and uncertain indications for CMR were related to assessment of structure and function. “These results support the strengths of CMR as a tool for defining the etiology of complex patient presentations where the clinical suspicion is high,” the authors said.

In addition, 12 CCT and 7 CMR indications were found to be uncertain. Indications were considered uncertain because either critical data were lacking or significant differences of opinion existed among panel members regarding the value of the method for that particular indication.

“Uncertain is an area that for the most part simply means that we just don't know enough yet,” said Dr. Rubin.

It is striking that the criteria were developed with buy-in from the American College of Radiology, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the American Society of Nuclear Cardiology, the North American Society for Cardiac Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society of Interventional Radiology.

It has been a matter of heated contention among cardiologists, radiologists, and interventionalists as to whom should be performing cardiac imaging in general. However, the technical panel included representatives from as many specialty and subspecialty organizations as possible and “we're very proud of this,” said Dr. Hendel, adding that the group hopes the criteria serve as an endorsement for a more collaborative approach to cardiac imaging.

On the flip side though, “it's usually not a problem when you can bring people together in a nonconfrontational environment where the issue of who should do what is not on the table,” said Dr. Rubin, who is chief of the cardiovascular imaging at Stanford (Calif.) University.

The document is also intended to serve as a template for better reimbursement for these tests.

Currently, cardiac MR studies are reimbursed for the most part, said Dr. James C. Carr, director of cardiovascular imaging at Northwestern Memorial Hospital in Chicago. Dr. Carr served on the technical panel, representing the Society of Interventional Radiology.

Cardiac CT studies are not consistently reimbursed now though. “One of the problems is that the indications have not been clearly established for insurance companies,” he said. “Hopefully, this document will convince them that there are many situations where [cardiac CT] is indicated and hopefully they will consider reimbursement for these indications.”

WASHINGTON – Researchers in Japan have used functional magnetic resonance imaging to identify brain activation deficits associated with olfactory dysfunction in patients with Parkinson's disease, according to data presented at the World Parkinson Congress.

In a study of 10 patients with Parkinson's disease (PD) compared with 10 healthy controls, the researchers found significant brain activation in the cerebral cortex in control patients exposed to strong odorants, while PD patients showed little brain activation. Olfactory dysfunction appears to be one of the earliest symptoms of the disease.

“In PD, brain activation by odorant stimulation was significantly decreased. Hyposmia in PD is not a simple reflection of impairment in sniffing,” said Atsushi Takeda, Ph.D., of Tohoku University in Sendai, Japan.

The PD study participants had an average Hoehn and Yahr stage score of 2.2 and their mean L-dopa dosage was 243 mg. “So they were in the early stage of Parkinson's disease,” Dr. Takeda noted.

However, current olfactory tests for early PD detection rely on subjective responses by the patient and can potentially be influenced by environmental factors, such as temperature and humidity. “Most importantly, possible impairment in sniffing, as one of the motor symptoms of Parkinson's disease, may influence olfactory perception,” said Dr. Takeda.

The researchers used vanillin and toluene as olfactory stimulants. Patients were exposed to no odorants for 30 seconds, followed by odorant exposure for 30 seconds. This cycle was repeated six times.

To maintain constant odorant stimulation during the “on” periods, the researchers designed a special system with an evaporator and computer-controlled valves to allow exposure to the odorant and a high-pressure compressor to move the odorant to the subject wearing a face mask in the MRI tube. The researchers used a 1.5-T machine to obtain T2* images that were analyzed using statistical parametric mapping.

WASHINGTON – Researchers in Japan have used functional magnetic resonance imaging to identify brain activation deficits associated with olfactory dysfunction in patients with Parkinson's disease, according to data presented at the World Parkinson Congress.

In a study of 10 patients with Parkinson's disease (PD) compared with 10 healthy controls, the researchers found significant brain activation in the cerebral cortex in control patients exposed to strong odorants, while PD patients showed little brain activation. Olfactory dysfunction appears to be one of the earliest symptoms of the disease.

“In PD, brain activation by odorant stimulation was significantly decreased. Hyposmia in PD is not a simple reflection of impairment in sniffing,” said Atsushi Takeda, Ph.D., of Tohoku University in Sendai, Japan.

The PD study participants had an average Hoehn and Yahr stage score of 2.2 and their mean L-dopa dosage was 243 mg. “So they were in the early stage of Parkinson's disease,” Dr. Takeda noted.

However, current olfactory tests for early PD detection rely on subjective responses by the patient and can potentially be influenced by environmental factors, such as temperature and humidity. “Most importantly, possible impairment in sniffing, as one of the motor symptoms of Parkinson's disease, may influence olfactory perception,” said Dr. Takeda.

The researchers used vanillin and toluene as olfactory stimulants. Patients were exposed to no odorants for 30 seconds, followed by odorant exposure for 30 seconds. This cycle was repeated six times.

To maintain constant odorant stimulation during the “on” periods, the researchers designed a special system with an evaporator and computer-controlled valves to allow exposure to the odorant and a high-pressure compressor to move the odorant to the subject wearing a face mask in the MRI tube. The researchers used a 1.5-T machine to obtain T2* images that were analyzed using statistical parametric mapping.

WASHINGTON – Researchers in Japan have used functional magnetic resonance imaging to identify brain activation deficits associated with olfactory dysfunction in patients with Parkinson's disease, according to data presented at the World Parkinson Congress.

In a study of 10 patients with Parkinson's disease (PD) compared with 10 healthy controls, the researchers found significant brain activation in the cerebral cortex in control patients exposed to strong odorants, while PD patients showed little brain activation. Olfactory dysfunction appears to be one of the earliest symptoms of the disease.

“In PD, brain activation by odorant stimulation was significantly decreased. Hyposmia in PD is not a simple reflection of impairment in sniffing,” said Atsushi Takeda, Ph.D., of Tohoku University in Sendai, Japan.

The PD study participants had an average Hoehn and Yahr stage score of 2.2 and their mean L-dopa dosage was 243 mg. “So they were in the early stage of Parkinson's disease,” Dr. Takeda noted.

However, current olfactory tests for early PD detection rely on subjective responses by the patient and can potentially be influenced by environmental factors, such as temperature and humidity. “Most importantly, possible impairment in sniffing, as one of the motor symptoms of Parkinson's disease, may influence olfactory perception,” said Dr. Takeda.

The researchers used vanillin and toluene as olfactory stimulants. Patients were exposed to no odorants for 30 seconds, followed by odorant exposure for 30 seconds. This cycle was repeated six times.

To maintain constant odorant stimulation during the “on” periods, the researchers designed a special system with an evaporator and computer-controlled valves to allow exposure to the odorant and a high-pressure compressor to move the odorant to the subject wearing a face mask in the MRI tube. The researchers used a 1.5-T machine to obtain T2* images that were analyzed using statistical parametric mapping.

WASHINGTON – Women who develop Parkinson's disease do so at an older age than affected men, are more likely to present with a tremor-dominant form, and have higher levels of striatal dopamine transporter, according to data presented at the World Parkinson Congress.

“Several findings in our study indicated a more benign phenotype for women with Parkinson's disease,” said Dr. Charlotte Haaxma of Raboud University in Nijmegen, the Netherlands.

Dr. Haaxma and her colleagues retrospectively studied 253 patients with Parkinson's disease (PD) seen at their clinic between 1988 and 2003 to assess gender differences. Men accounted for 62% of patients. Patients were excluded from the study if they were taking levodopa or another dopamine agonist, had the disease for longer than 10 years, had physical disabilities resulting from another disease, used non-PD drugs, or were demented.

The researchers assessed the age at onset, presenting symptoms, estrogen status, Unified Parkinson Disease Rating Scale (UPDRS) motor scores, and dopamine transporter levels measured by [I-123]FP-CIT single-proton emission computer tomography (SPECT) imaging. UPDRS motor scores were assessed every 3–6 months.

Women were slightly older at the age of onset (53 years) than men (51 years). Women were also more likely to present with tremor–67% vs. 48%. “This gender difference remained intact throughout all age categories,” said Dr. Haaxma.

This finding prompted the researchers to look more closely at patients with tremor as the presenting symptom. Patients who presented with tremor were on average age 55 years at onset, compared with patients who presented with bradykinetic rigidity (age 50 years at onset).

“Women were older at symptom onset. They presented more often with tremor, and, if so, had an even higher age at onset,” said Dr. Haaxma. In addition, “the more children that a woman had, the higher the age at onset–2.7 years later per child,” said Dr. Haaxma. Women also had onset 0.5 year later for each fertile year. No correlations were found for age of menarche or estrogen therapy with age at onset.

Mean UPDRS motor scores were comparable for both genders at onset and the rate of degeneration did not differ between genders. However, tremor-dominant patients had a 38% slower rate of UPDRS motor score decline than bradykinetic-rigid subtype patients.

In terms of [I-123]FP-CIT SPECT imaging, women had a 16% higher mean binding than men, indicating higher striatal levels of dopamine transporter. However, the rate of dopamine transporter loss did not differ between genders. The tremor-dominant group tended to have a slower rate of deterioration, though this trend did not reach statistical significance.

The researchers proposed two hypothetical models to interpret the findings. In the first model, women have higher dopamine striatal levels and therefore take longer to reach the point of symptom onset. “Further, the estrogen effect of parity and other items associated with high cumulative estrogen levels might … delay the moment of symptom onset further,” said Dr. Haaxma.

In the second model, women have a slower rate of progression, so they take longer to reach symptom onset. Estrogen effects would translate into an even slower rate of decline. However, once symptoms start, the estrogen effect decreases, and men and women deteriorate with similar speed.

WASHINGTON – Women who develop Parkinson's disease do so at an older age than affected men, are more likely to present with a tremor-dominant form, and have higher levels of striatal dopamine transporter, according to data presented at the World Parkinson Congress.

“Several findings in our study indicated a more benign phenotype for women with Parkinson's disease,” said Dr. Charlotte Haaxma of Raboud University in Nijmegen, the Netherlands.

Dr. Haaxma and her colleagues retrospectively studied 253 patients with Parkinson's disease (PD) seen at their clinic between 1988 and 2003 to assess gender differences. Men accounted for 62% of patients. Patients were excluded from the study if they were taking levodopa or another dopamine agonist, had the disease for longer than 10 years, had physical disabilities resulting from another disease, used non-PD drugs, or were demented.

The researchers assessed the age at onset, presenting symptoms, estrogen status, Unified Parkinson Disease Rating Scale (UPDRS) motor scores, and dopamine transporter levels measured by [I-123]FP-CIT single-proton emission computer tomography (SPECT) imaging. UPDRS motor scores were assessed every 3–6 months.

Women were slightly older at the age of onset (53 years) than men (51 years). Women were also more likely to present with tremor–67% vs. 48%. “This gender difference remained intact throughout all age categories,” said Dr. Haaxma.

This finding prompted the researchers to look more closely at patients with tremor as the presenting symptom. Patients who presented with tremor were on average age 55 years at onset, compared with patients who presented with bradykinetic rigidity (age 50 years at onset).

“Women were older at symptom onset. They presented more often with tremor, and, if so, had an even higher age at onset,” said Dr. Haaxma. In addition, “the more children that a woman had, the higher the age at onset–2.7 years later per child,” said Dr. Haaxma. Women also had onset 0.5 year later for each fertile year. No correlations were found for age of menarche or estrogen therapy with age at onset.

Mean UPDRS motor scores were comparable for both genders at onset and the rate of degeneration did not differ between genders. However, tremor-dominant patients had a 38% slower rate of UPDRS motor score decline than bradykinetic-rigid subtype patients.

In terms of [I-123]FP-CIT SPECT imaging, women had a 16% higher mean binding than men, indicating higher striatal levels of dopamine transporter. However, the rate of dopamine transporter loss did not differ between genders. The tremor-dominant group tended to have a slower rate of deterioration, though this trend did not reach statistical significance.

The researchers proposed two hypothetical models to interpret the findings. In the first model, women have higher dopamine striatal levels and therefore take longer to reach the point of symptom onset. “Further, the estrogen effect of parity and other items associated with high cumulative estrogen levels might … delay the moment of symptom onset further,” said Dr. Haaxma.

In the second model, women have a slower rate of progression, so they take longer to reach symptom onset. Estrogen effects would translate into an even slower rate of decline. However, once symptoms start, the estrogen effect decreases, and men and women deteriorate with similar speed.

WASHINGTON – Women who develop Parkinson's disease do so at an older age than affected men, are more likely to present with a tremor-dominant form, and have higher levels of striatal dopamine transporter, according to data presented at the World Parkinson Congress.

“Several findings in our study indicated a more benign phenotype for women with Parkinson's disease,” said Dr. Charlotte Haaxma of Raboud University in Nijmegen, the Netherlands.

Dr. Haaxma and her colleagues retrospectively studied 253 patients with Parkinson's disease (PD) seen at their clinic between 1988 and 2003 to assess gender differences. Men accounted for 62% of patients. Patients were excluded from the study if they were taking levodopa or another dopamine agonist, had the disease for longer than 10 years, had physical disabilities resulting from another disease, used non-PD drugs, or were demented.

The researchers assessed the age at onset, presenting symptoms, estrogen status, Unified Parkinson Disease Rating Scale (UPDRS) motor scores, and dopamine transporter levels measured by [I-123]FP-CIT single-proton emission computer tomography (SPECT) imaging. UPDRS motor scores were assessed every 3–6 months.

Women were slightly older at the age of onset (53 years) than men (51 years). Women were also more likely to present with tremor–67% vs. 48%. “This gender difference remained intact throughout all age categories,” said Dr. Haaxma.

This finding prompted the researchers to look more closely at patients with tremor as the presenting symptom. Patients who presented with tremor were on average age 55 years at onset, compared with patients who presented with bradykinetic rigidity (age 50 years at onset).

“Women were older at symptom onset. They presented more often with tremor, and, if so, had an even higher age at onset,” said Dr. Haaxma. In addition, “the more children that a woman had, the higher the age at onset–2.7 years later per child,” said Dr. Haaxma. Women also had onset 0.5 year later for each fertile year. No correlations were found for age of menarche or estrogen therapy with age at onset.

Mean UPDRS motor scores were comparable for both genders at onset and the rate of degeneration did not differ between genders. However, tremor-dominant patients had a 38% slower rate of UPDRS motor score decline than bradykinetic-rigid subtype patients.

In terms of [I-123]FP-CIT SPECT imaging, women had a 16% higher mean binding than men, indicating higher striatal levels of dopamine transporter. However, the rate of dopamine transporter loss did not differ between genders. The tremor-dominant group tended to have a slower rate of deterioration, though this trend did not reach statistical significance.

The researchers proposed two hypothetical models to interpret the findings. In the first model, women have higher dopamine striatal levels and therefore take longer to reach the point of symptom onset. “Further, the estrogen effect of parity and other items associated with high cumulative estrogen levels might … delay the moment of symptom onset further,” said Dr. Haaxma.

In the second model, women have a slower rate of progression, so they take longer to reach symptom onset. Estrogen effects would translate into an even slower rate of decline. However, once symptoms start, the estrogen effect decreases, and men and women deteriorate with similar speed.

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard two-dimensional format or a three-dimensional approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward.

“We can produce images that look just like an endoscopic examination of the colon,” said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis. “Much of the excitement about this technique revolves around its advantages relative to optical colonoscopy.”

These advantages include the following benefits:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. A number of studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an air contrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging is a technique that can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon. Residual stool tagged in this way has a very high density in a two-dimensional image, which clearly differentiates it from a polyp.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid will then appear high in density on a two-dimensional image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9 and Lancet 2005;365;305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and two-dimensional images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. This allows the examination to be performed in a much shorter time than with single-detector scanners. In addition, “our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in the reading of virtual colonoscopy images. “Reader training is a critical factor,” he said. All of these aspects help account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging are being utilized, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “Most of us who have experience with this believe that it takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends. It's also a much more efficient way of looking at the colon,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient by [more quickly] bringing our attention to lesions that we might have missed,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO₂ is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

Transaxial and sagittal views (left and middle) are shown of a rectosigmoid junction polyp imaged by a conventional CT scanner. A corresponding 3-D endoluminal view is shown of the same polyp (right). Photos courtesy Dr. Jay P. Heiken

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard two-dimensional format or a three-dimensional approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward.

“We can produce images that look just like an endoscopic examination of the colon,” said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis. “Much of the excitement about this technique revolves around its advantages relative to optical colonoscopy.”

These advantages include the following benefits:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. A number of studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an air contrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging is a technique that can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon. Residual stool tagged in this way has a very high density in a two-dimensional image, which clearly differentiates it from a polyp.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid will then appear high in density on a two-dimensional image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9 and Lancet 2005;365;305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and two-dimensional images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. This allows the examination to be performed in a much shorter time than with single-detector scanners. In addition, “our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in the reading of virtual colonoscopy images. “Reader training is a critical factor,” he said. All of these aspects help account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging are being utilized, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “Most of us who have experience with this believe that it takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends. It's also a much more efficient way of looking at the colon,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient by [more quickly] bringing our attention to lesions that we might have missed,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO₂ is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

Transaxial and sagittal views (left and middle) are shown of a rectosigmoid junction polyp imaged by a conventional CT scanner. A corresponding 3-D endoluminal view is shown of the same polyp (right). Photos courtesy Dr. Jay P. Heiken

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard two-dimensional format or a three-dimensional approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward.

“We can produce images that look just like an endoscopic examination of the colon,” said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis. “Much of the excitement about this technique revolves around its advantages relative to optical colonoscopy.”

These advantages include the following benefits:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. A number of studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an air contrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging is a technique that can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon. Residual stool tagged in this way has a very high density in a two-dimensional image, which clearly differentiates it from a polyp.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid will then appear high in density on a two-dimensional image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9 and Lancet 2005;365;305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and two-dimensional images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. This allows the examination to be performed in a much shorter time than with single-detector scanners. In addition, “our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in the reading of virtual colonoscopy images. “Reader training is a critical factor,” he said. All of these aspects help account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging are being utilized, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “Most of us who have experience with this believe that it takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends. It's also a much more efficient way of looking at the colon,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient by [more quickly] bringing our attention to lesions that we might have missed,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO₂ is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

Transaxial and sagittal views (left and middle) are shown of a rectosigmoid junction polyp imaged by a conventional CT scanner. A corresponding 3-D endoluminal view is shown of the same polyp (right). Photos courtesy Dr. Jay P. Heiken