Doug Brunk

Over a year after IVIG infusions ended, the patient had an elevated IgG level of 4,000 mg/dL. DR. WANG

CARMEL, CALIF. — A complication involving monoclonal gammopathy in a child who received cord blood for treatment of Chédiak-Higashi syndrome may be the first of its kind, Dr. Kevin Wang said at the Western regional meeting of the American Federation for Medical Research.

Dr. Wang, a visiting fellow in the department of pediatrics at the University of California, Los Angeles, Medical Center, discussed what is believed to be the first reported case of monoclonal gammopathy in a young boy following cord blood transplantation.

At 16 months of age, the boy was diagnosed with Chédiak-Higashi syndrome (CHS), but his parents declined bone marrow transplantation at that time. At age 2 years, he was started on granulocyte colony-stimulating factor for neutropenia and remained stable for the next 4 years.

At age 6 years, the boy presented to Dr. Wang and his associate, Dr. Robert L. Roberts, with pancytopenia, fever, respiratory distress, mental status changes, seizure activity, and hepatosplenomegaly.

Dr. Wang and Dr. Roberts determined that the boy was in the accelerated phase of CHS. Bone marrow biopsy showed cytoplasmic inclusions, granulocytes, and hemophagocytic cells. Brain MRI showed nonspecific focal hyperintensities in the white matter, which is consistent with lymphohistiocytic infiltration.

The boy received three courses of IV immunoglobulin (IG), then methylprednisolone for 10 days, and dexamethasone for 2 months, after which he remained on a maintenance dose of dexamethasone until the time of splenectomy that was necessitated by persistent thrombocytopenia. Over the next several weeks, the boy's condition improved.

A repeat bone marrow biopsy revealed rare hemophagocytic cells and a repeat MRI showed significant improvement, suggesting that he was in remission from the accelerated phase. Dr. Wang reported that the boy then received a 10/10 match cord blood transplantation. He appeared to engraft successfully, leading to discontinuation of his routine infusions of IVIG. About 15 months later, the boy was clinically stable but he had an elevated IgG level of 4,000 mg/dL. Immunoelectrophoresis revealed that he had developed a monoclonal IgG gammopathy.

“The patient is clinically stable but he is being monitored closely for the risk of developing lymphoma,” Dr. Wang said.

Over a year after IVIG infusions ended, the patient had an elevated IgG level of 4,000 mg/dL. DR. WANG

CARMEL, CALIF. — A complication involving monoclonal gammopathy in a child who received cord blood for treatment of Chédiak-Higashi syndrome may be the first of its kind, Dr. Kevin Wang said at the Western regional meeting of the American Federation for Medical Research.

Dr. Wang, a visiting fellow in the department of pediatrics at the University of California, Los Angeles, Medical Center, discussed what is believed to be the first reported case of monoclonal gammopathy in a young boy following cord blood transplantation.

At 16 months of age, the boy was diagnosed with Chédiak-Higashi syndrome (CHS), but his parents declined bone marrow transplantation at that time. At age 2 years, he was started on granulocyte colony-stimulating factor for neutropenia and remained stable for the next 4 years.

At age 6 years, the boy presented to Dr. Wang and his associate, Dr. Robert L. Roberts, with pancytopenia, fever, respiratory distress, mental status changes, seizure activity, and hepatosplenomegaly.

Dr. Wang and Dr. Roberts determined that the boy was in the accelerated phase of CHS. Bone marrow biopsy showed cytoplasmic inclusions, granulocytes, and hemophagocytic cells. Brain MRI showed nonspecific focal hyperintensities in the white matter, which is consistent with lymphohistiocytic infiltration.

The boy received three courses of IV immunoglobulin (IG), then methylprednisolone for 10 days, and dexamethasone for 2 months, after which he remained on a maintenance dose of dexamethasone until the time of splenectomy that was necessitated by persistent thrombocytopenia. Over the next several weeks, the boy's condition improved.

A repeat bone marrow biopsy revealed rare hemophagocytic cells and a repeat MRI showed significant improvement, suggesting that he was in remission from the accelerated phase. Dr. Wang reported that the boy then received a 10/10 match cord blood transplantation. He appeared to engraft successfully, leading to discontinuation of his routine infusions of IVIG. About 15 months later, the boy was clinically stable but he had an elevated IgG level of 4,000 mg/dL. Immunoelectrophoresis revealed that he had developed a monoclonal IgG gammopathy.

“The patient is clinically stable but he is being monitored closely for the risk of developing lymphoma,” Dr. Wang said.

Over a year after IVIG infusions ended, the patient had an elevated IgG level of 4,000 mg/dL. DR. WANG

CARMEL, CALIF. — A complication involving monoclonal gammopathy in a child who received cord blood for treatment of Chédiak-Higashi syndrome may be the first of its kind, Dr. Kevin Wang said at the Western regional meeting of the American Federation for Medical Research.

Dr. Wang, a visiting fellow in the department of pediatrics at the University of California, Los Angeles, Medical Center, discussed what is believed to be the first reported case of monoclonal gammopathy in a young boy following cord blood transplantation.

At 16 months of age, the boy was diagnosed with Chédiak-Higashi syndrome (CHS), but his parents declined bone marrow transplantation at that time. At age 2 years, he was started on granulocyte colony-stimulating factor for neutropenia and remained stable for the next 4 years.

At age 6 years, the boy presented to Dr. Wang and his associate, Dr. Robert L. Roberts, with pancytopenia, fever, respiratory distress, mental status changes, seizure activity, and hepatosplenomegaly.

Dr. Wang and Dr. Roberts determined that the boy was in the accelerated phase of CHS. Bone marrow biopsy showed cytoplasmic inclusions, granulocytes, and hemophagocytic cells. Brain MRI showed nonspecific focal hyperintensities in the white matter, which is consistent with lymphohistiocytic infiltration.

The boy received three courses of IV immunoglobulin (IG), then methylprednisolone for 10 days, and dexamethasone for 2 months, after which he remained on a maintenance dose of dexamethasone until the time of splenectomy that was necessitated by persistent thrombocytopenia. Over the next several weeks, the boy's condition improved.

A repeat bone marrow biopsy revealed rare hemophagocytic cells and a repeat MRI showed significant improvement, suggesting that he was in remission from the accelerated phase. Dr. Wang reported that the boy then received a 10/10 match cord blood transplantation. He appeared to engraft successfully, leading to discontinuation of his routine infusions of IVIG. About 15 months later, the boy was clinically stable but he had an elevated IgG level of 4,000 mg/dL. Immunoelectrophoresis revealed that he had developed a monoclonal IgG gammopathy.

“The patient is clinically stable but he is being monitored closely for the risk of developing lymphoma,” Dr. Wang said.

After routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube insertions among children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, results from a large birth cohort analysis showed.

The findings “are particularly encouraging in light of [seven-valent pneumococcal conjugate vaccine (PCV7)] shortages,” wrote the researchers led by Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University Medical Center, Winston-Salem, N.C.

“Furthermore, these reductions in frequent otitis media and PETs [pressure-equalizing tubes] are higher than that seen in randomized, controlled trials and may have important implications on the cost-effectiveness analyses for PCV7,” the authors stated.

Dr. Poehling and her associates reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth.

They focused on four birth cohorts: children born between July 1 and June 30, 1998–1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent otitis media or had pressure-equalizing tubes inserted (Pediatrics 2007;119:707–15).

National Immunization Survey data from Tennessee and New York were used to estimate the number of children in the four birth cohorts who were vaccinated by 2 years of age.

The researchers reported that the proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the researchers compared the 2000–2001 birth cohort with the 1998–1999 birth cohort, they found that the frequency of otitis media in Tennessee and New York declined by 17% and 28%, respectively, while pressure-equalizing tube insertions declined by 16% and 23%, respectively.

When they compared the 2000–2001 birth cohort with the 2001–2002 birth cohort, they observed that the cases of frequent otitis media and the need for insertion of pressure-equalizing tubes remained stable in New York but increased in Tennessee. Reasons for this could be multifactorial.

“The increase in laboratory-confirmed pneumococcal disease from nonvaccine serotypes from the pre-PCV7 to post-PCV7 era has been reported for invasive disease and in one study on otitis media,” the researchers wrote.

“Temporal changes in the children who are enrolled and disenrolled from insurance plans may have contributed to this discrepancy.”

Dr. Poehling and her associates acknowledged certain limitations of the study, including the possibility that other factors, “such as the encouragement of the judicious use of antibiotics, may have influenced physicians' diagnostic patterns for otitis media. Furthermore, administrative data claims incompletely capture individual vaccinations and the PCV7 status of the elderly population is not known.”

The study was funded with support from the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

After routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube insertions among children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, results from a large birth cohort analysis showed.

The findings “are particularly encouraging in light of [seven-valent pneumococcal conjugate vaccine (PCV7)] shortages,” wrote the researchers led by Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University Medical Center, Winston-Salem, N.C.

“Furthermore, these reductions in frequent otitis media and PETs [pressure-equalizing tubes] are higher than that seen in randomized, controlled trials and may have important implications on the cost-effectiveness analyses for PCV7,” the authors stated.

Dr. Poehling and her associates reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth.

They focused on four birth cohorts: children born between July 1 and June 30, 1998–1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent otitis media or had pressure-equalizing tubes inserted (Pediatrics 2007;119:707–15).

National Immunization Survey data from Tennessee and New York were used to estimate the number of children in the four birth cohorts who were vaccinated by 2 years of age.

The researchers reported that the proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the researchers compared the 2000–2001 birth cohort with the 1998–1999 birth cohort, they found that the frequency of otitis media in Tennessee and New York declined by 17% and 28%, respectively, while pressure-equalizing tube insertions declined by 16% and 23%, respectively.

When they compared the 2000–2001 birth cohort with the 2001–2002 birth cohort, they observed that the cases of frequent otitis media and the need for insertion of pressure-equalizing tubes remained stable in New York but increased in Tennessee. Reasons for this could be multifactorial.

“The increase in laboratory-confirmed pneumococcal disease from nonvaccine serotypes from the pre-PCV7 to post-PCV7 era has been reported for invasive disease and in one study on otitis media,” the researchers wrote.

“Temporal changes in the children who are enrolled and disenrolled from insurance plans may have contributed to this discrepancy.”

Dr. Poehling and her associates acknowledged certain limitations of the study, including the possibility that other factors, “such as the encouragement of the judicious use of antibiotics, may have influenced physicians' diagnostic patterns for otitis media. Furthermore, administrative data claims incompletely capture individual vaccinations and the PCV7 status of the elderly population is not known.”

The study was funded with support from the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

After routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube insertions among children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, results from a large birth cohort analysis showed.

The findings “are particularly encouraging in light of [seven-valent pneumococcal conjugate vaccine (PCV7)] shortages,” wrote the researchers led by Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University Medical Center, Winston-Salem, N.C.

“Furthermore, these reductions in frequent otitis media and PETs [pressure-equalizing tubes] are higher than that seen in randomized, controlled trials and may have important implications on the cost-effectiveness analyses for PCV7,” the authors stated.

Dr. Poehling and her associates reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth.

They focused on four birth cohorts: children born between July 1 and June 30, 1998–1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent otitis media or had pressure-equalizing tubes inserted (Pediatrics 2007;119:707–15).

National Immunization Survey data from Tennessee and New York were used to estimate the number of children in the four birth cohorts who were vaccinated by 2 years of age.

The researchers reported that the proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the researchers compared the 2000–2001 birth cohort with the 1998–1999 birth cohort, they found that the frequency of otitis media in Tennessee and New York declined by 17% and 28%, respectively, while pressure-equalizing tube insertions declined by 16% and 23%, respectively.

When they compared the 2000–2001 birth cohort with the 2001–2002 birth cohort, they observed that the cases of frequent otitis media and the need for insertion of pressure-equalizing tubes remained stable in New York but increased in Tennessee. Reasons for this could be multifactorial.

“The increase in laboratory-confirmed pneumococcal disease from nonvaccine serotypes from the pre-PCV7 to post-PCV7 era has been reported for invasive disease and in one study on otitis media,” the researchers wrote.

“Temporal changes in the children who are enrolled and disenrolled from insurance plans may have contributed to this discrepancy.”

Dr. Poehling and her associates acknowledged certain limitations of the study, including the possibility that other factors, “such as the encouragement of the judicious use of antibiotics, may have influenced physicians' diagnostic patterns for otitis media. Furthermore, administrative data claims incompletely capture individual vaccinations and the PCV7 status of the elderly population is not known.”

The study was funded with support from the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

SAN DIEGO — Ablative therapies are a promising alternative to esophagectomy for treating patients with high-grade dysplasia associated with Barrett's esophagus, Dr. Kenneth K. Wang said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

One reason to consider ablation is that esophagectomy has high mortality. A study showed that the mortality is 20% in hospitals that perform fewer than two esophagectomies per year, compared with about 8% in hospitals that perform more than 19 esophagectomies per year (N. Engl. J. Med. 2002;346:1128–37). “There's a learning curve to esophagectomies,” said Dr. Wang, who directs the Barrett's Esophagus Unit at the Mayo Clinic in Rochester, Minn.

In addition, new Barrett's disease can occur after esophagectomy for high-grade dysplasia. One study of 40 patients who underwent esophagectomy found that 29% had erosive esophagitis and 40% had a columnar esophagus (Br. J. Surg. 2003;90:1120–8). “So you have to be aware that if you subject these patients to esophagectomy, it may not be the best thing, even if they're young,” he said.

One ablative option includes endoscopic mucosal resection using a cap-fitted endoscope. The most difficult part of this procedure is forming the snare around the loop of the cap, but this is improved with a newer band ligation device, Dr. Wang said.

Another option is circumferential endoscopic mucosal resection, which involves removing the index lesion as well as the Barrett's epithelium. “You can take out the whole Barrett's segment this way,” he said. “However, there is a bit of residual. It's very hard to take out the entire esophageal mucosa in a piecemeal fashion.”

One study of 35 Barrett's patients who underwent circumferential endoscopic mucosal resection found that 6% had residual high-grade dysplasia and 17% had residual intestinal metaplasia (Gastrointest. Endosc. 2003;57:854–9).

With this technique, “there's a lot of scarring, so you have to use repeated mucosal resection,” Dr. Wang said. In one study, treatment for 1 of 10 patients could not be completed because of scarring (Gastrointest. Endosc. 2006;63:847–52).

Overall, the results of endoscopic mucosal resection techniques “are pretty good,” he said. One study of 19 Barrett's patients with high-grade dysplasia and 96 with early cancers found a local remission rate of 98%. However, because the researchers removed only high-grade dysplastic lesions, metachronous lesions occurred in 30% of patients over 34 months (Euro. J. Gastroenterol. Hepatol. 2002;14:1085–91). “Even though the treated area looks good and histology is improved, there are the same genetic defects in the areas around the treated site that must be dealt with,” Dr. Wang explained.

Complications occurred in 10% of the patients—mainly bleeding and stenosis.

Photodynamic therapy (PDT) is also being used to treat high-grade dysplasia and cancer associated with Barrett's. This technique “probably has the longest track record,” Dr. Wang said. “It's very easy to do and takes about 5 minutes of photoradiation time.”

In a trial presented at the 2006 Digestive Disease Week, researchers randomized 208 patients to either continued surveillance or PDT. At 24 months, 77% of those in the PDT group had elimination of high-grade dysplasia, compared with 39% of those in the surveillance arm.

The 5-year clinical response data showed that 52% of those in the PDT group had completely normal mucosa, compared with 7% in the surveillance arm.

Dr. Wang added that three Markov models have all shown “that PDT is more cost effective than surgery or surveillance.”

Other available techniques include multipolar electrocoagulation and argon plasma coagulation. Results from one randomized study of 52 patients suggest that the efficacy of these two techniques is about the same. The endoscopic and histologic ablation rates for patients who underwent multipolar electrocoagulation were 88% and 81%, respectively; the endoscopic and histologic ablation rates for patients who underwent argon plasma coagulation were 81% and 67%, respectively.

These techniques “are not perfect,” Dr. Wang said. “There are always bits of Barrett's left, and you still have to continue surveillance.”

New alternatives expected to hit the market soon include devices that use cryotherapy and radiofrequency to ablate Barrett's tissue.

Whether physicians implement ablative techniques into their practice or not “depends on a lot of factors,” he said. “It depends on your expertise and that of the surgeons in your institution. It depends on the patients, how long their longevity is, whether or not they're going to be willing to come back to you, and the length of the Barrett's segment.”

Dr. Wang disclosed that he has received research support from Axcan and BarRx and served as a paid consultant for InScope.

SAN DIEGO — Ablative therapies are a promising alternative to esophagectomy for treating patients with high-grade dysplasia associated with Barrett's esophagus, Dr. Kenneth K. Wang said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

One reason to consider ablation is that esophagectomy has high mortality. A study showed that the mortality is 20% in hospitals that perform fewer than two esophagectomies per year, compared with about 8% in hospitals that perform more than 19 esophagectomies per year (N. Engl. J. Med. 2002;346:1128–37). “There's a learning curve to esophagectomies,” said Dr. Wang, who directs the Barrett's Esophagus Unit at the Mayo Clinic in Rochester, Minn.

In addition, new Barrett's disease can occur after esophagectomy for high-grade dysplasia. One study of 40 patients who underwent esophagectomy found that 29% had erosive esophagitis and 40% had a columnar esophagus (Br. J. Surg. 2003;90:1120–8). “So you have to be aware that if you subject these patients to esophagectomy, it may not be the best thing, even if they're young,” he said.

One ablative option includes endoscopic mucosal resection using a cap-fitted endoscope. The most difficult part of this procedure is forming the snare around the loop of the cap, but this is improved with a newer band ligation device, Dr. Wang said.

Another option is circumferential endoscopic mucosal resection, which involves removing the index lesion as well as the Barrett's epithelium. “You can take out the whole Barrett's segment this way,” he said. “However, there is a bit of residual. It's very hard to take out the entire esophageal mucosa in a piecemeal fashion.”

One study of 35 Barrett's patients who underwent circumferential endoscopic mucosal resection found that 6% had residual high-grade dysplasia and 17% had residual intestinal metaplasia (Gastrointest. Endosc. 2003;57:854–9).

With this technique, “there's a lot of scarring, so you have to use repeated mucosal resection,” Dr. Wang said. In one study, treatment for 1 of 10 patients could not be completed because of scarring (Gastrointest. Endosc. 2006;63:847–52).

Overall, the results of endoscopic mucosal resection techniques “are pretty good,” he said. One study of 19 Barrett's patients with high-grade dysplasia and 96 with early cancers found a local remission rate of 98%. However, because the researchers removed only high-grade dysplastic lesions, metachronous lesions occurred in 30% of patients over 34 months (Euro. J. Gastroenterol. Hepatol. 2002;14:1085–91). “Even though the treated area looks good and histology is improved, there are the same genetic defects in the areas around the treated site that must be dealt with,” Dr. Wang explained.

Complications occurred in 10% of the patients—mainly bleeding and stenosis.

Photodynamic therapy (PDT) is also being used to treat high-grade dysplasia and cancer associated with Barrett's. This technique “probably has the longest track record,” Dr. Wang said. “It's very easy to do and takes about 5 minutes of photoradiation time.”

In a trial presented at the 2006 Digestive Disease Week, researchers randomized 208 patients to either continued surveillance or PDT. At 24 months, 77% of those in the PDT group had elimination of high-grade dysplasia, compared with 39% of those in the surveillance arm.

The 5-year clinical response data showed that 52% of those in the PDT group had completely normal mucosa, compared with 7% in the surveillance arm.

Dr. Wang added that three Markov models have all shown “that PDT is more cost effective than surgery or surveillance.”

Other available techniques include multipolar electrocoagulation and argon plasma coagulation. Results from one randomized study of 52 patients suggest that the efficacy of these two techniques is about the same. The endoscopic and histologic ablation rates for patients who underwent multipolar electrocoagulation were 88% and 81%, respectively; the endoscopic and histologic ablation rates for patients who underwent argon plasma coagulation were 81% and 67%, respectively.

These techniques “are not perfect,” Dr. Wang said. “There are always bits of Barrett's left, and you still have to continue surveillance.”

New alternatives expected to hit the market soon include devices that use cryotherapy and radiofrequency to ablate Barrett's tissue.

Whether physicians implement ablative techniques into their practice or not “depends on a lot of factors,” he said. “It depends on your expertise and that of the surgeons in your institution. It depends on the patients, how long their longevity is, whether or not they're going to be willing to come back to you, and the length of the Barrett's segment.”

Dr. Wang disclosed that he has received research support from Axcan and BarRx and served as a paid consultant for InScope.

SAN DIEGO — Ablative therapies are a promising alternative to esophagectomy for treating patients with high-grade dysplasia associated with Barrett's esophagus, Dr. Kenneth K. Wang said at a meeting jointly sponsored by the AGA Institute and the Japanese Society of Gastroenterology.

One reason to consider ablation is that esophagectomy has high mortality. A study showed that the mortality is 20% in hospitals that perform fewer than two esophagectomies per year, compared with about 8% in hospitals that perform more than 19 esophagectomies per year (N. Engl. J. Med. 2002;346:1128–37). “There's a learning curve to esophagectomies,” said Dr. Wang, who directs the Barrett's Esophagus Unit at the Mayo Clinic in Rochester, Minn.

In addition, new Barrett's disease can occur after esophagectomy for high-grade dysplasia. One study of 40 patients who underwent esophagectomy found that 29% had erosive esophagitis and 40% had a columnar esophagus (Br. J. Surg. 2003;90:1120–8). “So you have to be aware that if you subject these patients to esophagectomy, it may not be the best thing, even if they're young,” he said.

One ablative option includes endoscopic mucosal resection using a cap-fitted endoscope. The most difficult part of this procedure is forming the snare around the loop of the cap, but this is improved with a newer band ligation device, Dr. Wang said.

Another option is circumferential endoscopic mucosal resection, which involves removing the index lesion as well as the Barrett's epithelium. “You can take out the whole Barrett's segment this way,” he said. “However, there is a bit of residual. It's very hard to take out the entire esophageal mucosa in a piecemeal fashion.”

One study of 35 Barrett's patients who underwent circumferential endoscopic mucosal resection found that 6% had residual high-grade dysplasia and 17% had residual intestinal metaplasia (Gastrointest. Endosc. 2003;57:854–9).

With this technique, “there's a lot of scarring, so you have to use repeated mucosal resection,” Dr. Wang said. In one study, treatment for 1 of 10 patients could not be completed because of scarring (Gastrointest. Endosc. 2006;63:847–52).

Overall, the results of endoscopic mucosal resection techniques “are pretty good,” he said. One study of 19 Barrett's patients with high-grade dysplasia and 96 with early cancers found a local remission rate of 98%. However, because the researchers removed only high-grade dysplastic lesions, metachronous lesions occurred in 30% of patients over 34 months (Euro. J. Gastroenterol. Hepatol. 2002;14:1085–91). “Even though the treated area looks good and histology is improved, there are the same genetic defects in the areas around the treated site that must be dealt with,” Dr. Wang explained.

Complications occurred in 10% of the patients—mainly bleeding and stenosis.

Photodynamic therapy (PDT) is also being used to treat high-grade dysplasia and cancer associated with Barrett's. This technique “probably has the longest track record,” Dr. Wang said. “It's very easy to do and takes about 5 minutes of photoradiation time.”

In a trial presented at the 2006 Digestive Disease Week, researchers randomized 208 patients to either continued surveillance or PDT. At 24 months, 77% of those in the PDT group had elimination of high-grade dysplasia, compared with 39% of those in the surveillance arm.

The 5-year clinical response data showed that 52% of those in the PDT group had completely normal mucosa, compared with 7% in the surveillance arm.

Dr. Wang added that three Markov models have all shown “that PDT is more cost effective than surgery or surveillance.”

Other available techniques include multipolar electrocoagulation and argon plasma coagulation. Results from one randomized study of 52 patients suggest that the efficacy of these two techniques is about the same. The endoscopic and histologic ablation rates for patients who underwent multipolar electrocoagulation were 88% and 81%, respectively; the endoscopic and histologic ablation rates for patients who underwent argon plasma coagulation were 81% and 67%, respectively.

These techniques “are not perfect,” Dr. Wang said. “There are always bits of Barrett's left, and you still have to continue surveillance.”

New alternatives expected to hit the market soon include devices that use cryotherapy and radiofrequency to ablate Barrett's tissue.

Whether physicians implement ablative techniques into their practice or not “depends on a lot of factors,” he said. “It depends on your expertise and that of the surgeons in your institution. It depends on the patients, how long their longevity is, whether or not they're going to be willing to come back to you, and the length of the Barrett's segment.”

Dr. Wang disclosed that he has received research support from Axcan and BarRx and served as a paid consultant for InScope.

CARMEL, CALIF. — Taking the time to discuss reconstructive surgery with low-income women who undergo mastectomy for breast cancer has a direct, positive impact on their decision to have reconstructive surgery, results from a large survey showed.

Having such a discussion “may overcome disparities in receipt of reconstructive surgery in underserved women and is a potentially malleable factor,” Elaine Kwong said at the Western regional meeting of the American Federation for Medical Research. “Standardized protocols for discussion of breast cancer treatment options should be considered to overcome potential literacy and language barriers.”

Ms. Kwong, of the the University of California, Los Angeles, and her associates at the university's school of public health conducted a longitudinal survey of 357 breast cancer patients who were receiving breast cancer treatment through the Medi-Cal Breast and Cervical Cancer Treatment Program. Women eligible for this program live below 200% of the federal poverty level.

Study criteria included being over age 17, having a first diagnosis of breast cancer within the last 6 months, being English or Spanish speaking, and not currently being treated for other cancers.

During telephone interviews with the women at 6 months and 18 months after their breast cancer diagnosis, the researchers administered the five-item version of the Perceived Efficacy in Patient-Physician Interactions Questionnaire, a scale that indicates patients' confidence in communicating with providers.

Multiple regression analysis revealed that only discussion of reconstructive surgery by a health care professional had a significant relationship with reconstructive surgery that was either received or planned. This was independent of age, ethnicity, education, marital/partnered status, perceived health status, and other components of patient-physician communication.

Specifically, women who had discussions of reconstructive surgery with any health care provider were 5.8 times more likely to undergo or schedule surgery, compared with those who did not have such discussions.

Being of Asian/Pacific Islander descent and being married or partnered negatively predicted the likelihood of undergoing or scheduling reconstructive surgery.

Breast cancer is the most common cancer in women and is also the second leading cause of cancer-related death in women.

CARMEL, CALIF. — Taking the time to discuss reconstructive surgery with low-income women who undergo mastectomy for breast cancer has a direct, positive impact on their decision to have reconstructive surgery, results from a large survey showed.

Having such a discussion “may overcome disparities in receipt of reconstructive surgery in underserved women and is a potentially malleable factor,” Elaine Kwong said at the Western regional meeting of the American Federation for Medical Research. “Standardized protocols for discussion of breast cancer treatment options should be considered to overcome potential literacy and language barriers.”

Ms. Kwong, of the the University of California, Los Angeles, and her associates at the university's school of public health conducted a longitudinal survey of 357 breast cancer patients who were receiving breast cancer treatment through the Medi-Cal Breast and Cervical Cancer Treatment Program. Women eligible for this program live below 200% of the federal poverty level.

Study criteria included being over age 17, having a first diagnosis of breast cancer within the last 6 months, being English or Spanish speaking, and not currently being treated for other cancers.

During telephone interviews with the women at 6 months and 18 months after their breast cancer diagnosis, the researchers administered the five-item version of the Perceived Efficacy in Patient-Physician Interactions Questionnaire, a scale that indicates patients' confidence in communicating with providers.

Multiple regression analysis revealed that only discussion of reconstructive surgery by a health care professional had a significant relationship with reconstructive surgery that was either received or planned. This was independent of age, ethnicity, education, marital/partnered status, perceived health status, and other components of patient-physician communication.

Specifically, women who had discussions of reconstructive surgery with any health care provider were 5.8 times more likely to undergo or schedule surgery, compared with those who did not have such discussions.

Being of Asian/Pacific Islander descent and being married or partnered negatively predicted the likelihood of undergoing or scheduling reconstructive surgery.

Breast cancer is the most common cancer in women and is also the second leading cause of cancer-related death in women.

CARMEL, CALIF. — Taking the time to discuss reconstructive surgery with low-income women who undergo mastectomy for breast cancer has a direct, positive impact on their decision to have reconstructive surgery, results from a large survey showed.

Having such a discussion “may overcome disparities in receipt of reconstructive surgery in underserved women and is a potentially malleable factor,” Elaine Kwong said at the Western regional meeting of the American Federation for Medical Research. “Standardized protocols for discussion of breast cancer treatment options should be considered to overcome potential literacy and language barriers.”

Ms. Kwong, of the the University of California, Los Angeles, and her associates at the university's school of public health conducted a longitudinal survey of 357 breast cancer patients who were receiving breast cancer treatment through the Medi-Cal Breast and Cervical Cancer Treatment Program. Women eligible for this program live below 200% of the federal poverty level.

Study criteria included being over age 17, having a first diagnosis of breast cancer within the last 6 months, being English or Spanish speaking, and not currently being treated for other cancers.

During telephone interviews with the women at 6 months and 18 months after their breast cancer diagnosis, the researchers administered the five-item version of the Perceived Efficacy in Patient-Physician Interactions Questionnaire, a scale that indicates patients' confidence in communicating with providers.

Multiple regression analysis revealed that only discussion of reconstructive surgery by a health care professional had a significant relationship with reconstructive surgery that was either received or planned. This was independent of age, ethnicity, education, marital/partnered status, perceived health status, and other components of patient-physician communication.

Specifically, women who had discussions of reconstructive surgery with any health care provider were 5.8 times more likely to undergo or schedule surgery, compared with those who did not have such discussions.

Being of Asian/Pacific Islander descent and being married or partnered negatively predicted the likelihood of undergoing or scheduling reconstructive surgery.

Breast cancer is the most common cancer in women and is also the second leading cause of cancer-related death in women.

SAN DIEGO — More than 75% of children who have a wheezing illness at age 3 years will develop asthma by age 6 years.

In addition, children who develop a wheezing illness caused by rhinovirus during the first year of life are three times more likely to develop asthma by age 6, compared with those who develop a wheezing illnesses caused by respiratory syncytial virus (RSV) or parainfluenza virus, according to new findings from the Childhood Origins of Asthma (COAST) study presented during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“The big finding here is the association of the common cold virus with wheezing very early in life,” said principal investigator Dr. Robert F. Lemanske Jr., professor of pediatrics and medicine at the University of Wisconsin, Madison.

Dr. Lemanske and his associates at the University of Wisconsin School of Medicine and Public Health launched the study, funded by the National Institutes of Health, in 1998. It is a birth cohort study of 287 children designed to assess genetic and environmental factors influencing the development of asthma. Study participants had to have at least one parent with confirmed aeroallergen sensitization and/or asthma. The researchers collected cord and annual blood samples to evaluate cytokine response profiles. They also collected nasal lavage samples at the time of scheduled study visits and during significant respiratory illness to ascertain viral illness.

Previous findings from the study have reported the relationship between wheezing viral illness during the first year of life and continued wheezing at age 3, but this marks the first report of findings at age 6.

“Although findings from other research groups have demonstrated a relationship between persistent wheezing patterns and children previously hospitalized with respiratory syncytial virus, there was no association between wheezing with RSV or parainfluenza virus during the first year of life and a diagnosis of asthma at 6 years of age in the study,” said Kathleen A. Roberg, R.N., a study manager with department of medicine at the university. “But there was a threefold increase of an asthma diagnosis for those children who wheezed with rhinovirus during the first year of life.”

She went on to note that as the children reached 3 years of age, more than 75% of children who had a wheezing illness—regardless of the viral etiology—went on to develop asthma by age 6. “Rhinovirus continues to be the most striking in this relationship. However, at age 3, RSV and parainfluenza viral wheezing illnesses are similarly related to the diagnosis of asthma.” This suggests that “there is a time between ages 1 and 3 that is critical in the development of persistent wheezing in children.”

In an interview, Dr. Lemanske said more research was needed to determine what drives the apparent association between wheezing rhinovirus illness early in the life and the subsequent development of asthma. “We're trying to determine if this is a host defect in terms of how these kids handle the common cold versus whether or not there are certain strains of the common cold virus that are more likely to get kids to wheeze. In the next phase of this project we'll look at that.”

In another presentation, Rochelle A. Grabher reported that children in the COAST trial who had frequent respiratory illnesses during the first year of life had a higher incidence of asthma at age 6, compared with those who had no respiratory illnesses during the first year of life, yet other markers of atopy were unremarkable.

During the first year of life, 54 children had no respiratory illnesses, 204 had between one and four, and 29 had five or more, which was defined as frequent, said Ms. Grabher, a research coordinator with the university's department of medicine.

There were no statistically significant differences between the children with frequent respiratory illnesses and with no respiratory illnesses in terms of the incidence of a positive skin prick test at the 5-year study visit (52% vs. 45%, respectively), the incidence of a positive radioallergosorbent test at age 6 (58% vs. 36%, respectively), and the diagnosis of active atopic dermatitis at age 6 (38% vs. 23%, respectively).

However, 46% of children who had frequent respiratory illnesses during infancy had asthma at age 6 years, compared with 14% of children who had no respiratory illnesses during infancy, a statistically significant difference.

SAN DIEGO — More than 75% of children who have a wheezing illness at age 3 years will develop asthma by age 6 years.

In addition, children who develop a wheezing illness caused by rhinovirus during the first year of life are three times more likely to develop asthma by age 6, compared with those who develop a wheezing illnesses caused by respiratory syncytial virus (RSV) or parainfluenza virus, according to new findings from the Childhood Origins of Asthma (COAST) study presented during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“The big finding here is the association of the common cold virus with wheezing very early in life,” said principal investigator Dr. Robert F. Lemanske Jr., professor of pediatrics and medicine at the University of Wisconsin, Madison.

Dr. Lemanske and his associates at the University of Wisconsin School of Medicine and Public Health launched the study, funded by the National Institutes of Health, in 1998. It is a birth cohort study of 287 children designed to assess genetic and environmental factors influencing the development of asthma. Study participants had to have at least one parent with confirmed aeroallergen sensitization and/or asthma. The researchers collected cord and annual blood samples to evaluate cytokine response profiles. They also collected nasal lavage samples at the time of scheduled study visits and during significant respiratory illness to ascertain viral illness.

Previous findings from the study have reported the relationship between wheezing viral illness during the first year of life and continued wheezing at age 3, but this marks the first report of findings at age 6.

“Although findings from other research groups have demonstrated a relationship between persistent wheezing patterns and children previously hospitalized with respiratory syncytial virus, there was no association between wheezing with RSV or parainfluenza virus during the first year of life and a diagnosis of asthma at 6 years of age in the study,” said Kathleen A. Roberg, R.N., a study manager with department of medicine at the university. “But there was a threefold increase of an asthma diagnosis for those children who wheezed with rhinovirus during the first year of life.”

She went on to note that as the children reached 3 years of age, more than 75% of children who had a wheezing illness—regardless of the viral etiology—went on to develop asthma by age 6. “Rhinovirus continues to be the most striking in this relationship. However, at age 3, RSV and parainfluenza viral wheezing illnesses are similarly related to the diagnosis of asthma.” This suggests that “there is a time between ages 1 and 3 that is critical in the development of persistent wheezing in children.”

In an interview, Dr. Lemanske said more research was needed to determine what drives the apparent association between wheezing rhinovirus illness early in the life and the subsequent development of asthma. “We're trying to determine if this is a host defect in terms of how these kids handle the common cold versus whether or not there are certain strains of the common cold virus that are more likely to get kids to wheeze. In the next phase of this project we'll look at that.”

In another presentation, Rochelle A. Grabher reported that children in the COAST trial who had frequent respiratory illnesses during the first year of life had a higher incidence of asthma at age 6, compared with those who had no respiratory illnesses during the first year of life, yet other markers of atopy were unremarkable.

During the first year of life, 54 children had no respiratory illnesses, 204 had between one and four, and 29 had five or more, which was defined as frequent, said Ms. Grabher, a research coordinator with the university's department of medicine.

There were no statistically significant differences between the children with frequent respiratory illnesses and with no respiratory illnesses in terms of the incidence of a positive skin prick test at the 5-year study visit (52% vs. 45%, respectively), the incidence of a positive radioallergosorbent test at age 6 (58% vs. 36%, respectively), and the diagnosis of active atopic dermatitis at age 6 (38% vs. 23%, respectively).

However, 46% of children who had frequent respiratory illnesses during infancy had asthma at age 6 years, compared with 14% of children who had no respiratory illnesses during infancy, a statistically significant difference.

SAN DIEGO — More than 75% of children who have a wheezing illness at age 3 years will develop asthma by age 6 years.

In addition, children who develop a wheezing illness caused by rhinovirus during the first year of life are three times more likely to develop asthma by age 6, compared with those who develop a wheezing illnesses caused by respiratory syncytial virus (RSV) or parainfluenza virus, according to new findings from the Childhood Origins of Asthma (COAST) study presented during a press briefing at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“The big finding here is the association of the common cold virus with wheezing very early in life,” said principal investigator Dr. Robert F. Lemanske Jr., professor of pediatrics and medicine at the University of Wisconsin, Madison.

Dr. Lemanske and his associates at the University of Wisconsin School of Medicine and Public Health launched the study, funded by the National Institutes of Health, in 1998. It is a birth cohort study of 287 children designed to assess genetic and environmental factors influencing the development of asthma. Study participants had to have at least one parent with confirmed aeroallergen sensitization and/or asthma. The researchers collected cord and annual blood samples to evaluate cytokine response profiles. They also collected nasal lavage samples at the time of scheduled study visits and during significant respiratory illness to ascertain viral illness.

Previous findings from the study have reported the relationship between wheezing viral illness during the first year of life and continued wheezing at age 3, but this marks the first report of findings at age 6.

“Although findings from other research groups have demonstrated a relationship between persistent wheezing patterns and children previously hospitalized with respiratory syncytial virus, there was no association between wheezing with RSV or parainfluenza virus during the first year of life and a diagnosis of asthma at 6 years of age in the study,” said Kathleen A. Roberg, R.N., a study manager with department of medicine at the university. “But there was a threefold increase of an asthma diagnosis for those children who wheezed with rhinovirus during the first year of life.”

She went on to note that as the children reached 3 years of age, more than 75% of children who had a wheezing illness—regardless of the viral etiology—went on to develop asthma by age 6. “Rhinovirus continues to be the most striking in this relationship. However, at age 3, RSV and parainfluenza viral wheezing illnesses are similarly related to the diagnosis of asthma.” This suggests that “there is a time between ages 1 and 3 that is critical in the development of persistent wheezing in children.”

In an interview, Dr. Lemanske said more research was needed to determine what drives the apparent association between wheezing rhinovirus illness early in the life and the subsequent development of asthma. “We're trying to determine if this is a host defect in terms of how these kids handle the common cold versus whether or not there are certain strains of the common cold virus that are more likely to get kids to wheeze. In the next phase of this project we'll look at that.”

In another presentation, Rochelle A. Grabher reported that children in the COAST trial who had frequent respiratory illnesses during the first year of life had a higher incidence of asthma at age 6, compared with those who had no respiratory illnesses during the first year of life, yet other markers of atopy were unremarkable.

During the first year of life, 54 children had no respiratory illnesses, 204 had between one and four, and 29 had five or more, which was defined as frequent, said Ms. Grabher, a research coordinator with the university's department of medicine.

There were no statistically significant differences between the children with frequent respiratory illnesses and with no respiratory illnesses in terms of the incidence of a positive skin prick test at the 5-year study visit (52% vs. 45%, respectively), the incidence of a positive radioallergosorbent test at age 6 (58% vs. 36%, respectively), and the diagnosis of active atopic dermatitis at age 6 (38% vs. 23%, respectively).

However, 46% of children who had frequent respiratory illnesses during infancy had asthma at age 6 years, compared with 14% of children who had no respiratory illnesses during infancy, a statistically significant difference.

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, anemia including iron-deficiency anemia, weight loss, dermatitis herpetiformis, psoriasis, and chronic urticaria. “There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians are failing to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a March III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease. Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires, Argentina. In that country, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that in the future, more people will be diagnosed with celiac disease as physicians begin to learn about the wide variability of clinical presentation and the availability of sensitive and specific tests.

“As more people become diagnosed there will be greater awareness, and then people with celiac disease will get a better deal in this country,” he said.

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, anemia including iron-deficiency anemia, weight loss, dermatitis herpetiformis, psoriasis, and chronic urticaria. “There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians are failing to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a March III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease. Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires, Argentina. In that country, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that in the future, more people will be diagnosed with celiac disease as physicians begin to learn about the wide variability of clinical presentation and the availability of sensitive and specific tests.

“As more people become diagnosed there will be greater awareness, and then people with celiac disease will get a better deal in this country,” he said.

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, anemia including iron-deficiency anemia, weight loss, dermatitis herpetiformis, psoriasis, and chronic urticaria. “There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians are failing to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a March III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease. Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires, Argentina. In that country, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that in the future, more people will be diagnosed with celiac disease as physicians begin to learn about the wide variability of clinical presentation and the availability of sensitive and specific tests.

“As more people become diagnosed there will be greater awareness, and then people with celiac disease will get a better deal in this country,” he said.

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO — Serum IgE levels are increased in children aged 3–18 months with atopic dermatitis, suggesting they are at risk of developing asthma and allergies, baseline results from the Study of the Atopic March demonstrated.

The purpose of the Study of the Atopic March (SAM) trial is to determine if treatment with pimecrolimus 1% cream in infancy improves control of atopic dermatitis and reduces the incidence of asthma and allergies at 6 years of age, said Dr. Mark Boguniewicz in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study funded by Novartis Pharmaceuticals Corp., which developed and markets the pimecrolimus 1% cream Elidel, Dr. Boguniewicz and his associates enrolled 1,091 infants aged 3–18 months who have a family history of atopy and who had clinical evidence of atopic dermatitis for up to 3 months. They conducted an allergy history and total and antigen-specific IgE assessments.

In the treatment component of the trial, children are enrolled in a double-blind phase for 3 years, followed by a 33-month open-label phase for eligible participants. The study presented at the meeting was limited to baseline results.

The mean age of patients at baseline was 8 months, and more than half (62%) were male, reported Dr. Boguniewicz, a pediatric allergist with the National Jewish Medical and Research Center in Denver. The researchers conducted baseline IgE tests on 926 of the children. The median total IgE level was 14 kU/L and was higher for children with moderate atopic dermatitis than for those with mild atopic dermatitis (a median of 18 kU/L vs. 11 kU/L, respectively).

The researchers also observed that children who had more severe atopic dermatitis or who were older at baseline had higher total IgE levels, compared with children who had mild atopic dermatitis or who were younger at baseline.

Baseline tests for antigen-specific IgE showed that almost one-third (29%) were sensitive to egg, whereas 25% were positive to peanut, 22% were positive to milk, and 16% were positive to animal dander.

Dr. Boguniewicz is a scientific advisor to Novartis Pharmaceuticals Corp.

SAN DIEGO — Serum IgE levels are increased in children aged 3–18 months with atopic dermatitis, suggesting they are at risk of developing asthma and allergies, baseline results from the Study of the Atopic March demonstrated.

The purpose of the Study of the Atopic March (SAM) trial is to determine if treatment with pimecrolimus 1% cream in infancy improves control of atopic dermatitis and reduces the incidence of asthma and allergies at 6 years of age, said Dr. Mark Boguniewicz in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study funded by Novartis Pharmaceuticals Corp., which developed and markets the pimecrolimus 1% cream Elidel, Dr. Boguniewicz and his associates enrolled 1,091 infants aged 3–18 months who have a family history of atopy and who had clinical evidence of atopic dermatitis for up to 3 months. They conducted an allergy history and total and antigen-specific IgE assessments.

In the treatment component of the trial, children are enrolled in a double-blind phase for 3 years, followed by a 33-month open-label phase for eligible participants. The study presented at the meeting was limited to baseline results.

The mean age of patients at baseline was 8 months, and more than half (62%) were male, reported Dr. Boguniewicz, a pediatric allergist with the National Jewish Medical and Research Center in Denver. The researchers conducted baseline IgE tests on 926 of the children. The median total IgE level was 14 kU/L and was higher for children with moderate atopic dermatitis than for those with mild atopic dermatitis (a median of 18 kU/L vs. 11 kU/L, respectively).

The researchers also observed that children who had more severe atopic dermatitis or who were older at baseline had higher total IgE levels, compared with children who had mild atopic dermatitis or who were younger at baseline.

Baseline tests for antigen-specific IgE showed that almost one-third (29%) were sensitive to egg, whereas 25% were positive to peanut, 22% were positive to milk, and 16% were positive to animal dander.

Dr. Boguniewicz is a scientific advisor to Novartis Pharmaceuticals Corp.

SAN DIEGO — Serum IgE levels are increased in children aged 3–18 months with atopic dermatitis, suggesting they are at risk of developing asthma and allergies, baseline results from the Study of the Atopic March demonstrated.

The purpose of the Study of the Atopic March (SAM) trial is to determine if treatment with pimecrolimus 1% cream in infancy improves control of atopic dermatitis and reduces the incidence of asthma and allergies at 6 years of age, said Dr. Mark Boguniewicz in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study funded by Novartis Pharmaceuticals Corp., which developed and markets the pimecrolimus 1% cream Elidel, Dr. Boguniewicz and his associates enrolled 1,091 infants aged 3–18 months who have a family history of atopy and who had clinical evidence of atopic dermatitis for up to 3 months. They conducted an allergy history and total and antigen-specific IgE assessments.

In the treatment component of the trial, children are enrolled in a double-blind phase for 3 years, followed by a 33-month open-label phase for eligible participants. The study presented at the meeting was limited to baseline results.

The mean age of patients at baseline was 8 months, and more than half (62%) were male, reported Dr. Boguniewicz, a pediatric allergist with the National Jewish Medical and Research Center in Denver. The researchers conducted baseline IgE tests on 926 of the children. The median total IgE level was 14 kU/L and was higher for children with moderate atopic dermatitis than for those with mild atopic dermatitis (a median of 18 kU/L vs. 11 kU/L, respectively).

The researchers also observed that children who had more severe atopic dermatitis or who were older at baseline had higher total IgE levels, compared with children who had mild atopic dermatitis or who were younger at baseline.

Baseline tests for antigen-specific IgE showed that almost one-third (29%) were sensitive to egg, whereas 25% were positive to peanut, 22% were positive to milk, and 16% were positive to animal dander.

Dr. Boguniewicz is a scientific advisor to Novartis Pharmaceuticals Corp.

CARMEL, CALIF. – Cognitively impaired older adults who take part in exercise rehabilitation programs have similar strength and endurance outcomes as cognitively intact peers, results from a large meta-analysis showed.

The finding suggests that cognitively impaired older adults should not be excluded from rehabilitation programs, Kyle E. Johnson reported at the Western regional meeting of the American Federation for Medical Research.

“It's a fallacy that cognitively impaired older adults are unable to follow instructions and that they will not benefit from physical therapy,” said Mr. Johnson, who is a second-year medical student at the University of Colorado, Denver.

He and his associate, Patricia C. Heyn, Ph.D., of the university's division of geriatric medicine, searched electronic and printed databases for randomized, controlled trials that included physical rehabilitation outcomes of cognitively impaired older adults (defined as those with a Mini-Mental State Examination score of less than 24) and cognitively intact older adults (defined as those with an MMSE score of 24 or higher).

Of the more than 500 articles reviewed, 41 met inclusion criteria. Of these, 21 trials involved 1,411 older adults with cognitive impairment and 20 trials involved 1,565 older adults who were cognitively intact. The mean age of the patients was 81 years.

The mean MMSE score among the cognitively impaired older adults was 16, compared with a mean score of 28 among those who were cognitively intact.

When the researchers combined the strength and endurance outcomes from the two groups, they observed an effect size of 0.51 for the cognitively impaired elderly and an effect size of 0.49 for the cognitively intact elderly. No statistically significant differences were seen in the strength and endurance outcomes between the two groups.

“Every study showed a positive result” from physical exercise, Mr. Johnson said. “We need more research to directly compare these two groups and to consider the need for different exercise guidelines for varying degrees of cognitive impairment.”

He added that exercise rehabilitation for older adults “should be aimed to positively affect participants' quality of life. By doing so, there should be significant functional improvements in activities of daily living in cognitively impaired individuals.”

CARMEL, CALIF. – Cognitively impaired older adults who take part in exercise rehabilitation programs have similar strength and endurance outcomes as cognitively intact peers, results from a large meta-analysis showed.

The finding suggests that cognitively impaired older adults should not be excluded from rehabilitation programs, Kyle E. Johnson reported at the Western regional meeting of the American Federation for Medical Research.

“It's a fallacy that cognitively impaired older adults are unable to follow instructions and that they will not benefit from physical therapy,” said Mr. Johnson, who is a second-year medical student at the University of Colorado, Denver.

He and his associate, Patricia C. Heyn, Ph.D., of the university's division of geriatric medicine, searched electronic and printed databases for randomized, controlled trials that included physical rehabilitation outcomes of cognitively impaired older adults (defined as those with a Mini-Mental State Examination score of less than 24) and cognitively intact older adults (defined as those with an MMSE score of 24 or higher).

Of the more than 500 articles reviewed, 41 met inclusion criteria. Of these, 21 trials involved 1,411 older adults with cognitive impairment and 20 trials involved 1,565 older adults who were cognitively intact. The mean age of the patients was 81 years.

The mean MMSE score among the cognitively impaired older adults was 16, compared with a mean score of 28 among those who were cognitively intact.

When the researchers combined the strength and endurance outcomes from the two groups, they observed an effect size of 0.51 for the cognitively impaired elderly and an effect size of 0.49 for the cognitively intact elderly. No statistically significant differences were seen in the strength and endurance outcomes between the two groups.

“Every study showed a positive result” from physical exercise, Mr. Johnson said. “We need more research to directly compare these two groups and to consider the need for different exercise guidelines for varying degrees of cognitive impairment.”

He added that exercise rehabilitation for older adults “should be aimed to positively affect participants' quality of life. By doing so, there should be significant functional improvements in activities of daily living in cognitively impaired individuals.”

CARMEL, CALIF. – Cognitively impaired older adults who take part in exercise rehabilitation programs have similar strength and endurance outcomes as cognitively intact peers, results from a large meta-analysis showed.

The finding suggests that cognitively impaired older adults should not be excluded from rehabilitation programs, Kyle E. Johnson reported at the Western regional meeting of the American Federation for Medical Research.

“It's a fallacy that cognitively impaired older adults are unable to follow instructions and that they will not benefit from physical therapy,” said Mr. Johnson, who is a second-year medical student at the University of Colorado, Denver.

He and his associate, Patricia C. Heyn, Ph.D., of the university's division of geriatric medicine, searched electronic and printed databases for randomized, controlled trials that included physical rehabilitation outcomes of cognitively impaired older adults (defined as those with a Mini-Mental State Examination score of less than 24) and cognitively intact older adults (defined as those with an MMSE score of 24 or higher).

Of the more than 500 articles reviewed, 41 met inclusion criteria. Of these, 21 trials involved 1,411 older adults with cognitive impairment and 20 trials involved 1,565 older adults who were cognitively intact. The mean age of the patients was 81 years.

The mean MMSE score among the cognitively impaired older adults was 16, compared with a mean score of 28 among those who were cognitively intact.

When the researchers combined the strength and endurance outcomes from the two groups, they observed an effect size of 0.51 for the cognitively impaired elderly and an effect size of 0.49 for the cognitively intact elderly. No statistically significant differences were seen in the strength and endurance outcomes between the two groups.

“Every study showed a positive result” from physical exercise, Mr. Johnson said. “We need more research to directly compare these two groups and to consider the need for different exercise guidelines for varying degrees of cognitive impairment.”

He added that exercise rehabilitation for older adults “should be aimed to positively affect participants' quality of life. By doing so, there should be significant functional improvements in activities of daily living in cognitively impaired individuals.”

SAN DIEGO – By the age of 65, patients with epilepsy were found to have reduced cognitive function, a higher prevalence of depression and anxiety, and poorer sleep hygiene compared with their seizure-free peers, data from a small cross-sectional study showed.

The finding “underscores the need for looking at age-specific effects in epilepsy rather than assuming that everyone in the adult population is the same,” Dr. Sheryl R. Haut said in an interview during a poster session at the annual meetings of the American Epilepsy Society and the Canadian League Against Epilepsy. “When you're evaluating patients with epilepsy who are over the age of 65, you should be specifically inquiring not only about seizure frequency, but you must inquire and perhaps screen for depression, anxiety, and sleep [problems], because these are having an impact on their quality of life.”

Dr. Haut, of the department of neurology at Montefiore Medical Center and Albert Einstein College of Medicine, New York, and her associates recruited 32 patients aged 65 years and older who had a diagnosis of epilepsy confirmed by an epileptologist and 32 age-matched controls who had no history of seizures. The researchers administered a battery of tests to all study participants, including the Blessed Information Memory and Concentration Test (BIMC), the Prime-MD Depression and Anxiety Scale, and the Medical Outcomes Study (MOS) Sleep Scale.

The mean BIMC scores were significantly higher for epilepsy patients, showing a higher level of cognitive disturbance versus controls (6.3 vs. 1.2, respectively); while the mean Prime-MD Depression scores were significantly worse for epilepsy patients versus controls (4.2 vs. 0.8, respectively). Six cases (18%) met criteria for depression.

Similarly, the mean Prime-MD Anxiety scores were significantly worse for patients with epilepsy compared with controls (3.7 vs. 0.0, respectively).

Dr. Haut also reported that epilepsy patients scored significantly worse than controls on the MOS Sleep Scale measures of somnolence and shortness of breath/headache (13.1 vs. 3.3, respectively).

“Even though you sometimes assume that the elderly overall have worse sleep and may be more prone to depression and anxiety, in fact it's specific to epilepsy in our study,” she said. “What was surprising was that the depression and anxiety prevalence was so much higher in the cases than in the controls. In fact, none of the controls scored significantly in the anxiety scales whereas many of the cases did.”

She noted that she has started to include the battery of tests used in the study in her routine care of elderly epilepsy patients. “You can give them to the patient to take home and bring back to you. These are useful screening tests that don't take a long time to fill out.”

The study was supported in part by the National Institutes of Health and by an unrestricted grant from Pfizer Inc.

Mean depression scores were significantly worse for epilepsy patients compared with controls (4.2 vs. 0.8). DR. HAUT

SAN DIEGO – By the age of 65, patients with epilepsy were found to have reduced cognitive function, a higher prevalence of depression and anxiety, and poorer sleep hygiene compared with their seizure-free peers, data from a small cross-sectional study showed.

The finding “underscores the need for looking at age-specific effects in epilepsy rather than assuming that everyone in the adult population is the same,” Dr. Sheryl R. Haut said in an interview during a poster session at the annual meetings of the American Epilepsy Society and the Canadian League Against Epilepsy. “When you're evaluating patients with epilepsy who are over the age of 65, you should be specifically inquiring not only about seizure frequency, but you must inquire and perhaps screen for depression, anxiety, and sleep [problems], because these are having an impact on their quality of life.”

Dr. Haut, of the department of neurology at Montefiore Medical Center and Albert Einstein College of Medicine, New York, and her associates recruited 32 patients aged 65 years and older who had a diagnosis of epilepsy confirmed by an epileptologist and 32 age-matched controls who had no history of seizures. The researchers administered a battery of tests to all study participants, including the Blessed Information Memory and Concentration Test (BIMC), the Prime-MD Depression and Anxiety Scale, and the Medical Outcomes Study (MOS) Sleep Scale.

The mean BIMC scores were significantly higher for epilepsy patients, showing a higher level of cognitive disturbance versus controls (6.3 vs. 1.2, respectively); while the mean Prime-MD Depression scores were significantly worse for epilepsy patients versus controls (4.2 vs. 0.8, respectively). Six cases (18%) met criteria for depression.

Similarly, the mean Prime-MD Anxiety scores were significantly worse for patients with epilepsy compared with controls (3.7 vs. 0.0, respectively).

Dr. Haut also reported that epilepsy patients scored significantly worse than controls on the MOS Sleep Scale measures of somnolence and shortness of breath/headache (13.1 vs. 3.3, respectively).

“Even though you sometimes assume that the elderly overall have worse sleep and may be more prone to depression and anxiety, in fact it's specific to epilepsy in our study,” she said. “What was surprising was that the depression and anxiety prevalence was so much higher in the cases than in the controls. In fact, none of the controls scored significantly in the anxiety scales whereas many of the cases did.”

She noted that she has started to include the battery of tests used in the study in her routine care of elderly epilepsy patients. “You can give them to the patient to take home and bring back to you. These are useful screening tests that don't take a long time to fill out.”

The study was supported in part by the National Institutes of Health and by an unrestricted grant from Pfizer Inc.

Mean depression scores were significantly worse for epilepsy patients compared with controls (4.2 vs. 0.8). DR. HAUT

SAN DIEGO – By the age of 65, patients with epilepsy were found to have reduced cognitive function, a higher prevalence of depression and anxiety, and poorer sleep hygiene compared with their seizure-free peers, data from a small cross-sectional study showed.

The finding “underscores the need for looking at age-specific effects in epilepsy rather than assuming that everyone in the adult population is the same,” Dr. Sheryl R. Haut said in an interview during a poster session at the annual meetings of the American Epilepsy Society and the Canadian League Against Epilepsy. “When you're evaluating patients with epilepsy who are over the age of 65, you should be specifically inquiring not only about seizure frequency, but you must inquire and perhaps screen for depression, anxiety, and sleep [problems], because these are having an impact on their quality of life.”

Dr. Haut, of the department of neurology at Montefiore Medical Center and Albert Einstein College of Medicine, New York, and her associates recruited 32 patients aged 65 years and older who had a diagnosis of epilepsy confirmed by an epileptologist and 32 age-matched controls who had no history of seizures. The researchers administered a battery of tests to all study participants, including the Blessed Information Memory and Concentration Test (BIMC), the Prime-MD Depression and Anxiety Scale, and the Medical Outcomes Study (MOS) Sleep Scale.

The mean BIMC scores were significantly higher for epilepsy patients, showing a higher level of cognitive disturbance versus controls (6.3 vs. 1.2, respectively); while the mean Prime-MD Depression scores were significantly worse for epilepsy patients versus controls (4.2 vs. 0.8, respectively). Six cases (18%) met criteria for depression.

Similarly, the mean Prime-MD Anxiety scores were significantly worse for patients with epilepsy compared with controls (3.7 vs. 0.0, respectively).

Dr. Haut also reported that epilepsy patients scored significantly worse than controls on the MOS Sleep Scale measures of somnolence and shortness of breath/headache (13.1 vs. 3.3, respectively).

“Even though you sometimes assume that the elderly overall have worse sleep and may be more prone to depression and anxiety, in fact it's specific to epilepsy in our study,” she said. “What was surprising was that the depression and anxiety prevalence was so much higher in the cases than in the controls. In fact, none of the controls scored significantly in the anxiety scales whereas many of the cases did.”

She noted that she has started to include the battery of tests used in the study in her routine care of elderly epilepsy patients. “You can give them to the patient to take home and bring back to you. These are useful screening tests that don't take a long time to fill out.”

The study was supported in part by the National Institutes of Health and by an unrestricted grant from Pfizer Inc.

Mean depression scores were significantly worse for epilepsy patients compared with controls (4.2 vs. 0.8). DR. HAUT

The Food and Drug Administration has revised the boxed warning for erythropoiesis-stimulating agents in response to concern about the potential for complications associated with high doses of such agents.

The development comes on the heels of six recently completed studies that suggested an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure who took erythropoiesis-stimulating agents (ESAs) in higher than recommended doses. In studies of head and neck cancer patients who took ESAs, those on higher than recommended doses experienced more rapid tumor growth.

In light of the revised warnings, at press time the Centers for Medicare and Medicaid Services (CMS) had announced that it would review all Medicare coverage policies related to the administration of ESAs. CMS also announced that it opened a national coverage analysis to evaluate ESA use in non-renal disease applications.

“These [labeling changes] emphasize that physicians should prescribe the lowest dose of ESA that will gradually increase the hemoglobin to the lowest level sufficient to avoid blood transfusion,” Dr. Richard Pazdur, director of the FDA Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said during a teleconference announcing the changes.

The drugs affected by the action include darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit), all of which are manufactured by Amgen Inc.

The new information contained in the boxed warning consists of three key points, Dr. Pazdur said. They include:

▸ Administer the lowest dose of an ESA in order to gradually increase the hemoglobin concentration to the lowest level necessary to avoid blood transfusions.

▸ Know that using ESAs increases the risk for death and for serious cardiovascular events when administered to target a hemoglobin level of greater than 12 g/dL.

▸ Understand that a higher incidence of deep vein thrombosis has been documented in patients receiving epoetin alfa preoperatively for reduction of allogeneic blood transfusion. These patients did not receive prophylactic anticoagulation.

The revised boxed warning also includes new information for cancer patients receiving ESAs to target a hemoglobin level of greater than 12 g/dL. In these patients, ESAs shortened the time to progression in those with advanced head and neck cancer. They also shortened overall survival and increased death attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy.

In addition, the boxed warning now notes that cancer patients not receiving chemotherapy or radiation therapy demonstrated increased mortality when given ESAs to target a hemoglobin level of 12 g/dL; ESAs are not indicated for this population.

Dr. Pazdur emphasized that he and his associates have seen only the “top-line” data from the six ESA studies. More specific data are “being submitted to the agency by the investigators and various sponsors” and will be discussed at the Oncologic Drugs Advisory Committee meeting on May 10, where the labeling may be revised further.

ESAs are approved to treat anemia in patients with chronic kidney failure and in patients with cancer whose anemia is caused by chemotherapy.

“For oncology patients, these products have not been shown to improve or relieve symptoms of anemia or to improve the quality of life in patients with cancer,” Dr. Pazdur noted. “The FDA is currently reviewing all quality of life claims in the product label.”

He advised physicians to discuss the new safety information “with all patients receiving this class of agents. Particularly for patients that are in clinical trials, we ask physicians to inform patients and have written informed consent for continued participation in clinical trials.”

The Food and Drug Administration has revised the boxed warning for erythropoiesis-stimulating agents in response to concern about the potential for complications associated with high doses of such agents.

The development comes on the heels of six recently completed studies that suggested an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure who took erythropoiesis-stimulating agents (ESAs) in higher than recommended doses. In studies of head and neck cancer patients who took ESAs, those on higher than recommended doses experienced more rapid tumor growth.

In light of the revised warnings, at press time the Centers for Medicare and Medicaid Services (CMS) had announced that it would review all Medicare coverage policies related to the administration of ESAs. CMS also announced that it opened a national coverage analysis to evaluate ESA use in non-renal disease applications.

“These [labeling changes] emphasize that physicians should prescribe the lowest dose of ESA that will gradually increase the hemoglobin to the lowest level sufficient to avoid blood transfusion,” Dr. Richard Pazdur, director of the FDA Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said during a teleconference announcing the changes.

The drugs affected by the action include darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit), all of which are manufactured by Amgen Inc.

The new information contained in the boxed warning consists of three key points, Dr. Pazdur said. They include:

▸ Administer the lowest dose of an ESA in order to gradually increase the hemoglobin concentration to the lowest level necessary to avoid blood transfusions.

▸ Know that using ESAs increases the risk for death and for serious cardiovascular events when administered to target a hemoglobin level of greater than 12 g/dL.

▸ Understand that a higher incidence of deep vein thrombosis has been documented in patients receiving epoetin alfa preoperatively for reduction of allogeneic blood transfusion. These patients did not receive prophylactic anticoagulation.

The revised boxed warning also includes new information for cancer patients receiving ESAs to target a hemoglobin level of greater than 12 g/dL. In these patients, ESAs shortened the time to progression in those with advanced head and neck cancer. They also shortened overall survival and increased death attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy.

In addition, the boxed warning now notes that cancer patients not receiving chemotherapy or radiation therapy demonstrated increased mortality when given ESAs to target a hemoglobin level of 12 g/dL; ESAs are not indicated for this population.

Dr. Pazdur emphasized that he and his associates have seen only the “top-line” data from the six ESA studies. More specific data are “being submitted to the agency by the investigators and various sponsors” and will be discussed at the Oncologic Drugs Advisory Committee meeting on May 10, where the labeling may be revised further.

ESAs are approved to treat anemia in patients with chronic kidney failure and in patients with cancer whose anemia is caused by chemotherapy.

“For oncology patients, these products have not been shown to improve or relieve symptoms of anemia or to improve the quality of life in patients with cancer,” Dr. Pazdur noted. “The FDA is currently reviewing all quality of life claims in the product label.”

He advised physicians to discuss the new safety information “with all patients receiving this class of agents. Particularly for patients that are in clinical trials, we ask physicians to inform patients and have written informed consent for continued participation in clinical trials.”

The Food and Drug Administration has revised the boxed warning for erythropoiesis-stimulating agents in response to concern about the potential for complications associated with high doses of such agents.

The development comes on the heels of six recently completed studies that suggested an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure who took erythropoiesis-stimulating agents (ESAs) in higher than recommended doses. In studies of head and neck cancer patients who took ESAs, those on higher than recommended doses experienced more rapid tumor growth.

In light of the revised warnings, at press time the Centers for Medicare and Medicaid Services (CMS) had announced that it would review all Medicare coverage policies related to the administration of ESAs. CMS also announced that it opened a national coverage analysis to evaluate ESA use in non-renal disease applications.

“These [labeling changes] emphasize that physicians should prescribe the lowest dose of ESA that will gradually increase the hemoglobin to the lowest level sufficient to avoid blood transfusion,” Dr. Richard Pazdur, director of the FDA Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said during a teleconference announcing the changes.

The drugs affected by the action include darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit), all of which are manufactured by Amgen Inc.

The new information contained in the boxed warning consists of three key points, Dr. Pazdur said. They include:

▸ Administer the lowest dose of an ESA in order to gradually increase the hemoglobin concentration to the lowest level necessary to avoid blood transfusions.

▸ Know that using ESAs increases the risk for death and for serious cardiovascular events when administered to target a hemoglobin level of greater than 12 g/dL.

▸ Understand that a higher incidence of deep vein thrombosis has been documented in patients receiving epoetin alfa preoperatively for reduction of allogeneic blood transfusion. These patients did not receive prophylactic anticoagulation.

The revised boxed warning also includes new information for cancer patients receiving ESAs to target a hemoglobin level of greater than 12 g/dL. In these patients, ESAs shortened the time to progression in those with advanced head and neck cancer. They also shortened overall survival and increased death attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy.

In addition, the boxed warning now notes that cancer patients not receiving chemotherapy or radiation therapy demonstrated increased mortality when given ESAs to target a hemoglobin level of 12 g/dL; ESAs are not indicated for this population.

Dr. Pazdur emphasized that he and his associates have seen only the “top-line” data from the six ESA studies. More specific data are “being submitted to the agency by the investigators and various sponsors” and will be discussed at the Oncologic Drugs Advisory Committee meeting on May 10, where the labeling may be revised further.

ESAs are approved to treat anemia in patients with chronic kidney failure and in patients with cancer whose anemia is caused by chemotherapy.

“For oncology patients, these products have not been shown to improve or relieve symptoms of anemia or to improve the quality of life in patients with cancer,” Dr. Pazdur noted. “The FDA is currently reviewing all quality of life claims in the product label.”

He advised physicians to discuss the new safety information “with all patients receiving this class of agents. Particularly for patients that are in clinical trials, we ask physicians to inform patients and have written informed consent for continued participation in clinical trials.”