Otolaryngology

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

Testing for the presence of human papillomavirus DNA alone, especially using polymerase chain reaction methods, is not adequate to identify which head and neck squamous cell carcinomas are caused by the virus, according to two studies published online Sept. 18 in Cancer Research.

Identifying HPV-driven malignancies is important because they respond better to treatment and have better outcomes than those unrelated to HPV infection. Indeed, treatment of head and neck squamous cell carcinoma (HNSCC) may soon be guided by the tumor’s HPV status, since trials are now underway to determine whether de-escalation of chemo- and radiotherapy is safe and effective in such patients.

At present, however, the biomarkers that are best suited to making this identification are unclear.

Case Series Assesses Biomarkers

In the first study, researchers assessed the usefulness of four biomarkers in determining which HNSCCs in a case series were driven by HPV. They began by examining fresh-frozen tumor biopsy samples from 199 German adults diagnosed as having oropharyngeal squamous cell cancer between 1990 and 2008.

The four biomarkers were HPV-16 viral load, viral oncogene RNA (E6 and E7), p16^INK4a, and RNA patterns similar to those characteristic of cervical carcinomas (CxCa RNA), said Dr. Dana Holzinger of the German Cancer Research Center at Heidelberg (Germany) University and her associates.

The simple presence of HPV DNA in a tumor sample was found to be a poor indicator of prognosis, likely because it often signaled past HPV infections or recent oral exposure, rather than active HPV infection that progressed to malignancy, the investigators said (Cancer Res. 2012 Sept. 18 [doi: 10.1158/0008-5472.CAN-11-3934]).

Instead, "we showed that high viral load and a cancer-specific pattern of viral gene expression are most suited to identify patients with HPV-driven tumors among patients with oropharyngeal cancer. Viral expression pattern is a completely new marker in this field, and viral load has hardly been analyzed before," Dr. Holzinger said in a press statement accompanying the publication of these findings.

"Once standardized assays for these markers, applicable in routine clinical laboratories, are established, they will allow precise identification" of cancers that are or are not HPV-driven, which will in turn influence prognosis and treatment, she added.

Results Back Combination Approach

In the second study, Dr. Caihua Liang of Brown University, Providence, R.I., and her associates examined 488 HNSCC samples as well as serum samples collected in a population-based study in the Boston area during 1999-2003.

As in the first study, these investigators found that the mere presence of HPV-16 DNA in these tumors, particularly when detected by PCR analysis, did not accurately predict overall survival or progression-free survival.

Instead, "our study strongly suggests that the combination of detection of HPV-16 DNA in HNSCC tumors [plus] p16 immunostaining with E6/E7 antibodies represents the most clinically valuable surrogate marker for the identification of patients . . . who have a better prognosis," they said (Cancer Res. 2012 Sept. 28 [doi: 10.1158/0008-5472.CAN-11-3277]).

"Assessment of HPV DNA using polymerase chain reaction methods as a biomarker in individual head and neck cancers is a poor predictor of outcome, and is also poorly associated with antibody response indicative of exposure and/or infection by HPV," senior author Dr. Karl T. Kelsey added in the press statement.

"We may not be diagnosing these tumors as accurately and precisely as we need to for adjusting treatments," said Dr. Kelsey, a professor in the department of epidemiology and the department of pathology and laboratory medicine at Brown University.

Dr. Holzinger’s study was funded in part by the European Commission, BMBG/HGAF-Canceropole Grand-Est, and the German Research Foundation. Her associates reported ties to Qiagen and Roche. Dr. Liang’s study was supported by the National Institutes of Health and the Flight Attendant Medical Research Institute, and one associate reported ties to Bristol-Myers Squibb.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration issued a warning on Aug. 15 about the risk of death in children who receive codeine for postoperative pain, particularly after tonsillectomy and/or adenoidectomy, based on three deaths and a nonfatal case of life-threatening respiratory depression.

The three children who died had evidence of being ultrarapid metabolizers of codeine, and the fourth case was in a child with evidence of being an "extensive" metabolizer, the FDA said in a statement announcing the warning. All four children, aged 2-5 years, underwent a tonsillectomy and/or adenoidectomy for treating obstructive sleep apnea syndrome, and received codeine within the typical dose range.

"The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures," Dr. Bob Rappaport, director of the Division of Anesthesia, Analgesia, and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

For now, the FDA is advising health care professionals and parents to be aware of the risks of codeine in children, "particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome," and – when they prescribe medications that contain codeine to children – to use "the lowest effective dose for the shortest time on an as-needed basis." Parents and caregivers should stop codeine and get immediate medical attention if a child who has been receiving codeine after surgery has any symptoms of an overdose.

CYP2D6 (cytochrome P450 2D6) metabolizes codeine to morphine. Ultrametabolizers of codeine have a genetic variation in this enzyme and are more likely to have abnormally high levels of morphine after taking codeine, and therefore are at greater risk of related adverse events and death.

The four children started to show signs of morphine toxicity within 1-2 days of starting the codeine, and in the three children who died, postmortem morphine levels were "substantially higher" than the normal therapeutic range, according to the FDA. The four cases were also described in Pediatrics (2012;129:e1343-7).

An estimated 1%-7% of the general population are ultrarapid metabolizers, but the rate is much higher in certain ethnic groups, with the highest prevalence (29%) reported for people of Ethiopian descent. The reported prevalence is 6% in the Greek population, 3.4%-6.5% among the African American population, 3.6% in whites, and 1%-2% in northern Europeans.

When the FDA review is completed, the agency plans to provide an update.

The risk of morphine overdose in nursing infants whose mothers are taking codeine and who are ultrarapid metabolizers was recognized several years ago. In 2007, a year after the first case report was described in the Lancet (2006;368:704), the FDA issued a warning about this risk.

The FDA has also posted a consumer update on its website.

The full alert is available, and possible cases should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

BOSTON – Neuronal abnormalities in the brains of children with obstructive sleep apnea are reversible with treatment, a prospective study has shown.

The findings are the first to show that the altered brain metabolites of the frontal cortex – the neuronal network responsible for attention and executive function – normalize with treatment of pediatric obstructive sleep apnea, Dr. Ann C. Halbower reported at the annual meeting of the Associated Professional Sleep Societies.

Previous studies have demonstrated an association between obstructive sleep apnea (OSA) and deficits in attention, cognition, and executive function, "but ours is the first to look at the effect of [OSA] treatment on the neuronal brain injury and to show a relationship between treatment and improvements in attention and verbal memory in these patients," said Dr. Halbower of the Children’s Hospital Colorado Sleep Center and the University of Colorado at Denver.

The study included 28 children aged 8-11 years; 17 had moderate or severe OSA and 11 were healthy controls matched by age, sex, race, and socioeconomic status. At study baseline, all participants underwent neuropsychological testing, and 22 of the children (15 with OSA and 7 healthy controls) also underwent magnetic resonance spectroscopy imaging. Six months post treatment, 11 of the OSA patients underwent repeat brain imaging and neuropsychological testing, Dr. Halbower said. Treatment for OSA consisted of adenotonsillectomy followed by monitored continuous positive airway pressure (CPAP) for children whose apnea-hypopnea index (AHI) score was higher than 3, or nasal treatments for those with an AHI score of 2-3, she explained.

Among the OSA patients, the mean AHI score at baseline was 13.6, compared with 0.3 for the healthy controls – a discrepancy mirrored by differences observed in both the brain imaging and the function tests. Specifically, Dr. Halbower reported, "the N-acetyl aspartate to choline (NAA/Cho) ratios in the left hippocampus and left frontal cortex were significantly decreased in [OSA] patients, compared with healthy controls, and the [OSA] patients had significant decreases in the executive function of working memory, attention, and verbal memory."

After treatment, "the neuronal metabolites of the right and left frontal cortex normalized, and the hippocampal metabolites improved with a medium effect size," Dr. Halbower said. The follow-up neuropsychological testing showed significant improvements in verbal memory and attention, "which correlated with the normalization of the [NAA/Cho] ratios in the frontal lobes," she said. A further analysis of the data linked improvement on the AHI with a more complete reversal of the hippocampal abnormalities in children with mild OSA, she said, noting, however, that this finding "is very preliminary."

Based on the study results, "we speculate that early diagnosis and treatment of obstructive sleep apnea in children could have profound effects on the trajectory of their development," Dr. Halbower said. In particular, she suggested, earlier treatment may lead to a "more brisk improvement" in the hippocampus, which is the "relay station" for executive function, learning, and memory.

Dr. Halbower said she had no relevant financial disclosures.

BOSTON – Neuronal abnormalities in the brains of children with obstructive sleep apnea are reversible with treatment, a prospective study has shown.

The findings are the first to show that the altered brain metabolites of the frontal cortex – the neuronal network responsible for attention and executive function – normalize with treatment of pediatric obstructive sleep apnea, Dr. Ann C. Halbower reported at the annual meeting of the Associated Professional Sleep Societies.

Previous studies have demonstrated an association between obstructive sleep apnea (OSA) and deficits in attention, cognition, and executive function, "but ours is the first to look at the effect of [OSA] treatment on the neuronal brain injury and to show a relationship between treatment and improvements in attention and verbal memory in these patients," said Dr. Halbower of the Children’s Hospital Colorado Sleep Center and the University of Colorado at Denver.

The study included 28 children aged 8-11 years; 17 had moderate or severe OSA and 11 were healthy controls matched by age, sex, race, and socioeconomic status. At study baseline, all participants underwent neuropsychological testing, and 22 of the children (15 with OSA and 7 healthy controls) also underwent magnetic resonance spectroscopy imaging. Six months post treatment, 11 of the OSA patients underwent repeat brain imaging and neuropsychological testing, Dr. Halbower said. Treatment for OSA consisted of adenotonsillectomy followed by monitored continuous positive airway pressure (CPAP) for children whose apnea-hypopnea index (AHI) score was higher than 3, or nasal treatments for those with an AHI score of 2-3, she explained.

Among the OSA patients, the mean AHI score at baseline was 13.6, compared with 0.3 for the healthy controls – a discrepancy mirrored by differences observed in both the brain imaging and the function tests. Specifically, Dr. Halbower reported, "the N-acetyl aspartate to choline (NAA/Cho) ratios in the left hippocampus and left frontal cortex were significantly decreased in [OSA] patients, compared with healthy controls, and the [OSA] patients had significant decreases in the executive function of working memory, attention, and verbal memory."

After treatment, "the neuronal metabolites of the right and left frontal cortex normalized, and the hippocampal metabolites improved with a medium effect size," Dr. Halbower said. The follow-up neuropsychological testing showed significant improvements in verbal memory and attention, "which correlated with the normalization of the [NAA/Cho] ratios in the frontal lobes," she said. A further analysis of the data linked improvement on the AHI with a more complete reversal of the hippocampal abnormalities in children with mild OSA, she said, noting, however, that this finding "is very preliminary."

Based on the study results, "we speculate that early diagnosis and treatment of obstructive sleep apnea in children could have profound effects on the trajectory of their development," Dr. Halbower said. In particular, she suggested, earlier treatment may lead to a "more brisk improvement" in the hippocampus, which is the "relay station" for executive function, learning, and memory.

Dr. Halbower said she had no relevant financial disclosures.

BOSTON – Neuronal abnormalities in the brains of children with obstructive sleep apnea are reversible with treatment, a prospective study has shown.

The findings are the first to show that the altered brain metabolites of the frontal cortex – the neuronal network responsible for attention and executive function – normalize with treatment of pediatric obstructive sleep apnea, Dr. Ann C. Halbower reported at the annual meeting of the Associated Professional Sleep Societies.

Previous studies have demonstrated an association between obstructive sleep apnea (OSA) and deficits in attention, cognition, and executive function, "but ours is the first to look at the effect of [OSA] treatment on the neuronal brain injury and to show a relationship between treatment and improvements in attention and verbal memory in these patients," said Dr. Halbower of the Children’s Hospital Colorado Sleep Center and the University of Colorado at Denver.

The study included 28 children aged 8-11 years; 17 had moderate or severe OSA and 11 were healthy controls matched by age, sex, race, and socioeconomic status. At study baseline, all participants underwent neuropsychological testing, and 22 of the children (15 with OSA and 7 healthy controls) also underwent magnetic resonance spectroscopy imaging. Six months post treatment, 11 of the OSA patients underwent repeat brain imaging and neuropsychological testing, Dr. Halbower said. Treatment for OSA consisted of adenotonsillectomy followed by monitored continuous positive airway pressure (CPAP) for children whose apnea-hypopnea index (AHI) score was higher than 3, or nasal treatments for those with an AHI score of 2-3, she explained.

Among the OSA patients, the mean AHI score at baseline was 13.6, compared with 0.3 for the healthy controls – a discrepancy mirrored by differences observed in both the brain imaging and the function tests. Specifically, Dr. Halbower reported, "the N-acetyl aspartate to choline (NAA/Cho) ratios in the left hippocampus and left frontal cortex were significantly decreased in [OSA] patients, compared with healthy controls, and the [OSA] patients had significant decreases in the executive function of working memory, attention, and verbal memory."

After treatment, "the neuronal metabolites of the right and left frontal cortex normalized, and the hippocampal metabolites improved with a medium effect size," Dr. Halbower said. The follow-up neuropsychological testing showed significant improvements in verbal memory and attention, "which correlated with the normalization of the [NAA/Cho] ratios in the frontal lobes," she said. A further analysis of the data linked improvement on the AHI with a more complete reversal of the hippocampal abnormalities in children with mild OSA, she said, noting, however, that this finding "is very preliminary."

Based on the study results, "we speculate that early diagnosis and treatment of obstructive sleep apnea in children could have profound effects on the trajectory of their development," Dr. Halbower said. In particular, she suggested, earlier treatment may lead to a "more brisk improvement" in the hippocampus, which is the "relay station" for executive function, learning, and memory.

Dr. Halbower said she had no relevant financial disclosures.

MIAMI BEACH – Patients with head and neck cancers who develop alcohol withdrawal syndrome perioperatively experience significantly more complications after undergoing surgery, a large database analysis indicates.

The presence of withdrawal symptoms was associated with a 25% incidence of postoperative complications, compared with 14% among patients who abused alcohol and 7% among those without alcohol abuse, Dr. Dane J. Genther said at the Triological Society’s Combined Sections Meeting. The risk for wound complications was nearly double in this population (odds ratio, 1.9).

Dr. Genther, a resident in otolaryngologyhead and neck surgery at Johns Hopkins Hospital in Baltimore, and his associates used ICD-9 codes in the Nationwide Inpatient Sample discharge database to identify more than 92,000 patients who underwent an ablative procedure for head and neck cancer in 2003-2008. The retrospective, cross-sectional study included patients with malignant oral cavity, laryngeal, hypopharyngeal, and oropharyngeal neoplasms.

In a multivariate analysis, alcohol withdrawal syndrome was significantly more likely for patients undergoing a major procedure (OR, 2.0) and was significantly associated with Medicare payer status and a need for additional health care following discharge, Dr. Genther said.

The researchers found no significant association between alcohol withdrawal syndrome and increased risk for postoperative infections or in-hospital mortality, but there was a significant increase in hospital stay and related costs associated with the syndrome.

Having a major procedure and experiencing alcohol withdrawal contributed approximately $15,000 per admission in 2011 U.S. dollars, Dr. Genther said.

The findings point to a need for alternatives to current alcohol withdrawal prevention therapies, Dr. Genther said. "Despite prophylaxis, which is our current treatment to attempt to stem the onset of alcohol withdrawal syndrome, complications do occur and they are no less severe or frequent than in the absence of prophylaxis."

Abstinence from alcohol for at least 4 weeks is another strategy proposed to minimize risk of alcohol withdrawal syndrome for any at-risk surgical patient, said Dr. Genther. However, he added, "for many cancer patients, especially those with more advanced disease, waiting a prolonged period of time to possibly gain that benefit from abstinence is not necessarily a viable option."

Another aim of the study was to assess factors contributing to alcohol abuse. Patients aged 40-64 years had the highest proportion of alcohol abuse, and this age range was a significant factor (OR, 2.37). Those who abused alcohol were more often male and more often underwent major procedures, Dr. Genther said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. In addition, alcohol abuse was significantly associated with pneumonia and need for additional postdischarge health care.

Dr. Genther received a G. Slaughter Fitz-Hugh Resident Research Award for this study from the Triological Society. He reported having no financial disclosures.

MIAMI BEACH – Patients with head and neck cancers who develop alcohol withdrawal syndrome perioperatively experience significantly more complications after undergoing surgery, a large database analysis indicates.

The presence of withdrawal symptoms was associated with a 25% incidence of postoperative complications, compared with 14% among patients who abused alcohol and 7% among those without alcohol abuse, Dr. Dane J. Genther said at the Triological Society’s Combined Sections Meeting. The risk for wound complications was nearly double in this population (odds ratio, 1.9).

Dr. Genther, a resident in otolaryngologyhead and neck surgery at Johns Hopkins Hospital in Baltimore, and his associates used ICD-9 codes in the Nationwide Inpatient Sample discharge database to identify more than 92,000 patients who underwent an ablative procedure for head and neck cancer in 2003-2008. The retrospective, cross-sectional study included patients with malignant oral cavity, laryngeal, hypopharyngeal, and oropharyngeal neoplasms.

In a multivariate analysis, alcohol withdrawal syndrome was significantly more likely for patients undergoing a major procedure (OR, 2.0) and was significantly associated with Medicare payer status and a need for additional health care following discharge, Dr. Genther said.

The researchers found no significant association between alcohol withdrawal syndrome and increased risk for postoperative infections or in-hospital mortality, but there was a significant increase in hospital stay and related costs associated with the syndrome.

Having a major procedure and experiencing alcohol withdrawal contributed approximately $15,000 per admission in 2011 U.S. dollars, Dr. Genther said.

The findings point to a need for alternatives to current alcohol withdrawal prevention therapies, Dr. Genther said. "Despite prophylaxis, which is our current treatment to attempt to stem the onset of alcohol withdrawal syndrome, complications do occur and they are no less severe or frequent than in the absence of prophylaxis."

Abstinence from alcohol for at least 4 weeks is another strategy proposed to minimize risk of alcohol withdrawal syndrome for any at-risk surgical patient, said Dr. Genther. However, he added, "for many cancer patients, especially those with more advanced disease, waiting a prolonged period of time to possibly gain that benefit from abstinence is not necessarily a viable option."

Another aim of the study was to assess factors contributing to alcohol abuse. Patients aged 40-64 years had the highest proportion of alcohol abuse, and this age range was a significant factor (OR, 2.37). Those who abused alcohol were more often male and more often underwent major procedures, Dr. Genther said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. In addition, alcohol abuse was significantly associated with pneumonia and need for additional postdischarge health care.

Dr. Genther received a G. Slaughter Fitz-Hugh Resident Research Award for this study from the Triological Society. He reported having no financial disclosures.

MIAMI BEACH – Patients with head and neck cancers who develop alcohol withdrawal syndrome perioperatively experience significantly more complications after undergoing surgery, a large database analysis indicates.

The presence of withdrawal symptoms was associated with a 25% incidence of postoperative complications, compared with 14% among patients who abused alcohol and 7% among those without alcohol abuse, Dr. Dane J. Genther said at the Triological Society’s Combined Sections Meeting. The risk for wound complications was nearly double in this population (odds ratio, 1.9).

Dr. Genther, a resident in otolaryngologyhead and neck surgery at Johns Hopkins Hospital in Baltimore, and his associates used ICD-9 codes in the Nationwide Inpatient Sample discharge database to identify more than 92,000 patients who underwent an ablative procedure for head and neck cancer in 2003-2008. The retrospective, cross-sectional study included patients with malignant oral cavity, laryngeal, hypopharyngeal, and oropharyngeal neoplasms.

In a multivariate analysis, alcohol withdrawal syndrome was significantly more likely for patients undergoing a major procedure (OR, 2.0) and was significantly associated with Medicare payer status and a need for additional health care following discharge, Dr. Genther said.

The researchers found no significant association between alcohol withdrawal syndrome and increased risk for postoperative infections or in-hospital mortality, but there was a significant increase in hospital stay and related costs associated with the syndrome.

Having a major procedure and experiencing alcohol withdrawal contributed approximately $15,000 per admission in 2011 U.S. dollars, Dr. Genther said.

The findings point to a need for alternatives to current alcohol withdrawal prevention therapies, Dr. Genther said. "Despite prophylaxis, which is our current treatment to attempt to stem the onset of alcohol withdrawal syndrome, complications do occur and they are no less severe or frequent than in the absence of prophylaxis."

Abstinence from alcohol for at least 4 weeks is another strategy proposed to minimize risk of alcohol withdrawal syndrome for any at-risk surgical patient, said Dr. Genther. However, he added, "for many cancer patients, especially those with more advanced disease, waiting a prolonged period of time to possibly gain that benefit from abstinence is not necessarily a viable option."

Another aim of the study was to assess factors contributing to alcohol abuse. Patients aged 40-64 years had the highest proportion of alcohol abuse, and this age range was a significant factor (OR, 2.37). Those who abused alcohol were more often male and more often underwent major procedures, Dr. Genther said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons. In addition, alcohol abuse was significantly associated with pneumonia and need for additional postdischarge health care.

Dr. Genther received a G. Slaughter Fitz-Hugh Resident Research Award for this study from the Triological Society. He reported having no financial disclosures.

MIAMI BEACH – Cardiac and respiratory comorbidities were "common culprits" and present in more than half of thyroidectomy patients who died in the hospital, according to analysis of a large inpatient database.

Although overall mortality is less than 1% for thyroidectomy patients nationwide, researcher Rishi Vashishta said, "Patient comorbidities can often contribute to perioperative death and should really be considered when discussing treatment options with patients."

Mr. Vashishta and his associates identified 11,862 patients who underwent thyroidectomy using ICD-9 codes from the Healthcare Cost Utilization Project Nationwide Inpatient Sample (NIS) database for 2009. Two-thirds of patients were white and three-fourths were female A total of 73 of these patients died during their hospitalization that year.

"We calculated the mortality rate during hospitalization to be 0.61%," Mr. Vashishta, a medical student at George Washington University, Washington, said at the Triological Society Combined Sections meeting.

Other aims of the study were to assess thyroid surgery complications, length of stay, and total hospital charges. "There are a large number of institutional studies, but there remains a relative paucity of studies examining this procedure on a more macro and socioeconomic level," said Mr. Vashishta.

Among the nearly 12,000 admissions, mean length of stay was 2.97 days and mean total hospital charges accrued was $39,236.

In contrast, a subgroup analysis revealed mean length of stay was 13.8 days and mean increase in total hospital charges was nearly $218,855 among patients who died during hospitalization. "Interestingly, the respiratory status in these patients was markedly worse, with a tracheostomy required in 28%, prolonged mechanical ventilation required in 43%, and endotracheal intubation in 55%," Mr. Vashishta said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

Acute cerebrovascular disease was involved in 62% of deaths, he reported.

The mean age of patients who died was 65 years, compared with a mean of 53 years for all thyroidectomy patients in the study.

Approximately 80% of all surgeries in the study were elective. The majority of patients, 55%, underwent total thyroidectomy, 32% underwent unilateral lobectomy, and the remainder had partial thyroidectomy.

When Mr. Vashishta and his colleagues assessed complications, they found hypocalcemia present in 6%, vocal cord paresis in 1.4%, and hypoparathyroidism in 0.77% of patients using bivariate analyses. The incidence of hematoma and hemorrhage were low at 1.43% and 0.67%, respectively. "Our complication rates were generally consistent with those from institutional studies published in the literature."

"We found strong predictors of [these] complications during hospitalization included female gender; hospital location and teaching status; and type of thyroid diagnosis," he said. "Although the majority of cases were conducted at large teaching hospitals in urban centers, no socioeconomic or regional differences were observed," the investigators noted in their abstract but did not offer further explanation.

Admissions data showed that nontoxic nodular goiter was a diagnosis code for 36% of patients. In addition, malignant neoplasm was a code for 31% and benign neoplasm for 11%, "Graves’ disease, which we classified under acquired hypothyroidism, was much less common, around 8%," Mr. Vashishta said. ICD-9 codes for thyrotoxicosis and thyroiditis each were noted on 8% of records.

Errors in coding and sampling are a potential limitation of this and any study based on a large administrative database, Mr. Vashishta said. For example, use of ICD-9 codes "inevitably included patients in our stratified sample admitted for some other problem who underwent incidental thyroidectomies during their hospitalization." Furthermore, thyroidectomy is increasingly being performed as an outpatient procedure and the NIS is an inpatient database. "This effectively skewed our mean total charges and mean length of stay in the hospital upwards."

The study was not funded by industry. Mr. Vashishta said that he had no relevant financial disclosures.

MIAMI BEACH – Cardiac and respiratory comorbidities were "common culprits" and present in more than half of thyroidectomy patients who died in the hospital, according to analysis of a large inpatient database.

Although overall mortality is less than 1% for thyroidectomy patients nationwide, researcher Rishi Vashishta said, "Patient comorbidities can often contribute to perioperative death and should really be considered when discussing treatment options with patients."

Mr. Vashishta and his associates identified 11,862 patients who underwent thyroidectomy using ICD-9 codes from the Healthcare Cost Utilization Project Nationwide Inpatient Sample (NIS) database for 2009. Two-thirds of patients were white and three-fourths were female A total of 73 of these patients died during their hospitalization that year.

"We calculated the mortality rate during hospitalization to be 0.61%," Mr. Vashishta, a medical student at George Washington University, Washington, said at the Triological Society Combined Sections meeting.

Other aims of the study were to assess thyroid surgery complications, length of stay, and total hospital charges. "There are a large number of institutional studies, but there remains a relative paucity of studies examining this procedure on a more macro and socioeconomic level," said Mr. Vashishta.

Among the nearly 12,000 admissions, mean length of stay was 2.97 days and mean total hospital charges accrued was $39,236.

In contrast, a subgroup analysis revealed mean length of stay was 13.8 days and mean increase in total hospital charges was nearly $218,855 among patients who died during hospitalization. "Interestingly, the respiratory status in these patients was markedly worse, with a tracheostomy required in 28%, prolonged mechanical ventilation required in 43%, and endotracheal intubation in 55%," Mr. Vashishta said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

Acute cerebrovascular disease was involved in 62% of deaths, he reported.

The mean age of patients who died was 65 years, compared with a mean of 53 years for all thyroidectomy patients in the study.

Approximately 80% of all surgeries in the study were elective. The majority of patients, 55%, underwent total thyroidectomy, 32% underwent unilateral lobectomy, and the remainder had partial thyroidectomy.

When Mr. Vashishta and his colleagues assessed complications, they found hypocalcemia present in 6%, vocal cord paresis in 1.4%, and hypoparathyroidism in 0.77% of patients using bivariate analyses. The incidence of hematoma and hemorrhage were low at 1.43% and 0.67%, respectively. "Our complication rates were generally consistent with those from institutional studies published in the literature."

"We found strong predictors of [these] complications during hospitalization included female gender; hospital location and teaching status; and type of thyroid diagnosis," he said. "Although the majority of cases were conducted at large teaching hospitals in urban centers, no socioeconomic or regional differences were observed," the investigators noted in their abstract but did not offer further explanation.

Admissions data showed that nontoxic nodular goiter was a diagnosis code for 36% of patients. In addition, malignant neoplasm was a code for 31% and benign neoplasm for 11%, "Graves’ disease, which we classified under acquired hypothyroidism, was much less common, around 8%," Mr. Vashishta said. ICD-9 codes for thyrotoxicosis and thyroiditis each were noted on 8% of records.

Errors in coding and sampling are a potential limitation of this and any study based on a large administrative database, Mr. Vashishta said. For example, use of ICD-9 codes "inevitably included patients in our stratified sample admitted for some other problem who underwent incidental thyroidectomies during their hospitalization." Furthermore, thyroidectomy is increasingly being performed as an outpatient procedure and the NIS is an inpatient database. "This effectively skewed our mean total charges and mean length of stay in the hospital upwards."

The study was not funded by industry. Mr. Vashishta said that he had no relevant financial disclosures.

MIAMI BEACH – Cardiac and respiratory comorbidities were "common culprits" and present in more than half of thyroidectomy patients who died in the hospital, according to analysis of a large inpatient database.

Although overall mortality is less than 1% for thyroidectomy patients nationwide, researcher Rishi Vashishta said, "Patient comorbidities can often contribute to perioperative death and should really be considered when discussing treatment options with patients."

Mr. Vashishta and his associates identified 11,862 patients who underwent thyroidectomy using ICD-9 codes from the Healthcare Cost Utilization Project Nationwide Inpatient Sample (NIS) database for 2009. Two-thirds of patients were white and three-fourths were female A total of 73 of these patients died during their hospitalization that year.

"We calculated the mortality rate during hospitalization to be 0.61%," Mr. Vashishta, a medical student at George Washington University, Washington, said at the Triological Society Combined Sections meeting.

Other aims of the study were to assess thyroid surgery complications, length of stay, and total hospital charges. "There are a large number of institutional studies, but there remains a relative paucity of studies examining this procedure on a more macro and socioeconomic level," said Mr. Vashishta.

Among the nearly 12,000 admissions, mean length of stay was 2.97 days and mean total hospital charges accrued was $39,236.

In contrast, a subgroup analysis revealed mean length of stay was 13.8 days and mean increase in total hospital charges was nearly $218,855 among patients who died during hospitalization. "Interestingly, the respiratory status in these patients was markedly worse, with a tracheostomy required in 28%, prolonged mechanical ventilation required in 43%, and endotracheal intubation in 55%," Mr. Vashishta said at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

Acute cerebrovascular disease was involved in 62% of deaths, he reported.

The mean age of patients who died was 65 years, compared with a mean of 53 years for all thyroidectomy patients in the study.

Approximately 80% of all surgeries in the study were elective. The majority of patients, 55%, underwent total thyroidectomy, 32% underwent unilateral lobectomy, and the remainder had partial thyroidectomy.

When Mr. Vashishta and his colleagues assessed complications, they found hypocalcemia present in 6%, vocal cord paresis in 1.4%, and hypoparathyroidism in 0.77% of patients using bivariate analyses. The incidence of hematoma and hemorrhage were low at 1.43% and 0.67%, respectively. "Our complication rates were generally consistent with those from institutional studies published in the literature."

"We found strong predictors of [these] complications during hospitalization included female gender; hospital location and teaching status; and type of thyroid diagnosis," he said. "Although the majority of cases were conducted at large teaching hospitals in urban centers, no socioeconomic or regional differences were observed," the investigators noted in their abstract but did not offer further explanation.

Admissions data showed that nontoxic nodular goiter was a diagnosis code for 36% of patients. In addition, malignant neoplasm was a code for 31% and benign neoplasm for 11%, "Graves’ disease, which we classified under acquired hypothyroidism, was much less common, around 8%," Mr. Vashishta said. ICD-9 codes for thyrotoxicosis and thyroiditis each were noted on 8% of records.

Errors in coding and sampling are a potential limitation of this and any study based on a large administrative database, Mr. Vashishta said. For example, use of ICD-9 codes "inevitably included patients in our stratified sample admitted for some other problem who underwent incidental thyroidectomies during their hospitalization." Furthermore, thyroidectomy is increasingly being performed as an outpatient procedure and the NIS is an inpatient database. "This effectively skewed our mean total charges and mean length of stay in the hospital upwards."

The study was not funded by industry. Mr. Vashishta said that he had no relevant financial disclosures.