Jeff Evans

ORLANDO, FLA.—New data suggest that product labeling stating that capsule endoscopy is contraindicated in patients with implantable pacemakers or defibrillators may be unnecessary, Manish S. Patel, M.D., reported at the annual meeting of the American College of Gastroenterology.

The scant data that are available do not support the contraindication. In several case series, no complications or loss of images have been reported in 18 patients with either implantable pacemakers or implantable cardioverter defibrillators (ICDs) who underwent capsule endoscopy, noted Dr. Patel, a resident in gastroenterology at the Eastern Virginia Medical School, Norfolk.

The basis for the contraindication stems from concern that the 100- to 472-kHz radiofrequency band used by the PillCam SB capsule (formerly called the M2A capsule) might interfere with the operation of pacemakers and ICDs, which use the 100- to 175-kHz band.

Electromagnetic interference from the environment has the potential to inhibit pacing, trigger inappropriate pacing, cause a spurious ICD discharge, cause physical damage to the device's circuitry, and reset the device to a different mode, possibly causing asynchrony and hemodynamic instability.

The number of people in the United States who have implantable pacemakers is expected to rise from about 2.4 million in 2004 to 3.2 million in 2008. Similarly, the number of individuals with implantable cardioverter defibrillators (ICDs) may rise from 460,000 in 2004 to 1 million in 2008.

Dr. Patel and his colleagues tested two pacemakers (AT501 and KDR901) and one ICD (7274 Marquis DR) manufactured by Medtronic Inc. and one pacemaker (1296 Insignia) and one ICD (A155 Vitality AVT) made by Guidant Corp. Together, the five devices represent 80% of the U.S. and world market for implantable pacemakers and ICDs, Dr. Patel said.

The investigators placed each device in an electrode gel bath at distances of 2, 6, 12, and 18 cm away from a PillCam SB capsule in a random sequence in three 30-second trials at each distance. In a separate set of similar trials, the pacemakers and defibrillators were attached to standard unipolar and bipolar pacing and defibrillation leads. During each set of trials, Dr. Patel and his associates varied the output of each device from a “nominal” to its most sensitive programmable setting at each distance.

An electrophysiologist who was blinded to all of the test parameters did not detect any abnormalities in atrial or ventricular electrograms recorded from a Virtual Interactive Patient (model 9595, Medtronic) during any trial.

“This study shows that there is no interaction between capsule endoscopy and pacemakers and defibrillators, which is consistent with clinical observational reports,” Dr. Patel said. “We suggest that exclusionary criteria on pacemakers and defibrillators as listed on the formal product label of the M2A capsule endoscopy should be reevaluated and revised to reflect this new information.”

ORLANDO, FLA.—New data suggest that product labeling stating that capsule endoscopy is contraindicated in patients with implantable pacemakers or defibrillators may be unnecessary, Manish S. Patel, M.D., reported at the annual meeting of the American College of Gastroenterology.

The scant data that are available do not support the contraindication. In several case series, no complications or loss of images have been reported in 18 patients with either implantable pacemakers or implantable cardioverter defibrillators (ICDs) who underwent capsule endoscopy, noted Dr. Patel, a resident in gastroenterology at the Eastern Virginia Medical School, Norfolk.

The basis for the contraindication stems from concern that the 100- to 472-kHz radiofrequency band used by the PillCam SB capsule (formerly called the M2A capsule) might interfere with the operation of pacemakers and ICDs, which use the 100- to 175-kHz band.

Electromagnetic interference from the environment has the potential to inhibit pacing, trigger inappropriate pacing, cause a spurious ICD discharge, cause physical damage to the device's circuitry, and reset the device to a different mode, possibly causing asynchrony and hemodynamic instability.

The number of people in the United States who have implantable pacemakers is expected to rise from about 2.4 million in 2004 to 3.2 million in 2008. Similarly, the number of individuals with implantable cardioverter defibrillators (ICDs) may rise from 460,000 in 2004 to 1 million in 2008.

Dr. Patel and his colleagues tested two pacemakers (AT501 and KDR901) and one ICD (7274 Marquis DR) manufactured by Medtronic Inc. and one pacemaker (1296 Insignia) and one ICD (A155 Vitality AVT) made by Guidant Corp. Together, the five devices represent 80% of the U.S. and world market for implantable pacemakers and ICDs, Dr. Patel said.

The investigators placed each device in an electrode gel bath at distances of 2, 6, 12, and 18 cm away from a PillCam SB capsule in a random sequence in three 30-second trials at each distance. In a separate set of similar trials, the pacemakers and defibrillators were attached to standard unipolar and bipolar pacing and defibrillation leads. During each set of trials, Dr. Patel and his associates varied the output of each device from a “nominal” to its most sensitive programmable setting at each distance.

An electrophysiologist who was blinded to all of the test parameters did not detect any abnormalities in atrial or ventricular electrograms recorded from a Virtual Interactive Patient (model 9595, Medtronic) during any trial.

“This study shows that there is no interaction between capsule endoscopy and pacemakers and defibrillators, which is consistent with clinical observational reports,” Dr. Patel said. “We suggest that exclusionary criteria on pacemakers and defibrillators as listed on the formal product label of the M2A capsule endoscopy should be reevaluated and revised to reflect this new information.”

ORLANDO, FLA.—New data suggest that product labeling stating that capsule endoscopy is contraindicated in patients with implantable pacemakers or defibrillators may be unnecessary, Manish S. Patel, M.D., reported at the annual meeting of the American College of Gastroenterology.

The scant data that are available do not support the contraindication. In several case series, no complications or loss of images have been reported in 18 patients with either implantable pacemakers or implantable cardioverter defibrillators (ICDs) who underwent capsule endoscopy, noted Dr. Patel, a resident in gastroenterology at the Eastern Virginia Medical School, Norfolk.

The basis for the contraindication stems from concern that the 100- to 472-kHz radiofrequency band used by the PillCam SB capsule (formerly called the M2A capsule) might interfere with the operation of pacemakers and ICDs, which use the 100- to 175-kHz band.

Electromagnetic interference from the environment has the potential to inhibit pacing, trigger inappropriate pacing, cause a spurious ICD discharge, cause physical damage to the device's circuitry, and reset the device to a different mode, possibly causing asynchrony and hemodynamic instability.

The number of people in the United States who have implantable pacemakers is expected to rise from about 2.4 million in 2004 to 3.2 million in 2008. Similarly, the number of individuals with implantable cardioverter defibrillators (ICDs) may rise from 460,000 in 2004 to 1 million in 2008.

Dr. Patel and his colleagues tested two pacemakers (AT501 and KDR901) and one ICD (7274 Marquis DR) manufactured by Medtronic Inc. and one pacemaker (1296 Insignia) and one ICD (A155 Vitality AVT) made by Guidant Corp. Together, the five devices represent 80% of the U.S. and world market for implantable pacemakers and ICDs, Dr. Patel said.

The investigators placed each device in an electrode gel bath at distances of 2, 6, 12, and 18 cm away from a PillCam SB capsule in a random sequence in three 30-second trials at each distance. In a separate set of similar trials, the pacemakers and defibrillators were attached to standard unipolar and bipolar pacing and defibrillation leads. During each set of trials, Dr. Patel and his associates varied the output of each device from a “nominal” to its most sensitive programmable setting at each distance.

An electrophysiologist who was blinded to all of the test parameters did not detect any abnormalities in atrial or ventricular electrograms recorded from a Virtual Interactive Patient (model 9595, Medtronic) during any trial.

“This study shows that there is no interaction between capsule endoscopy and pacemakers and defibrillators, which is consistent with clinical observational reports,” Dr. Patel said. “We suggest that exclusionary criteria on pacemakers and defibrillators as listed on the formal product label of the M2A capsule endoscopy should be reevaluated and revised to reflect this new information.”

Calcium and Colorectal Cancer Risk

High intake of dietary calcium in women is significantly associated with reduction in the risk of colorectal cancer in a dose-response fashion, reported Andrew Flood, Ph.D., of the University of Minnesota, Minneapolis, and his colleagues.

In a prospective cohort of 45,354 women who completed dietary questionnaires over an average of 8.5 years, those in the highest quintile of calcium consumption (median of 985 mg /day) had a significant, 26% reduction in risk of colorectal cancer, compared with women in the lowest quintile (median of 337 mg/day), after adjustment for age. Supplemental calcium alone did not show the same dose-response relationship with colorectal cancer risk.

But women who had high intakes of calcium from their diet and supplements had a significant, 46% reduction in the risk of colorectal cancer after an adjustment was performed for age.

None of the associations changed after adjustment for other confounding factors (Cancer Epidemiol. Biomarkers Prev. 2005;14:126-32).

Predicting Fatal Alcoholic Hepatitis

The model for end-stage liver disease may offer a more practical method of predicting mortality from alcoholic hepatitis than the Maddrey discriminant function, despite similar accuracy between the two models, reported Winston Dunn, M.D., and his colleagues at the Mayo Clinic, Rochester, Minn.

With the optimal cut points for both models in a retrospective study of 73 patients with alcoholic hepatitis, the model for end-stage liver disease (MELD) had 75% sensitivity and specificity for both 30- and 90-day mortality. The discriminant function (DF) had 75% sensitivity and 69% specificity in predicting mortality at 30 days, and 88% sensitivity and 65% specificity at 90 days (Hepatology 2005;41:353-8).

MELD uses serum creatinine, serum bilirubin, and the international normalized ratio for prothrombin time, whereas DF uses prothrombin time in seconds and serum bilirubin. The investigators suggested that MELD may be more practical than DF because prothrombin time expressed as the international normalized ratio is comparable across all laboratories, unlike prothrombin time expressed in seconds. MELD also has been prospectively and retrospectively validated in heterogeneous cohorts of patients.

Lymph Nodes Missed in Colorectal Ca

Most patients with colorectal cancer who underwent radical surgery with no preoperative radiation during 1988-2001 did not receive adequate lymph node evaluation, according to findings from a population-based study of the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry.

Of 116,995 patients, only 37% received adequate lymph node evaluation (at least 12 nodes), reported Nancy N. Baxter, M.D., of the University of Minnesota, Minneapolis, and her associates. The percentage of patients who received adequate lymph node evaluation was significantly higher among those who had stage II (41%) or III (46%) disease, compared with stage I (25%).

Patients with left-sided colon or rectal cancer had a significant, 50% lower likelihood of receiving adequate lymph node evaluation than those with right-sided colon cancer. Age of 71 years or older significantly reduced by 55% the likelihood of receiving adequate evaluation, compared with age of 50 years or younger (J. Natl. Cancer Inst. 2005;97:219-25). The investigators noted that a variety of factors influences the number of lymph nodes evaluated: number of nodes present in the patient, obesity, size of nodes and thickness of tumor penetration into the bowel, and underlying surgical and pathologic practice patterns.

Hepatitis B: Mono vs. Combo Therapy

In patients with hepatitis B e antigen-positive chronic hepatitis B, sustained viral response rates after discontinuing treatment were similar to those treated with pegylated interferon alfa-2b alone and those who received the interferon in combination with lamivudine, reported Harry L.A. Janssen, M.D., of Erasmus MC, Rotterdam (Netherlands), and his colleagues.

At the end of 52 weeks of treatment, hepatitis B e antigen was undetectable in significantly more patients in the combination therapy group (44%, 57 of 130) than in the monotherapy group (29%, 40 of 136). But 26 weeks after the end of treatment in the randomized, double-blind trial, the rate of sustained virologic response was similar in the monotherapy and combination-therapy patients (36% vs. 35%). The same trend in outcomes occurred when the investigators assessed hepatitis B virus DNA concentrations or alanine aminotransferase levels at the end of treatment and after follow-up (Lancet 2005;365:123-9).

Calcium and Colorectal Cancer Risk

High intake of dietary calcium in women is significantly associated with reduction in the risk of colorectal cancer in a dose-response fashion, reported Andrew Flood, Ph.D., of the University of Minnesota, Minneapolis, and his colleagues.

In a prospective cohort of 45,354 women who completed dietary questionnaires over an average of 8.5 years, those in the highest quintile of calcium consumption (median of 985 mg /day) had a significant, 26% reduction in risk of colorectal cancer, compared with women in the lowest quintile (median of 337 mg/day), after adjustment for age. Supplemental calcium alone did not show the same dose-response relationship with colorectal cancer risk.

But women who had high intakes of calcium from their diet and supplements had a significant, 46% reduction in the risk of colorectal cancer after an adjustment was performed for age.

None of the associations changed after adjustment for other confounding factors (Cancer Epidemiol. Biomarkers Prev. 2005;14:126-32).

Predicting Fatal Alcoholic Hepatitis

The model for end-stage liver disease may offer a more practical method of predicting mortality from alcoholic hepatitis than the Maddrey discriminant function, despite similar accuracy between the two models, reported Winston Dunn, M.D., and his colleagues at the Mayo Clinic, Rochester, Minn.

With the optimal cut points for both models in a retrospective study of 73 patients with alcoholic hepatitis, the model for end-stage liver disease (MELD) had 75% sensitivity and specificity for both 30- and 90-day mortality. The discriminant function (DF) had 75% sensitivity and 69% specificity in predicting mortality at 30 days, and 88% sensitivity and 65% specificity at 90 days (Hepatology 2005;41:353-8).

MELD uses serum creatinine, serum bilirubin, and the international normalized ratio for prothrombin time, whereas DF uses prothrombin time in seconds and serum bilirubin. The investigators suggested that MELD may be more practical than DF because prothrombin time expressed as the international normalized ratio is comparable across all laboratories, unlike prothrombin time expressed in seconds. MELD also has been prospectively and retrospectively validated in heterogeneous cohorts of patients.

Lymph Nodes Missed in Colorectal Ca

Most patients with colorectal cancer who underwent radical surgery with no preoperative radiation during 1988-2001 did not receive adequate lymph node evaluation, according to findings from a population-based study of the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry.

Of 116,995 patients, only 37% received adequate lymph node evaluation (at least 12 nodes), reported Nancy N. Baxter, M.D., of the University of Minnesota, Minneapolis, and her associates. The percentage of patients who received adequate lymph node evaluation was significantly higher among those who had stage II (41%) or III (46%) disease, compared with stage I (25%).

Patients with left-sided colon or rectal cancer had a significant, 50% lower likelihood of receiving adequate lymph node evaluation than those with right-sided colon cancer. Age of 71 years or older significantly reduced by 55% the likelihood of receiving adequate evaluation, compared with age of 50 years or younger (J. Natl. Cancer Inst. 2005;97:219-25). The investigators noted that a variety of factors influences the number of lymph nodes evaluated: number of nodes present in the patient, obesity, size of nodes and thickness of tumor penetration into the bowel, and underlying surgical and pathologic practice patterns.

Hepatitis B: Mono vs. Combo Therapy

In patients with hepatitis B e antigen-positive chronic hepatitis B, sustained viral response rates after discontinuing treatment were similar to those treated with pegylated interferon alfa-2b alone and those who received the interferon in combination with lamivudine, reported Harry L.A. Janssen, M.D., of Erasmus MC, Rotterdam (Netherlands), and his colleagues.

At the end of 52 weeks of treatment, hepatitis B e antigen was undetectable in significantly more patients in the combination therapy group (44%, 57 of 130) than in the monotherapy group (29%, 40 of 136). But 26 weeks after the end of treatment in the randomized, double-blind trial, the rate of sustained virologic response was similar in the monotherapy and combination-therapy patients (36% vs. 35%). The same trend in outcomes occurred when the investigators assessed hepatitis B virus DNA concentrations or alanine aminotransferase levels at the end of treatment and after follow-up (Lancet 2005;365:123-9).

Calcium and Colorectal Cancer Risk

High intake of dietary calcium in women is significantly associated with reduction in the risk of colorectal cancer in a dose-response fashion, reported Andrew Flood, Ph.D., of the University of Minnesota, Minneapolis, and his colleagues.

In a prospective cohort of 45,354 women who completed dietary questionnaires over an average of 8.5 years, those in the highest quintile of calcium consumption (median of 985 mg /day) had a significant, 26% reduction in risk of colorectal cancer, compared with women in the lowest quintile (median of 337 mg/day), after adjustment for age. Supplemental calcium alone did not show the same dose-response relationship with colorectal cancer risk.

But women who had high intakes of calcium from their diet and supplements had a significant, 46% reduction in the risk of colorectal cancer after an adjustment was performed for age.

None of the associations changed after adjustment for other confounding factors (Cancer Epidemiol. Biomarkers Prev. 2005;14:126-32).

Predicting Fatal Alcoholic Hepatitis

The model for end-stage liver disease may offer a more practical method of predicting mortality from alcoholic hepatitis than the Maddrey discriminant function, despite similar accuracy between the two models, reported Winston Dunn, M.D., and his colleagues at the Mayo Clinic, Rochester, Minn.

With the optimal cut points for both models in a retrospective study of 73 patients with alcoholic hepatitis, the model for end-stage liver disease (MELD) had 75% sensitivity and specificity for both 30- and 90-day mortality. The discriminant function (DF) had 75% sensitivity and 69% specificity in predicting mortality at 30 days, and 88% sensitivity and 65% specificity at 90 days (Hepatology 2005;41:353-8).

MELD uses serum creatinine, serum bilirubin, and the international normalized ratio for prothrombin time, whereas DF uses prothrombin time in seconds and serum bilirubin. The investigators suggested that MELD may be more practical than DF because prothrombin time expressed as the international normalized ratio is comparable across all laboratories, unlike prothrombin time expressed in seconds. MELD also has been prospectively and retrospectively validated in heterogeneous cohorts of patients.

Lymph Nodes Missed in Colorectal Ca

Most patients with colorectal cancer who underwent radical surgery with no preoperative radiation during 1988-2001 did not receive adequate lymph node evaluation, according to findings from a population-based study of the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry.

Of 116,995 patients, only 37% received adequate lymph node evaluation (at least 12 nodes), reported Nancy N. Baxter, M.D., of the University of Minnesota, Minneapolis, and her associates. The percentage of patients who received adequate lymph node evaluation was significantly higher among those who had stage II (41%) or III (46%) disease, compared with stage I (25%).

Patients with left-sided colon or rectal cancer had a significant, 50% lower likelihood of receiving adequate lymph node evaluation than those with right-sided colon cancer. Age of 71 years or older significantly reduced by 55% the likelihood of receiving adequate evaluation, compared with age of 50 years or younger (J. Natl. Cancer Inst. 2005;97:219-25). The investigators noted that a variety of factors influences the number of lymph nodes evaluated: number of nodes present in the patient, obesity, size of nodes and thickness of tumor penetration into the bowel, and underlying surgical and pathologic practice patterns.

Hepatitis B: Mono vs. Combo Therapy

In patients with hepatitis B e antigen-positive chronic hepatitis B, sustained viral response rates after discontinuing treatment were similar to those treated with pegylated interferon alfa-2b alone and those who received the interferon in combination with lamivudine, reported Harry L.A. Janssen, M.D., of Erasmus MC, Rotterdam (Netherlands), and his colleagues.

At the end of 52 weeks of treatment, hepatitis B e antigen was undetectable in significantly more patients in the combination therapy group (44%, 57 of 130) than in the monotherapy group (29%, 40 of 136). But 26 weeks after the end of treatment in the randomized, double-blind trial, the rate of sustained virologic response was similar in the monotherapy and combination-therapy patients (36% vs. 35%). The same trend in outcomes occurred when the investigators assessed hepatitis B virus DNA concentrations or alanine aminotransferase levels at the end of treatment and after follow-up (Lancet 2005;365:123-9).

Human metapneumovirus may be underreported as a pathogen in bronchiolitis and may lead to admittance to intensive care, especially when it infects infants in combination with human respiratory syncytial virus, reported Malcolm G. Semple, M.D., of the University of Liverpool (England), and his associates.

During the 2001-2002 winter season at one hospital, dual infection human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) occurred at a significantly higher rate in infants with bronchiolitis who were admitted to the pediatric intensive care unit on mechanical ventilation (72', 18 of 25) than in infants with bronchiolitis who were sent to the general wards (10', 15 of 171). The investigators said that the temporal distribution of hMPV infections in infants in the pediatric ICU made it unlikely that the infections were nosocomial. In a subset of infants with complete clinical information, dual infection with hMPV and hRSV was not statistically significantly associated with disease severity in the retrospective study (J. Infect. Dis. 2005;191:382-6).

In nasopharyngeal aspirate and bronchoalveolar lavage samples that were taken at the same time from nine hMPV-infected infants on mechanical ventilation, reverse-transcriptase polymerase chain reaction (RT-PCR) detected hMPV in only one nasopharyngeal aspirate and in all nine bronchoalveolar lavages. Of 18 infants who received mechanical ventilation, RT-PCR found hMPV infection in bronchoalveolar lavages from 15 infants and in nasopharyngeal aspirates from 4 infants.

“Collection of [bronchoalveolar lavage] samples would therefore appear to be the preferred sampling method for the detection of hMPV in infants receiving mechanical ventilation.”

Human metapneumovirus may be underreported as a pathogen in bronchiolitis and may lead to admittance to intensive care, especially when it infects infants in combination with human respiratory syncytial virus, reported Malcolm G. Semple, M.D., of the University of Liverpool (England), and his associates.

During the 2001-2002 winter season at one hospital, dual infection human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) occurred at a significantly higher rate in infants with bronchiolitis who were admitted to the pediatric intensive care unit on mechanical ventilation (72', 18 of 25) than in infants with bronchiolitis who were sent to the general wards (10', 15 of 171). The investigators said that the temporal distribution of hMPV infections in infants in the pediatric ICU made it unlikely that the infections were nosocomial. In a subset of infants with complete clinical information, dual infection with hMPV and hRSV was not statistically significantly associated with disease severity in the retrospective study (J. Infect. Dis. 2005;191:382-6).

In nasopharyngeal aspirate and bronchoalveolar lavage samples that were taken at the same time from nine hMPV-infected infants on mechanical ventilation, reverse-transcriptase polymerase chain reaction (RT-PCR) detected hMPV in only one nasopharyngeal aspirate and in all nine bronchoalveolar lavages. Of 18 infants who received mechanical ventilation, RT-PCR found hMPV infection in bronchoalveolar lavages from 15 infants and in nasopharyngeal aspirates from 4 infants.

“Collection of [bronchoalveolar lavage] samples would therefore appear to be the preferred sampling method for the detection of hMPV in infants receiving mechanical ventilation.”

Human metapneumovirus may be underreported as a pathogen in bronchiolitis and may lead to admittance to intensive care, especially when it infects infants in combination with human respiratory syncytial virus, reported Malcolm G. Semple, M.D., of the University of Liverpool (England), and his associates.

During the 2001-2002 winter season at one hospital, dual infection human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) occurred at a significantly higher rate in infants with bronchiolitis who were admitted to the pediatric intensive care unit on mechanical ventilation (72', 18 of 25) than in infants with bronchiolitis who were sent to the general wards (10', 15 of 171). The investigators said that the temporal distribution of hMPV infections in infants in the pediatric ICU made it unlikely that the infections were nosocomial. In a subset of infants with complete clinical information, dual infection with hMPV and hRSV was not statistically significantly associated with disease severity in the retrospective study (J. Infect. Dis. 2005;191:382-6).

In nasopharyngeal aspirate and bronchoalveolar lavage samples that were taken at the same time from nine hMPV-infected infants on mechanical ventilation, reverse-transcriptase polymerase chain reaction (RT-PCR) detected hMPV in only one nasopharyngeal aspirate and in all nine bronchoalveolar lavages. Of 18 infants who received mechanical ventilation, RT-PCR found hMPV infection in bronchoalveolar lavages from 15 infants and in nasopharyngeal aspirates from 4 infants.

“Collection of [bronchoalveolar lavage] samples would therefore appear to be the preferred sampling method for the detection of hMPV in infants receiving mechanical ventilation.”

Preventing Recurrent Ulcer Bleeding

Rather than clopidogrel, aspirin plus a proton-pump inhibitor should be prescribed to prevent recurrent bleeding from ulcers in high-risk patients, according to results of a double-blind, randomized trial.

Francis K.L. Chan, M.D., of the Chinese University of Hong Kong and his associates reported that recurrent ulcer bleeding occurred at a significantly higher rate in 161 patients who received clopidogrel (Plavix) plus a placebo than in 159 patients who received aspirin plus esomeprazole (Nexium) during a median follow-up of 12 months (8.6% vs. 0.7%). Patients took either 75 mg clopidogrel daily or 80 mg aspirin daily plus 20 mg esomeprazole twice daily (N. Engl. J. Med. 2005;352:238-44).

The study included patients who had endoscopically confirmed ulcer healing, had negative tests for or successful eradication of Helicobacter pylori and were not taking anticoagulants or corticosteroids. Study participants had presented with upper GI bleeding after taking low-dose aspirin for prevention of vascular diseases.

The results go against American College of Cardiology/American Heart Association guidelines that advise using clopidogrel as an alternative antiplatelet agent for patients with major GI intolerance of aspirin, he noted. The study “clearly indicates that this recommendation is harmful and that such patients should be given aspirin plus a proton-pump inhibitor,” said Byron Cryer, M.D., of the University of Texas Southwestern Medical Center, Dallas, in an editorial. Antiplatelet agents may cause bleeding ulcers primarily by impairment of healing (N. Engl. J. Med. 2005;352:287-9).

Colorectal Adenoma Chemoprevention

Calcium supplements appear to reduce the risk of developing recurrent colorectal adenomas, according to findings from a metaanalysis of three randomized controlled trials.

In 1,279 patients aged 35-76 years who completed a follow-up colonoscopy after 3-4 years, supplemental calcium (1,200 mg, 1,600 mg, and 2,000 mg daily in the three studies) significantly reduced the risk of recurrent adenomas by 20%, compared with placebo. The patients had a dietary calcium intake ranging from 940 mg to 1,600 mg, reported Aasma Shaukat, M.D., of the State University of New York, Buffalo, and colleagues (Am. J. Gastroenterol. 2005;100:390-4).

Calcium is thought to decrease the risk of recurrent adenomas by binding to and precipitating bile acids and soluble fatty acids. The results of the metaanalysis suggest that recommending a calcium supplement to patients with prior adenomas is a reasonable strategy for achieving a modest decrease in future adenomas. Calcium is cheap and safe, and only about 14 patients need to be treated to prevent 1 patient from having recurrent polyps during a 3- to 4-year period, said Robert S. Sandler, M.D., of the University of North Carolina, Chapel Hill, in an editorial (Am. J. Gastroenterol. 2005;100:395-6).

Colorectal Ca Risk and Eating Meat

High intake of red or processed meat over long periods of time is associated with an increased risk of cancer in the distal colon, rectosigmoid colon, or rectum, reported Ann Chao, Ph.D., of the American Cancer Society, Atlanta, and her associates.

The prospective study included data obtained from about 149,000 men and women who completed a questionnaire in 1982 for the Cancer Prevention Study II and then completed a follow-up questionnaire in 1992 or 1993. Men and women who consumed the most red meat during 1992-1993 had a significant, 71% increase in their risk of cancer of the rectosigmoid colon or rectum. The risk increased progressively from lower to higher intakes of red meat (JAMA 2005;293:172-82).

Men and women who consumed large amounts of processed meats (preserved by salting, smoking, or addition of nitrites or nitrates) in 1982 and in 1992-1993 had a significant, 50% increase in risk of cancer in the distal colon, compared with people who consumed low amounts of processed meats during both periods.

Magnesium and Rectal Ca Risk

Higher magnesium intakes are associated with decreased risk of rectal cancer in women, reported Susanna C. Larsson of the Karolinska Institute, Stockholm, and her colleagues.

After a mean follow-up of nearly 15 years, women with magnesium intakes in the top quintile (at least 255 mg/day) had a rectal cancer risk that was 55% lower than the risk in women with magnesium intakes in the bottom quintile (less than 209 mg/day). Risk reductions were 52%, 46%, and 36%, respectively, in the second-highest, third-highest, and fourth-highest quintiles. The prospective study included about 61,000 women in the Swedish Mammography Cohort who completed a questionnaire between 1987 and 1990 and a second questionnaire in 1997 (JAMA 2005;293:86-9).

Preventing Recurrent Ulcer Bleeding

Rather than clopidogrel, aspirin plus a proton-pump inhibitor should be prescribed to prevent recurrent bleeding from ulcers in high-risk patients, according to results of a double-blind, randomized trial.

Francis K.L. Chan, M.D., of the Chinese University of Hong Kong and his associates reported that recurrent ulcer bleeding occurred at a significantly higher rate in 161 patients who received clopidogrel (Plavix) plus a placebo than in 159 patients who received aspirin plus esomeprazole (Nexium) during a median follow-up of 12 months (8.6% vs. 0.7%). Patients took either 75 mg clopidogrel daily or 80 mg aspirin daily plus 20 mg esomeprazole twice daily (N. Engl. J. Med. 2005;352:238-44).

The study included patients who had endoscopically confirmed ulcer healing, had negative tests for or successful eradication of Helicobacter pylori and were not taking anticoagulants or corticosteroids. Study participants had presented with upper GI bleeding after taking low-dose aspirin for prevention of vascular diseases.

The results go against American College of Cardiology/American Heart Association guidelines that advise using clopidogrel as an alternative antiplatelet agent for patients with major GI intolerance of aspirin, he noted. The study “clearly indicates that this recommendation is harmful and that such patients should be given aspirin plus a proton-pump inhibitor,” said Byron Cryer, M.D., of the University of Texas Southwestern Medical Center, Dallas, in an editorial. Antiplatelet agents may cause bleeding ulcers primarily by impairment of healing (N. Engl. J. Med. 2005;352:287-9).

Colorectal Adenoma Chemoprevention

Calcium supplements appear to reduce the risk of developing recurrent colorectal adenomas, according to findings from a metaanalysis of three randomized controlled trials.

In 1,279 patients aged 35-76 years who completed a follow-up colonoscopy after 3-4 years, supplemental calcium (1,200 mg, 1,600 mg, and 2,000 mg daily in the three studies) significantly reduced the risk of recurrent adenomas by 20%, compared with placebo. The patients had a dietary calcium intake ranging from 940 mg to 1,600 mg, reported Aasma Shaukat, M.D., of the State University of New York, Buffalo, and colleagues (Am. J. Gastroenterol. 2005;100:390-4).

Calcium is thought to decrease the risk of recurrent adenomas by binding to and precipitating bile acids and soluble fatty acids. The results of the metaanalysis suggest that recommending a calcium supplement to patients with prior adenomas is a reasonable strategy for achieving a modest decrease in future adenomas. Calcium is cheap and safe, and only about 14 patients need to be treated to prevent 1 patient from having recurrent polyps during a 3- to 4-year period, said Robert S. Sandler, M.D., of the University of North Carolina, Chapel Hill, in an editorial (Am. J. Gastroenterol. 2005;100:395-6).

Colorectal Ca Risk and Eating Meat

High intake of red or processed meat over long periods of time is associated with an increased risk of cancer in the distal colon, rectosigmoid colon, or rectum, reported Ann Chao, Ph.D., of the American Cancer Society, Atlanta, and her associates.

The prospective study included data obtained from about 149,000 men and women who completed a questionnaire in 1982 for the Cancer Prevention Study II and then completed a follow-up questionnaire in 1992 or 1993. Men and women who consumed the most red meat during 1992-1993 had a significant, 71% increase in their risk of cancer of the rectosigmoid colon or rectum. The risk increased progressively from lower to higher intakes of red meat (JAMA 2005;293:172-82).

Men and women who consumed large amounts of processed meats (preserved by salting, smoking, or addition of nitrites or nitrates) in 1982 and in 1992-1993 had a significant, 50% increase in risk of cancer in the distal colon, compared with people who consumed low amounts of processed meats during both periods.

Magnesium and Rectal Ca Risk

Higher magnesium intakes are associated with decreased risk of rectal cancer in women, reported Susanna C. Larsson of the Karolinska Institute, Stockholm, and her colleagues.

After a mean follow-up of nearly 15 years, women with magnesium intakes in the top quintile (at least 255 mg/day) had a rectal cancer risk that was 55% lower than the risk in women with magnesium intakes in the bottom quintile (less than 209 mg/day). Risk reductions were 52%, 46%, and 36%, respectively, in the second-highest, third-highest, and fourth-highest quintiles. The prospective study included about 61,000 women in the Swedish Mammography Cohort who completed a questionnaire between 1987 and 1990 and a second questionnaire in 1997 (JAMA 2005;293:86-9).

Preventing Recurrent Ulcer Bleeding

Rather than clopidogrel, aspirin plus a proton-pump inhibitor should be prescribed to prevent recurrent bleeding from ulcers in high-risk patients, according to results of a double-blind, randomized trial.

Francis K.L. Chan, M.D., of the Chinese University of Hong Kong and his associates reported that recurrent ulcer bleeding occurred at a significantly higher rate in 161 patients who received clopidogrel (Plavix) plus a placebo than in 159 patients who received aspirin plus esomeprazole (Nexium) during a median follow-up of 12 months (8.6% vs. 0.7%). Patients took either 75 mg clopidogrel daily or 80 mg aspirin daily plus 20 mg esomeprazole twice daily (N. Engl. J. Med. 2005;352:238-44).

The study included patients who had endoscopically confirmed ulcer healing, had negative tests for or successful eradication of Helicobacter pylori and were not taking anticoagulants or corticosteroids. Study participants had presented with upper GI bleeding after taking low-dose aspirin for prevention of vascular diseases.

The results go against American College of Cardiology/American Heart Association guidelines that advise using clopidogrel as an alternative antiplatelet agent for patients with major GI intolerance of aspirin, he noted. The study “clearly indicates that this recommendation is harmful and that such patients should be given aspirin plus a proton-pump inhibitor,” said Byron Cryer, M.D., of the University of Texas Southwestern Medical Center, Dallas, in an editorial. Antiplatelet agents may cause bleeding ulcers primarily by impairment of healing (N. Engl. J. Med. 2005;352:287-9).

Colorectal Adenoma Chemoprevention

Calcium supplements appear to reduce the risk of developing recurrent colorectal adenomas, according to findings from a metaanalysis of three randomized controlled trials.

In 1,279 patients aged 35-76 years who completed a follow-up colonoscopy after 3-4 years, supplemental calcium (1,200 mg, 1,600 mg, and 2,000 mg daily in the three studies) significantly reduced the risk of recurrent adenomas by 20%, compared with placebo. The patients had a dietary calcium intake ranging from 940 mg to 1,600 mg, reported Aasma Shaukat, M.D., of the State University of New York, Buffalo, and colleagues (Am. J. Gastroenterol. 2005;100:390-4).

Calcium is thought to decrease the risk of recurrent adenomas by binding to and precipitating bile acids and soluble fatty acids. The results of the metaanalysis suggest that recommending a calcium supplement to patients with prior adenomas is a reasonable strategy for achieving a modest decrease in future adenomas. Calcium is cheap and safe, and only about 14 patients need to be treated to prevent 1 patient from having recurrent polyps during a 3- to 4-year period, said Robert S. Sandler, M.D., of the University of North Carolina, Chapel Hill, in an editorial (Am. J. Gastroenterol. 2005;100:395-6).

Colorectal Ca Risk and Eating Meat

High intake of red or processed meat over long periods of time is associated with an increased risk of cancer in the distal colon, rectosigmoid colon, or rectum, reported Ann Chao, Ph.D., of the American Cancer Society, Atlanta, and her associates.

The prospective study included data obtained from about 149,000 men and women who completed a questionnaire in 1982 for the Cancer Prevention Study II and then completed a follow-up questionnaire in 1992 or 1993. Men and women who consumed the most red meat during 1992-1993 had a significant, 71% increase in their risk of cancer of the rectosigmoid colon or rectum. The risk increased progressively from lower to higher intakes of red meat (JAMA 2005;293:172-82).

Men and women who consumed large amounts of processed meats (preserved by salting, smoking, or addition of nitrites or nitrates) in 1982 and in 1992-1993 had a significant, 50% increase in risk of cancer in the distal colon, compared with people who consumed low amounts of processed meats during both periods.

Magnesium and Rectal Ca Risk

Higher magnesium intakes are associated with decreased risk of rectal cancer in women, reported Susanna C. Larsson of the Karolinska Institute, Stockholm, and her colleagues.

After a mean follow-up of nearly 15 years, women with magnesium intakes in the top quintile (at least 255 mg/day) had a rectal cancer risk that was 55% lower than the risk in women with magnesium intakes in the bottom quintile (less than 209 mg/day). Risk reductions were 52%, 46%, and 36%, respectively, in the second-highest, third-highest, and fourth-highest quintiles. The prospective study included about 61,000 women in the Swedish Mammography Cohort who completed a questionnaire between 1987 and 1990 and a second questionnaire in 1997 (JAMA 2005;293:86-9).

Women are more likely than men to benefit from treatment with tissue plasminogen activator after an acute ischemic stroke, reported David M. Kent, M.D., of the Tufts-New England Medical Center, Boston, and his associates.

The finding arose from a pooled analysis of four randomized trials comprising 2,178 patients who suffered an acute ischemic stroke.

In the pooled analysis, men did not differ in the probability of a normal or near-normal outcome at 90 days when treated with either tissue plasminogen activator (39%) or placebo (37%). But women treated with tissue plasminogen activator (t-PA) within 6 hours of symptom onset were significantly more likely to have a normal or near-normal outcome than were women who received a placebo (41% vs. 30%).

Treatment with t-PA enabled women in the analysis to have a probability of a normal or near-normal outcome comparable with men who received t-PA (41% vs. 39%). The trials defined normal or near-normal outcome as a score of 1 or less on the modified Rankin scores (Stroke 2005;36:62-5).

Women are known to be more likely than men to have a poor outcome after an acute ischemic stroke. Women on placebo had a significantly lower probability (30%) of a normal or near-normal outcome than did men who received a placebo (37%).

The significance of t-PA treatment according to sex did not change when the investigators controlled for age, systolic blood pressure, diabetes, baseline score on the National Institute of Health Stroke Scale, the symptom onset to treatment time (OTT), the Alberta Stroke Program Early CT Score, the effects of OTT on treatment, and the interaction of diabetes and OTT.

The researchers postulated that female sex might affect the likelihood of reperfusion because of sex-based differences in coagulation and fibrinolysis and that it might affect the response of the brain to ischemia and reperfusion because of some as-yet unknown effect of estrogen, the vascular anatomy of stroke, or the particular stroke subtype.

Only 45% of the patients in the four studies combined were women despite the fact that the overall lifetime risk of stroke is higher in women than in men. A recent report suggesting that women are less likely than men to receive IV thrombolytic therapy highlights the fact that a bias toward t-PA treatment in men may result in the unintended “targeting of treatment to patients who are actually less likely to benefit from therapy (i.e., men),” the investigators said.

Women are more likely than men to benefit from treatment with tissue plasminogen activator after an acute ischemic stroke, reported David M. Kent, M.D., of the Tufts-New England Medical Center, Boston, and his associates.

The finding arose from a pooled analysis of four randomized trials comprising 2,178 patients who suffered an acute ischemic stroke.

In the pooled analysis, men did not differ in the probability of a normal or near-normal outcome at 90 days when treated with either tissue plasminogen activator (39%) or placebo (37%). But women treated with tissue plasminogen activator (t-PA) within 6 hours of symptom onset were significantly more likely to have a normal or near-normal outcome than were women who received a placebo (41% vs. 30%).

Treatment with t-PA enabled women in the analysis to have a probability of a normal or near-normal outcome comparable with men who received t-PA (41% vs. 39%). The trials defined normal or near-normal outcome as a score of 1 or less on the modified Rankin scores (Stroke 2005;36:62-5).

Women are known to be more likely than men to have a poor outcome after an acute ischemic stroke. Women on placebo had a significantly lower probability (30%) of a normal or near-normal outcome than did men who received a placebo (37%).

The significance of t-PA treatment according to sex did not change when the investigators controlled for age, systolic blood pressure, diabetes, baseline score on the National Institute of Health Stroke Scale, the symptom onset to treatment time (OTT), the Alberta Stroke Program Early CT Score, the effects of OTT on treatment, and the interaction of diabetes and OTT.

The researchers postulated that female sex might affect the likelihood of reperfusion because of sex-based differences in coagulation and fibrinolysis and that it might affect the response of the brain to ischemia and reperfusion because of some as-yet unknown effect of estrogen, the vascular anatomy of stroke, or the particular stroke subtype.

Only 45% of the patients in the four studies combined were women despite the fact that the overall lifetime risk of stroke is higher in women than in men. A recent report suggesting that women are less likely than men to receive IV thrombolytic therapy highlights the fact that a bias toward t-PA treatment in men may result in the unintended “targeting of treatment to patients who are actually less likely to benefit from therapy (i.e., men),” the investigators said.

Women are more likely than men to benefit from treatment with tissue plasminogen activator after an acute ischemic stroke, reported David M. Kent, M.D., of the Tufts-New England Medical Center, Boston, and his associates.

The finding arose from a pooled analysis of four randomized trials comprising 2,178 patients who suffered an acute ischemic stroke.

In the pooled analysis, men did not differ in the probability of a normal or near-normal outcome at 90 days when treated with either tissue plasminogen activator (39%) or placebo (37%). But women treated with tissue plasminogen activator (t-PA) within 6 hours of symptom onset were significantly more likely to have a normal or near-normal outcome than were women who received a placebo (41% vs. 30%).

Treatment with t-PA enabled women in the analysis to have a probability of a normal or near-normal outcome comparable with men who received t-PA (41% vs. 39%). The trials defined normal or near-normal outcome as a score of 1 or less on the modified Rankin scores (Stroke 2005;36:62-5).

Women are known to be more likely than men to have a poor outcome after an acute ischemic stroke. Women on placebo had a significantly lower probability (30%) of a normal or near-normal outcome than did men who received a placebo (37%).

The significance of t-PA treatment according to sex did not change when the investigators controlled for age, systolic blood pressure, diabetes, baseline score on the National Institute of Health Stroke Scale, the symptom onset to treatment time (OTT), the Alberta Stroke Program Early CT Score, the effects of OTT on treatment, and the interaction of diabetes and OTT.

The researchers postulated that female sex might affect the likelihood of reperfusion because of sex-based differences in coagulation and fibrinolysis and that it might affect the response of the brain to ischemia and reperfusion because of some as-yet unknown effect of estrogen, the vascular anatomy of stroke, or the particular stroke subtype.

Only 45% of the patients in the four studies combined were women despite the fact that the overall lifetime risk of stroke is higher in women than in men. A recent report suggesting that women are less likely than men to receive IV thrombolytic therapy highlights the fact that a bias toward t-PA treatment in men may result in the unintended “targeting of treatment to patients who are actually less likely to benefit from therapy (i.e., men),” the investigators said.

ORLANDO, FLA. — A new diagnostic tool that can detect reflux regardless of pH may help clinicians offer individualized treatment for gastroesophageal reflux disease, Inder Mainie, M.D., said at the annual meeting of the American College of Gastroenterology.

Used in conjunction with esophageal pH monitoring, multichannel intraluminal impedance (MII) monitoring can show whether symptoms of gastroesophageal reflux disease (GERD) are associated with acid or nonacid reflux events—or with no reflux at all, said Dr. Mainie of the digestive disease center at the Medical University of South Carolina, Charleston.

About 35% or more of patients with GERD have persistent reflux symptoms while on proton-pump inhibitor (PPI) therapy, Dr. Mainie noted.

Esophageal pH monitoring alone cannot detect reflux episodes that occur at a pH of 4 or higher (nonacid reflux). But MII devices can detect gastroesophageal reflux independent of pH based on the changes in the electrical conductivity in the lumen of the esophagus.

A combined approach that uses MII plus pH detection “brings a change in the paradigm for reflux detection,” Dr. Mainie said. “The impedance information identifies reflux episodes, while the pH electrode is used simply to categorize them as acid or nonacid.”

In 125 patients (average age 43 years) with symptoms of GERD who took PPIs twice per day, Dr. Mainie and his colleagues simultaneously measured acid and nonacid reflux at 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter with a combined MII-pH device that is approved by the Food and Drug Administration.

Overall, 101 of the patients had reflux symptoms on the day of testing. Each patient had nonacid reflux events. Typical GERD symptoms (heartburn, regurgitation, and chest pain) occurred in 58 patients. Among these patients, a positive symptom index occurred with nonacid reflux in 45% and with acid reflux in 10%. Another 45% of patients had typical symptoms without reflux.

The symptom index (SI) represents the percentage of perceived gastroesophageal reflux-related symptoms that correlate with esophageal acid (or nonacid) reflux events. An SI score is positive if 50% or more of the perceived gastroesophageal reflux-related symptoms correlate with acid (or nonacid) reflux events.

In 43 patients who showed atypical GERD symptoms (abdominal discomfort, belch, catarrh, dysphagia, choking, globus, hoarseness, cough, wheeze, or acid taste), a positive SI occurred with nonacid reflux in 23% and with acid reflux in 2% of the patients. Reflux did not occur in 75% of patients who had atypical symptoms.

A positive SI was associated with nonacid reflux in 36% of all patients who experienced GERD-related symptoms during the study; 7% of patients with GERD-related symptoms had a positive SI for acid reflux.

In contrast, 58% of patients had no reflux associated with their symptoms. The percentage of patients with typical symptoms associated with reflux (55%) was significantly higher than the percentage of patients with atypical symptoms associated with reflux (25%).

A total of 15 of the symptomatic patients were younger than 16 years old. No differences occurred in the types of reflux associated with symptoms between children or adults.

“MII-pH helps to clarify underlying, persistent GERD-related symptoms during PPI therapy,” Dr. Mainie said. “Clinical presentation alone is not sufficient to identify the presence or absence of reflux-causing symptoms.”

Dr. Mainie and his colleagues at the university are gathering data on the outcomes of these patients to determine the role of MII-pH in directing therapy.

ORLANDO, FLA. — A new diagnostic tool that can detect reflux regardless of pH may help clinicians offer individualized treatment for gastroesophageal reflux disease, Inder Mainie, M.D., said at the annual meeting of the American College of Gastroenterology.

Used in conjunction with esophageal pH monitoring, multichannel intraluminal impedance (MII) monitoring can show whether symptoms of gastroesophageal reflux disease (GERD) are associated with acid or nonacid reflux events—or with no reflux at all, said Dr. Mainie of the digestive disease center at the Medical University of South Carolina, Charleston.

About 35% or more of patients with GERD have persistent reflux symptoms while on proton-pump inhibitor (PPI) therapy, Dr. Mainie noted.

Esophageal pH monitoring alone cannot detect reflux episodes that occur at a pH of 4 or higher (nonacid reflux). But MII devices can detect gastroesophageal reflux independent of pH based on the changes in the electrical conductivity in the lumen of the esophagus.

A combined approach that uses MII plus pH detection “brings a change in the paradigm for reflux detection,” Dr. Mainie said. “The impedance information identifies reflux episodes, while the pH electrode is used simply to categorize them as acid or nonacid.”

In 125 patients (average age 43 years) with symptoms of GERD who took PPIs twice per day, Dr. Mainie and his colleagues simultaneously measured acid and nonacid reflux at 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter with a combined MII-pH device that is approved by the Food and Drug Administration.

Overall, 101 of the patients had reflux symptoms on the day of testing. Each patient had nonacid reflux events. Typical GERD symptoms (heartburn, regurgitation, and chest pain) occurred in 58 patients. Among these patients, a positive symptom index occurred with nonacid reflux in 45% and with acid reflux in 10%. Another 45% of patients had typical symptoms without reflux.

The symptom index (SI) represents the percentage of perceived gastroesophageal reflux-related symptoms that correlate with esophageal acid (or nonacid) reflux events. An SI score is positive if 50% or more of the perceived gastroesophageal reflux-related symptoms correlate with acid (or nonacid) reflux events.

In 43 patients who showed atypical GERD symptoms (abdominal discomfort, belch, catarrh, dysphagia, choking, globus, hoarseness, cough, wheeze, or acid taste), a positive SI occurred with nonacid reflux in 23% and with acid reflux in 2% of the patients. Reflux did not occur in 75% of patients who had atypical symptoms.

A positive SI was associated with nonacid reflux in 36% of all patients who experienced GERD-related symptoms during the study; 7% of patients with GERD-related symptoms had a positive SI for acid reflux.

In contrast, 58% of patients had no reflux associated with their symptoms. The percentage of patients with typical symptoms associated with reflux (55%) was significantly higher than the percentage of patients with atypical symptoms associated with reflux (25%).

A total of 15 of the symptomatic patients were younger than 16 years old. No differences occurred in the types of reflux associated with symptoms between children or adults.

“MII-pH helps to clarify underlying, persistent GERD-related symptoms during PPI therapy,” Dr. Mainie said. “Clinical presentation alone is not sufficient to identify the presence or absence of reflux-causing symptoms.”

Dr. Mainie and his colleagues at the university are gathering data on the outcomes of these patients to determine the role of MII-pH in directing therapy.

ORLANDO, FLA. — A new diagnostic tool that can detect reflux regardless of pH may help clinicians offer individualized treatment for gastroesophageal reflux disease, Inder Mainie, M.D., said at the annual meeting of the American College of Gastroenterology.

Used in conjunction with esophageal pH monitoring, multichannel intraluminal impedance (MII) monitoring can show whether symptoms of gastroesophageal reflux disease (GERD) are associated with acid or nonacid reflux events—or with no reflux at all, said Dr. Mainie of the digestive disease center at the Medical University of South Carolina, Charleston.

About 35% or more of patients with GERD have persistent reflux symptoms while on proton-pump inhibitor (PPI) therapy, Dr. Mainie noted.

Esophageal pH monitoring alone cannot detect reflux episodes that occur at a pH of 4 or higher (nonacid reflux). But MII devices can detect gastroesophageal reflux independent of pH based on the changes in the electrical conductivity in the lumen of the esophagus.

A combined approach that uses MII plus pH detection “brings a change in the paradigm for reflux detection,” Dr. Mainie said. “The impedance information identifies reflux episodes, while the pH electrode is used simply to categorize them as acid or nonacid.”

In 125 patients (average age 43 years) with symptoms of GERD who took PPIs twice per day, Dr. Mainie and his colleagues simultaneously measured acid and nonacid reflux at 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter with a combined MII-pH device that is approved by the Food and Drug Administration.

Overall, 101 of the patients had reflux symptoms on the day of testing. Each patient had nonacid reflux events. Typical GERD symptoms (heartburn, regurgitation, and chest pain) occurred in 58 patients. Among these patients, a positive symptom index occurred with nonacid reflux in 45% and with acid reflux in 10%. Another 45% of patients had typical symptoms without reflux.

The symptom index (SI) represents the percentage of perceived gastroesophageal reflux-related symptoms that correlate with esophageal acid (or nonacid) reflux events. An SI score is positive if 50% or more of the perceived gastroesophageal reflux-related symptoms correlate with acid (or nonacid) reflux events.

In 43 patients who showed atypical GERD symptoms (abdominal discomfort, belch, catarrh, dysphagia, choking, globus, hoarseness, cough, wheeze, or acid taste), a positive SI occurred with nonacid reflux in 23% and with acid reflux in 2% of the patients. Reflux did not occur in 75% of patients who had atypical symptoms.

A positive SI was associated with nonacid reflux in 36% of all patients who experienced GERD-related symptoms during the study; 7% of patients with GERD-related symptoms had a positive SI for acid reflux.

In contrast, 58% of patients had no reflux associated with their symptoms. The percentage of patients with typical symptoms associated with reflux (55%) was significantly higher than the percentage of patients with atypical symptoms associated with reflux (25%).

A total of 15 of the symptomatic patients were younger than 16 years old. No differences occurred in the types of reflux associated with symptoms between children or adults.

“MII-pH helps to clarify underlying, persistent GERD-related symptoms during PPI therapy,” Dr. Mainie said. “Clinical presentation alone is not sufficient to identify the presence or absence of reflux-causing symptoms.”

Dr. Mainie and his colleagues at the university are gathering data on the outcomes of these patients to determine the role of MII-pH in directing therapy.

The focus of liver and biliary disease research in the United States through 2015 has been set with the release of the National Institutes of Health's Action Plan for Liver Disease Research.

The decade-long initiative is the result of coordinated effort between federal health agencies and the 18 institutes, centers, and offices in the NIH that support liver and biliary disease research. It is geared toward the rapid translation of findings from basic research to clinical practice, and vice versa. The plan includes 214 research goals, but 10 major goals cut across multiple disciplines in liver and biliary disease research:

▸ Improve the success rate of therapy for chronic hepatitis C.

▸ Develop effective antiviral therapy regimens for the long-term management of chronic hepatitis B.

▸ Develop effective therapies for the treatment of both nonalcoholic and alcoholic fatty liver disease.

▸ Detect hepatic fibrosis with sensitive, specific, and noninvasive tests.

▸ Detect hepatocellular carcinoma at earlier stages in high-risk patients with new screening tests.

▸ Develop ways to prevent gallstones.

▸ Elucidate the etiology of biliary atresia.

▸ Improve the safety, and determine the best use, of living donor liver transplantation.

▸ Develop standardized and objective diagnostic criteria of major liver diseases and their grading and staging.

▸ Reduce the overall mortality from chronic liver disease and cirrhosis.

The full action plan is located atwww.niddk.nih.gov/fund/divisions/ddn/ldrb/ldrb_action_plan.htm

The focus of liver and biliary disease research in the United States through 2015 has been set with the release of the National Institutes of Health's Action Plan for Liver Disease Research.

The decade-long initiative is the result of coordinated effort between federal health agencies and the 18 institutes, centers, and offices in the NIH that support liver and biliary disease research. It is geared toward the rapid translation of findings from basic research to clinical practice, and vice versa. The plan includes 214 research goals, but 10 major goals cut across multiple disciplines in liver and biliary disease research:

▸ Improve the success rate of therapy for chronic hepatitis C.

▸ Develop effective antiviral therapy regimens for the long-term management of chronic hepatitis B.

▸ Develop effective therapies for the treatment of both nonalcoholic and alcoholic fatty liver disease.

▸ Detect hepatic fibrosis with sensitive, specific, and noninvasive tests.

▸ Detect hepatocellular carcinoma at earlier stages in high-risk patients with new screening tests.

▸ Develop ways to prevent gallstones.

▸ Elucidate the etiology of biliary atresia.

▸ Improve the safety, and determine the best use, of living donor liver transplantation.

▸ Develop standardized and objective diagnostic criteria of major liver diseases and their grading and staging.

▸ Reduce the overall mortality from chronic liver disease and cirrhosis.

The full action plan is located atwww.niddk.nih.gov/fund/divisions/ddn/ldrb/ldrb_action_plan.htm

The focus of liver and biliary disease research in the United States through 2015 has been set with the release of the National Institutes of Health's Action Plan for Liver Disease Research.

The decade-long initiative is the result of coordinated effort between federal health agencies and the 18 institutes, centers, and offices in the NIH that support liver and biliary disease research. It is geared toward the rapid translation of findings from basic research to clinical practice, and vice versa. The plan includes 214 research goals, but 10 major goals cut across multiple disciplines in liver and biliary disease research:

▸ Improve the success rate of therapy for chronic hepatitis C.

▸ Develop effective antiviral therapy regimens for the long-term management of chronic hepatitis B.

▸ Develop effective therapies for the treatment of both nonalcoholic and alcoholic fatty liver disease.

▸ Detect hepatic fibrosis with sensitive, specific, and noninvasive tests.

▸ Detect hepatocellular carcinoma at earlier stages in high-risk patients with new screening tests.

▸ Develop ways to prevent gallstones.

▸ Elucidate the etiology of biliary atresia.

▸ Improve the safety, and determine the best use, of living donor liver transplantation.

▸ Develop standardized and objective diagnostic criteria of major liver diseases and their grading and staging.

▸ Reduce the overall mortality from chronic liver disease and cirrhosis.

The full action plan is located atwww.niddk.nih.gov/fund/divisions/ddn/ldrb/ldrb_action_plan.htm

Aerosol devices that deliver therapy to patients with asthma or chronic obstructive pulmonary disease are similarly effective in a broad range of clinical settings.

But such devices must be carefully selected to match the needs of individual patients, according to new evidence-based guidelines issued by the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology.

Several systemic reviews and metaanalyses have been published on the selection of aerosol delivery devices, but “evidence-based guidelines are still needed,” said Myrna B. Dolovich, an engineer at McMaster University, Hamilton, Ont., and her colleagues on the panel that drafted the guidelines.

The guidelines were based on data from 59 randomized, controlled trials that tested the same drug with different devices (Chest 2005;127:335–71). They include a list of questions to keep in mind when selecting the best device for a particular setting. (See box.)

In the emergency department and inpatient hospital settings, the panel found that delivery of short-acting β₂-agonists with nebulizers or metered-dose inhalers (MDIs) with a spacer/holding chamber produces similar improvements in lung function. Not enough data were available to recommend the use of dry powder inhalers (DPIs), MDIs without a spacer/holding chamber, or breath-actuated MDIs in emergency department or inpatient settings.

Continuous use or frequent intermittent nebulization of β₂-agonists for severe bronchospasms in the emergency department or ICU have the same safety and effectiveness in improving pulmonary function and asthma symptom scores. Continuous nebulization required significantly less time for staff to administer and maintain than did intermittent therapy.

Nebulizers or MDIs are similarly effective in delivering β₂-agonists to patients on mechanical ventilation.

A careful attention to detail must be used to administer drugs with either device to patients on mechanical ventilation since multiple technical factors can influence the efficiency of aerosol delivery, the guidelines caution.

All of the studies conducted in acute care settings took place in conditions of actual clinical use, rather than under clinical laboratory conditions.

MDIs with or without a spacer/holding chamber or DPIs delivered short-acting β₂-agonists with equal effectiveness and safety in the outpatient treatment of asthma, the guidelines stated. Equal doses of corticosteroids had the same effectiveness in outpatients with asthma when delivered with either an MDI with a spacer/holder chamber or a DPI.

The panel found that MDIs with or without a spacer/holder chamber, nebulizers, and DPIs have equal effectiveness in delivering β₂-agonists or anticholinergic agents to outpatients with chronic obstructive pulmonary disease.

Outpatient studies performed under laboratory conditions “do not indicate that the device would perform equally well in more adverse, real-world situations,” the panel warned.

Considerations in Selecting a Device

▸ In what devices is the desired drug available?

▸ What device is the patient likely to be able to use properly, given the patient's age and the clinical setting?

▸ For which device and drug combination is reimbursement available?

▸ Which devices are the least costly?

▸ Can all types of asthma/COPD drugs that are prescribed for the patient be delivered with the same type of device?

▸ Which devices are the most convenient for the patient, family (outpatient use), or medical staff (acute care setting) to use, given the time required for drug administration and device cleaning and the portability of the device?

▸ How durable is the device?

▸ Does the patient or clinician have any specific device preferences?

Aerosol devices that deliver therapy to patients with asthma or chronic obstructive pulmonary disease are similarly effective in a broad range of clinical settings.

But such devices must be carefully selected to match the needs of individual patients, according to new evidence-based guidelines issued by the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology.

Several systemic reviews and metaanalyses have been published on the selection of aerosol delivery devices, but “evidence-based guidelines are still needed,” said Myrna B. Dolovich, an engineer at McMaster University, Hamilton, Ont., and her colleagues on the panel that drafted the guidelines.

The guidelines were based on data from 59 randomized, controlled trials that tested the same drug with different devices (Chest 2005;127:335–71). They include a list of questions to keep in mind when selecting the best device for a particular setting. (See box.)

In the emergency department and inpatient hospital settings, the panel found that delivery of short-acting β₂-agonists with nebulizers or metered-dose inhalers (MDIs) with a spacer/holding chamber produces similar improvements in lung function. Not enough data were available to recommend the use of dry powder inhalers (DPIs), MDIs without a spacer/holding chamber, or breath-actuated MDIs in emergency department or inpatient settings.

Continuous use or frequent intermittent nebulization of β₂-agonists for severe bronchospasms in the emergency department or ICU have the same safety and effectiveness in improving pulmonary function and asthma symptom scores. Continuous nebulization required significantly less time for staff to administer and maintain than did intermittent therapy.

Nebulizers or MDIs are similarly effective in delivering β₂-agonists to patients on mechanical ventilation.

A careful attention to detail must be used to administer drugs with either device to patients on mechanical ventilation since multiple technical factors can influence the efficiency of aerosol delivery, the guidelines caution.

All of the studies conducted in acute care settings took place in conditions of actual clinical use, rather than under clinical laboratory conditions.

MDIs with or without a spacer/holding chamber or DPIs delivered short-acting β₂-agonists with equal effectiveness and safety in the outpatient treatment of asthma, the guidelines stated. Equal doses of corticosteroids had the same effectiveness in outpatients with asthma when delivered with either an MDI with a spacer/holder chamber or a DPI.

The panel found that MDIs with or without a spacer/holder chamber, nebulizers, and DPIs have equal effectiveness in delivering β₂-agonists or anticholinergic agents to outpatients with chronic obstructive pulmonary disease.

Outpatient studies performed under laboratory conditions “do not indicate that the device would perform equally well in more adverse, real-world situations,” the panel warned.

Considerations in Selecting a Device

▸ In what devices is the desired drug available?

▸ What device is the patient likely to be able to use properly, given the patient's age and the clinical setting?

▸ For which device and drug combination is reimbursement available?

▸ Which devices are the least costly?

▸ Can all types of asthma/COPD drugs that are prescribed for the patient be delivered with the same type of device?

▸ Which devices are the most convenient for the patient, family (outpatient use), or medical staff (acute care setting) to use, given the time required for drug administration and device cleaning and the portability of the device?

▸ How durable is the device?

▸ Does the patient or clinician have any specific device preferences?

Aerosol devices that deliver therapy to patients with asthma or chronic obstructive pulmonary disease are similarly effective in a broad range of clinical settings.

But such devices must be carefully selected to match the needs of individual patients, according to new evidence-based guidelines issued by the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology.

Several systemic reviews and metaanalyses have been published on the selection of aerosol delivery devices, but “evidence-based guidelines are still needed,” said Myrna B. Dolovich, an engineer at McMaster University, Hamilton, Ont., and her colleagues on the panel that drafted the guidelines.

The guidelines were based on data from 59 randomized, controlled trials that tested the same drug with different devices (Chest 2005;127:335–71). They include a list of questions to keep in mind when selecting the best device for a particular setting. (See box.)

In the emergency department and inpatient hospital settings, the panel found that delivery of short-acting β₂-agonists with nebulizers or metered-dose inhalers (MDIs) with a spacer/holding chamber produces similar improvements in lung function. Not enough data were available to recommend the use of dry powder inhalers (DPIs), MDIs without a spacer/holding chamber, or breath-actuated MDIs in emergency department or inpatient settings.

Continuous use or frequent intermittent nebulization of β₂-agonists for severe bronchospasms in the emergency department or ICU have the same safety and effectiveness in improving pulmonary function and asthma symptom scores. Continuous nebulization required significantly less time for staff to administer and maintain than did intermittent therapy.

Nebulizers or MDIs are similarly effective in delivering β₂-agonists to patients on mechanical ventilation.

A careful attention to detail must be used to administer drugs with either device to patients on mechanical ventilation since multiple technical factors can influence the efficiency of aerosol delivery, the guidelines caution.

All of the studies conducted in acute care settings took place in conditions of actual clinical use, rather than under clinical laboratory conditions.

MDIs with or without a spacer/holding chamber or DPIs delivered short-acting β₂-agonists with equal effectiveness and safety in the outpatient treatment of asthma, the guidelines stated. Equal doses of corticosteroids had the same effectiveness in outpatients with asthma when delivered with either an MDI with a spacer/holder chamber or a DPI.

The panel found that MDIs with or without a spacer/holder chamber, nebulizers, and DPIs have equal effectiveness in delivering β₂-agonists or anticholinergic agents to outpatients with chronic obstructive pulmonary disease.

Outpatient studies performed under laboratory conditions “do not indicate that the device would perform equally well in more adverse, real-world situations,” the panel warned.

Considerations in Selecting a Device

▸ In what devices is the desired drug available?

▸ What device is the patient likely to be able to use properly, given the patient's age and the clinical setting?

▸ For which device and drug combination is reimbursement available?

▸ Which devices are the least costly?

▸ Can all types of asthma/COPD drugs that are prescribed for the patient be delivered with the same type of device?

▸ Which devices are the most convenient for the patient, family (outpatient use), or medical staff (acute care setting) to use, given the time required for drug administration and device cleaning and the portability of the device?

▸ How durable is the device?

▸ Does the patient or clinician have any specific device preferences?

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified. This project asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code. Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified. This project asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code. Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified. This project asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code. Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

WASHINGTON — Older age and disease location appear to contribute to the generally poor prognosis of patients who have mucosal melanoma, according to two retrospective studies reported at the Sixth International Conference on Head and Neck Cancer.

Reports in the medical literature note that mucosal melanoma, which occurs most often in the head and neck, constitutes 0.8%–3.7% of all melanomas. It is diagnosed so infrequently that identifying prognostic variables has been difficult, said Thomas Loh, M.D., of the department of otolaryngology and surgical oncology at the National University of Singapore.

When Dr. Loh was a fellow at the University of Toronto's Princess Margaret Hospital, he and his colleagues conducted a retrospective cohort study of 61 patients who had presented to the hospital with mucosal melanoma during a 41-year period. The cancers included melanomas of the oral cavity, oropharynx, hypopharynx, larynx, and nasal cavity. Most of the melanomas were in the sinonasal (80%) or oral (16%) cavities.

Single-modality treatment with surgery or radiation accounted for therapy for 61% of patients, whereas 38% received treatment with multiple modalities. Local (61%) and distant (50%) residual disease accounted for most tumor recurrences, and 21% of recurrences occurred regionally.

Overall, 28% of the patients had not died specifically of melanoma 5 years after diagnosis. Only a “dismal” 26% were free of disease 2 years after diagnosis, and 8% were free after 5 years, Dr. Loh said at the conference, which was sponsored by the American Head and Neck Society.

However, patients younger than 50 years when diagnosed had a 5-year survival rate of 63%, while those older than 50 years had a 21% 5-year survival rate. Patients, on average, were 65 years old.

In the largest study of its kind to date, Eileen H. Dauer, M.D., and her colleagues in the department of otolaryngology at the Mayo Clinic, Rochester, Minn., reviewed all 78 cases of sinonasal melanoma that presented to the clinic during 1963–2003.

Sinonasal melanomas accounted for fewer than 1% of all malignant melanomas and 4% of sinonasal tumors overall. Estimated survival rates ranged from 13% to 45%, according to small retrospective studies.

Patients most commonly presented with symptoms of nasal obstruction and epistaxis. Tumors were located in a variety of subsites, typically the lateral nasal wall and turbinates (57%) and the septum (25%).

Treatments included wide local excision alone in 48% of patients, a combination of wide local excision and radiation in 28%, radiation alone in 16%, and chemotherapy in 8%. Of the 78 patients at Mayo, 17 were not included in the survival analysis because they were treated elsewhere or were only biopsied or debulked.

“It is our practice still to mainly rely on surgery, with radiation therapy as a useful adjunct,” Dr. Dauer said.

Tumors recurred locally in 36 patients after an average of 21 months (median of 9 months). The recurrence rate was 36% after 1 year and 61% after 3 years. Regional metastases developed in 19 patients after an average of 22 months (median of 16 months). A total of 38 patients had distant metastases, which occurred after an average of 28 months (median of 12 months, with a range of 1 month to 212 months). After 1 year, 30% of patients had distant metastases, 53% had them after 3 years.

“Quite sobering,” Dr Dauer said concerning the expected survival of a patient with distant metastases: The median time to death was 3 months. In this study, 53% of patients were alive at 3 months, 32% at 6 months, and 15% at 12 months. One year after treatment, 74% of patients had not died specifically of melanoma, but this dropped to 52% at 3 years and to 23% at 5 years. On average, patients died after 35 months (median of 20 months, ranging from 3 months to 223 months).

After a mean follow-up of 43 months (median of 21 months) among the 61 patients, 46 died from the disease and 11 died from other or unknown causes. Four patients are still alive.

Patients with septal involvement had a significantly greater rate of overall survival than did those without it.

Location and volume of the tumor were the only significant prognostic factors for sinonasal melanoma in a multivariate analysis.

WASHINGTON — Older age and disease location appear to contribute to the generally poor prognosis of patients who have mucosal melanoma, according to two retrospective studies reported at the Sixth International Conference on Head and Neck Cancer.

Reports in the medical literature note that mucosal melanoma, which occurs most often in the head and neck, constitutes 0.8%–3.7% of all melanomas. It is diagnosed so infrequently that identifying prognostic variables has been difficult, said Thomas Loh, M.D., of the department of otolaryngology and surgical oncology at the National University of Singapore.

When Dr. Loh was a fellow at the University of Toronto's Princess Margaret Hospital, he and his colleagues conducted a retrospective cohort study of 61 patients who had presented to the hospital with mucosal melanoma during a 41-year period. The cancers included melanomas of the oral cavity, oropharynx, hypopharynx, larynx, and nasal cavity. Most of the melanomas were in the sinonasal (80%) or oral (16%) cavities.

Single-modality treatment with surgery or radiation accounted for therapy for 61% of patients, whereas 38% received treatment with multiple modalities. Local (61%) and distant (50%) residual disease accounted for most tumor recurrences, and 21% of recurrences occurred regionally.

Overall, 28% of the patients had not died specifically of melanoma 5 years after diagnosis. Only a “dismal” 26% were free of disease 2 years after diagnosis, and 8% were free after 5 years, Dr. Loh said at the conference, which was sponsored by the American Head and Neck Society.

However, patients younger than 50 years when diagnosed had a 5-year survival rate of 63%, while those older than 50 years had a 21% 5-year survival rate. Patients, on average, were 65 years old.

In the largest study of its kind to date, Eileen H. Dauer, M.D., and her colleagues in the department of otolaryngology at the Mayo Clinic, Rochester, Minn., reviewed all 78 cases of sinonasal melanoma that presented to the clinic during 1963–2003.

Sinonasal melanomas accounted for fewer than 1% of all malignant melanomas and 4% of sinonasal tumors overall. Estimated survival rates ranged from 13% to 45%, according to small retrospective studies.

Patients most commonly presented with symptoms of nasal obstruction and epistaxis. Tumors were located in a variety of subsites, typically the lateral nasal wall and turbinates (57%) and the septum (25%).

Treatments included wide local excision alone in 48% of patients, a combination of wide local excision and radiation in 28%, radiation alone in 16%, and chemotherapy in 8%. Of the 78 patients at Mayo, 17 were not included in the survival analysis because they were treated elsewhere or were only biopsied or debulked.

“It is our practice still to mainly rely on surgery, with radiation therapy as a useful adjunct,” Dr. Dauer said.

Tumors recurred locally in 36 patients after an average of 21 months (median of 9 months). The recurrence rate was 36% after 1 year and 61% after 3 years. Regional metastases developed in 19 patients after an average of 22 months (median of 16 months). A total of 38 patients had distant metastases, which occurred after an average of 28 months (median of 12 months, with a range of 1 month to 212 months). After 1 year, 30% of patients had distant metastases, 53% had them after 3 years.

“Quite sobering,” Dr Dauer said concerning the expected survival of a patient with distant metastases: The median time to death was 3 months. In this study, 53% of patients were alive at 3 months, 32% at 6 months, and 15% at 12 months. One year after treatment, 74% of patients had not died specifically of melanoma, but this dropped to 52% at 3 years and to 23% at 5 years. On average, patients died after 35 months (median of 20 months, ranging from 3 months to 223 months).

After a mean follow-up of 43 months (median of 21 months) among the 61 patients, 46 died from the disease and 11 died from other or unknown causes. Four patients are still alive.

Patients with septal involvement had a significantly greater rate of overall survival than did those without it.

Location and volume of the tumor were the only significant prognostic factors for sinonasal melanoma in a multivariate analysis.

WASHINGTON — Older age and disease location appear to contribute to the generally poor prognosis of patients who have mucosal melanoma, according to two retrospective studies reported at the Sixth International Conference on Head and Neck Cancer.

Reports in the medical literature note that mucosal melanoma, which occurs most often in the head and neck, constitutes 0.8%–3.7% of all melanomas. It is diagnosed so infrequently that identifying prognostic variables has been difficult, said Thomas Loh, M.D., of the department of otolaryngology and surgical oncology at the National University of Singapore.

When Dr. Loh was a fellow at the University of Toronto's Princess Margaret Hospital, he and his colleagues conducted a retrospective cohort study of 61 patients who had presented to the hospital with mucosal melanoma during a 41-year period. The cancers included melanomas of the oral cavity, oropharynx, hypopharynx, larynx, and nasal cavity. Most of the melanomas were in the sinonasal (80%) or oral (16%) cavities.

Single-modality treatment with surgery or radiation accounted for therapy for 61% of patients, whereas 38% received treatment with multiple modalities. Local (61%) and distant (50%) residual disease accounted for most tumor recurrences, and 21% of recurrences occurred regionally.

Overall, 28% of the patients had not died specifically of melanoma 5 years after diagnosis. Only a “dismal” 26% were free of disease 2 years after diagnosis, and 8% were free after 5 years, Dr. Loh said at the conference, which was sponsored by the American Head and Neck Society.

However, patients younger than 50 years when diagnosed had a 5-year survival rate of 63%, while those older than 50 years had a 21% 5-year survival rate. Patients, on average, were 65 years old.

In the largest study of its kind to date, Eileen H. Dauer, M.D., and her colleagues in the department of otolaryngology at the Mayo Clinic, Rochester, Minn., reviewed all 78 cases of sinonasal melanoma that presented to the clinic during 1963–2003.

Sinonasal melanomas accounted for fewer than 1% of all malignant melanomas and 4% of sinonasal tumors overall. Estimated survival rates ranged from 13% to 45%, according to small retrospective studies.

Patients most commonly presented with symptoms of nasal obstruction and epistaxis. Tumors were located in a variety of subsites, typically the lateral nasal wall and turbinates (57%) and the septum (25%).

Treatments included wide local excision alone in 48% of patients, a combination of wide local excision and radiation in 28%, radiation alone in 16%, and chemotherapy in 8%. Of the 78 patients at Mayo, 17 were not included in the survival analysis because they were treated elsewhere or were only biopsied or debulked.

“It is our practice still to mainly rely on surgery, with radiation therapy as a useful adjunct,” Dr. Dauer said.

Tumors recurred locally in 36 patients after an average of 21 months (median of 9 months). The recurrence rate was 36% after 1 year and 61% after 3 years. Regional metastases developed in 19 patients after an average of 22 months (median of 16 months). A total of 38 patients had distant metastases, which occurred after an average of 28 months (median of 12 months, with a range of 1 month to 212 months). After 1 year, 30% of patients had distant metastases, 53% had them after 3 years.

“Quite sobering,” Dr Dauer said concerning the expected survival of a patient with distant metastases: The median time to death was 3 months. In this study, 53% of patients were alive at 3 months, 32% at 6 months, and 15% at 12 months. One year after treatment, 74% of patients had not died specifically of melanoma, but this dropped to 52% at 3 years and to 23% at 5 years. On average, patients died after 35 months (median of 20 months, ranging from 3 months to 223 months).

After a mean follow-up of 43 months (median of 21 months) among the 61 patients, 46 died from the disease and 11 died from other or unknown causes. Four patients are still alive.

Patients with septal involvement had a significantly greater rate of overall survival than did those without it.

Location and volume of the tumor were the only significant prognostic factors for sinonasal melanoma in a multivariate analysis.