Upper GI Tract

Electrical stimulation of the lower esophageal sphincter using an implanted device shows promise for the treatment of gastroesophageal reflux, according to findings from three recent studies.

In one open-label pilot extension study, 77% of 23 patients treated with EndoStim’s Lower Esophageal Sphincter (LES) stimulation system reported normalization of (or at least a 50% reduction in) distal esophageal acid exposure at 12 months’ follow-up, Dr. Edy Soffer reported in October at the annual meeting of the American College of Gastroenterology.

Courtesy Dr. Mark I. van Berge Henegouwen

The patients also experienced significant improvement in their median GERD-Health Related Quality of Life (GERD-HRQL) score while implanted with the LES stimulation system (LES-EST), compared with their score while on proton pump inhibitor (PPI) therapy (increase of 9 vs. 2 points) and while off PPI therapy (increase of 23.5 vs. 2), said Dr. Soffer, professor of clinical medicine and director of the GI motility program at the University of Southern California, Los Angeles.

All but one patient reported cessation of regular PPI use, and no implantation- or stimulation-related unanticipated adverse events or "untoward sensation" due to stimulation occurred during follow-up; nor was swallowing function as assessed by manometry affected.

Patients included in the study were GERD patients with a mean age of 53 years who were at least partially responsive to PPI therapy, and who had off-PPI GERD-HRQL scores of at least 20, as well as hiatal hernia.

The findings indicate that LES-EST, which uses low-energy electrical pulses to strengthen a weak or dysfunctional lower esophageal sphincter, is safe and effective for long-term use, he said.

In an interview, Dr. Soffer said that the findings have held up at 18 months of follow-up.

"The results are comparable to those observed at 12 months with regard to control of symptoms, and with near elimination of the use of PPIs," he said, noting that the safety profile remains excellent, with no new adverse event reported beyond those seen at 12 months’ follow-up.

Physiological studies such as esophageal pH will be conducted at 24 months, he said.

In a related study presented in a poster at the meeting, Michael Crowell, Ph.D., looked more closely at the effects of LES-EST on both distal and proximal esophageal acid exposure in a post hoc analysis.

In 19 patients with a median age of 54 years, LES-EST was associated with normalization of total and upright proximal esophageal acid exposure, which improved from 0.4% and 0.6%, respectively, at baseline to 0% at 12 months’ follow-up. Supine esophageal acid exposure was unchanged from 0% at baseline, said Dr. Crowell of the Mayo Clinic, Scottsdale, Ariz.

This was true even among seven patients with abnormal proximal esophageal pH, whose total, upright, and supine proximal esophageal acid exposure values at baseline were 1.7%, 2.9%, and 0.3%, respectively. Distal esophageal pH improved from 10.2% to 3.6% for the entire cohort, and from 9.3% to 3.4% in those seven patients.

Patients in this study had GERD that was at least partially responsive to PPIs, a hiatal hernia of less than 3 cm, and esophagitis of less than Los Angeles Classification grade D. Electrical stimulation was administered for 220 microseconds at 20 Hz and 5-8 mA in 6-12 30-minute sessions starting on day 1 after implantation.

No gastrointestinal side effects occurred in the patients, nor were there any device- or procedure-related adverse events.

LES-EST may be effective in treating proximal GERD, Dr. Crowell concluded.

In an interview, he added that the findings are important, particularly for the one-third of patients who remain symptomatic on PPIs.

"LES dysfunction is the root cause of GERD. Medications such as PPIs block stomach acid production, but do not address the pathophysiology of GERD. Hence, more than a third of patients continue to suffer from symptoms despite maximal medical therapy," he said.

Additionally, there are significant safety concerns with long-term acid suppression, he noted.

LES-EST, on the other hand, addresses the root cause of GERD by improving LES pressure and function, thereby restoring the LES physiology and its barrier function, preventing reflux of gastric acid into the esophagus.

"LES stimulation does not affect normal LES relaxation, allowing for the patient to swallow normally, and has no side effects," he said.

In a third, unrelated study also reported in a poster at the meeting, LES-EST was similarly effective.

Of 11 patients treated with EndoStim’s LES stimulation system as part of an international multicenter study, 10 were able to discontinue PPI therapy at 3-6 months of follow-up, according to Dr. Arjan J. Bredenoord of Academic Medical Center Utrecht, Rotterdam.

Those 10 patients experienced significant improvements in median GERD-HRQL scores from 32 (off PPIs) and 22 (on PPIs) to 9 (on LES-EST) at 3 months, and the scores remained stable at 9 points in 3 patients who were followed for 6 months.

Median esophageal acid exposure improved from 11.8% at baseline to 7.8% at 3 months and 7.3% at 6 months, Dr. Bredenoord said.

The remaining patient suffered a small bowl trocar perforation during implantation of the device and underwent successful repair. An additional 13 adverse events, including 1 serious adverse event, were reported in 4 patients. Nine of these were related to the device or procedure, including seven complaints of pain at the implant site and one case of postoperative nausea.

The treatment was safe, with no GI or cardiac side effects, Dr. Bredenoord concluded, noting that long-term safety and efficacy results in a larger group of patients are currently being analyzed.

In an interview, Dr. Bredenoord noted that the findings are among the first in patients outside South America, where the earliest trials of the EndoStim LES stimulation system were conducted.

"The data confirm the favorable outcome of the patients in Chile, and show that both symptoms and reflux are reduced in European patients as well," he said.

However, the experience remains limited, and additional study comparing the device with other treatments and/or with placebo is needed, as are longer-term outcomes data.

"I think that although these results suggest this is a promising treatment, it would be best to treat patients only in trials" at this point, he said. Because trial participants have been carefully selected, it remains unclear whether this treatment is suitable for the entire GERD population, he added.

Dr. Soffer agreed, and said that if the results are reproduced in additional studies with a larger number of patients, the intervention will provide an alternative therapy for GERD patients who are not satisfied with PPIs or who have concerns about side effects and the chronic use of treatment, and who also have concerns about the established surgical treatment for GERD.

"The importance of this intervention is in providing a bridge between the currently established drug therapy for GERD [PPIs] and the established surgical therapy [fundoplication]. While PPIs are effective in a substantial number of GERD patients, they do not correct the underlying pathophysiology of GERD, resulting in a substantial number of patients who remain symptomatic in spite of therapy," he said.

These patients can be offered fundoplication, which is effective in expert hands, but the surgery has side effects and is performed less and less often, he added.

"Consequently, there is a search for a bridge intervention, endoscopic or surgical, for the treatment of GERD," he said.

LES-EST appears to have the potential to be such a bridge intervention.

"The procedure is simple and nondisruptive, and addresses pathophysiology. The safety profile thus far is excellent, and the effect on esophageal acid exposure, symptoms, and PPI use is sustained over a period of 12-18 moths. Furthermore, the treatment can be optimized to individual needs by adjusting delivery of stimulation to coincide with periods when symptoms and acid reflux are detected," he said.

All three of these studies presented at the meeting were supported by EndoStim BV. Dr. Soffer disclosed that he has stockholder/ownership interest in the company. Dr. Crowell disclosed that he has served as a consultant to the company. Dr. Bredenoord reported receiving grant and/or research support from the company.

Electrical stimulation of the lower esophageal sphincter using an implanted device shows promise for the treatment of gastroesophageal reflux, according to findings from three recent studies.

In one open-label pilot extension study, 77% of 23 patients treated with EndoStim’s Lower Esophageal Sphincter (LES) stimulation system reported normalization of (or at least a 50% reduction in) distal esophageal acid exposure at 12 months’ follow-up, Dr. Edy Soffer reported in October at the annual meeting of the American College of Gastroenterology.

Courtesy Dr. Mark I. van Berge Henegouwen

The patients also experienced significant improvement in their median GERD-Health Related Quality of Life (GERD-HRQL) score while implanted with the LES stimulation system (LES-EST), compared with their score while on proton pump inhibitor (PPI) therapy (increase of 9 vs. 2 points) and while off PPI therapy (increase of 23.5 vs. 2), said Dr. Soffer, professor of clinical medicine and director of the GI motility program at the University of Southern California, Los Angeles.

All but one patient reported cessation of regular PPI use, and no implantation- or stimulation-related unanticipated adverse events or "untoward sensation" due to stimulation occurred during follow-up; nor was swallowing function as assessed by manometry affected.

Patients included in the study were GERD patients with a mean age of 53 years who were at least partially responsive to PPI therapy, and who had off-PPI GERD-HRQL scores of at least 20, as well as hiatal hernia.

The findings indicate that LES-EST, which uses low-energy electrical pulses to strengthen a weak or dysfunctional lower esophageal sphincter, is safe and effective for long-term use, he said.

In an interview, Dr. Soffer said that the findings have held up at 18 months of follow-up.

"The results are comparable to those observed at 12 months with regard to control of symptoms, and with near elimination of the use of PPIs," he said, noting that the safety profile remains excellent, with no new adverse event reported beyond those seen at 12 months’ follow-up.

Physiological studies such as esophageal pH will be conducted at 24 months, he said.

In a related study presented in a poster at the meeting, Michael Crowell, Ph.D., looked more closely at the effects of LES-EST on both distal and proximal esophageal acid exposure in a post hoc analysis.

In 19 patients with a median age of 54 years, LES-EST was associated with normalization of total and upright proximal esophageal acid exposure, which improved from 0.4% and 0.6%, respectively, at baseline to 0% at 12 months’ follow-up. Supine esophageal acid exposure was unchanged from 0% at baseline, said Dr. Crowell of the Mayo Clinic, Scottsdale, Ariz.

This was true even among seven patients with abnormal proximal esophageal pH, whose total, upright, and supine proximal esophageal acid exposure values at baseline were 1.7%, 2.9%, and 0.3%, respectively. Distal esophageal pH improved from 10.2% to 3.6% for the entire cohort, and from 9.3% to 3.4% in those seven patients.

Patients in this study had GERD that was at least partially responsive to PPIs, a hiatal hernia of less than 3 cm, and esophagitis of less than Los Angeles Classification grade D. Electrical stimulation was administered for 220 microseconds at 20 Hz and 5-8 mA in 6-12 30-minute sessions starting on day 1 after implantation.

No gastrointestinal side effects occurred in the patients, nor were there any device- or procedure-related adverse events.

LES-EST may be effective in treating proximal GERD, Dr. Crowell concluded.

In an interview, he added that the findings are important, particularly for the one-third of patients who remain symptomatic on PPIs.

"LES dysfunction is the root cause of GERD. Medications such as PPIs block stomach acid production, but do not address the pathophysiology of GERD. Hence, more than a third of patients continue to suffer from symptoms despite maximal medical therapy," he said.

Additionally, there are significant safety concerns with long-term acid suppression, he noted.

LES-EST, on the other hand, addresses the root cause of GERD by improving LES pressure and function, thereby restoring the LES physiology and its barrier function, preventing reflux of gastric acid into the esophagus.

"LES stimulation does not affect normal LES relaxation, allowing for the patient to swallow normally, and has no side effects," he said.

In a third, unrelated study also reported in a poster at the meeting, LES-EST was similarly effective.

Of 11 patients treated with EndoStim’s LES stimulation system as part of an international multicenter study, 10 were able to discontinue PPI therapy at 3-6 months of follow-up, according to Dr. Arjan J. Bredenoord of Academic Medical Center Utrecht, Rotterdam.

Those 10 patients experienced significant improvements in median GERD-HRQL scores from 32 (off PPIs) and 22 (on PPIs) to 9 (on LES-EST) at 3 months, and the scores remained stable at 9 points in 3 patients who were followed for 6 months.

Median esophageal acid exposure improved from 11.8% at baseline to 7.8% at 3 months and 7.3% at 6 months, Dr. Bredenoord said.

The remaining patient suffered a small bowl trocar perforation during implantation of the device and underwent successful repair. An additional 13 adverse events, including 1 serious adverse event, were reported in 4 patients. Nine of these were related to the device or procedure, including seven complaints of pain at the implant site and one case of postoperative nausea.

The treatment was safe, with no GI or cardiac side effects, Dr. Bredenoord concluded, noting that long-term safety and efficacy results in a larger group of patients are currently being analyzed.

In an interview, Dr. Bredenoord noted that the findings are among the first in patients outside South America, where the earliest trials of the EndoStim LES stimulation system were conducted.

"The data confirm the favorable outcome of the patients in Chile, and show that both symptoms and reflux are reduced in European patients as well," he said.

However, the experience remains limited, and additional study comparing the device with other treatments and/or with placebo is needed, as are longer-term outcomes data.

"I think that although these results suggest this is a promising treatment, it would be best to treat patients only in trials" at this point, he said. Because trial participants have been carefully selected, it remains unclear whether this treatment is suitable for the entire GERD population, he added.

Dr. Soffer agreed, and said that if the results are reproduced in additional studies with a larger number of patients, the intervention will provide an alternative therapy for GERD patients who are not satisfied with PPIs or who have concerns about side effects and the chronic use of treatment, and who also have concerns about the established surgical treatment for GERD.

"The importance of this intervention is in providing a bridge between the currently established drug therapy for GERD [PPIs] and the established surgical therapy [fundoplication]. While PPIs are effective in a substantial number of GERD patients, they do not correct the underlying pathophysiology of GERD, resulting in a substantial number of patients who remain symptomatic in spite of therapy," he said.

These patients can be offered fundoplication, which is effective in expert hands, but the surgery has side effects and is performed less and less often, he added.

"Consequently, there is a search for a bridge intervention, endoscopic or surgical, for the treatment of GERD," he said.

LES-EST appears to have the potential to be such a bridge intervention.

"The procedure is simple and nondisruptive, and addresses pathophysiology. The safety profile thus far is excellent, and the effect on esophageal acid exposure, symptoms, and PPI use is sustained over a period of 12-18 moths. Furthermore, the treatment can be optimized to individual needs by adjusting delivery of stimulation to coincide with periods when symptoms and acid reflux are detected," he said.

All three of these studies presented at the meeting were supported by EndoStim BV. Dr. Soffer disclosed that he has stockholder/ownership interest in the company. Dr. Crowell disclosed that he has served as a consultant to the company. Dr. Bredenoord reported receiving grant and/or research support from the company.

Electrical stimulation of the lower esophageal sphincter using an implanted device shows promise for the treatment of gastroesophageal reflux, according to findings from three recent studies.

In one open-label pilot extension study, 77% of 23 patients treated with EndoStim’s Lower Esophageal Sphincter (LES) stimulation system reported normalization of (or at least a 50% reduction in) distal esophageal acid exposure at 12 months’ follow-up, Dr. Edy Soffer reported in October at the annual meeting of the American College of Gastroenterology.

Courtesy Dr. Mark I. van Berge Henegouwen

The patients also experienced significant improvement in their median GERD-Health Related Quality of Life (GERD-HRQL) score while implanted with the LES stimulation system (LES-EST), compared with their score while on proton pump inhibitor (PPI) therapy (increase of 9 vs. 2 points) and while off PPI therapy (increase of 23.5 vs. 2), said Dr. Soffer, professor of clinical medicine and director of the GI motility program at the University of Southern California, Los Angeles.

All but one patient reported cessation of regular PPI use, and no implantation- or stimulation-related unanticipated adverse events or "untoward sensation" due to stimulation occurred during follow-up; nor was swallowing function as assessed by manometry affected.

Patients included in the study were GERD patients with a mean age of 53 years who were at least partially responsive to PPI therapy, and who had off-PPI GERD-HRQL scores of at least 20, as well as hiatal hernia.

The findings indicate that LES-EST, which uses low-energy electrical pulses to strengthen a weak or dysfunctional lower esophageal sphincter, is safe and effective for long-term use, he said.

In an interview, Dr. Soffer said that the findings have held up at 18 months of follow-up.

"The results are comparable to those observed at 12 months with regard to control of symptoms, and with near elimination of the use of PPIs," he said, noting that the safety profile remains excellent, with no new adverse event reported beyond those seen at 12 months’ follow-up.

Physiological studies such as esophageal pH will be conducted at 24 months, he said.

In a related study presented in a poster at the meeting, Michael Crowell, Ph.D., looked more closely at the effects of LES-EST on both distal and proximal esophageal acid exposure in a post hoc analysis.

In 19 patients with a median age of 54 years, LES-EST was associated with normalization of total and upright proximal esophageal acid exposure, which improved from 0.4% and 0.6%, respectively, at baseline to 0% at 12 months’ follow-up. Supine esophageal acid exposure was unchanged from 0% at baseline, said Dr. Crowell of the Mayo Clinic, Scottsdale, Ariz.

This was true even among seven patients with abnormal proximal esophageal pH, whose total, upright, and supine proximal esophageal acid exposure values at baseline were 1.7%, 2.9%, and 0.3%, respectively. Distal esophageal pH improved from 10.2% to 3.6% for the entire cohort, and from 9.3% to 3.4% in those seven patients.

Patients in this study had GERD that was at least partially responsive to PPIs, a hiatal hernia of less than 3 cm, and esophagitis of less than Los Angeles Classification grade D. Electrical stimulation was administered for 220 microseconds at 20 Hz and 5-8 mA in 6-12 30-minute sessions starting on day 1 after implantation.

No gastrointestinal side effects occurred in the patients, nor were there any device- or procedure-related adverse events.

LES-EST may be effective in treating proximal GERD, Dr. Crowell concluded.

In an interview, he added that the findings are important, particularly for the one-third of patients who remain symptomatic on PPIs.

"LES dysfunction is the root cause of GERD. Medications such as PPIs block stomach acid production, but do not address the pathophysiology of GERD. Hence, more than a third of patients continue to suffer from symptoms despite maximal medical therapy," he said.

Additionally, there are significant safety concerns with long-term acid suppression, he noted.

LES-EST, on the other hand, addresses the root cause of GERD by improving LES pressure and function, thereby restoring the LES physiology and its barrier function, preventing reflux of gastric acid into the esophagus.

"LES stimulation does not affect normal LES relaxation, allowing for the patient to swallow normally, and has no side effects," he said.

In a third, unrelated study also reported in a poster at the meeting, LES-EST was similarly effective.

Of 11 patients treated with EndoStim’s LES stimulation system as part of an international multicenter study, 10 were able to discontinue PPI therapy at 3-6 months of follow-up, according to Dr. Arjan J. Bredenoord of Academic Medical Center Utrecht, Rotterdam.

Those 10 patients experienced significant improvements in median GERD-HRQL scores from 32 (off PPIs) and 22 (on PPIs) to 9 (on LES-EST) at 3 months, and the scores remained stable at 9 points in 3 patients who were followed for 6 months.

Median esophageal acid exposure improved from 11.8% at baseline to 7.8% at 3 months and 7.3% at 6 months, Dr. Bredenoord said.

The remaining patient suffered a small bowl trocar perforation during implantation of the device and underwent successful repair. An additional 13 adverse events, including 1 serious adverse event, were reported in 4 patients. Nine of these were related to the device or procedure, including seven complaints of pain at the implant site and one case of postoperative nausea.

The treatment was safe, with no GI or cardiac side effects, Dr. Bredenoord concluded, noting that long-term safety and efficacy results in a larger group of patients are currently being analyzed.

In an interview, Dr. Bredenoord noted that the findings are among the first in patients outside South America, where the earliest trials of the EndoStim LES stimulation system were conducted.

"The data confirm the favorable outcome of the patients in Chile, and show that both symptoms and reflux are reduced in European patients as well," he said.

However, the experience remains limited, and additional study comparing the device with other treatments and/or with placebo is needed, as are longer-term outcomes data.

"I think that although these results suggest this is a promising treatment, it would be best to treat patients only in trials" at this point, he said. Because trial participants have been carefully selected, it remains unclear whether this treatment is suitable for the entire GERD population, he added.

Dr. Soffer agreed, and said that if the results are reproduced in additional studies with a larger number of patients, the intervention will provide an alternative therapy for GERD patients who are not satisfied with PPIs or who have concerns about side effects and the chronic use of treatment, and who also have concerns about the established surgical treatment for GERD.

"The importance of this intervention is in providing a bridge between the currently established drug therapy for GERD [PPIs] and the established surgical therapy [fundoplication]. While PPIs are effective in a substantial number of GERD patients, they do not correct the underlying pathophysiology of GERD, resulting in a substantial number of patients who remain symptomatic in spite of therapy," he said.

These patients can be offered fundoplication, which is effective in expert hands, but the surgery has side effects and is performed less and less often, he added.

"Consequently, there is a search for a bridge intervention, endoscopic or surgical, for the treatment of GERD," he said.

LES-EST appears to have the potential to be such a bridge intervention.

"The procedure is simple and nondisruptive, and addresses pathophysiology. The safety profile thus far is excellent, and the effect on esophageal acid exposure, symptoms, and PPI use is sustained over a period of 12-18 moths. Furthermore, the treatment can be optimized to individual needs by adjusting delivery of stimulation to coincide with periods when symptoms and acid reflux are detected," he said.

All three of these studies presented at the meeting were supported by EndoStim BV. Dr. Soffer disclosed that he has stockholder/ownership interest in the company. Dr. Crowell disclosed that he has served as a consultant to the company. Dr. Bredenoord reported receiving grant and/or research support from the company.

In a study of 400 healthy adults, measurements indicating the presence of what has been thought to be aspirin resistance were evident only with enteric-coated aspirin, not immediate-release aspirin, which the authors have described as aspirin "pseudoresistance."

The researchers used several measurements to evaluate responses reflecting the activity of cyclooxygenase-1 (COX-1), the molecular target of aspirin, including platelet aggregation and serum thromboxane formation, which could indicate a genetic cause of aspirin resistance. Still, "we failed to find a single person who satisfied" the criteria for true aspirin resistance, reported Dr. Tilo Grosser, of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine in Philadelphia, and his associates. "By contrast, pseudoresistance, due to delayed and reduced drug absorption, was common after ingestion of enteric-coated aspirin," they said.

"These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric-coated preparations of aspirin," they concluded. The study appeared in Circulation online Dec. 4 (2012 [doi: 10.1161/CIRCULATIONAHA.112.117283]).

The concept of aspirin resistance has been used to explain treatment failures occurring in patients, with estimates of incidence ranging from 5% to 20% in studies, they noted.

The study had several phases, which included screening the study participants, aged 18-55 years, for their response to a single 325-mg dose of immediate-release or enteric-coated aspirin, repeating testing among those who appeared to be resistant to aspirin, and comparing responses in responders and nonresponders.

Among the specific findings: All of the individuals who received a dose of immediate-release aspirin were responders, but up to 49% of those who received enteric aspirin were considered nonresponders. With repeated exposure, individuals categorized as nonresponders when given enteric-coated aspirin showed evidence of responses when administered immediate-release aspirin.

"What they have shown in an extremely elegant way is that aspirin resistance, at least in healthy volunteers, doesn’t exist," Dr. Deepak Bhatt said in an interview.

Of great interest to physicians and patients is the finding that in the individuals who appeared to be aspirin resistant, enteric coating on aspirin was delaying and reducing absorption, which is consistent with old data that indicate enteric coating can interfere with aspirin absorption, he said. While this may have been suspected as an explanation for so-called aspirin resistance, "this is the first time someone has really nailed it down in a scientifically unassailable way," said Dr. Bhatt, professor of medicine at Harvard University, Boston, and chief of cardiology at VA Boston Healthcare System.

Although the results need to be replicated in patients with actual disease, such as diabetes or atherosclerosis, he said the results will potentially impact practice, although immediate-release aspirin is recommended for patients who are being stented or are having a myocardial infarction, for the rapid pharmacologic effect.

But the results raise further questions about more chronic administration of aspirin in patients who are not acutely ill and how many of these patients may not be fully absorbing aspirin if they are taking an enteric-coated formulation. "If there is a proportion of patients who are not getting the full anticlotting effect of aspirin ... that means potentially millions of patients are taking enteric-coated aspirin and not getting the protection they or their doctors are assuming they are getting," he said.

Another consideration, which he said is not widely appreciated, is that evidence that enteric coating reduces stomach bleeding "is quite scant, some might even say nonexistent." While enteric coated aspirin does reduce stomach upset, it is used for GI bleeding protection, "but if you’re not getting the GI benefit, and now potentially there is this issue of pseudoresistance these authors are raising, you’ve got to think twice about whether enteric coating is doing anything useful or good."

Dr. Bhatt’s recommendation to clinicians, which predates the publication of this study, is to make sure that patients who are prescribed the immediate-release aspirin get the correct formulation, and not end up with an enteric-coated formulation unintentionally.

Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, also advised caution about extrapolating the results of a study of healthy volunteers to patients with heart disease or chronic illnesses that may affect how aspirin works in the body. The study was not designed to address comparative clinical efficacy or safety between the two formulations, and he views it as "a mechanistic study demonstrating a pharmacokinetic reason for variability in aspirin responsiveness."

In an interview, he added that testing for aspirin resistance is "of dubious value," and the concept, like resistance to clopidogrel, "is driven to a large extent by marketing considerations," and the development of tests to assess aspirin responsiveness.

Dr. Kaul said he will continue to recommend immediate-release formulation for rapid onset of action and switch to enteric-coated aspirin for chronic use, especially in patients with a history of gastric intolerance or side effects. Although "unequivocal evidence" of safety advantages over immediate-release aspirin, such as GI bleeding, is lacking, data have shown reduced rates of gastric erosions on endoscopy associated with enteric-coated aspirin, although the clinical relevance of the erosions is unclear, he said.

The study was funded by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the American Heart Association; and Bayer HealthCare. Coauthor Dr. Garret FitzGerald of the University of Pennsylvania, Philadelphia, received research funding from Bayer HealthCare to support partial funding of this study, and Dr. Grosser received consultancy fees from PLx Pharma. The four remaining coauthors had no potential conflicts of interest to disclose.

Dr. Bhatt said his disclosures include being an unpaid consultant to PLx Pharma. Dr. Kaul said he had no relevant disclosures.

In a study of 400 healthy adults, measurements indicating the presence of what has been thought to be aspirin resistance were evident only with enteric-coated aspirin, not immediate-release aspirin, which the authors have described as aspirin "pseudoresistance."

The researchers used several measurements to evaluate responses reflecting the activity of cyclooxygenase-1 (COX-1), the molecular target of aspirin, including platelet aggregation and serum thromboxane formation, which could indicate a genetic cause of aspirin resistance. Still, "we failed to find a single person who satisfied" the criteria for true aspirin resistance, reported Dr. Tilo Grosser, of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine in Philadelphia, and his associates. "By contrast, pseudoresistance, due to delayed and reduced drug absorption, was common after ingestion of enteric-coated aspirin," they said.

"These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric-coated preparations of aspirin," they concluded. The study appeared in Circulation online Dec. 4 (2012 [doi: 10.1161/CIRCULATIONAHA.112.117283]).

The concept of aspirin resistance has been used to explain treatment failures occurring in patients, with estimates of incidence ranging from 5% to 20% in studies, they noted.

The study had several phases, which included screening the study participants, aged 18-55 years, for their response to a single 325-mg dose of immediate-release or enteric-coated aspirin, repeating testing among those who appeared to be resistant to aspirin, and comparing responses in responders and nonresponders.

Among the specific findings: All of the individuals who received a dose of immediate-release aspirin were responders, but up to 49% of those who received enteric aspirin were considered nonresponders. With repeated exposure, individuals categorized as nonresponders when given enteric-coated aspirin showed evidence of responses when administered immediate-release aspirin.

"What they have shown in an extremely elegant way is that aspirin resistance, at least in healthy volunteers, doesn’t exist," Dr. Deepak Bhatt said in an interview.

Of great interest to physicians and patients is the finding that in the individuals who appeared to be aspirin resistant, enteric coating on aspirin was delaying and reducing absorption, which is consistent with old data that indicate enteric coating can interfere with aspirin absorption, he said. While this may have been suspected as an explanation for so-called aspirin resistance, "this is the first time someone has really nailed it down in a scientifically unassailable way," said Dr. Bhatt, professor of medicine at Harvard University, Boston, and chief of cardiology at VA Boston Healthcare System.

Although the results need to be replicated in patients with actual disease, such as diabetes or atherosclerosis, he said the results will potentially impact practice, although immediate-release aspirin is recommended for patients who are being stented or are having a myocardial infarction, for the rapid pharmacologic effect.

But the results raise further questions about more chronic administration of aspirin in patients who are not acutely ill and how many of these patients may not be fully absorbing aspirin if they are taking an enteric-coated formulation. "If there is a proportion of patients who are not getting the full anticlotting effect of aspirin ... that means potentially millions of patients are taking enteric-coated aspirin and not getting the protection they or their doctors are assuming they are getting," he said.

Another consideration, which he said is not widely appreciated, is that evidence that enteric coating reduces stomach bleeding "is quite scant, some might even say nonexistent." While enteric coated aspirin does reduce stomach upset, it is used for GI bleeding protection, "but if you’re not getting the GI benefit, and now potentially there is this issue of pseudoresistance these authors are raising, you’ve got to think twice about whether enteric coating is doing anything useful or good."

Dr. Bhatt’s recommendation to clinicians, which predates the publication of this study, is to make sure that patients who are prescribed the immediate-release aspirin get the correct formulation, and not end up with an enteric-coated formulation unintentionally.

Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, also advised caution about extrapolating the results of a study of healthy volunteers to patients with heart disease or chronic illnesses that may affect how aspirin works in the body. The study was not designed to address comparative clinical efficacy or safety between the two formulations, and he views it as "a mechanistic study demonstrating a pharmacokinetic reason for variability in aspirin responsiveness."

In an interview, he added that testing for aspirin resistance is "of dubious value," and the concept, like resistance to clopidogrel, "is driven to a large extent by marketing considerations," and the development of tests to assess aspirin responsiveness.

Dr. Kaul said he will continue to recommend immediate-release formulation for rapid onset of action and switch to enteric-coated aspirin for chronic use, especially in patients with a history of gastric intolerance or side effects. Although "unequivocal evidence" of safety advantages over immediate-release aspirin, such as GI bleeding, is lacking, data have shown reduced rates of gastric erosions on endoscopy associated with enteric-coated aspirin, although the clinical relevance of the erosions is unclear, he said.

The study was funded by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the American Heart Association; and Bayer HealthCare. Coauthor Dr. Garret FitzGerald of the University of Pennsylvania, Philadelphia, received research funding from Bayer HealthCare to support partial funding of this study, and Dr. Grosser received consultancy fees from PLx Pharma. The four remaining coauthors had no potential conflicts of interest to disclose.

Dr. Bhatt said his disclosures include being an unpaid consultant to PLx Pharma. Dr. Kaul said he had no relevant disclosures.

In a study of 400 healthy adults, measurements indicating the presence of what has been thought to be aspirin resistance were evident only with enteric-coated aspirin, not immediate-release aspirin, which the authors have described as aspirin "pseudoresistance."

The researchers used several measurements to evaluate responses reflecting the activity of cyclooxygenase-1 (COX-1), the molecular target of aspirin, including platelet aggregation and serum thromboxane formation, which could indicate a genetic cause of aspirin resistance. Still, "we failed to find a single person who satisfied" the criteria for true aspirin resistance, reported Dr. Tilo Grosser, of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine in Philadelphia, and his associates. "By contrast, pseudoresistance, due to delayed and reduced drug absorption, was common after ingestion of enteric-coated aspirin," they said.

"These observations question the value of seeking to diagnose aspirin resistance with single point-of-care diagnostic approaches and support the finding of inconsistent platelet inhibition following enteric-coated preparations of aspirin," they concluded. The study appeared in Circulation online Dec. 4 (2012 [doi: 10.1161/CIRCULATIONAHA.112.117283]).

The concept of aspirin resistance has been used to explain treatment failures occurring in patients, with estimates of incidence ranging from 5% to 20% in studies, they noted.

The study had several phases, which included screening the study participants, aged 18-55 years, for their response to a single 325-mg dose of immediate-release or enteric-coated aspirin, repeating testing among those who appeared to be resistant to aspirin, and comparing responses in responders and nonresponders.

Among the specific findings: All of the individuals who received a dose of immediate-release aspirin were responders, but up to 49% of those who received enteric aspirin were considered nonresponders. With repeated exposure, individuals categorized as nonresponders when given enteric-coated aspirin showed evidence of responses when administered immediate-release aspirin.

"What they have shown in an extremely elegant way is that aspirin resistance, at least in healthy volunteers, doesn’t exist," Dr. Deepak Bhatt said in an interview.

Of great interest to physicians and patients is the finding that in the individuals who appeared to be aspirin resistant, enteric coating on aspirin was delaying and reducing absorption, which is consistent with old data that indicate enteric coating can interfere with aspirin absorption, he said. While this may have been suspected as an explanation for so-called aspirin resistance, "this is the first time someone has really nailed it down in a scientifically unassailable way," said Dr. Bhatt, professor of medicine at Harvard University, Boston, and chief of cardiology at VA Boston Healthcare System.

Although the results need to be replicated in patients with actual disease, such as diabetes or atherosclerosis, he said the results will potentially impact practice, although immediate-release aspirin is recommended for patients who are being stented or are having a myocardial infarction, for the rapid pharmacologic effect.

But the results raise further questions about more chronic administration of aspirin in patients who are not acutely ill and how many of these patients may not be fully absorbing aspirin if they are taking an enteric-coated formulation. "If there is a proportion of patients who are not getting the full anticlotting effect of aspirin ... that means potentially millions of patients are taking enteric-coated aspirin and not getting the protection they or their doctors are assuming they are getting," he said.

Another consideration, which he said is not widely appreciated, is that evidence that enteric coating reduces stomach bleeding "is quite scant, some might even say nonexistent." While enteric coated aspirin does reduce stomach upset, it is used for GI bleeding protection, "but if you’re not getting the GI benefit, and now potentially there is this issue of pseudoresistance these authors are raising, you’ve got to think twice about whether enteric coating is doing anything useful or good."

Dr. Bhatt’s recommendation to clinicians, which predates the publication of this study, is to make sure that patients who are prescribed the immediate-release aspirin get the correct formulation, and not end up with an enteric-coated formulation unintentionally.

Dr. Sanjay Kaul, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, also advised caution about extrapolating the results of a study of healthy volunteers to patients with heart disease or chronic illnesses that may affect how aspirin works in the body. The study was not designed to address comparative clinical efficacy or safety between the two formulations, and he views it as "a mechanistic study demonstrating a pharmacokinetic reason for variability in aspirin responsiveness."

In an interview, he added that testing for aspirin resistance is "of dubious value," and the concept, like resistance to clopidogrel, "is driven to a large extent by marketing considerations," and the development of tests to assess aspirin responsiveness.

Dr. Kaul said he will continue to recommend immediate-release formulation for rapid onset of action and switch to enteric-coated aspirin for chronic use, especially in patients with a history of gastric intolerance or side effects. Although "unequivocal evidence" of safety advantages over immediate-release aspirin, such as GI bleeding, is lacking, data have shown reduced rates of gastric erosions on endoscopy associated with enteric-coated aspirin, although the clinical relevance of the erosions is unclear, he said.

The study was funded by the National Heart, Lung, and Blood Institute; the National Center for Research Resources; the American Heart Association; and Bayer HealthCare. Coauthor Dr. Garret FitzGerald of the University of Pennsylvania, Philadelphia, received research funding from Bayer HealthCare to support partial funding of this study, and Dr. Grosser received consultancy fees from PLx Pharma. The four remaining coauthors had no potential conflicts of interest to disclose.

Dr. Bhatt said his disclosures include being an unpaid consultant to PLx Pharma. Dr. Kaul said he had no relevant disclosures.

The 32-mg intravenous dose of the antinausea drug ondansetron will no longer be marketed because it has been linked to a risk of QT prolongation, the Food and Drug Administration announced.

A statement on the agency’s MedWatch website said that the withdrawal of the 32-mg dose, available in premixed solutions of dextrose or sodium chloride, is expected to last through early 2013. Since this dose accounts for a "very small percentage" of the market, the voluntary withdrawal is not expected to contribute to a shortage of intravenous ondansetron, the Dec. 4 statement said.

The drug is marketed as Zofran and is available in generic formulations for preventing chemotherapy-induced nausea and vomiting. The FDA is recommending three doses of IV ondansetron at a dose of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting but added: "If the calculated weight-based dose were to exceed 16 mg, the potential for prolonged QT interval would be greater; therefore, no single intravenous dose should exceed 16 mg." QT prolongation can result in the potentially fatal arrhythmia, torsades de pointes.

The FDA also stated that, currently, there is not enough information to recommend another single-dose intravenous regimen and that oral ondansetron "remains effective for the prevention of chemotherapy-induced nausea and vomiting."

Ondansetron also is approved for postoperative nausea and vomiting.

The announcement follows a previous FDA notice in June 2012 that the 32-mg single-IV dose of ondansetron should be avoided, citing preliminary results from a study suggesting that the 32-mg dose may cause QT prolongation. The agency first announced that it was conducting a safety review of ondansetron in September 2011.

At the time of the June 2012 statement, GlaxoSmithKline, the manufacturer of Zofran, which conducted the QT study, announced that it was removing the 32-mg single-IV dose from the drug’s label. In November, the labeling was revised and no longer includes the 32-mg IV dose; it includes information about QT prolongation and dosing information that no single-IV weight-based dose should exceed 16 mg.

Manufacturers of ondansetron intravenous products are Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris Lifesciences.

Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/default.htm.

The 32-mg intravenous dose of the antinausea drug ondansetron will no longer be marketed because it has been linked to a risk of QT prolongation, the Food and Drug Administration announced.

A statement on the agency’s MedWatch website said that the withdrawal of the 32-mg dose, available in premixed solutions of dextrose or sodium chloride, is expected to last through early 2013. Since this dose accounts for a "very small percentage" of the market, the voluntary withdrawal is not expected to contribute to a shortage of intravenous ondansetron, the Dec. 4 statement said.

The drug is marketed as Zofran and is available in generic formulations for preventing chemotherapy-induced nausea and vomiting. The FDA is recommending three doses of IV ondansetron at a dose of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting but added: "If the calculated weight-based dose were to exceed 16 mg, the potential for prolonged QT interval would be greater; therefore, no single intravenous dose should exceed 16 mg." QT prolongation can result in the potentially fatal arrhythmia, torsades de pointes.

The FDA also stated that, currently, there is not enough information to recommend another single-dose intravenous regimen and that oral ondansetron "remains effective for the prevention of chemotherapy-induced nausea and vomiting."

Ondansetron also is approved for postoperative nausea and vomiting.

The announcement follows a previous FDA notice in June 2012 that the 32-mg single-IV dose of ondansetron should be avoided, citing preliminary results from a study suggesting that the 32-mg dose may cause QT prolongation. The agency first announced that it was conducting a safety review of ondansetron in September 2011.

At the time of the June 2012 statement, GlaxoSmithKline, the manufacturer of Zofran, which conducted the QT study, announced that it was removing the 32-mg single-IV dose from the drug’s label. In November, the labeling was revised and no longer includes the 32-mg IV dose; it includes information about QT prolongation and dosing information that no single-IV weight-based dose should exceed 16 mg.

Manufacturers of ondansetron intravenous products are Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris Lifesciences.

Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/default.htm.

The 32-mg intravenous dose of the antinausea drug ondansetron will no longer be marketed because it has been linked to a risk of QT prolongation, the Food and Drug Administration announced.

A statement on the agency’s MedWatch website said that the withdrawal of the 32-mg dose, available in premixed solutions of dextrose or sodium chloride, is expected to last through early 2013. Since this dose accounts for a "very small percentage" of the market, the voluntary withdrawal is not expected to contribute to a shortage of intravenous ondansetron, the Dec. 4 statement said.

The drug is marketed as Zofran and is available in generic formulations for preventing chemotherapy-induced nausea and vomiting. The FDA is recommending three doses of IV ondansetron at a dose of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting but added: "If the calculated weight-based dose were to exceed 16 mg, the potential for prolonged QT interval would be greater; therefore, no single intravenous dose should exceed 16 mg." QT prolongation can result in the potentially fatal arrhythmia, torsades de pointes.

The FDA also stated that, currently, there is not enough information to recommend another single-dose intravenous regimen and that oral ondansetron "remains effective for the prevention of chemotherapy-induced nausea and vomiting."

Ondansetron also is approved for postoperative nausea and vomiting.

The announcement follows a previous FDA notice in June 2012 that the 32-mg single-IV dose of ondansetron should be avoided, citing preliminary results from a study suggesting that the 32-mg dose may cause QT prolongation. The agency first announced that it was conducting a safety review of ondansetron in September 2011.

At the time of the June 2012 statement, GlaxoSmithKline, the manufacturer of Zofran, which conducted the QT study, announced that it was removing the 32-mg single-IV dose from the drug’s label. In November, the labeling was revised and no longer includes the 32-mg IV dose; it includes information about QT prolongation and dosing information that no single-IV weight-based dose should exceed 16 mg.

Manufacturers of ondansetron intravenous products are Baxter Healthcare, Hospira, Teva, Bedford Labs, and Claris Lifesciences.

Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/default.htm.

Empiric acid suppression with the "PPI test," widely used to assess whether upper-GI symptoms are due to gastroesophageal reflux disease, actually performs poorly as a predictor of GERD, Dr. Peter Bytzer and his colleagues wrote in the December issue of Clinical Gastroenterology and Hepatology.

Typically, clinicians perform a PPI test to diagnose GERD without the need for endoscopy. They give patients a 2-week course of a proton pump inhibitor and then determine whether the brief treatment ameliorated upper GI symptoms. If so, the symptoms are assumed to be acid related, said Dr. Bytzer of Copenhagen University and his associates.

But in their study, such a PPI test "showed a disappointingly low validity" for diagnosing GERD, and couldn’t reliably distinguish between reflux esophagitis and nonerosive reflux disease. Even when combined with a clinical diagnosis made by a primary care physician, a clinical diagnosis made by a gastroenterologist, or the results of a detailed diagnostic questionnaire, the outcome of a PPI test didn’t add reliable information allowing clinicians to separate patients who had GERD from those who did not, the researchers said (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.06.030]).

Dr. Bytzer and his colleagues analyzed data originally collected in the DIAMOND clinical trial, an international study that found the Reflux Disease Questionnaire to be useful in diagnosing GERD among patients who consulted primary care physicians because of frequent upper GI symptoms. The DIAMOND study results indicated that unlike the Reflux Disease Questionnaire, PPI testing had very limited diagnostic value.

Dr. Bytzer and his associates performed more detailed analyses of the data, using different combinations of three main symptoms (heartburn, central chest pain, and dysphagia or regurgitation); different definitions of "PPI response"; and assessments of various subgroups of patients, all in the hope of improving the diagnostic yield of PPI testing. They compared the diagnostic usefulness of PPI testing against state-of-the-art comprehensive diagnostic work-ups for GERD in 299 of the DIAMOND study subjects.

"This large database provides the best platform so far to test whether there are better approaches for scoring a test of PPI therapy," the investigators noted.

All of the subjects underwent endoscopy with concomitant wireless esophageal pH monitoring and symptom assessment. They then completed the detailed Reflux Disease Questionnaire, and participated in a 2-week PPI test using esomeprazole (Nexium), during which they recorded GI symptoms in a diary.

A total of 69% of the patients who did have GERD showed a positive response to the PPI test. This means that 31% of the study participants with GERD were not identified by PPI testing.

Moreover, 51% of the patients who did not have GERD also showed a positive response to the PPI test, the investigators said.

Both patients who had GERD and patients who did not reported that their symptom response to acid suppression increased over the course of the first 5-6 days of treatment and then leveled off for the remaining 8-9 days.

The PPI test performed only marginally better across various subgroups of patients, such as those with GERD plus reflux esophagitis (as compared with patients who had GERD but no reflux esophagitis) or those whose physicians were certain of their GERD diagnosis (compared with patients whose physicians were uncertain about their GERD diagnosis).

For example, 48% of the study participants whose physicians predicted that they had GERD showed a positive response on PPI testing – a rate that was nearly identical to the 47% of study subjects whose physicians predicted that they had some disorder other than GERD.

Similarly, the PPI test performed only marginally better when different symptom combinations and different definitions of "PPI response" were assessed.

"In line with other researchers, we found that ... the clinical value of [the PPI test] is very limited," Dr. Bytzer and his colleagues said.

This study was funded by AstraZeneca. Dr. Bytzer reported ties to AstraZeneca, Boehringer Ingelheim, Eisai, Nycomed, Reckitt Benckiser, Takeda, and Wyeth, and his associates reported ties to numerous industry sources, including employment by AstraZeneca.

Empiric acid suppression with the "PPI test," widely used to assess whether upper-GI symptoms are due to gastroesophageal reflux disease, actually performs poorly as a predictor of GERD, Dr. Peter Bytzer and his colleagues wrote in the December issue of Clinical Gastroenterology and Hepatology.

Typically, clinicians perform a PPI test to diagnose GERD without the need for endoscopy. They give patients a 2-week course of a proton pump inhibitor and then determine whether the brief treatment ameliorated upper GI symptoms. If so, the symptoms are assumed to be acid related, said Dr. Bytzer of Copenhagen University and his associates.

But in their study, such a PPI test "showed a disappointingly low validity" for diagnosing GERD, and couldn’t reliably distinguish between reflux esophagitis and nonerosive reflux disease. Even when combined with a clinical diagnosis made by a primary care physician, a clinical diagnosis made by a gastroenterologist, or the results of a detailed diagnostic questionnaire, the outcome of a PPI test didn’t add reliable information allowing clinicians to separate patients who had GERD from those who did not, the researchers said (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.06.030]).

Dr. Bytzer and his colleagues analyzed data originally collected in the DIAMOND clinical trial, an international study that found the Reflux Disease Questionnaire to be useful in diagnosing GERD among patients who consulted primary care physicians because of frequent upper GI symptoms. The DIAMOND study results indicated that unlike the Reflux Disease Questionnaire, PPI testing had very limited diagnostic value.

Dr. Bytzer and his associates performed more detailed analyses of the data, using different combinations of three main symptoms (heartburn, central chest pain, and dysphagia or regurgitation); different definitions of "PPI response"; and assessments of various subgroups of patients, all in the hope of improving the diagnostic yield of PPI testing. They compared the diagnostic usefulness of PPI testing against state-of-the-art comprehensive diagnostic work-ups for GERD in 299 of the DIAMOND study subjects.

"This large database provides the best platform so far to test whether there are better approaches for scoring a test of PPI therapy," the investigators noted.

All of the subjects underwent endoscopy with concomitant wireless esophageal pH monitoring and symptom assessment. They then completed the detailed Reflux Disease Questionnaire, and participated in a 2-week PPI test using esomeprazole (Nexium), during which they recorded GI symptoms in a diary.

A total of 69% of the patients who did have GERD showed a positive response to the PPI test. This means that 31% of the study participants with GERD were not identified by PPI testing.

Moreover, 51% of the patients who did not have GERD also showed a positive response to the PPI test, the investigators said.

Both patients who had GERD and patients who did not reported that their symptom response to acid suppression increased over the course of the first 5-6 days of treatment and then leveled off for the remaining 8-9 days.

The PPI test performed only marginally better across various subgroups of patients, such as those with GERD plus reflux esophagitis (as compared with patients who had GERD but no reflux esophagitis) or those whose physicians were certain of their GERD diagnosis (compared with patients whose physicians were uncertain about their GERD diagnosis).

For example, 48% of the study participants whose physicians predicted that they had GERD showed a positive response on PPI testing – a rate that was nearly identical to the 47% of study subjects whose physicians predicted that they had some disorder other than GERD.

Similarly, the PPI test performed only marginally better when different symptom combinations and different definitions of "PPI response" were assessed.

"In line with other researchers, we found that ... the clinical value of [the PPI test] is very limited," Dr. Bytzer and his colleagues said.

This study was funded by AstraZeneca. Dr. Bytzer reported ties to AstraZeneca, Boehringer Ingelheim, Eisai, Nycomed, Reckitt Benckiser, Takeda, and Wyeth, and his associates reported ties to numerous industry sources, including employment by AstraZeneca.

Empiric acid suppression with the "PPI test," widely used to assess whether upper-GI symptoms are due to gastroesophageal reflux disease, actually performs poorly as a predictor of GERD, Dr. Peter Bytzer and his colleagues wrote in the December issue of Clinical Gastroenterology and Hepatology.

Typically, clinicians perform a PPI test to diagnose GERD without the need for endoscopy. They give patients a 2-week course of a proton pump inhibitor and then determine whether the brief treatment ameliorated upper GI symptoms. If so, the symptoms are assumed to be acid related, said Dr. Bytzer of Copenhagen University and his associates.

But in their study, such a PPI test "showed a disappointingly low validity" for diagnosing GERD, and couldn’t reliably distinguish between reflux esophagitis and nonerosive reflux disease. Even when combined with a clinical diagnosis made by a primary care physician, a clinical diagnosis made by a gastroenterologist, or the results of a detailed diagnostic questionnaire, the outcome of a PPI test didn’t add reliable information allowing clinicians to separate patients who had GERD from those who did not, the researchers said (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.06.030]).

Dr. Bytzer and his colleagues analyzed data originally collected in the DIAMOND clinical trial, an international study that found the Reflux Disease Questionnaire to be useful in diagnosing GERD among patients who consulted primary care physicians because of frequent upper GI symptoms. The DIAMOND study results indicated that unlike the Reflux Disease Questionnaire, PPI testing had very limited diagnostic value.

Dr. Bytzer and his associates performed more detailed analyses of the data, using different combinations of three main symptoms (heartburn, central chest pain, and dysphagia or regurgitation); different definitions of "PPI response"; and assessments of various subgroups of patients, all in the hope of improving the diagnostic yield of PPI testing. They compared the diagnostic usefulness of PPI testing against state-of-the-art comprehensive diagnostic work-ups for GERD in 299 of the DIAMOND study subjects.

"This large database provides the best platform so far to test whether there are better approaches for scoring a test of PPI therapy," the investigators noted.

All of the subjects underwent endoscopy with concomitant wireless esophageal pH monitoring and symptom assessment. They then completed the detailed Reflux Disease Questionnaire, and participated in a 2-week PPI test using esomeprazole (Nexium), during which they recorded GI symptoms in a diary.

A total of 69% of the patients who did have GERD showed a positive response to the PPI test. This means that 31% of the study participants with GERD were not identified by PPI testing.

Moreover, 51% of the patients who did not have GERD also showed a positive response to the PPI test, the investigators said.

Both patients who had GERD and patients who did not reported that their symptom response to acid suppression increased over the course of the first 5-6 days of treatment and then leveled off for the remaining 8-9 days.

The PPI test performed only marginally better across various subgroups of patients, such as those with GERD plus reflux esophagitis (as compared with patients who had GERD but no reflux esophagitis) or those whose physicians were certain of their GERD diagnosis (compared with patients whose physicians were uncertain about their GERD diagnosis).

For example, 48% of the study participants whose physicians predicted that they had GERD showed a positive response on PPI testing – a rate that was nearly identical to the 47% of study subjects whose physicians predicted that they had some disorder other than GERD.

Similarly, the PPI test performed only marginally better when different symptom combinations and different definitions of "PPI response" were assessed.

"In line with other researchers, we found that ... the clinical value of [the PPI test] is very limited," Dr. Bytzer and his colleagues said.

This study was funded by AstraZeneca. Dr. Bytzer reported ties to AstraZeneca, Boehringer Ingelheim, Eisai, Nycomed, Reckitt Benckiser, Takeda, and Wyeth, and his associates reported ties to numerous industry sources, including employment by AstraZeneca.

CHICAGO – Complication rates for bariatric surgery patients on Medicare declined after Medicare began to cover the procedure in 2006, an analysis of state inpatient data from 12 states has found.

Data from previous studies suggest that bariatric surgery outcomes for Medicare patients improved after the implementation of Medicare’s National Coverage Determination in 2006, said Dr. Justin B. Dimick of the University of Michigan, Ann Arbor. But specific safety data on Medicare patients who have undergone bariatric surgery since the time of the decision are limited, Dr. Dimick said. The decision allowed for Medicare coverage of patients who sought care at facilities certified by the American College of Surgeons or the American Society for Metabolic and Bariatric Surgery.

To assess the impact of the National Coverage Determination on the safety of bariatric surgery, Dr. Dimick and his colleagues reviewed state inpatient data from 12 large, geographically dispersed states. Patients were identified on the basis of ICD-9 codes and diagnosis-related groups for weight loss surgery.

The outcomes were categorized according to any complication, a serious complication, or a reoperation.

The percentage of Medicare patients with any complications dropped from 12% before the determination to 8% afterward. Similarly, the percentage of non-Medicare patients with any complications dropped from 7% before to 5% after the determination.

In a multivariate analysis, the factors contributing to improved outcomes for bariatric surgery in Medicare patients were an increase in the use of laparoscopic gastric banding (lap band surgery), the transfer of patients to better hospitals, and quality improvement within individual hospitals, Dr. Dimick said.

Improvements in the safety of bariatric surgery did not, however, result from patients being redirected to safer hospitals, said Dr. Dimick. In fact, complication rates for procedures performed at Centers of Excellence versus non–Centers of Excellence were not significantly different (odds ratio for any complications, 0.97), he noted.

"CMS should consider dropping the COE [Centers of Excellence] aspect of the coverage decision [that] limits patient access without a beneficial improvement in outcomes," Dr. Dimick said. "Alternatively, CMS could revise the national coverage decision to further encourage participation in a quality improvement registry." Such a registry would need to include measures of long-term effectiveness to identify any unintended consequences of the increase in lap band surgery, he added.

Dr. Dimick is an equity owner and cofounder of ArborMetrix, a health care analytics and software firm.

CHICAGO – Complication rates for bariatric surgery patients on Medicare declined after Medicare began to cover the procedure in 2006, an analysis of state inpatient data from 12 states has found.

Data from previous studies suggest that bariatric surgery outcomes for Medicare patients improved after the implementation of Medicare’s National Coverage Determination in 2006, said Dr. Justin B. Dimick of the University of Michigan, Ann Arbor. But specific safety data on Medicare patients who have undergone bariatric surgery since the time of the decision are limited, Dr. Dimick said. The decision allowed for Medicare coverage of patients who sought care at facilities certified by the American College of Surgeons or the American Society for Metabolic and Bariatric Surgery.

To assess the impact of the National Coverage Determination on the safety of bariatric surgery, Dr. Dimick and his colleagues reviewed state inpatient data from 12 large, geographically dispersed states. Patients were identified on the basis of ICD-9 codes and diagnosis-related groups for weight loss surgery.

The outcomes were categorized according to any complication, a serious complication, or a reoperation.

The percentage of Medicare patients with any complications dropped from 12% before the determination to 8% afterward. Similarly, the percentage of non-Medicare patients with any complications dropped from 7% before to 5% after the determination.

In a multivariate analysis, the factors contributing to improved outcomes for bariatric surgery in Medicare patients were an increase in the use of laparoscopic gastric banding (lap band surgery), the transfer of patients to better hospitals, and quality improvement within individual hospitals, Dr. Dimick said.

Improvements in the safety of bariatric surgery did not, however, result from patients being redirected to safer hospitals, said Dr. Dimick. In fact, complication rates for procedures performed at Centers of Excellence versus non–Centers of Excellence were not significantly different (odds ratio for any complications, 0.97), he noted.

"CMS should consider dropping the COE [Centers of Excellence] aspect of the coverage decision [that] limits patient access without a beneficial improvement in outcomes," Dr. Dimick said. "Alternatively, CMS could revise the national coverage decision to further encourage participation in a quality improvement registry." Such a registry would need to include measures of long-term effectiveness to identify any unintended consequences of the increase in lap band surgery, he added.

Dr. Dimick is an equity owner and cofounder of ArborMetrix, a health care analytics and software firm.

CHICAGO – Complication rates for bariatric surgery patients on Medicare declined after Medicare began to cover the procedure in 2006, an analysis of state inpatient data from 12 states has found.

Data from previous studies suggest that bariatric surgery outcomes for Medicare patients improved after the implementation of Medicare’s National Coverage Determination in 2006, said Dr. Justin B. Dimick of the University of Michigan, Ann Arbor. But specific safety data on Medicare patients who have undergone bariatric surgery since the time of the decision are limited, Dr. Dimick said. The decision allowed for Medicare coverage of patients who sought care at facilities certified by the American College of Surgeons or the American Society for Metabolic and Bariatric Surgery.

To assess the impact of the National Coverage Determination on the safety of bariatric surgery, Dr. Dimick and his colleagues reviewed state inpatient data from 12 large, geographically dispersed states. Patients were identified on the basis of ICD-9 codes and diagnosis-related groups for weight loss surgery.

The outcomes were categorized according to any complication, a serious complication, or a reoperation.

The percentage of Medicare patients with any complications dropped from 12% before the determination to 8% afterward. Similarly, the percentage of non-Medicare patients with any complications dropped from 7% before to 5% after the determination.

In a multivariate analysis, the factors contributing to improved outcomes for bariatric surgery in Medicare patients were an increase in the use of laparoscopic gastric banding (lap band surgery), the transfer of patients to better hospitals, and quality improvement within individual hospitals, Dr. Dimick said.

Improvements in the safety of bariatric surgery did not, however, result from patients being redirected to safer hospitals, said Dr. Dimick. In fact, complication rates for procedures performed at Centers of Excellence versus non–Centers of Excellence were not significantly different (odds ratio for any complications, 0.97), he noted.

"CMS should consider dropping the COE [Centers of Excellence] aspect of the coverage decision [that] limits patient access without a beneficial improvement in outcomes," Dr. Dimick said. "Alternatively, CMS could revise the national coverage decision to further encourage participation in a quality improvement registry." Such a registry would need to include measures of long-term effectiveness to identify any unintended consequences of the increase in lap band surgery, he added.

Dr. Dimick is an equity owner and cofounder of ArborMetrix, a health care analytics and software firm.

Two common genetic variants on chromosomes 6p21 and 16q24 were found to be associated with Barrett’s esophagus in the first genome-wide association study of susceptibility to the disorder, according to a letter to the editor published online Sept. 9 in Nature Genetics.

Genetic factors have long been suspected to play a role in the development of Barrett’s esophagus since relative risks for the disorder, as well as for gastroesophageal reflux disease and esophageal adenocarcinoma, are increased two- to fourfold in first-degree relatives of affected patients.

However, "extensive candidate gene and linkage searches have to date been unsuccessful in identifying genetic variants that are associated with risk of Barrett’s esophagus," wrote Dr. Zhan Su of the Wellcome Trust Centre for Human Genetics in Oxford, England, and his associates.

Their findings provide the first direct evidence that the etiology of Barrett’s esophagus has a genetic component, the researchers noted.

Dr. Su and his colleagues performed the genome-wide association study as part of a Wellcome Trust consortium study of the genetic components of 15 common disorders and traits. They identified the two genetic variants in a discovery analysis and confirmed the findings in another five replication cohorts.

The discovery analysis involved genotyping of 1,852 adults with histologically confirmed Barrett’s esophagus who were recruited from sites across the United Kingdom. A representative sample of 5,172 control subjects also was analyzed. A total of 521,744 single-nucleotide polymorphisms (SNPs) were typed.

The 100 SNPs that were associated to some degree with Barrett’s esophagus were then analyzed in a separate cohort of 1,105 cases from two clinical trials, 4,421 controls from another U.K. sample, and 2,578 controls from yet another U.K .sample.

The top 16 SNPs from these analyses were then analyzed in a second replication cohort of 473 cases and 1,780 controls from a Dutch genotyping database. Two of the SNPs were found to be significantly associated with Barrett\'’s esophagus: rs9257809 on chromosome 6p21 and rs9936833 on chromosome 16q24.

It is notable that the closest coding gene to the rs9936833 SNP on chromosome 16q24 is a gene that encodes a protein involved in the development of the gastrointestinal tract. It has been reported that, when this gene is inactivated, structural alterations in the esophagus, especially atresia, occur. The rs9257809 SNP on 6p21 is near the telomeric edge of the major histocompatibility complex region.

The two SNPs were then examined further in an Irish cohort of 245 cases and 473 controls, a U.K. cohort of 1,765 cases and 1,586 controls, and a cohort of 2,398 cases and 2,167 controls from Europe, Australia, and the United States.

Overall, the two SNPs "showed compelling evidence for association," with Barrett’s esophagus, reflected in the significance of the combined P values for rs9257809 (odds ratio, 1.21) and rs9936833 (odds ratio, 1.14), the investigators reported (Nat. Genet. 2012 Sept. 9 [doi:10.1038/ng.2408]).

In a subgroup analysis involving only patients who had histologic evidence of intestinal metaplasia, the same two SNPs were again strongly associated with Barrett’s esophagus. Neither SNP, however, was associated with either the circumferential extent or the maximal length of the affected segment of esophagus.

Given that men are known to be more susceptible than women to Barrett’s esophagus, the investigators also performed a sex-stratified analysis of the data and found that the association between both SNPs and the disorder was stronger in men than in women. "This finding warrants further investigation," they noted.

Similarly, given the known association between obesity and Barrett’s esophagus, the researchers analyzed the 40 SNPs that previously have been linked with either body mass index or waist-to-hip ratio. These latter SNPs were "more likely than expected by chance to show effects in the same direction in association with Barrett’s esophagus, suggesting that genetic effects may in part underpin the epidemiologic observation that BMI is a risk factor for Barrett’s esophagus," Dr. Su and his associates said.

"Given that Barrett’s esophagus has an accepted status as a precursor lesion, the SNPs that we have identified could also essentially be risk factors for esophageal adenocarcinoma and may give clues as to the biology of both of these important phenotypes," they added.

The financial disclosures of Dr. Su and his 143 coauthors are listed in the online version of this article.

Two common genetic variants on chromosomes 6p21 and 16q24 were found to be associated with Barrett’s esophagus in the first genome-wide association study of susceptibility to the disorder, according to a letter to the editor published online Sept. 9 in Nature Genetics.

Genetic factors have long been suspected to play a role in the development of Barrett’s esophagus since relative risks for the disorder, as well as for gastroesophageal reflux disease and esophageal adenocarcinoma, are increased two- to fourfold in first-degree relatives of affected patients.

However, "extensive candidate gene and linkage searches have to date been unsuccessful in identifying genetic variants that are associated with risk of Barrett’s esophagus," wrote Dr. Zhan Su of the Wellcome Trust Centre for Human Genetics in Oxford, England, and his associates.

Their findings provide the first direct evidence that the etiology of Barrett’s esophagus has a genetic component, the researchers noted.

Dr. Su and his colleagues performed the genome-wide association study as part of a Wellcome Trust consortium study of the genetic components of 15 common disorders and traits. They identified the two genetic variants in a discovery analysis and confirmed the findings in another five replication cohorts.

The discovery analysis involved genotyping of 1,852 adults with histologically confirmed Barrett’s esophagus who were recruited from sites across the United Kingdom. A representative sample of 5,172 control subjects also was analyzed. A total of 521,744 single-nucleotide polymorphisms (SNPs) were typed.

The 100 SNPs that were associated to some degree with Barrett’s esophagus were then analyzed in a separate cohort of 1,105 cases from two clinical trials, 4,421 controls from another U.K. sample, and 2,578 controls from yet another U.K .sample.

The top 16 SNPs from these analyses were then analyzed in a second replication cohort of 473 cases and 1,780 controls from a Dutch genotyping database. Two of the SNPs were found to be significantly associated with Barrett\'’s esophagus: rs9257809 on chromosome 6p21 and rs9936833 on chromosome 16q24.

It is notable that the closest coding gene to the rs9936833 SNP on chromosome 16q24 is a gene that encodes a protein involved in the development of the gastrointestinal tract. It has been reported that, when this gene is inactivated, structural alterations in the esophagus, especially atresia, occur. The rs9257809 SNP on 6p21 is near the telomeric edge of the major histocompatibility complex region.

The two SNPs were then examined further in an Irish cohort of 245 cases and 473 controls, a U.K. cohort of 1,765 cases and 1,586 controls, and a cohort of 2,398 cases and 2,167 controls from Europe, Australia, and the United States.

Overall, the two SNPs "showed compelling evidence for association," with Barrett’s esophagus, reflected in the significance of the combined P values for rs9257809 (odds ratio, 1.21) and rs9936833 (odds ratio, 1.14), the investigators reported (Nat. Genet. 2012 Sept. 9 [doi:10.1038/ng.2408]).

In a subgroup analysis involving only patients who had histologic evidence of intestinal metaplasia, the same two SNPs were again strongly associated with Barrett’s esophagus. Neither SNP, however, was associated with either the circumferential extent or the maximal length of the affected segment of esophagus.

Given that men are known to be more susceptible than women to Barrett’s esophagus, the investigators also performed a sex-stratified analysis of the data and found that the association between both SNPs and the disorder was stronger in men than in women. "This finding warrants further investigation," they noted.

Similarly, given the known association between obesity and Barrett’s esophagus, the researchers analyzed the 40 SNPs that previously have been linked with either body mass index or waist-to-hip ratio. These latter SNPs were "more likely than expected by chance to show effects in the same direction in association with Barrett’s esophagus, suggesting that genetic effects may in part underpin the epidemiologic observation that BMI is a risk factor for Barrett’s esophagus," Dr. Su and his associates said.

"Given that Barrett’s esophagus has an accepted status as a precursor lesion, the SNPs that we have identified could also essentially be risk factors for esophageal adenocarcinoma and may give clues as to the biology of both of these important phenotypes," they added.

The financial disclosures of Dr. Su and his 143 coauthors are listed in the online version of this article.

Two common genetic variants on chromosomes 6p21 and 16q24 were found to be associated with Barrett’s esophagus in the first genome-wide association study of susceptibility to the disorder, according to a letter to the editor published online Sept. 9 in Nature Genetics.

Genetic factors have long been suspected to play a role in the development of Barrett’s esophagus since relative risks for the disorder, as well as for gastroesophageal reflux disease and esophageal adenocarcinoma, are increased two- to fourfold in first-degree relatives of affected patients.

However, "extensive candidate gene and linkage searches have to date been unsuccessful in identifying genetic variants that are associated with risk of Barrett’s esophagus," wrote Dr. Zhan Su of the Wellcome Trust Centre for Human Genetics in Oxford, England, and his associates.

Their findings provide the first direct evidence that the etiology of Barrett’s esophagus has a genetic component, the researchers noted.

Dr. Su and his colleagues performed the genome-wide association study as part of a Wellcome Trust consortium study of the genetic components of 15 common disorders and traits. They identified the two genetic variants in a discovery analysis and confirmed the findings in another five replication cohorts.

The discovery analysis involved genotyping of 1,852 adults with histologically confirmed Barrett’s esophagus who were recruited from sites across the United Kingdom. A representative sample of 5,172 control subjects also was analyzed. A total of 521,744 single-nucleotide polymorphisms (SNPs) were typed.

The 100 SNPs that were associated to some degree with Barrett’s esophagus were then analyzed in a separate cohort of 1,105 cases from two clinical trials, 4,421 controls from another U.K. sample, and 2,578 controls from yet another U.K .sample.

The top 16 SNPs from these analyses were then analyzed in a second replication cohort of 473 cases and 1,780 controls from a Dutch genotyping database. Two of the SNPs were found to be significantly associated with Barrett\'’s esophagus: rs9257809 on chromosome 6p21 and rs9936833 on chromosome 16q24.

It is notable that the closest coding gene to the rs9936833 SNP on chromosome 16q24 is a gene that encodes a protein involved in the development of the gastrointestinal tract. It has been reported that, when this gene is inactivated, structural alterations in the esophagus, especially atresia, occur. The rs9257809 SNP on 6p21 is near the telomeric edge of the major histocompatibility complex region.

The two SNPs were then examined further in an Irish cohort of 245 cases and 473 controls, a U.K. cohort of 1,765 cases and 1,586 controls, and a cohort of 2,398 cases and 2,167 controls from Europe, Australia, and the United States.

Overall, the two SNPs "showed compelling evidence for association," with Barrett’s esophagus, reflected in the significance of the combined P values for rs9257809 (odds ratio, 1.21) and rs9936833 (odds ratio, 1.14), the investigators reported (Nat. Genet. 2012 Sept. 9 [doi:10.1038/ng.2408]).

In a subgroup analysis involving only patients who had histologic evidence of intestinal metaplasia, the same two SNPs were again strongly associated with Barrett’s esophagus. Neither SNP, however, was associated with either the circumferential extent or the maximal length of the affected segment of esophagus.

Given that men are known to be more susceptible than women to Barrett’s esophagus, the investigators also performed a sex-stratified analysis of the data and found that the association between both SNPs and the disorder was stronger in men than in women. "This finding warrants further investigation," they noted.

Similarly, given the known association between obesity and Barrett’s esophagus, the researchers analyzed the 40 SNPs that previously have been linked with either body mass index or waist-to-hip ratio. These latter SNPs were "more likely than expected by chance to show effects in the same direction in association with Barrett’s esophagus, suggesting that genetic effects may in part underpin the epidemiologic observation that BMI is a risk factor for Barrett’s esophagus," Dr. Su and his associates said.

"Given that Barrett’s esophagus has an accepted status as a precursor lesion, the SNPs that we have identified could also essentially be risk factors for esophageal adenocarcinoma and may give clues as to the biology of both of these important phenotypes," they added.

The financial disclosures of Dr. Su and his 143 coauthors are listed in the online version of this article.

Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.