Upper GI Tract

SAN DIEGO – Laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy is a safe and feasible operation, results from a two-center study showed.

"Since the Lap-Band was introduced in the United States in 2001, it has been a popular minimally invasive procedure for weight loss," Dr. Abdelkader A. Hawasli said at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "However, recent reports have shown that there’s an increased rate of explantation (up to 49%)" because of complications or failure to lose weight. Options are removal, reversion, or reversal to a nonphysiological procedure, "such as Roux-en-Y gastric bypass or biliopancreatic diversion. However, recent reports have been showing that sleeve gastrectomy could be a possible physiologic alternative."

For the current study, Dr. Hawasli, a surgeon at St. John Hospital and Medical Center in Detroit and Beaumont Hospital in Grosse Pointe, Mich., and his associates set out to evaluate the safety of the laparoscopic reversal of the Lap-Band to sleeve gastrectomy, the feasibility of performing simultaneous laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy, and the results of the sleeve gastrectomy after reversal as the final bariatric procedure in continuing or maintaining weight loss.

Dr. Hawasli reported on 485 patients who had undergone Lap-Band placement at St. John Hospital and Medical Center and 4 who had undergone the procedure at another institution from January 2004 to October 2011.

Of the 489 patients, 34 (7%) had reversal of the Lap-Band to sleeve gastrectomy. Of these, 20 patients (group 1) underwent reversal because of slippage in 15 cases, erosion in 3 cases, and infection in 2 cases, whereas 14 patients (group 2) underwent reversal because they were dissatisfied with their weight loss. The mean time of the reversal to sleeve gastrectomy was more than 3 years from Lap-Band insertion among the slippage subset patients in group 1 and among all patients in group 2 (36.5 vs. 43.3 months, respectively).

The majority of patients (32) underwent simultaneous removal of the band with reversal to sleeve gastrectomy, whereas 2 underwent a staged sleeve gastrectomy.

Dr. Hawasli reported that there were just two complications in group 1: one leak, which occurred because of erosion, and one narrowing. Both cases were treated conservatively. There were no complications in group 2. There were no readmissions in group 1, whereas in group 2 one patient was readmitted for nausea and one for dehydration.

Patients in both groups lost weight after the reversal, but the loss was more pronounced in group 1, compared with group 2 (mean total body mass index loss, –15.8 kg/m² vs. –10.8, respectively; mean percentage of excess BMI loss, –66.5% vs. –44.6%; all P less than .05).

To explain this difference in weight loss, Dr. Hawasli said that patients in group 1 lost most of their weight before the reversal (mean BMI loss, –11.7) and lost additional weight after the reversal (mean BMI loss, –3.8). However, group 2 patients struggled with weight loss before the reversal (mean BMI loss, –3.6) and they may have continued to struggle after the reversal, even though they lost more weight after the reversal than did group 1 patients (mean BMI loss, –7.2 vs. –3.8, respectively), which is expected.

"Another reason could be the short postreversal follow-up period (a mean of 9 months)," during which they did not get enough time to lose more weight, he explained.

In group 1, the mean operative time was 159 minutes for patients with Lap-Band slippage and 174 minutes for those with erosion or infection. The mean operative time in group 2 was 106 minutes.

Length of stay was about 2 days in both groups, but reached a mean of 3.6 days for the subset of group 1 patients who had reversal because of infection or erosion.

"The short-term results of weight loss after the reversal are better in patients who had the reversal secondary to complications," Dr. Hawasli concluded. "Concomitant removal of the band and reversal to sleeve gastrectomy did not increase the risk of complications except in patients with erosion. Thus, patients with erosion may benefit better from staged reversal."

Dr. Hawasli disclosed that he receives compensation from Covidien as a proctor.

SAN DIEGO – Laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy is a safe and feasible operation, results from a two-center study showed.

"Since the Lap-Band was introduced in the United States in 2001, it has been a popular minimally invasive procedure for weight loss," Dr. Abdelkader A. Hawasli said at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "However, recent reports have shown that there’s an increased rate of explantation (up to 49%)" because of complications or failure to lose weight. Options are removal, reversion, or reversal to a nonphysiological procedure, "such as Roux-en-Y gastric bypass or biliopancreatic diversion. However, recent reports have been showing that sleeve gastrectomy could be a possible physiologic alternative."

For the current study, Dr. Hawasli, a surgeon at St. John Hospital and Medical Center in Detroit and Beaumont Hospital in Grosse Pointe, Mich., and his associates set out to evaluate the safety of the laparoscopic reversal of the Lap-Band to sleeve gastrectomy, the feasibility of performing simultaneous laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy, and the results of the sleeve gastrectomy after reversal as the final bariatric procedure in continuing or maintaining weight loss.

Dr. Hawasli reported on 485 patients who had undergone Lap-Band placement at St. John Hospital and Medical Center and 4 who had undergone the procedure at another institution from January 2004 to October 2011.

Of the 489 patients, 34 (7%) had reversal of the Lap-Band to sleeve gastrectomy. Of these, 20 patients (group 1) underwent reversal because of slippage in 15 cases, erosion in 3 cases, and infection in 2 cases, whereas 14 patients (group 2) underwent reversal because they were dissatisfied with their weight loss. The mean time of the reversal to sleeve gastrectomy was more than 3 years from Lap-Band insertion among the slippage subset patients in group 1 and among all patients in group 2 (36.5 vs. 43.3 months, respectively).

The majority of patients (32) underwent simultaneous removal of the band with reversal to sleeve gastrectomy, whereas 2 underwent a staged sleeve gastrectomy.

Dr. Hawasli reported that there were just two complications in group 1: one leak, which occurred because of erosion, and one narrowing. Both cases were treated conservatively. There were no complications in group 2. There were no readmissions in group 1, whereas in group 2 one patient was readmitted for nausea and one for dehydration.

Patients in both groups lost weight after the reversal, but the loss was more pronounced in group 1, compared with group 2 (mean total body mass index loss, –15.8 kg/m² vs. –10.8, respectively; mean percentage of excess BMI loss, –66.5% vs. –44.6%; all P less than .05).

To explain this difference in weight loss, Dr. Hawasli said that patients in group 1 lost most of their weight before the reversal (mean BMI loss, –11.7) and lost additional weight after the reversal (mean BMI loss, –3.8). However, group 2 patients struggled with weight loss before the reversal (mean BMI loss, –3.6) and they may have continued to struggle after the reversal, even though they lost more weight after the reversal than did group 1 patients (mean BMI loss, –7.2 vs. –3.8, respectively), which is expected.

"Another reason could be the short postreversal follow-up period (a mean of 9 months)," during which they did not get enough time to lose more weight, he explained.

In group 1, the mean operative time was 159 minutes for patients with Lap-Band slippage and 174 minutes for those with erosion or infection. The mean operative time in group 2 was 106 minutes.

Length of stay was about 2 days in both groups, but reached a mean of 3.6 days for the subset of group 1 patients who had reversal because of infection or erosion.

"The short-term results of weight loss after the reversal are better in patients who had the reversal secondary to complications," Dr. Hawasli concluded. "Concomitant removal of the band and reversal to sleeve gastrectomy did not increase the risk of complications except in patients with erosion. Thus, patients with erosion may benefit better from staged reversal."

Dr. Hawasli disclosed that he receives compensation from Covidien as a proctor.

SAN DIEGO – Laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy is a safe and feasible operation, results from a two-center study showed.

"Since the Lap-Band was introduced in the United States in 2001, it has been a popular minimally invasive procedure for weight loss," Dr. Abdelkader A. Hawasli said at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "However, recent reports have shown that there’s an increased rate of explantation (up to 49%)" because of complications or failure to lose weight. Options are removal, reversion, or reversal to a nonphysiological procedure, "such as Roux-en-Y gastric bypass or biliopancreatic diversion. However, recent reports have been showing that sleeve gastrectomy could be a possible physiologic alternative."

For the current study, Dr. Hawasli, a surgeon at St. John Hospital and Medical Center in Detroit and Beaumont Hospital in Grosse Pointe, Mich., and his associates set out to evaluate the safety of the laparoscopic reversal of the Lap-Band to sleeve gastrectomy, the feasibility of performing simultaneous laparoscopic removal of the Lap-Band and reversal to sleeve gastrectomy, and the results of the sleeve gastrectomy after reversal as the final bariatric procedure in continuing or maintaining weight loss.

Dr. Hawasli reported on 485 patients who had undergone Lap-Band placement at St. John Hospital and Medical Center and 4 who had undergone the procedure at another institution from January 2004 to October 2011.

Of the 489 patients, 34 (7%) had reversal of the Lap-Band to sleeve gastrectomy. Of these, 20 patients (group 1) underwent reversal because of slippage in 15 cases, erosion in 3 cases, and infection in 2 cases, whereas 14 patients (group 2) underwent reversal because they were dissatisfied with their weight loss. The mean time of the reversal to sleeve gastrectomy was more than 3 years from Lap-Band insertion among the slippage subset patients in group 1 and among all patients in group 2 (36.5 vs. 43.3 months, respectively).

The majority of patients (32) underwent simultaneous removal of the band with reversal to sleeve gastrectomy, whereas 2 underwent a staged sleeve gastrectomy.

Dr. Hawasli reported that there were just two complications in group 1: one leak, which occurred because of erosion, and one narrowing. Both cases were treated conservatively. There were no complications in group 2. There were no readmissions in group 1, whereas in group 2 one patient was readmitted for nausea and one for dehydration.

Patients in both groups lost weight after the reversal, but the loss was more pronounced in group 1, compared with group 2 (mean total body mass index loss, –15.8 kg/m² vs. –10.8, respectively; mean percentage of excess BMI loss, –66.5% vs. –44.6%; all P less than .05).

To explain this difference in weight loss, Dr. Hawasli said that patients in group 1 lost most of their weight before the reversal (mean BMI loss, –11.7) and lost additional weight after the reversal (mean BMI loss, –3.8). However, group 2 patients struggled with weight loss before the reversal (mean BMI loss, –3.6) and they may have continued to struggle after the reversal, even though they lost more weight after the reversal than did group 1 patients (mean BMI loss, –7.2 vs. –3.8, respectively), which is expected.

"Another reason could be the short postreversal follow-up period (a mean of 9 months)," during which they did not get enough time to lose more weight, he explained.

In group 1, the mean operative time was 159 minutes for patients with Lap-Band slippage and 174 minutes for those with erosion or infection. The mean operative time in group 2 was 106 minutes.

Length of stay was about 2 days in both groups, but reached a mean of 3.6 days for the subset of group 1 patients who had reversal because of infection or erosion.

"The short-term results of weight loss after the reversal are better in patients who had the reversal secondary to complications," Dr. Hawasli concluded. "Concomitant removal of the band and reversal to sleeve gastrectomy did not increase the risk of complications except in patients with erosion. Thus, patients with erosion may benefit better from staged reversal."

Dr. Hawasli disclosed that he receives compensation from Covidien as a proctor.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Laparoscopic sleeve gastrectomy is positioned between gastric banding and the laparoscopic gastric bypass for both safety and efficacy, results from the largest comparative study of its kind demonstrated.

The finding comes at a time when the Centers for Medicare and Medicaid Services is reviewing evidence to consider including sleeve gastrectomy as a covered benefit. Currently, gastric bypass, vertical banded gastroplasty, duodenal switch, and gastric banding are the only CMS-sanctioned bariatric procedures.

The study, which involved nearly 300,000 patients, "shows that across the board, regardless of the procedure, bariatric surgery is safe and effective," Dr. John M. Morton said in an interview at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "The emerging new procedure, the sleeve gastrectomy, is shown to be right between the bypass and the band. As a result, we have seen more interest from payers to cover it. In fact there are about 100 million lives that are covered. Our only outlier is CMS in deciding to cover. We hope that these data will help influence CMS in granting coverage for the sleeve gastrectomy."

Dr. Morton, associate professor of surgery and director of bariatric surgery at Stanford Hospitals and Clinics at Stanford (Calif.) University, and his associates examined BOLD (Bariatric Outcomes Longitudinal Database) to identify patients who had undergone laparoscopic Roux-en-Y gastric bypass (LRNYGB), gastric banding (LAGB), and sleeve gastrectomy (LSG) from June 2007 to December 2010. BOLD, the largest bariatric-specific database, is maintained by the ASMBS Bariatric Surgery Center of Excellence program, and includes more than 1,200 surgeons at 540 hospitals. Dr. Morton described the data as a "clinically rich" variable set that includes age, gender, race, insurance status, body mass index, excess body weight, and comorbidities.

"There is a definite need for more data around comparison of different procedures," Dr. Morton said at the meeting. "Our study hypothesis is very straightforward: Do demographics and outcomes for bariatric surgery vary by procedure?"

The primary outcomes were 30-day mortality, serious complications, and readmissions. The definitions of serious complications included death, anastomotic leakage, cardiac arrest, deep venous thrombosis, evisceration, heart failure and/or pulmonary edema, liver failure, and bleeding requiring transfusion.

Dr. Morton reported outcomes from 117,365 patients in the LAGB group, 138,222 in the LRNYGB group, and 16,139 in the LSG group. Patients in each group were generally the same age (a mean of 45, 46, and 45 years, respectively), mostly female (78%, 79%, and 74%), and mostly white (72%, 73%, and 72%). "The one area where there was a sizable difference was around self-pay," Dr. Morton said. About 21% of patients in the LSG group paid out-of-pocket, compared with 6% of those in the LAGB group and 2% of those in the LRNYGB group.

The proportion of preoperative comorbidities was similar among the three groups, with two exceptions. The prevalence of diabetes was highest in the LRNYGB group (37%, compared with 30% in the LSG group and 28% in the LAGB group; P less than .0001). A similar association was seen in the proportion of patients with five or more preoperative comorbidities (62%, 55%, and 52%, respectively; P less than .0001).

The mean length of stay was 0.7 days for the LAGB group, 1.9 days for the LSG group, and 2.3 days for the LRNYGB group. The percent change in BMI at 12 months was 7.6%, 13.4%, and 16.4%, respectively; the rate of 30-day serious complications was 0.25%, 0.96%, and 1.25%; and the rate of 30-day mortality was 0.03%, 0.08%, and 0.14%. All differences between the groups were significant (P less than .0001).

"If you look at the remainder of the safety outcomes – everything from 30-day readmission to 30-day reoperation – it’s pretty much the same order, with the band group having the lowest [percentage], and the bypass having the highest, and the sleeve being right in between," Dr. Morton said. "When we looked at age greater than 65 in isolation, we found that the order of safety remains, with the banding having the least amount of mortality and the sleeve being right between the band procedure and the bypass."

Logistic regression analysis revealed several significant factors that predicted serious adverse events at 30 days: male gender (odds ratio, 1.67), having nonprivate insurance (OR, 1.15), stepwise progression with increasing age (for example, an OR of 1.27 for those aged 26-35 years and an OR of 4.42 for those above age 65), and stepwise progression with increasing BMI (for example, an OR of 1.37 for those with a BMI of 46-55 kg/m² and an OR of 3.03 for those with a BMI greater than 65).

The invited discussant, Dr. Matthew M. Hutter, of Massachusetts General Hospital, Boston, described the size of the overall study cohort as remarkable. "What I find most interesting about this study is that it shows that sleeve gastrectomy – a brand-new, very complex procedure – can be introduced safely and effectively when performed under the standards of a bariatric accreditation program," Dr. Hutter said. "Other surgical procedures such as laparoscopic cholecystectomy or laparoscopic colectomy had very high morbidity and conversion rates when they were first implemented. However, this new complex procedure has been safe and effective from the get-go, and that is really quite impressive. The other remarkable finding is how consistent this is with all of the other major [bariatric surgery] data collection programs."

Dr. Morton acknowledged certain limitations of the study, including the fact that 1-year follow-up was available in only 60% of patients, while 30-day follow-up was available in 98% of the cohort. "Potentially, patients could have been admitted to other hospitals," he added. "These are research-consented patients, so about 70% consented. Some of this is surgeon-directed reporting."

Dr. Morton said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Laparoscopic sleeve gastrectomy is positioned between gastric banding and the laparoscopic gastric bypass for both safety and efficacy, results from the largest comparative study of its kind demonstrated.

The finding comes at a time when the Centers for Medicare and Medicaid Services is reviewing evidence to consider including sleeve gastrectomy as a covered benefit. Currently, gastric bypass, vertical banded gastroplasty, duodenal switch, and gastric banding are the only CMS-sanctioned bariatric procedures.

The study, which involved nearly 300,000 patients, "shows that across the board, regardless of the procedure, bariatric surgery is safe and effective," Dr. John M. Morton said in an interview at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "The emerging new procedure, the sleeve gastrectomy, is shown to be right between the bypass and the band. As a result, we have seen more interest from payers to cover it. In fact there are about 100 million lives that are covered. Our only outlier is CMS in deciding to cover. We hope that these data will help influence CMS in granting coverage for the sleeve gastrectomy."

Dr. Morton, associate professor of surgery and director of bariatric surgery at Stanford Hospitals and Clinics at Stanford (Calif.) University, and his associates examined BOLD (Bariatric Outcomes Longitudinal Database) to identify patients who had undergone laparoscopic Roux-en-Y gastric bypass (LRNYGB), gastric banding (LAGB), and sleeve gastrectomy (LSG) from June 2007 to December 2010. BOLD, the largest bariatric-specific database, is maintained by the ASMBS Bariatric Surgery Center of Excellence program, and includes more than 1,200 surgeons at 540 hospitals. Dr. Morton described the data as a "clinically rich" variable set that includes age, gender, race, insurance status, body mass index, excess body weight, and comorbidities.

"There is a definite need for more data around comparison of different procedures," Dr. Morton said at the meeting. "Our study hypothesis is very straightforward: Do demographics and outcomes for bariatric surgery vary by procedure?"

The primary outcomes were 30-day mortality, serious complications, and readmissions. The definitions of serious complications included death, anastomotic leakage, cardiac arrest, deep venous thrombosis, evisceration, heart failure and/or pulmonary edema, liver failure, and bleeding requiring transfusion.

Dr. Morton reported outcomes from 117,365 patients in the LAGB group, 138,222 in the LRNYGB group, and 16,139 in the LSG group. Patients in each group were generally the same age (a mean of 45, 46, and 45 years, respectively), mostly female (78%, 79%, and 74%), and mostly white (72%, 73%, and 72%). "The one area where there was a sizable difference was around self-pay," Dr. Morton said. About 21% of patients in the LSG group paid out-of-pocket, compared with 6% of those in the LAGB group and 2% of those in the LRNYGB group.

The proportion of preoperative comorbidities was similar among the three groups, with two exceptions. The prevalence of diabetes was highest in the LRNYGB group (37%, compared with 30% in the LSG group and 28% in the LAGB group; P less than .0001). A similar association was seen in the proportion of patients with five or more preoperative comorbidities (62%, 55%, and 52%, respectively; P less than .0001).

The mean length of stay was 0.7 days for the LAGB group, 1.9 days for the LSG group, and 2.3 days for the LRNYGB group. The percent change in BMI at 12 months was 7.6%, 13.4%, and 16.4%, respectively; the rate of 30-day serious complications was 0.25%, 0.96%, and 1.25%; and the rate of 30-day mortality was 0.03%, 0.08%, and 0.14%. All differences between the groups were significant (P less than .0001).

"If you look at the remainder of the safety outcomes – everything from 30-day readmission to 30-day reoperation – it’s pretty much the same order, with the band group having the lowest [percentage], and the bypass having the highest, and the sleeve being right in between," Dr. Morton said. "When we looked at age greater than 65 in isolation, we found that the order of safety remains, with the banding having the least amount of mortality and the sleeve being right between the band procedure and the bypass."

Logistic regression analysis revealed several significant factors that predicted serious adverse events at 30 days: male gender (odds ratio, 1.67), having nonprivate insurance (OR, 1.15), stepwise progression with increasing age (for example, an OR of 1.27 for those aged 26-35 years and an OR of 4.42 for those above age 65), and stepwise progression with increasing BMI (for example, an OR of 1.37 for those with a BMI of 46-55 kg/m² and an OR of 3.03 for those with a BMI greater than 65).

The invited discussant, Dr. Matthew M. Hutter, of Massachusetts General Hospital, Boston, described the size of the overall study cohort as remarkable. "What I find most interesting about this study is that it shows that sleeve gastrectomy – a brand-new, very complex procedure – can be introduced safely and effectively when performed under the standards of a bariatric accreditation program," Dr. Hutter said. "Other surgical procedures such as laparoscopic cholecystectomy or laparoscopic colectomy had very high morbidity and conversion rates when they were first implemented. However, this new complex procedure has been safe and effective from the get-go, and that is really quite impressive. The other remarkable finding is how consistent this is with all of the other major [bariatric surgery] data collection programs."

Dr. Morton acknowledged certain limitations of the study, including the fact that 1-year follow-up was available in only 60% of patients, while 30-day follow-up was available in 98% of the cohort. "Potentially, patients could have been admitted to other hospitals," he added. "These are research-consented patients, so about 70% consented. Some of this is surgeon-directed reporting."

Dr. Morton said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Laparoscopic sleeve gastrectomy is positioned between gastric banding and the laparoscopic gastric bypass for both safety and efficacy, results from the largest comparative study of its kind demonstrated.

The finding comes at a time when the Centers for Medicare and Medicaid Services is reviewing evidence to consider including sleeve gastrectomy as a covered benefit. Currently, gastric bypass, vertical banded gastroplasty, duodenal switch, and gastric banding are the only CMS-sanctioned bariatric procedures.

The study, which involved nearly 300,000 patients, "shows that across the board, regardless of the procedure, bariatric surgery is safe and effective," Dr. John M. Morton said in an interview at the annual meeting of the American Society for Metabolic and Bariatric Surgery. "The emerging new procedure, the sleeve gastrectomy, is shown to be right between the bypass and the band. As a result, we have seen more interest from payers to cover it. In fact there are about 100 million lives that are covered. Our only outlier is CMS in deciding to cover. We hope that these data will help influence CMS in granting coverage for the sleeve gastrectomy."

Dr. Morton, associate professor of surgery and director of bariatric surgery at Stanford Hospitals and Clinics at Stanford (Calif.) University, and his associates examined BOLD (Bariatric Outcomes Longitudinal Database) to identify patients who had undergone laparoscopic Roux-en-Y gastric bypass (LRNYGB), gastric banding (LAGB), and sleeve gastrectomy (LSG) from June 2007 to December 2010. BOLD, the largest bariatric-specific database, is maintained by the ASMBS Bariatric Surgery Center of Excellence program, and includes more than 1,200 surgeons at 540 hospitals. Dr. Morton described the data as a "clinically rich" variable set that includes age, gender, race, insurance status, body mass index, excess body weight, and comorbidities.

"There is a definite need for more data around comparison of different procedures," Dr. Morton said at the meeting. "Our study hypothesis is very straightforward: Do demographics and outcomes for bariatric surgery vary by procedure?"

The primary outcomes were 30-day mortality, serious complications, and readmissions. The definitions of serious complications included death, anastomotic leakage, cardiac arrest, deep venous thrombosis, evisceration, heart failure and/or pulmonary edema, liver failure, and bleeding requiring transfusion.

Dr. Morton reported outcomes from 117,365 patients in the LAGB group, 138,222 in the LRNYGB group, and 16,139 in the LSG group. Patients in each group were generally the same age (a mean of 45, 46, and 45 years, respectively), mostly female (78%, 79%, and 74%), and mostly white (72%, 73%, and 72%). "The one area where there was a sizable difference was around self-pay," Dr. Morton said. About 21% of patients in the LSG group paid out-of-pocket, compared with 6% of those in the LAGB group and 2% of those in the LRNYGB group.

The proportion of preoperative comorbidities was similar among the three groups, with two exceptions. The prevalence of diabetes was highest in the LRNYGB group (37%, compared with 30% in the LSG group and 28% in the LAGB group; P less than .0001). A similar association was seen in the proportion of patients with five or more preoperative comorbidities (62%, 55%, and 52%, respectively; P less than .0001).

The mean length of stay was 0.7 days for the LAGB group, 1.9 days for the LSG group, and 2.3 days for the LRNYGB group. The percent change in BMI at 12 months was 7.6%, 13.4%, and 16.4%, respectively; the rate of 30-day serious complications was 0.25%, 0.96%, and 1.25%; and the rate of 30-day mortality was 0.03%, 0.08%, and 0.14%. All differences between the groups were significant (P less than .0001).

"If you look at the remainder of the safety outcomes – everything from 30-day readmission to 30-day reoperation – it’s pretty much the same order, with the band group having the lowest [percentage], and the bypass having the highest, and the sleeve being right in between," Dr. Morton said. "When we looked at age greater than 65 in isolation, we found that the order of safety remains, with the banding having the least amount of mortality and the sleeve being right between the band procedure and the bypass."

Logistic regression analysis revealed several significant factors that predicted serious adverse events at 30 days: male gender (odds ratio, 1.67), having nonprivate insurance (OR, 1.15), stepwise progression with increasing age (for example, an OR of 1.27 for those aged 26-35 years and an OR of 4.42 for those above age 65), and stepwise progression with increasing BMI (for example, an OR of 1.37 for those with a BMI of 46-55 kg/m² and an OR of 3.03 for those with a BMI greater than 65).

The invited discussant, Dr. Matthew M. Hutter, of Massachusetts General Hospital, Boston, described the size of the overall study cohort as remarkable. "What I find most interesting about this study is that it shows that sleeve gastrectomy – a brand-new, very complex procedure – can be introduced safely and effectively when performed under the standards of a bariatric accreditation program," Dr. Hutter said. "Other surgical procedures such as laparoscopic cholecystectomy or laparoscopic colectomy had very high morbidity and conversion rates when they were first implemented. However, this new complex procedure has been safe and effective from the get-go, and that is really quite impressive. The other remarkable finding is how consistent this is with all of the other major [bariatric surgery] data collection programs."

Dr. Morton acknowledged certain limitations of the study, including the fact that 1-year follow-up was available in only 60% of patients, while 30-day follow-up was available in 98% of the cohort. "Potentially, patients could have been admitted to other hospitals," he added. "These are research-consented patients, so about 70% consented. Some of this is surgeon-directed reporting."

Dr. Morton said that he had no relevant financial conflicts to disclose.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

SAN DIEGO – Patients with Helicobacter pylori infection face a significantly increased risk for developing colonic neoplasms, according to what is believed to be the largest investigation of the association.

Several studies have suggested that H. pylori infection is a risk factor for colonic neoplasms, but all of them involved relatively small case populations, Dr. Amnon Sonnenberg explained at the annual Digestive Disease Week.

Photo courtesy nddic.nih.gov

Dr. Sonnenberg, a gastroenterologist with the Portland (Ore.) VA Medical Center, investigated the relationship between H. pylori infection and the presence of colonic neoplasms in 156,269 patients who had undergone both a colonoscopy and an esophagogastroduodenoscopy. Surgical pathology samples from all the patients were stored in an electronic database at the Miraca Research Institute, a specialized gastrointestinal lab that serves private outpatient endoscopy centers throughout the United States. More than 1,500 gastroenterologists contributed to the database between January 2008 and December 2011.

Patients were an average age of 58 years, and 59% were female. Among the total, 16,759 (11%) had H. pylori gastritis on immunochemistry. The prevalence of H. pylori gastritis was 9% in patients without polyps, 11% in patients with hyperplastic polyps, 12% in patients with adenoma, 14% in patients with advanced adenoma, 15% in patients with villous adenoma or polyps with high-grade dysplasia, and 18% in patients with colonic adenocarcinoma.

There was a slight trend for the prevalence of H. pylori to rise with the increasing number, as well as the size, of adenomatous polyps. The prevalence of H. pylori was similar for all colon sites.

Significant associations also were noted between the development of colonic adenoma and the following other types of gastric histopathology: intestinal metaplasia, gastric adenoma, gastric cancer, and gastric lymphoma. Similar but even more significant associations were seen between advanced adenoma and these types of gastric histopathology.

Multivariate logistic regression confirmed that the development of H. pylori gastritis was associated with advanced age, male gender, hyperplastic polyps, adenoma, villous adenoma or high-grade dysplasia, and adenocarcinoma.

"H. pylori gastritis confers an increased risk for colonic neoplasm," concluded Dr. Sonnenberg, who is also professor of medicine in the division of gastroenterology and hepatology at Oregon Health and Science University.

"The risk applies to all types of colonic neoplasms and appears to increase with advancing stage of the neoplasm from hyperplastic and adenomatous polyps to tubulovillous adenoma, adenoma with high-grade dysplasia, and adenocarcinoma. Such risk is not limited to chronic active gastritis but is found in other types of gastric histopathology related to H. pylori, such as gastric intestinal metaplasia, gastric adenoma, gastric lymphoma, and gastric cancer," he said.

Long-term infection with H. pylori "may be related to elevated gastrin levels that may act as a growth factor," he speculated.

Dr. Sonnenberg disclosed having received a research grant from Takeda Pharmaceutical Company. No support was received for this study.

SAN DIEGO – Patients with Helicobacter pylori infection face a significantly increased risk for developing colonic neoplasms, according to what is believed to be the largest investigation of the association.

Several studies have suggested that H. pylori infection is a risk factor for colonic neoplasms, but all of them involved relatively small case populations, Dr. Amnon Sonnenberg explained at the annual Digestive Disease Week.

Photo courtesy nddic.nih.gov

Dr. Sonnenberg, a gastroenterologist with the Portland (Ore.) VA Medical Center, investigated the relationship between H. pylori infection and the presence of colonic neoplasms in 156,269 patients who had undergone both a colonoscopy and an esophagogastroduodenoscopy. Surgical pathology samples from all the patients were stored in an electronic database at the Miraca Research Institute, a specialized gastrointestinal lab that serves private outpatient endoscopy centers throughout the United States. More than 1,500 gastroenterologists contributed to the database between January 2008 and December 2011.

Patients were an average age of 58 years, and 59% were female. Among the total, 16,759 (11%) had H. pylori gastritis on immunochemistry. The prevalence of H. pylori gastritis was 9% in patients without polyps, 11% in patients with hyperplastic polyps, 12% in patients with adenoma, 14% in patients with advanced adenoma, 15% in patients with villous adenoma or polyps with high-grade dysplasia, and 18% in patients with colonic adenocarcinoma.

There was a slight trend for the prevalence of H. pylori to rise with the increasing number, as well as the size, of adenomatous polyps. The prevalence of H. pylori was similar for all colon sites.

Significant associations also were noted between the development of colonic adenoma and the following other types of gastric histopathology: intestinal metaplasia, gastric adenoma, gastric cancer, and gastric lymphoma. Similar but even more significant associations were seen between advanced adenoma and these types of gastric histopathology.

Multivariate logistic regression confirmed that the development of H. pylori gastritis was associated with advanced age, male gender, hyperplastic polyps, adenoma, villous adenoma or high-grade dysplasia, and adenocarcinoma.

"H. pylori gastritis confers an increased risk for colonic neoplasm," concluded Dr. Sonnenberg, who is also professor of medicine in the division of gastroenterology and hepatology at Oregon Health and Science University.

"The risk applies to all types of colonic neoplasms and appears to increase with advancing stage of the neoplasm from hyperplastic and adenomatous polyps to tubulovillous adenoma, adenoma with high-grade dysplasia, and adenocarcinoma. Such risk is not limited to chronic active gastritis but is found in other types of gastric histopathology related to H. pylori, such as gastric intestinal metaplasia, gastric adenoma, gastric lymphoma, and gastric cancer," he said.

Long-term infection with H. pylori "may be related to elevated gastrin levels that may act as a growth factor," he speculated.

Dr. Sonnenberg disclosed having received a research grant from Takeda Pharmaceutical Company. No support was received for this study.

SAN DIEGO – Patients with Helicobacter pylori infection face a significantly increased risk for developing colonic neoplasms, according to what is believed to be the largest investigation of the association.

Several studies have suggested that H. pylori infection is a risk factor for colonic neoplasms, but all of them involved relatively small case populations, Dr. Amnon Sonnenberg explained at the annual Digestive Disease Week.

Photo courtesy nddic.nih.gov

Dr. Sonnenberg, a gastroenterologist with the Portland (Ore.) VA Medical Center, investigated the relationship between H. pylori infection and the presence of colonic neoplasms in 156,269 patients who had undergone both a colonoscopy and an esophagogastroduodenoscopy. Surgical pathology samples from all the patients were stored in an electronic database at the Miraca Research Institute, a specialized gastrointestinal lab that serves private outpatient endoscopy centers throughout the United States. More than 1,500 gastroenterologists contributed to the database between January 2008 and December 2011.

Patients were an average age of 58 years, and 59% were female. Among the total, 16,759 (11%) had H. pylori gastritis on immunochemistry. The prevalence of H. pylori gastritis was 9% in patients without polyps, 11% in patients with hyperplastic polyps, 12% in patients with adenoma, 14% in patients with advanced adenoma, 15% in patients with villous adenoma or polyps with high-grade dysplasia, and 18% in patients with colonic adenocarcinoma.

There was a slight trend for the prevalence of H. pylori to rise with the increasing number, as well as the size, of adenomatous polyps. The prevalence of H. pylori was similar for all colon sites.

Significant associations also were noted between the development of colonic adenoma and the following other types of gastric histopathology: intestinal metaplasia, gastric adenoma, gastric cancer, and gastric lymphoma. Similar but even more significant associations were seen between advanced adenoma and these types of gastric histopathology.

Multivariate logistic regression confirmed that the development of H. pylori gastritis was associated with advanced age, male gender, hyperplastic polyps, adenoma, villous adenoma or high-grade dysplasia, and adenocarcinoma.

"H. pylori gastritis confers an increased risk for colonic neoplasm," concluded Dr. Sonnenberg, who is also professor of medicine in the division of gastroenterology and hepatology at Oregon Health and Science University.

"The risk applies to all types of colonic neoplasms and appears to increase with advancing stage of the neoplasm from hyperplastic and adenomatous polyps to tubulovillous adenoma, adenoma with high-grade dysplasia, and adenocarcinoma. Such risk is not limited to chronic active gastritis but is found in other types of gastric histopathology related to H. pylori, such as gastric intestinal metaplasia, gastric adenoma, gastric lymphoma, and gastric cancer," he said.

Long-term infection with H. pylori "may be related to elevated gastrin levels that may act as a growth factor," he speculated.

Dr. Sonnenberg disclosed having received a research grant from Takeda Pharmaceutical Company. No support was received for this study.

SAN DIEGO – Radiofrequency ablation was found to be safe and effective in treating Barrett’s esophagus patients, whether or not they had undergone a prior fundoplication, based on results from a multicenter registry study.

"Gastroesophageal reflux causes esophageal mucosal injury and inflammation that may impair healing and squamous re-epithelialization after treatment of Barrett’s esophagus [BE] with radiofrequency ablation [RFA]," Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Photo courtesy Dr. Nicholas J. Shaheen

"It is unclear if fundoplication surgery, as a mechanical barrier to all reflux, improves treatment outcomes of RFA for BE. Similarly, some have postulated that change in the conformation of the hiatus with surgery might make ablation problematic."

Dr. Shaheen, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and his associates conducted the largest study of its kind, he said. They evaluated records from the RFA Patient Registry to assess the relationship between prior fundoplication and both efficacy and safety outcomes in patients with BE who were treated with RFA.

The registry comprises 113 community-based and 35 academic-affiliated medical institutions in the United States. "About 75% of these institutions are private practices, so this is an interesting snapshot of RFA as it’s practiced outside of tertiary care centers," Dr. Shaheen said.

All study patients had BE confirmed by endoscopy and histology, and had undergone treatment with RFA. Enrollment commenced in July 2007 and ended in July 2011. Data were gleaned from standard case report forms and included demographics; relevant medical history; histologic grade prior to treatment; endoscopic findings; dates and total number of RFA treatment sessions; and ablation outcomes and complications.

"The vast amount of data is prospective, but less than 15% is retrospective," Dr. Shaheen said. "This is a registry study, so we could not mandate treatment, but a treatment protocol was suggested." Twice-daily use of proton pump inhibitors (PPIs) was recommended to everyone in the study, including those post fundoplication.

The mean age of patients was 61 years, and the majority were white. The mean pretreatment length of BE was about 4 cm, and patients received an average of 2.5 treatments with RFA. "Importantly, in this registry, about half of the patients had nondysplastic disease," Dr. Shaheen said. "Also, roughly 20% in each group had low- and high-grade dysplasia."

Dr. Shaheen reported results from the safety cohort, which included 5,537 patients who received RFA, and results from the efficacy cohort, which included 2,466 patients with biopsies performed 12 months after enrollment. Safety outcomes included perforation, stricture that required dilation, bleeding that required hospitalization or transfusion, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia and dysplasia.

Among patients in the safety cohort, 301 had a prior fundoplication, whereas 5,236 had received medical therapy only. Patients in the fundoplication group had a somewhat lower mean age than those in the medical therapy group (59 vs. 62 years, P = .0002), and were slightly less likely to be African American (0.3% vs. 1.6%, P = .03) or Hispanic (0.7% vs. 2.6%, P = .03). In the fundoplication group, the length of BE was greater (5.0 cm vs. 4.1 cm, P less than .0001), and the prevalence of nondysplastic BE was higher (53% vs. 49%, P = .05).

In addition, fewer patients in the fundoplication group were taking twice-daily PPIs compared with those in the medical therapy group (82% vs. 95%, P less than .001). There were no significant between-group differences in the rates of bleeding, hospitalization, or stricture.

Among patients in the efficacy cohort, 136 had a prior fundoplication and 2,330 had received medical therapy only. The fundoplication patients were slightly younger than the medical therapy patients (59 vs. 62 years, P = .004), had a somewhat greater length of BE (5.0 cm vs. 4.3 cm, P = .009), and were less likely to be taking twice-daily PPIs (75% vs. 93%, P less than .001).

Rates of complete eradication of intestinal metaplasia were 71% in the fundoplication group vs. 73% in the medical therapy group, a nonsignificant difference, while the rate of complete eradication of dysplasia was identical in both groups at 87%.

Among patients who had nondysplastic BE, 75% in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 81% in the medical therapy group, a nonsignificant difference.

Regarding combined efficacy for dysplastic BE and intramucosal carcinoma, 67% of patients in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 66% in the medical therapy group, and both groups had a rate of 87% for complete eradication of dysplasia; none of these differences were significant.

Dr. Shaheen acknowledged certain limitations of the study, including the fact that the functional status of the fundoplications was not known. "All we know is that some patients had them," he said. "These are observational data and subject to selection bias. Also note that this is hardly a pure comparison, because the people who got fundoplication were also getting PPIs. However, one might expect that to bias the study in favor of fundoplication, to the degree that the addition of PPIs helps."

The study was funded by Covidien, which provided the RFA equipment used in the study, and by grants from the National Institutes of Health. Dr. Shaheen disclosed that he has consulting relationships with numerous pharmaceutical and medical device companies, but none with Covidien.

SAN DIEGO – Radiofrequency ablation was found to be safe and effective in treating Barrett’s esophagus patients, whether or not they had undergone a prior fundoplication, based on results from a multicenter registry study.

"Gastroesophageal reflux causes esophageal mucosal injury and inflammation that may impair healing and squamous re-epithelialization after treatment of Barrett’s esophagus [BE] with radiofrequency ablation [RFA]," Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Photo courtesy Dr. Nicholas J. Shaheen

"It is unclear if fundoplication surgery, as a mechanical barrier to all reflux, improves treatment outcomes of RFA for BE. Similarly, some have postulated that change in the conformation of the hiatus with surgery might make ablation problematic."

Dr. Shaheen, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and his associates conducted the largest study of its kind, he said. They evaluated records from the RFA Patient Registry to assess the relationship between prior fundoplication and both efficacy and safety outcomes in patients with BE who were treated with RFA.

The registry comprises 113 community-based and 35 academic-affiliated medical institutions in the United States. "About 75% of these institutions are private practices, so this is an interesting snapshot of RFA as it’s practiced outside of tertiary care centers," Dr. Shaheen said.

All study patients had BE confirmed by endoscopy and histology, and had undergone treatment with RFA. Enrollment commenced in July 2007 and ended in July 2011. Data were gleaned from standard case report forms and included demographics; relevant medical history; histologic grade prior to treatment; endoscopic findings; dates and total number of RFA treatment sessions; and ablation outcomes and complications.

"The vast amount of data is prospective, but less than 15% is retrospective," Dr. Shaheen said. "This is a registry study, so we could not mandate treatment, but a treatment protocol was suggested." Twice-daily use of proton pump inhibitors (PPIs) was recommended to everyone in the study, including those post fundoplication.

The mean age of patients was 61 years, and the majority were white. The mean pretreatment length of BE was about 4 cm, and patients received an average of 2.5 treatments with RFA. "Importantly, in this registry, about half of the patients had nondysplastic disease," Dr. Shaheen said. "Also, roughly 20% in each group had low- and high-grade dysplasia."

Dr. Shaheen reported results from the safety cohort, which included 5,537 patients who received RFA, and results from the efficacy cohort, which included 2,466 patients with biopsies performed 12 months after enrollment. Safety outcomes included perforation, stricture that required dilation, bleeding that required hospitalization or transfusion, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia and dysplasia.

Among patients in the safety cohort, 301 had a prior fundoplication, whereas 5,236 had received medical therapy only. Patients in the fundoplication group had a somewhat lower mean age than those in the medical therapy group (59 vs. 62 years, P = .0002), and were slightly less likely to be African American (0.3% vs. 1.6%, P = .03) or Hispanic (0.7% vs. 2.6%, P = .03). In the fundoplication group, the length of BE was greater (5.0 cm vs. 4.1 cm, P less than .0001), and the prevalence of nondysplastic BE was higher (53% vs. 49%, P = .05).

In addition, fewer patients in the fundoplication group were taking twice-daily PPIs compared with those in the medical therapy group (82% vs. 95%, P less than .001). There were no significant between-group differences in the rates of bleeding, hospitalization, or stricture.

Among patients in the efficacy cohort, 136 had a prior fundoplication and 2,330 had received medical therapy only. The fundoplication patients were slightly younger than the medical therapy patients (59 vs. 62 years, P = .004), had a somewhat greater length of BE (5.0 cm vs. 4.3 cm, P = .009), and were less likely to be taking twice-daily PPIs (75% vs. 93%, P less than .001).

Rates of complete eradication of intestinal metaplasia were 71% in the fundoplication group vs. 73% in the medical therapy group, a nonsignificant difference, while the rate of complete eradication of dysplasia was identical in both groups at 87%.

Among patients who had nondysplastic BE, 75% in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 81% in the medical therapy group, a nonsignificant difference.

Regarding combined efficacy for dysplastic BE and intramucosal carcinoma, 67% of patients in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 66% in the medical therapy group, and both groups had a rate of 87% for complete eradication of dysplasia; none of these differences were significant.

Dr. Shaheen acknowledged certain limitations of the study, including the fact that the functional status of the fundoplications was not known. "All we know is that some patients had them," he said. "These are observational data and subject to selection bias. Also note that this is hardly a pure comparison, because the people who got fundoplication were also getting PPIs. However, one might expect that to bias the study in favor of fundoplication, to the degree that the addition of PPIs helps."

The study was funded by Covidien, which provided the RFA equipment used in the study, and by grants from the National Institutes of Health. Dr. Shaheen disclosed that he has consulting relationships with numerous pharmaceutical and medical device companies, but none with Covidien.

SAN DIEGO – Radiofrequency ablation was found to be safe and effective in treating Barrett’s esophagus patients, whether or not they had undergone a prior fundoplication, based on results from a multicenter registry study.

"Gastroesophageal reflux causes esophageal mucosal injury and inflammation that may impair healing and squamous re-epithelialization after treatment of Barrett’s esophagus [BE] with radiofrequency ablation [RFA]," Dr. Nicholas J. Shaheen said at the annual Digestive Disease Week.

Photo courtesy Dr. Nicholas J. Shaheen

"It is unclear if fundoplication surgery, as a mechanical barrier to all reflux, improves treatment outcomes of RFA for BE. Similarly, some have postulated that change in the conformation of the hiatus with surgery might make ablation problematic."

Dr. Shaheen, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and his associates conducted the largest study of its kind, he said. They evaluated records from the RFA Patient Registry to assess the relationship between prior fundoplication and both efficacy and safety outcomes in patients with BE who were treated with RFA.

The registry comprises 113 community-based and 35 academic-affiliated medical institutions in the United States. "About 75% of these institutions are private practices, so this is an interesting snapshot of RFA as it’s practiced outside of tertiary care centers," Dr. Shaheen said.

All study patients had BE confirmed by endoscopy and histology, and had undergone treatment with RFA. Enrollment commenced in July 2007 and ended in July 2011. Data were gleaned from standard case report forms and included demographics; relevant medical history; histologic grade prior to treatment; endoscopic findings; dates and total number of RFA treatment sessions; and ablation outcomes and complications.

"The vast amount of data is prospective, but less than 15% is retrospective," Dr. Shaheen said. "This is a registry study, so we could not mandate treatment, but a treatment protocol was suggested." Twice-daily use of proton pump inhibitors (PPIs) was recommended to everyone in the study, including those post fundoplication.

The mean age of patients was 61 years, and the majority were white. The mean pretreatment length of BE was about 4 cm, and patients received an average of 2.5 treatments with RFA. "Importantly, in this registry, about half of the patients had nondysplastic disease," Dr. Shaheen said. "Also, roughly 20% in each group had low- and high-grade dysplasia."

Dr. Shaheen reported results from the safety cohort, which included 5,537 patients who received RFA, and results from the efficacy cohort, which included 2,466 patients with biopsies performed 12 months after enrollment. Safety outcomes included perforation, stricture that required dilation, bleeding that required hospitalization or transfusion, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia and dysplasia.

Among patients in the safety cohort, 301 had a prior fundoplication, whereas 5,236 had received medical therapy only. Patients in the fundoplication group had a somewhat lower mean age than those in the medical therapy group (59 vs. 62 years, P = .0002), and were slightly less likely to be African American (0.3% vs. 1.6%, P = .03) or Hispanic (0.7% vs. 2.6%, P = .03). In the fundoplication group, the length of BE was greater (5.0 cm vs. 4.1 cm, P less than .0001), and the prevalence of nondysplastic BE was higher (53% vs. 49%, P = .05).

In addition, fewer patients in the fundoplication group were taking twice-daily PPIs compared with those in the medical therapy group (82% vs. 95%, P less than .001). There were no significant between-group differences in the rates of bleeding, hospitalization, or stricture.

Among patients in the efficacy cohort, 136 had a prior fundoplication and 2,330 had received medical therapy only. The fundoplication patients were slightly younger than the medical therapy patients (59 vs. 62 years, P = .004), had a somewhat greater length of BE (5.0 cm vs. 4.3 cm, P = .009), and were less likely to be taking twice-daily PPIs (75% vs. 93%, P less than .001).

Rates of complete eradication of intestinal metaplasia were 71% in the fundoplication group vs. 73% in the medical therapy group, a nonsignificant difference, while the rate of complete eradication of dysplasia was identical in both groups at 87%.

Among patients who had nondysplastic BE, 75% in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 81% in the medical therapy group, a nonsignificant difference.

Regarding combined efficacy for dysplastic BE and intramucosal carcinoma, 67% of patients in the fundoplication group achieved complete eradication of intestinal metaplasia, compared with 66% in the medical therapy group, and both groups had a rate of 87% for complete eradication of dysplasia; none of these differences were significant.

Dr. Shaheen acknowledged certain limitations of the study, including the fact that the functional status of the fundoplications was not known. "All we know is that some patients had them," he said. "These are observational data and subject to selection bias. Also note that this is hardly a pure comparison, because the people who got fundoplication were also getting PPIs. However, one might expect that to bias the study in favor of fundoplication, to the degree that the addition of PPIs helps."

The study was funded by Covidien, which provided the RFA equipment used in the study, and by grants from the National Institutes of Health. Dr. Shaheen disclosed that he has consulting relationships with numerous pharmaceutical and medical device companies, but none with Covidien.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.

The risk of major bleeding events in Italians taking low-dose aspirin was more than 50% higher than in those not on the regimen in a large population-based cohort study.

However, those with diabetes had showed no increase in bleeding risk.

"Weighing the benefits of aspirin therapy against the potential harms is of particular relevance in the primary prevention setting, in which benefits seem to be lower than expected based on results in high risk populations," concluded Giorgia De Berardis of the department of clinical pharmacology and epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy, and her associates. The study was published online on June 6 (JAMA 2012;307:2286-94).

Although low-dose aspirin was associated with an increased risk of major bleeding in people with hypertension and most other subgroups they identified, it was not independently associated with such a risk in people with diabetes, a finding that indicates that "diabetes might represent a different population in terms of both expected benefits and risks associated with antiplatelet therapy," they wrote.

In the study, the investigators used administrative data on people living in 12 local health authorities in Puglia, Italy, which is in the southeastern part of the country, linking data from hospital discharge records, prescription databases (including information on aspirin, which in Italy is prescribed for CV prevention), and the civil registry. They compared hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage among 186,425 users of low-dose aspirin (300 mg or less) during 2003-2008, to matched controls who had never used aspirin. A little over half were women; the mean age was about 69 years.

Over a median follow-up of almost 6 years, 5.58 hemorrhagic events/1,000 person-years occurred in persons on aspirin, compared with 3.60 events/1,000 person-years in those who had never used aspirin, for an increased risk of 55%. Among those on aspirin, the risk of GI bleeding was increased by 55% and the risk of intracranial bleed was increased by 54%, compared with those who had never used aspirin.

Among those on aspirin, the risk of bleeding was increased in most of the subgroups evaluated, and was "particularly high" among those younger than age 50 years(an incidence rate ratio of 1.93 – about a threefold greater risk when compared with people under 50 years who were not on aspirin). It was also increased in aspirin users who had not been treated for hypertension. They pointed out that this increased risk was seen in most of the subgroups they evaluated, except for patients with diabetes and those who had previously been admitted to the hospital for GI or CV problems, which they said could be "partially" attributed to the use of proton pump inhibitors (PPIs).

Those with diabetes who were not taking aspirin had a 59% increased risk for GI bleeding and a 64% increase risk for intracranial bleeding. But among those with diabetes who were on aspirin, the risk of bleeding was only slightly elevated. "Our study shows, for the first time, to our knowledge, that aspirin therapy only marginally increases the risk of bleeding in individuals with diabetes," the authors wrote, adding that these results "can represent indirect evidence that the efficacy of aspirin in suppressing platelet function is reduced in this population."

A notable finding, they said, was that the use of statins was associated with a significant reduction of gastrointestinal bleeding (35%) and intracranial bleeding (31%).

The authors said that the incidence of major bleeding events associated with aspirin identified in their study was "much higher" than reported in randomized prospective studies. The 55% increase in the relative risk of major bleeding, over no aspirin, "translates to 2 excess cases for 1,000 patients treated per year," they said. "In other words, the excess number of major bleeding events associated with the use of aspirin is of the same magnitude of the number of major cardiovascular events avoided in the primary prevention setting for individuals with a 10-year risk of between 10% and 20%."

Limitations of their study include the not being able to adjust for all potential factors that can affect bleeding, including over-the-counter aspirin use, although in Italy, low-dose aspirin for CV prevention in high-risk individuals is available by prescription and is fully covered.

Four of the seven authors, including the lead author, reported no disclosures. One author reported receiving a research grant from Bristol-Myers Squibb, another reported receiving a research grant from Bayer, and another reported receiving a research grant and lecture fees, including service on speakers bureaus from Bayer.