Naseem S. Miller

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – In patients with secondary-progressive multiple sclerosis, rituximab could potentially stabilize or reverse the rate of disease progression, according to a small, retrospective, single-center study.

Given the findings, rituximab, a B-cell depletion therapy, is a reasonable option for patients with secondary-progressive multiple sclerosis (SPMS) who no longer respond to primary and secondary lines of treatment, said Christopher M. Perrone, a fourth-year medical student at the University of Massachusetts, Worcester.

Mr. Perrone presented his poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Patients with SPMS have few treatment options. The only FDA-approved therapy for SPMS is mitoxantrone, which, because of severe side effects, is used only after patients stop responding to first and second-line treatments.

Phase I and II studies have shown rituximab’s safety in relapsing-remitting MS. The National Institute of Neurological Disorders and Stroke is recruiting patients for a double-blind, placebo-controlled, single center, phase I/II study on the safety and efficacy of combined systemic and intrathecal rituximab in patients with SPMS.

Mr. Perrone’s review of 25 patients at the University of Massachusetts Multiple Sclerosis Center showed that the disability score for patients with SPMS treated with rituximab for 2 years either stabilized or improved in 84% of the patients.

Four patients (16%) did not respond to rituximab and their disease continued to progress.

Mr. Perrone and his colleagues evaluated the Expanded Disability Status Scale (EDSS), 25-foot walk, and nine-hole peg test scores for 30 patients who were on rituximab therapy for 2 years.

Inclusion criteria were diagnosis of SPMS, at least two cycles of rituximab therapy (each treatment cycle included 1g rituximab IV, 2 weeks apart), and records of the three primary outcomes analyzed in the study.

There were 13 men and 17 women, mean age 56 years, with an average disease duration of 12 years. Five patients were later excluded.

Researchers obtained patient scores 2 years before rituximab therapy to establish rate of progression, and they obtained scores 1 year before treatment to establish baseline. The study had no control groups.

Results showed that 2 years before rituximab therapy, there were statistically significant increases in EDSS scores (0.5 points per year; P = .02), Mr. Perrone and his colleagues reported. However, after the therapy began, there were no significant differences, when compared with baseline values in the majority of the patients (less than 0.1-point increase between first and second treatment cycle, and 0.05-point increase between second and third treatment cycle), "suggesting that patients were at least stabilized on therapy," the authors reported. The treatment cycles were 6 months apart.

Authors then stratified the patients based on EDSS scores. At 2 years, 12 patients (48%) were stable and showed no change in EDSS score, 9 patients (36%) showed significant improvement in EDSS scores, and, in 4 patients (16%), the disease continued to progress.

The researchers noted that it was interesting to find that patients with higher initial EDSS scores were more likely to stabilize after treatment, while patients with lower initial EDSS scores were more likely to exhibit a significant change in EDSS.

There were no changes in MRI activity throughout the course of treatment, except for a nonenhancing lesion in one patient. The reported adverse events, including UTI, rash, fatigue, headache, and serum sickness disease, were not severe.

Mr. Perrone said that given the limited options available, rituximab should be considered an option for patients who have failed primary and secondary therapy, and that the study’s findings were encouraging.

His study has not been published and he said that larger studies are needed to confirm the findings.

Mr. Perrone had no disclosures. The study was funded by a grant from the Foundation of the Consortium of Multiple Sclerosis Centers’ MS Workforce of the Future program.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

[email protected]

On Twitter @NaseemSMiller

There has been much progress in multiple sclerosis research in the past decade. Researchers are now armed with more evidence that halting inflammation in the early stages of the disease can protect patients decades down the road. Dr. Stephen L. Hauser, chair of the department of neurology at the University of California, San Francisco, talks about the current state of MS research, the challenges, and the opportunities for progress.

There has been much progress in multiple sclerosis research in the past decade. Researchers are now armed with more evidence that halting inflammation in the early stages of the disease can protect patients decades down the road. Dr. Stephen L. Hauser, chair of the department of neurology at the University of California, San Francisco, talks about the current state of MS research, the challenges, and the opportunities for progress.

There has been much progress in multiple sclerosis research in the past decade. Researchers are now armed with more evidence that halting inflammation in the early stages of the disease can protect patients decades down the road. Dr. Stephen L. Hauser, chair of the department of neurology at the University of California, San Francisco, talks about the current state of MS research, the challenges, and the opportunities for progress.

ORLANDO – The investigational drug plecanatide appears to be safe and effective for patients with chronic idiopathic constipation, according to a 12-week randomized, double-blind, placebo-controlled trial.

Patients who received 3.0 mg of plecanatide daily had a statistically significant improvement in the number of complete spontaneous bowel movements (CSBMs), compared with the placebo group, reported Dr. Philip B. Miner, who is a consultant and researcher for the drug’s developer, Synergy Pharmaceuticals. He presented the abstract at the annual Digestive Disease Week.

Patients receiving 0.3 mg or 1.0 mg of plecanatide daily also achieved statistical significance in some of the other primary and secondary endpoints of the study, said Dr. Miner, president and medical director of the Oklahoma Foundation for Digestive Research. The reported diarrhea rate was roughly 10% at the highest dose.

But from the results so far, "I can’t tell if it’s any different compared to what we have available now," said Dr. Lauren B. Gerson, an assistant professor at Stanford (Calif.) University, who was not involved in the study. "It looks like it’ll probably be as efficacious, but you have to do a head-to-head trial to see if it’s any better. So it’s another drug we can use, but I’m not sure if it has additional benefits."

Plecanatide belongs to a new class of essentially nonsystemic oral drugs, guanylate cyclase C (GC-C) receptor agonists. The investigational drug mimics the natriuretic peptide uroguanylin, and induces intestinal fluid secretion into the lumen of the gastrointestinal tract.

Phase I and IIa trials have suggested that the drug will be useful in treating chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), said Dr. Miner (Dig. Dis. Sci. 2013 April 27). The phase II trial, completed in December 2012, aimed to evaluate the safety, effectiveness, and dose-response profile of plecanatide in CIC patients.

The primary efficacy endpoint was the number of CSBMs per week. A weekly responder had more than three CSBMs per week and an increase of more than one CSBM from baseline.

Secondary endpoints included time to first spontaneous bowel movement (SBM) or CSBM; stool consistency, straining, and severity of constipation; Patient Assessment of Constipation Symptoms (PAC-SYM); and quality of life.

The 12-week study enrolled 951 patients with CIC, 946 of whom received the drug or placebo. The patients were randomized to four arms: 0.3 mg of plecanatide (237 patients), 1.0 mg (238), 3.0 mg (237), and placebo (234). The patients had fewer than three CSBMs per week, according to the modified Rome III CIC criteria. Patients were excluded if they had a Rome III IBS-C diagnosis; a previous major GI surgical history; or recognized causes of constipation, such as opioid use or hypothyroidism.

The majority of the patients were white women (85%), the mean patient age was 47 years, and the mean BMI was 27 kg/m².

The trial included a 5-week screening, a 2-week run-in, 12 weeks of treatment, and 2 weeks of post-treatment evaluation.

Of the 951 enrollees, 738 patients (77.3%) completed the treatment. The main reasons for withdrawal included adverse events (46 patients), administrative issues (95), and lack of efficacy (51), Dr. Miner reported.

Results showed that there were significantly more responders in the plecanatide groups in at least 9 of 12 weeks of the study. The greatest response was observed among patients on 3.0 mg of plecanatide (21.5%), compared with placebo (11.5%; P = .003). In the other two arms, 17.2% of the patients on 1.0 mg of plecanatide (P greater than .05), and 19% on 0.3 mg of plecanatide (P less than .05) were responders.

The durable responder rate – defined as responders in at least 9 of 12 weeks and in at least 3 of the last 4 weeks of treatment – was 19% for 3.0 mg of plecanatide, compared with 10.7% for placebo (P = .009).

The weekly responder rates for 3.0 mg of plecanatide were significantly superior to placebo from week 1 through 12, the results showed. More than half of patients had one or more CSBM weekly compared with baseline, over 12 weeks (52.3% of 3.0 mg vs. 36.8% of placebo, P less than .001).

Patients on 3.0 mg of plecanatide also achieved their first CSBM in nearly half the time of patients in the placebo group (54.7 hours vs. 124.5 hours for placebo, P less than .001). They also achieved their first SBM sooner (12.5 hours vs. 27.3 hours, P less than .001).

The median time to first SBM was 9.6 hours at 3.0 mg of plecanatide, compared with 25.1 hours for placebo (P less than .001).

The 3.0-mg plecanatide arm also showed significant improvements in secondary endpoints, including stool consistency and straining, compared with placebo (P less than .001). In addition, that arm had significant improvements in constipation-associated symptoms and quality of life relative to baseline (P less than .001), the results showed.

The cumulative days that rescue medication was used per month also significantly decreased among patients on 3.0 mg of plecanatide, compared with placebo (P less than .001).

Patients on 3.0 mg of plecanatide had the highest percentage of treatment-emergent adverse events (106 patients or 44.7%), compared with 1.0 mg of plecanatide (103 patients or 43.3%), 0.3 mg (99 or 31.8%), and placebo (96 or 40.7%).

The most common adverse event on the drug was diarrhea (9.7% on 3.0 mg of plecanatide vs. 1.3% on placebo). Seven patients (3%) on 3.0 mg of plecanatide withdrew due to diarrhea, compared with eight patients (3.4%) on 1.0 mg of plecanatide, two patients (0.8%) on 0.3 mg, and 1 patient (0.4%) in the placebo group.

Other adverse events included flatulence, abdominal pain, abdominal distention, nausea, nasopharyngitis, urinary tract infection, and headache. Serious adverse events, which were considered unrelated to the treatment, included noncardiac chest pain (1 patient on 0.3 mg of plecanatide), endometriosis (1 patient on 1.0 mg), and acute cholecystitis and hypoaesthesia with weakness (2 patients on 3.0 mg). Five patients in the placebo group experienced hypertension exacerbation, gastroenteritis, spontaneous abortion, atypical chest pain, and asthma exacerbation. Dr. Miner said he could not share the bloating data at the time of his presentation.

Dr. Gerson said that the ideal drug would "relieve constipation and other symptoms, but doesn’t have a lot of side effects. It’ll be nice to have a drug that is better tolerated than what’s available out there."

Synergy is preparing a clinical study report for submission to the Food and Drug Administration. It is presenting additional data in upcoming scientific meetings in 2013, according to a company news release.

The FDA approved linaclotide (Linzess) in August 2012 for treatment of CIC and IBS-C. Linaclotide, also a guanylate cyclase C agonist, is comarketed by Ironwood Pharmaceuticals and Forest Pharmaceuticals.

Dr. Miner is a consultant and has done research for Ventrus Biosciences and Synergy Pharmaceuticals. Dr. Gerson had no disclosures.

[email protected]

On Twitter @naseemsmiller

ORLANDO – The investigational drug plecanatide appears to be safe and effective for patients with chronic idiopathic constipation, according to a 12-week randomized, double-blind, placebo-controlled trial.

Patients who received 3.0 mg of plecanatide daily had a statistically significant improvement in the number of complete spontaneous bowel movements (CSBMs), compared with the placebo group, reported Dr. Philip B. Miner, who is a consultant and researcher for the drug’s developer, Synergy Pharmaceuticals. He presented the abstract at the annual Digestive Disease Week.

Patients receiving 0.3 mg or 1.0 mg of plecanatide daily also achieved statistical significance in some of the other primary and secondary endpoints of the study, said Dr. Miner, president and medical director of the Oklahoma Foundation for Digestive Research. The reported diarrhea rate was roughly 10% at the highest dose.

But from the results so far, "I can’t tell if it’s any different compared to what we have available now," said Dr. Lauren B. Gerson, an assistant professor at Stanford (Calif.) University, who was not involved in the study. "It looks like it’ll probably be as efficacious, but you have to do a head-to-head trial to see if it’s any better. So it’s another drug we can use, but I’m not sure if it has additional benefits."

Plecanatide belongs to a new class of essentially nonsystemic oral drugs, guanylate cyclase C (GC-C) receptor agonists. The investigational drug mimics the natriuretic peptide uroguanylin, and induces intestinal fluid secretion into the lumen of the gastrointestinal tract.

Phase I and IIa trials have suggested that the drug will be useful in treating chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), said Dr. Miner (Dig. Dis. Sci. 2013 April 27). The phase II trial, completed in December 2012, aimed to evaluate the safety, effectiveness, and dose-response profile of plecanatide in CIC patients.

The primary efficacy endpoint was the number of CSBMs per week. A weekly responder had more than three CSBMs per week and an increase of more than one CSBM from baseline.

Secondary endpoints included time to first spontaneous bowel movement (SBM) or CSBM; stool consistency, straining, and severity of constipation; Patient Assessment of Constipation Symptoms (PAC-SYM); and quality of life.

The 12-week study enrolled 951 patients with CIC, 946 of whom received the drug or placebo. The patients were randomized to four arms: 0.3 mg of plecanatide (237 patients), 1.0 mg (238), 3.0 mg (237), and placebo (234). The patients had fewer than three CSBMs per week, according to the modified Rome III CIC criteria. Patients were excluded if they had a Rome III IBS-C diagnosis; a previous major GI surgical history; or recognized causes of constipation, such as opioid use or hypothyroidism.

The majority of the patients were white women (85%), the mean patient age was 47 years, and the mean BMI was 27 kg/m².

The trial included a 5-week screening, a 2-week run-in, 12 weeks of treatment, and 2 weeks of post-treatment evaluation.

Of the 951 enrollees, 738 patients (77.3%) completed the treatment. The main reasons for withdrawal included adverse events (46 patients), administrative issues (95), and lack of efficacy (51), Dr. Miner reported.

Results showed that there were significantly more responders in the plecanatide groups in at least 9 of 12 weeks of the study. The greatest response was observed among patients on 3.0 mg of plecanatide (21.5%), compared with placebo (11.5%; P = .003). In the other two arms, 17.2% of the patients on 1.0 mg of plecanatide (P greater than .05), and 19% on 0.3 mg of plecanatide (P less than .05) were responders.

The durable responder rate – defined as responders in at least 9 of 12 weeks and in at least 3 of the last 4 weeks of treatment – was 19% for 3.0 mg of plecanatide, compared with 10.7% for placebo (P = .009).

The weekly responder rates for 3.0 mg of plecanatide were significantly superior to placebo from week 1 through 12, the results showed. More than half of patients had one or more CSBM weekly compared with baseline, over 12 weeks (52.3% of 3.0 mg vs. 36.8% of placebo, P less than .001).

Patients on 3.0 mg of plecanatide also achieved their first CSBM in nearly half the time of patients in the placebo group (54.7 hours vs. 124.5 hours for placebo, P less than .001). They also achieved their first SBM sooner (12.5 hours vs. 27.3 hours, P less than .001).

The median time to first SBM was 9.6 hours at 3.0 mg of plecanatide, compared with 25.1 hours for placebo (P less than .001).

The 3.0-mg plecanatide arm also showed significant improvements in secondary endpoints, including stool consistency and straining, compared with placebo (P less than .001). In addition, that arm had significant improvements in constipation-associated symptoms and quality of life relative to baseline (P less than .001), the results showed.

The cumulative days that rescue medication was used per month also significantly decreased among patients on 3.0 mg of plecanatide, compared with placebo (P less than .001).

Patients on 3.0 mg of plecanatide had the highest percentage of treatment-emergent adverse events (106 patients or 44.7%), compared with 1.0 mg of plecanatide (103 patients or 43.3%), 0.3 mg (99 or 31.8%), and placebo (96 or 40.7%).

The most common adverse event on the drug was diarrhea (9.7% on 3.0 mg of plecanatide vs. 1.3% on placebo). Seven patients (3%) on 3.0 mg of plecanatide withdrew due to diarrhea, compared with eight patients (3.4%) on 1.0 mg of plecanatide, two patients (0.8%) on 0.3 mg, and 1 patient (0.4%) in the placebo group.

Other adverse events included flatulence, abdominal pain, abdominal distention, nausea, nasopharyngitis, urinary tract infection, and headache. Serious adverse events, which were considered unrelated to the treatment, included noncardiac chest pain (1 patient on 0.3 mg of plecanatide), endometriosis (1 patient on 1.0 mg), and acute cholecystitis and hypoaesthesia with weakness (2 patients on 3.0 mg). Five patients in the placebo group experienced hypertension exacerbation, gastroenteritis, spontaneous abortion, atypical chest pain, and asthma exacerbation. Dr. Miner said he could not share the bloating data at the time of his presentation.

Dr. Gerson said that the ideal drug would "relieve constipation and other symptoms, but doesn’t have a lot of side effects. It’ll be nice to have a drug that is better tolerated than what’s available out there."

Synergy is preparing a clinical study report for submission to the Food and Drug Administration. It is presenting additional data in upcoming scientific meetings in 2013, according to a company news release.

The FDA approved linaclotide (Linzess) in August 2012 for treatment of CIC and IBS-C. Linaclotide, also a guanylate cyclase C agonist, is comarketed by Ironwood Pharmaceuticals and Forest Pharmaceuticals.

Dr. Miner is a consultant and has done research for Ventrus Biosciences and Synergy Pharmaceuticals. Dr. Gerson had no disclosures.

[email protected]

On Twitter @naseemsmiller

ORLANDO – The investigational drug plecanatide appears to be safe and effective for patients with chronic idiopathic constipation, according to a 12-week randomized, double-blind, placebo-controlled trial.

Patients who received 3.0 mg of plecanatide daily had a statistically significant improvement in the number of complete spontaneous bowel movements (CSBMs), compared with the placebo group, reported Dr. Philip B. Miner, who is a consultant and researcher for the drug’s developer, Synergy Pharmaceuticals. He presented the abstract at the annual Digestive Disease Week.

Patients receiving 0.3 mg or 1.0 mg of plecanatide daily also achieved statistical significance in some of the other primary and secondary endpoints of the study, said Dr. Miner, president and medical director of the Oklahoma Foundation for Digestive Research. The reported diarrhea rate was roughly 10% at the highest dose.

But from the results so far, "I can’t tell if it’s any different compared to what we have available now," said Dr. Lauren B. Gerson, an assistant professor at Stanford (Calif.) University, who was not involved in the study. "It looks like it’ll probably be as efficacious, but you have to do a head-to-head trial to see if it’s any better. So it’s another drug we can use, but I’m not sure if it has additional benefits."

Plecanatide belongs to a new class of essentially nonsystemic oral drugs, guanylate cyclase C (GC-C) receptor agonists. The investigational drug mimics the natriuretic peptide uroguanylin, and induces intestinal fluid secretion into the lumen of the gastrointestinal tract.

Phase I and IIa trials have suggested that the drug will be useful in treating chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), said Dr. Miner (Dig. Dis. Sci. 2013 April 27). The phase II trial, completed in December 2012, aimed to evaluate the safety, effectiveness, and dose-response profile of plecanatide in CIC patients.

The primary efficacy endpoint was the number of CSBMs per week. A weekly responder had more than three CSBMs per week and an increase of more than one CSBM from baseline.

Secondary endpoints included time to first spontaneous bowel movement (SBM) or CSBM; stool consistency, straining, and severity of constipation; Patient Assessment of Constipation Symptoms (PAC-SYM); and quality of life.

The 12-week study enrolled 951 patients with CIC, 946 of whom received the drug or placebo. The patients were randomized to four arms: 0.3 mg of plecanatide (237 patients), 1.0 mg (238), 3.0 mg (237), and placebo (234). The patients had fewer than three CSBMs per week, according to the modified Rome III CIC criteria. Patients were excluded if they had a Rome III IBS-C diagnosis; a previous major GI surgical history; or recognized causes of constipation, such as opioid use or hypothyroidism.

The majority of the patients were white women (85%), the mean patient age was 47 years, and the mean BMI was 27 kg/m².

The trial included a 5-week screening, a 2-week run-in, 12 weeks of treatment, and 2 weeks of post-treatment evaluation.

Of the 951 enrollees, 738 patients (77.3%) completed the treatment. The main reasons for withdrawal included adverse events (46 patients), administrative issues (95), and lack of efficacy (51), Dr. Miner reported.

Results showed that there were significantly more responders in the plecanatide groups in at least 9 of 12 weeks of the study. The greatest response was observed among patients on 3.0 mg of plecanatide (21.5%), compared with placebo (11.5%; P = .003). In the other two arms, 17.2% of the patients on 1.0 mg of plecanatide (P greater than .05), and 19% on 0.3 mg of plecanatide (P less than .05) were responders.

The durable responder rate – defined as responders in at least 9 of 12 weeks and in at least 3 of the last 4 weeks of treatment – was 19% for 3.0 mg of plecanatide, compared with 10.7% for placebo (P = .009).

The weekly responder rates for 3.0 mg of plecanatide were significantly superior to placebo from week 1 through 12, the results showed. More than half of patients had one or more CSBM weekly compared with baseline, over 12 weeks (52.3% of 3.0 mg vs. 36.8% of placebo, P less than .001).

Patients on 3.0 mg of plecanatide also achieved their first CSBM in nearly half the time of patients in the placebo group (54.7 hours vs. 124.5 hours for placebo, P less than .001). They also achieved their first SBM sooner (12.5 hours vs. 27.3 hours, P less than .001).

The median time to first SBM was 9.6 hours at 3.0 mg of plecanatide, compared with 25.1 hours for placebo (P less than .001).

The 3.0-mg plecanatide arm also showed significant improvements in secondary endpoints, including stool consistency and straining, compared with placebo (P less than .001). In addition, that arm had significant improvements in constipation-associated symptoms and quality of life relative to baseline (P less than .001), the results showed.

The cumulative days that rescue medication was used per month also significantly decreased among patients on 3.0 mg of plecanatide, compared with placebo (P less than .001).

Patients on 3.0 mg of plecanatide had the highest percentage of treatment-emergent adverse events (106 patients or 44.7%), compared with 1.0 mg of plecanatide (103 patients or 43.3%), 0.3 mg (99 or 31.8%), and placebo (96 or 40.7%).

The most common adverse event on the drug was diarrhea (9.7% on 3.0 mg of plecanatide vs. 1.3% on placebo). Seven patients (3%) on 3.0 mg of plecanatide withdrew due to diarrhea, compared with eight patients (3.4%) on 1.0 mg of plecanatide, two patients (0.8%) on 0.3 mg, and 1 patient (0.4%) in the placebo group.

Other adverse events included flatulence, abdominal pain, abdominal distention, nausea, nasopharyngitis, urinary tract infection, and headache. Serious adverse events, which were considered unrelated to the treatment, included noncardiac chest pain (1 patient on 0.3 mg of plecanatide), endometriosis (1 patient on 1.0 mg), and acute cholecystitis and hypoaesthesia with weakness (2 patients on 3.0 mg). Five patients in the placebo group experienced hypertension exacerbation, gastroenteritis, spontaneous abortion, atypical chest pain, and asthma exacerbation. Dr. Miner said he could not share the bloating data at the time of his presentation.

Dr. Gerson said that the ideal drug would "relieve constipation and other symptoms, but doesn’t have a lot of side effects. It’ll be nice to have a drug that is better tolerated than what’s available out there."

Synergy is preparing a clinical study report for submission to the Food and Drug Administration. It is presenting additional data in upcoming scientific meetings in 2013, according to a company news release.

The FDA approved linaclotide (Linzess) in August 2012 for treatment of CIC and IBS-C. Linaclotide, also a guanylate cyclase C agonist, is comarketed by Ironwood Pharmaceuticals and Forest Pharmaceuticals.

Dr. Miner is a consultant and has done research for Ventrus Biosciences and Synergy Pharmaceuticals. Dr. Gerson had no disclosures.

[email protected]

On Twitter @naseemsmiller

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – When neurologists select or switch medications for multiple sclerosis, they are most concerned with the drugs’ efficacy and patients’ relapse frequency, according to an online survey.

The survey, which included 63 neurologists and 39 multiple sclerosis specialists, also showed that the most commonly prescribed disease-modifying therapies were glatiramer acetate and subcutaneous and intramuscular interferon beta-1a.

The results of such a survey among physicians are "what you might expect," said Dr. Robert P. Lisak, professor of neurology at Wayne State University, Detroit, and president-elect of the Consortium of Multiple Sclerosis Centers (CMSC).

"I think you’ll see a lot of patients on those [drugs] in my own experience, because a lot of patients do very well on them, although there could be injection fatigue. But a lot of patients and physicians work on, ‘If it ain’t broke, don’t fix it.’ I think you’re going to see that people either get resistant, or finally get tired of the injection, and you’ll probably see an increasing shift towards the oral agents," he said. Meanwhile, insurance coverage and side effects are two issues to take into account, added Dr. Lisak, who was not involved with the survey.

So far, "little is known about how neurologists select available disease-modifying therapies (DMTs) for their patients," said Kristin A. Hanson, Pharm.D., of United BioSource, Dorval, Que., who presented her poster at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Hanson and colleagues sent out the online survey to members of a physician market research panel between December 2012 and January 2013.

All physicians, 81% of whom were male, lived in the United States and were treating at least 20 MS patients.

Respondents said that the most important medication attributes for patients starting their first DMT, in order, were efficacy, safety, tolerability, patient preference, and convenience.

Nearly 95% of the respondents said that they would switch medications if they observed an increase in relapse frequency. Other factors influencing the change in medication were worsening of MRI (75% of respondents) and worsening of disability (73%).

On average, 5.5% of the physicians’ patients were not on therapy for their condition, with individual physician reports ranging from 0% to 23% of patients not being on any therapy.

The study was supported by Novartis Pharmaceuticals. Dr. Hanson had no disclosures. Some of her coauthors are employees of Novartis, or have been speakers or advisors for Acorda, Avanir, Bayer, Genzyme/Sanofi, Novartis, Questcor, and Teva. Dr. Lisak has received research grants from and has been an advisor for several companies, including Avanir, Bayer, Novartis, Questcor, and Teva.

[email protected]

On Twitter @NaseemSMiller

FORT LAUDERDALE, FLA. – Analysis of data from more than 13,000 patients at a large pain management practice shows that a self-reported history of sexual abuse and issues with anger, impairment of life control, marital status, and level of education are among predictors of patients’ tendency to misuse opioids. 

The physician group, led by Dr. Mark Gostine, is planning to use the findings to help refine the specificity and sensitivity of an existing opioid risk assessment tool called the Opioid Risk Tool (ORT).

"What we’re trying to do is to take ORT 1.0 and create ORT 2.0," said Dr. Gostine, president of Michigan Pain Consultants in Grand Rapids. 

The ORT was developed by Dr. Lynn Webster with the aim of identifying patients at risk of misusing opioids (Pain Med. 2005;6:432-42). The questionnaireseeks personal and family history of substance abuse, history of preadolescent sexual abuse, and a history of certain psychological disorders.

"The Gostine study is a significant contribution because of the number of subjects in the analysis," said Dr. Webster, who was not involved in the study. "I’m not aware of any opioid risk tool that has been evaluated in such a large population. It supports the risk factors that are identified in the Opioid Risk Tool but also suggests that the ORT could be improved with some modification."

The abuse of prescription drugs and overdoses stemming from their use became one of the top public health concerns starting in the 1990s. Their abuse continues to be the fastest-growing drug problem in the United States (MMWR 2012;61:10-13). The increase in unintentional overdoses has been mostly driven by opioids in recent years, according to the Centers for Disease Control and Prevention. 

Physicians at Michigan Pain Consultants have been using the five-question ORT as part of their 120-question Pain Health Assessment that they give to chronic pain patients on an iPad prior to seeing the doctor. The form assesses disease presence, pain characteristics, physical function, and psychosocial function.

"Anybody with a high ORT score had a problem with narcotics," said Dr. Gostine in an interview. "However, two-thirds of the patients who misused narcotics had low ORT scores. So we wanted to find out what other elements in our database indicated that these patients are problematic, and can we use that to predict which patients will misuse medications."

They conducted an analysis of observed behaviors associated with narcotic misuse and/or patients on high-dose narcotics. 

Dr. Gostine and his colleagues identified "miscreants" (256 patients) as patients who were flagged by the Michigan Automated Pharmacy Surveillance Program, had abnormal urine drug screens, had problems managing opiate prescriptions, and/or had poor behavior with clinic staff regarding opiate prescriptions. They also identified an additional 704 patients who consumed a high dose of narcotics, defined as greater than 100 mg of oral morphine equivalents per day. The investigators then compared the data on these two groups with the rest of their patient population (n = 13,026).

The investigators found a higher ORT score significantly more often among people with miscreant behavior (11%) than among those with high-dose opioid use (5%) or controls (4%). Low ORT scores occurred in 66% of individuals with miscreant behavior, compared with 73% of people in the high-dose group and 82% of the control group, Dr. Gostine said at the annual meeting of the American Academy of Pain Medicine.

The results also showed a correlation between the distress index – which uses a Likert-type numerical scale to score responses to questions relating to anger, depression/anxiety, and life control – and those identified as miscreants and those who consumed high doses of narcotics.

In addition, a history of sexual abuse was associated with being a miscreant (14%) and high-dose consumer (12%), compared with the control group (8%).

"Two other factors emerged: Marital status seems to be predictive, and patients with a higher level of education seem to be less likely to misuse," said Dr. Gostine. "Never married increases the risk of being a miscreant by 100% versus currently married. With our large numbers of miscreants and controls, this is highly significant, but these are early, provisional numbers."

He added that the rate of miscreant behavior among high school graduates is 50% higher than that of 4-year college graduates. "This is also significant, but these are provisional numbers," he said. "We have also confirmed the link with smoking and prescription drug misuse. Smoking almost doubles the risk of opioid misuse, again a provisional number, which we will look at in more detail with the larger numbers [1,800] we have now accrued."

Dr. Gostine said that he is planning to publish the findings. After refinement of the ORT, which is currently in the public domain and available to physicians, the tool might expand to 15 questions – a short-enough questionnaire that patients can fill out in 2 or 3 minutes. If the questionnaires are fed into electronic medical records, as they are in Dr. Gostine’s practice, "the doctor can find out whether [the patient] is someone they should be nervous about or someone they can trust" when it comes to prescribing opioids. 

Dr. Gostine and his partner, Dr. Fred Davis, developed the Prism Pain Health Assessment that was used to capture and analyze the data. The product is now commercially available. Dr. Webster has received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, and other companies.

[email protected]

On Twitter @naseemsmiller

FORT LAUDERDALE, FLA. – Analysis of data from more than 13,000 patients at a large pain management practice shows that a self-reported history of sexual abuse and issues with anger, impairment of life control, marital status, and level of education are among predictors of patients’ tendency to misuse opioids. 

The physician group, led by Dr. Mark Gostine, is planning to use the findings to help refine the specificity and sensitivity of an existing opioid risk assessment tool called the Opioid Risk Tool (ORT).

"What we’re trying to do is to take ORT 1.0 and create ORT 2.0," said Dr. Gostine, president of Michigan Pain Consultants in Grand Rapids. 

The ORT was developed by Dr. Lynn Webster with the aim of identifying patients at risk of misusing opioids (Pain Med. 2005;6:432-42). The questionnaireseeks personal and family history of substance abuse, history of preadolescent sexual abuse, and a history of certain psychological disorders.

"The Gostine study is a significant contribution because of the number of subjects in the analysis," said Dr. Webster, who was not involved in the study. "I’m not aware of any opioid risk tool that has been evaluated in such a large population. It supports the risk factors that are identified in the Opioid Risk Tool but also suggests that the ORT could be improved with some modification."

The abuse of prescription drugs and overdoses stemming from their use became one of the top public health concerns starting in the 1990s. Their abuse continues to be the fastest-growing drug problem in the United States (MMWR 2012;61:10-13). The increase in unintentional overdoses has been mostly driven by opioids in recent years, according to the Centers for Disease Control and Prevention. 

Physicians at Michigan Pain Consultants have been using the five-question ORT as part of their 120-question Pain Health Assessment that they give to chronic pain patients on an iPad prior to seeing the doctor. The form assesses disease presence, pain characteristics, physical function, and psychosocial function.

"Anybody with a high ORT score had a problem with narcotics," said Dr. Gostine in an interview. "However, two-thirds of the patients who misused narcotics had low ORT scores. So we wanted to find out what other elements in our database indicated that these patients are problematic, and can we use that to predict which patients will misuse medications."

They conducted an analysis of observed behaviors associated with narcotic misuse and/or patients on high-dose narcotics. 

Dr. Gostine and his colleagues identified "miscreants" (256 patients) as patients who were flagged by the Michigan Automated Pharmacy Surveillance Program, had abnormal urine drug screens, had problems managing opiate prescriptions, and/or had poor behavior with clinic staff regarding opiate prescriptions. They also identified an additional 704 patients who consumed a high dose of narcotics, defined as greater than 100 mg of oral morphine equivalents per day. The investigators then compared the data on these two groups with the rest of their patient population (n = 13,026).

The investigators found a higher ORT score significantly more often among people with miscreant behavior (11%) than among those with high-dose opioid use (5%) or controls (4%). Low ORT scores occurred in 66% of individuals with miscreant behavior, compared with 73% of people in the high-dose group and 82% of the control group, Dr. Gostine said at the annual meeting of the American Academy of Pain Medicine.

The results also showed a correlation between the distress index – which uses a Likert-type numerical scale to score responses to questions relating to anger, depression/anxiety, and life control – and those identified as miscreants and those who consumed high doses of narcotics.

In addition, a history of sexual abuse was associated with being a miscreant (14%) and high-dose consumer (12%), compared with the control group (8%).

"Two other factors emerged: Marital status seems to be predictive, and patients with a higher level of education seem to be less likely to misuse," said Dr. Gostine. "Never married increases the risk of being a miscreant by 100% versus currently married. With our large numbers of miscreants and controls, this is highly significant, but these are early, provisional numbers."

He added that the rate of miscreant behavior among high school graduates is 50% higher than that of 4-year college graduates. "This is also significant, but these are provisional numbers," he said. "We have also confirmed the link with smoking and prescription drug misuse. Smoking almost doubles the risk of opioid misuse, again a provisional number, which we will look at in more detail with the larger numbers [1,800] we have now accrued."

Dr. Gostine said that he is planning to publish the findings. After refinement of the ORT, which is currently in the public domain and available to physicians, the tool might expand to 15 questions – a short-enough questionnaire that patients can fill out in 2 or 3 minutes. If the questionnaires are fed into electronic medical records, as they are in Dr. Gostine’s practice, "the doctor can find out whether [the patient] is someone they should be nervous about or someone they can trust" when it comes to prescribing opioids. 

Dr. Gostine and his partner, Dr. Fred Davis, developed the Prism Pain Health Assessment that was used to capture and analyze the data. The product is now commercially available. Dr. Webster has received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, and other companies.

[email protected]

On Twitter @naseemsmiller

FORT LAUDERDALE, FLA. – Analysis of data from more than 13,000 patients at a large pain management practice shows that a self-reported history of sexual abuse and issues with anger, impairment of life control, marital status, and level of education are among predictors of patients’ tendency to misuse opioids. 

The physician group, led by Dr. Mark Gostine, is planning to use the findings to help refine the specificity and sensitivity of an existing opioid risk assessment tool called the Opioid Risk Tool (ORT).

"What we’re trying to do is to take ORT 1.0 and create ORT 2.0," said Dr. Gostine, president of Michigan Pain Consultants in Grand Rapids. 

The ORT was developed by Dr. Lynn Webster with the aim of identifying patients at risk of misusing opioids (Pain Med. 2005;6:432-42). The questionnaireseeks personal and family history of substance abuse, history of preadolescent sexual abuse, and a history of certain psychological disorders.

"The Gostine study is a significant contribution because of the number of subjects in the analysis," said Dr. Webster, who was not involved in the study. "I’m not aware of any opioid risk tool that has been evaluated in such a large population. It supports the risk factors that are identified in the Opioid Risk Tool but also suggests that the ORT could be improved with some modification."

The abuse of prescription drugs and overdoses stemming from their use became one of the top public health concerns starting in the 1990s. Their abuse continues to be the fastest-growing drug problem in the United States (MMWR 2012;61:10-13). The increase in unintentional overdoses has been mostly driven by opioids in recent years, according to the Centers for Disease Control and Prevention. 

Physicians at Michigan Pain Consultants have been using the five-question ORT as part of their 120-question Pain Health Assessment that they give to chronic pain patients on an iPad prior to seeing the doctor. The form assesses disease presence, pain characteristics, physical function, and psychosocial function.

"Anybody with a high ORT score had a problem with narcotics," said Dr. Gostine in an interview. "However, two-thirds of the patients who misused narcotics had low ORT scores. So we wanted to find out what other elements in our database indicated that these patients are problematic, and can we use that to predict which patients will misuse medications."

They conducted an analysis of observed behaviors associated with narcotic misuse and/or patients on high-dose narcotics. 

Dr. Gostine and his colleagues identified "miscreants" (256 patients) as patients who were flagged by the Michigan Automated Pharmacy Surveillance Program, had abnormal urine drug screens, had problems managing opiate prescriptions, and/or had poor behavior with clinic staff regarding opiate prescriptions. They also identified an additional 704 patients who consumed a high dose of narcotics, defined as greater than 100 mg of oral morphine equivalents per day. The investigators then compared the data on these two groups with the rest of their patient population (n = 13,026).

The investigators found a higher ORT score significantly more often among people with miscreant behavior (11%) than among those with high-dose opioid use (5%) or controls (4%). Low ORT scores occurred in 66% of individuals with miscreant behavior, compared with 73% of people in the high-dose group and 82% of the control group, Dr. Gostine said at the annual meeting of the American Academy of Pain Medicine.

The results also showed a correlation between the distress index – which uses a Likert-type numerical scale to score responses to questions relating to anger, depression/anxiety, and life control – and those identified as miscreants and those who consumed high doses of narcotics.

In addition, a history of sexual abuse was associated with being a miscreant (14%) and high-dose consumer (12%), compared with the control group (8%).

"Two other factors emerged: Marital status seems to be predictive, and patients with a higher level of education seem to be less likely to misuse," said Dr. Gostine. "Never married increases the risk of being a miscreant by 100% versus currently married. With our large numbers of miscreants and controls, this is highly significant, but these are early, provisional numbers."

He added that the rate of miscreant behavior among high school graduates is 50% higher than that of 4-year college graduates. "This is also significant, but these are provisional numbers," he said. "We have also confirmed the link with smoking and prescription drug misuse. Smoking almost doubles the risk of opioid misuse, again a provisional number, which we will look at in more detail with the larger numbers [1,800] we have now accrued."

Dr. Gostine said that he is planning to publish the findings. After refinement of the ORT, which is currently in the public domain and available to physicians, the tool might expand to 15 questions – a short-enough questionnaire that patients can fill out in 2 or 3 minutes. If the questionnaires are fed into electronic medical records, as they are in Dr. Gostine’s practice, "the doctor can find out whether [the patient] is someone they should be nervous about or someone they can trust" when it comes to prescribing opioids. 

Dr. Gostine and his partner, Dr. Fred Davis, developed the Prism Pain Health Assessment that was used to capture and analyze the data. The product is now commercially available. Dr. Webster has received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, and other companies.

[email protected]

On Twitter @naseemsmiller

ORLANDO – Metformin may be associated with a reduced risk of colorectal cancer in patients with type 2 diabetes, according to a meta-analysis that included mostly observational studies.

Sulfonylurea and insulin were not associated with a reduced risk and showed a nonsignificant trend toward a higher risk for colorectal cancer (CRC). No association was noted between CRC and thiazolidinedione (TZD), Dr. Siddharth Singh reported at the annual Digestive Disease Week.

CRC incidence was reduced by 10% among patients who were on metformin (n = 10 studies; adjusted odds ratio [AOR], 0.90; 95% confidence interval, 0.82-0.99; P = .02). The results were stable when the analysis was restricted to high-quality observational studies (n = 7 studies; AOR, 0.88; 95% CI, 0.79-0.98).

CRC risk was higher in patients on a sulfonylurea (n = 8 studies; AOR 1.12; 95% CI 0.99-1.26; P = .07) or on insulin (n = 10 studies; AOR, 1.25; 95% CI, 0.91-1.71; P = 0.17). Neither result was statistically significant, however.

Dr. Singh said that the findings warrant prospective cohort studies or randomized controlled trials of the chemopreventive effect of metformin in adults with type 2 diabetes.

Diabetes is an established risk factor for colorectal cancer, and preclinical and observational studies have shown that antidiabetes drugs may affect CRC risk. The relative affect of various antidiabetes drugs on CRC risk is unclear, said Dr. Singh of the Mayo Clinic in Rochester, Minn.

Dr. Singh and his colleagues conducted a systematic review and meta-analysis of 15 studies evaluating the effects of metformin, TZDs, sulfonylureas, and insulin on colorectal cancer risk. There was considerable heterogeneity across the studies, which may be explained by study design, location, and whether the study accounted for the effects of other antidiabetic drugs, Dr. Singh said.

Five case-control studies, eight cohort studies, and two randomized controlled trials with a total of nearly 14,000 CRC cases in 841,000 diabetes patients were included in the meta-analysis.

TZD was not associated with CRC risk (n = 6 studies; AOR, 0.95; 95% CI, 0.87-1.03; P = .24).

One of the main limitations of the unpublished study was that the significant results were seen only in observational studies and not in post-hoc analysis of the randomized controlled trials. Also, there are residual confounding factors, including failure to adjust for obesity, and confounding by indication and severity of diabetes, Dr. Singh said.

"Before we take part in any proactive treatment regimen, we have to have well-designed, randomized controlled trials," said Dr. N. Jewel Samadder, assistant professor of medicine at the University of Utah, Salt Lake City. "However, the observational studies, and the meta-analysis that [follow], are certainly hypothesis driving. Diabetes itself is a risk factor [for CRC], and some of the medications may alter that risk," said Dr. Samadder, who was not involved in the study.

Dr. Singh had no disclosures. Dr. Samadder has received speaking and teaching honoraria from Cook.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Metformin may be associated with a reduced risk of colorectal cancer in patients with type 2 diabetes, according to a meta-analysis that included mostly observational studies.

Sulfonylurea and insulin were not associated with a reduced risk and showed a nonsignificant trend toward a higher risk for colorectal cancer (CRC). No association was noted between CRC and thiazolidinedione (TZD), Dr. Siddharth Singh reported at the annual Digestive Disease Week.

CRC incidence was reduced by 10% among patients who were on metformin (n = 10 studies; adjusted odds ratio [AOR], 0.90; 95% confidence interval, 0.82-0.99; P = .02). The results were stable when the analysis was restricted to high-quality observational studies (n = 7 studies; AOR, 0.88; 95% CI, 0.79-0.98).

CRC risk was higher in patients on a sulfonylurea (n = 8 studies; AOR 1.12; 95% CI 0.99-1.26; P = .07) or on insulin (n = 10 studies; AOR, 1.25; 95% CI, 0.91-1.71; P = 0.17). Neither result was statistically significant, however.

Dr. Singh said that the findings warrant prospective cohort studies or randomized controlled trials of the chemopreventive effect of metformin in adults with type 2 diabetes.

Diabetes is an established risk factor for colorectal cancer, and preclinical and observational studies have shown that antidiabetes drugs may affect CRC risk. The relative affect of various antidiabetes drugs on CRC risk is unclear, said Dr. Singh of the Mayo Clinic in Rochester, Minn.

Dr. Singh and his colleagues conducted a systematic review and meta-analysis of 15 studies evaluating the effects of metformin, TZDs, sulfonylureas, and insulin on colorectal cancer risk. There was considerable heterogeneity across the studies, which may be explained by study design, location, and whether the study accounted for the effects of other antidiabetic drugs, Dr. Singh said.

Five case-control studies, eight cohort studies, and two randomized controlled trials with a total of nearly 14,000 CRC cases in 841,000 diabetes patients were included in the meta-analysis.

TZD was not associated with CRC risk (n = 6 studies; AOR, 0.95; 95% CI, 0.87-1.03; P = .24).

One of the main limitations of the unpublished study was that the significant results were seen only in observational studies and not in post-hoc analysis of the randomized controlled trials. Also, there are residual confounding factors, including failure to adjust for obesity, and confounding by indication and severity of diabetes, Dr. Singh said.

"Before we take part in any proactive treatment regimen, we have to have well-designed, randomized controlled trials," said Dr. N. Jewel Samadder, assistant professor of medicine at the University of Utah, Salt Lake City. "However, the observational studies, and the meta-analysis that [follow], are certainly hypothesis driving. Diabetes itself is a risk factor [for CRC], and some of the medications may alter that risk," said Dr. Samadder, who was not involved in the study.

Dr. Singh had no disclosures. Dr. Samadder has received speaking and teaching honoraria from Cook.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – Metformin may be associated with a reduced risk of colorectal cancer in patients with type 2 diabetes, according to a meta-analysis that included mostly observational studies.

Sulfonylurea and insulin were not associated with a reduced risk and showed a nonsignificant trend toward a higher risk for colorectal cancer (CRC). No association was noted between CRC and thiazolidinedione (TZD), Dr. Siddharth Singh reported at the annual Digestive Disease Week.

CRC incidence was reduced by 10% among patients who were on metformin (n = 10 studies; adjusted odds ratio [AOR], 0.90; 95% confidence interval, 0.82-0.99; P = .02). The results were stable when the analysis was restricted to high-quality observational studies (n = 7 studies; AOR, 0.88; 95% CI, 0.79-0.98).

CRC risk was higher in patients on a sulfonylurea (n = 8 studies; AOR 1.12; 95% CI 0.99-1.26; P = .07) or on insulin (n = 10 studies; AOR, 1.25; 95% CI, 0.91-1.71; P = 0.17). Neither result was statistically significant, however.

Dr. Singh said that the findings warrant prospective cohort studies or randomized controlled trials of the chemopreventive effect of metformin in adults with type 2 diabetes.

Diabetes is an established risk factor for colorectal cancer, and preclinical and observational studies have shown that antidiabetes drugs may affect CRC risk. The relative affect of various antidiabetes drugs on CRC risk is unclear, said Dr. Singh of the Mayo Clinic in Rochester, Minn.

Dr. Singh and his colleagues conducted a systematic review and meta-analysis of 15 studies evaluating the effects of metformin, TZDs, sulfonylureas, and insulin on colorectal cancer risk. There was considerable heterogeneity across the studies, which may be explained by study design, location, and whether the study accounted for the effects of other antidiabetic drugs, Dr. Singh said.

Five case-control studies, eight cohort studies, and two randomized controlled trials with a total of nearly 14,000 CRC cases in 841,000 diabetes patients were included in the meta-analysis.

TZD was not associated with CRC risk (n = 6 studies; AOR, 0.95; 95% CI, 0.87-1.03; P = .24).

One of the main limitations of the unpublished study was that the significant results were seen only in observational studies and not in post-hoc analysis of the randomized controlled trials. Also, there are residual confounding factors, including failure to adjust for obesity, and confounding by indication and severity of diabetes, Dr. Singh said.

"Before we take part in any proactive treatment regimen, we have to have well-designed, randomized controlled trials," said Dr. N. Jewel Samadder, assistant professor of medicine at the University of Utah, Salt Lake City. "However, the observational studies, and the meta-analysis that [follow], are certainly hypothesis driving. Diabetes itself is a risk factor [for CRC], and some of the medications may alter that risk," said Dr. Samadder, who was not involved in the study.

Dr. Singh had no disclosures. Dr. Samadder has received speaking and teaching honoraria from Cook.

[email protected]

On Twitter @NaseemSMiller