DDW 2013

ORLANDO – While esophageal cancer survival rates have improved over the past four decades, the prevalence of adenocarcinoma has also increased significantly, according to an analysis of a national database.

"Our study emphasized the importance of early detection of disease and increased utilization of locoregional therapies," said Dr. Basile Njei of the University of Connecticut, Farmington. He presented his abstract, which is not published, at the annual Digestive Disease Week.

Dr. Njei said that although the rise in the incidence of esophageal cancer in the United States has been well documented, there is a lack of data on trends in long-term survival and prognostic factors associated with esophageal cancer survival.

The authors analyzed the national Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2009. The database included 18 cancer registries representing about 26% of the U.S. population.

The majority of the 93,191 patients included in the analysis were older white males. Patients diagnosed by autopsy or death certificates were excluded.

The number of patients increased from 6,700 in the 1970s to 53,000 in the 2000s. In addition, the median age of patients at baseline increased significantly, from 63 years to 68 years, as did the percentage of white patients, from 74% to 86%, and the rate of adenocarcinoma, from 35% to 61% (P for trend less than .05 for all).

Dr. Njei said that while in the 1990s squamous cell carcinoma (SCC) was the most prevalent type of esophageal cancer, after the 1990s adenocarcinoma became more prevalent. He attributed the rise and fall of the two types of cancer to etiology.

The investigators divided the study population according to histology (adenocarcinoma, AC vs. squamous cell carcinoma, SCC), and by decade of diagnosis. They also analyzed independent predictors of mortality across subgroups. These factors included age, gender, ethnicity, tumor location, stage of disease, and treatment modality.

The results showed that the overall median survival was 9 months. There was a significant increase in overall median survival between the 1970s and the 2000s, from 6 months to 10 months (P less than .001). The overall 5-year survival rate was 15.5%, and there was a significant increase in overall 5-year survival, from 8.1% to 21.3%.

There were also significant improvements in survival for local, regional, and metastatic esophageal cancer during the 40 years, the authors found.

The diagnosis of esophageal cancer at a localized stage increased significantly during the study period, from 11% to 35% (P less than .001).

In addition, there were significant increases in surgical treatment (50% to 64%; P less than .05) and adjuvant radiotherapy (47% to 53%; P less than .05) during the four decades.

Meanwhile, age, sex, tumor histology, stage at diagnosis, node status, adjuvant radiotherapy, and surgery were independently associated with overall survival, the authors reported.

"There’s not much that’s really new in terms of the overall presentation here," said Dr. David C. Metz, professor of medicine at the University of Pennsylvania, Philadelphia. "But it does cement what we’ve been thinking over time, that the shift between squamous cell carcinoma and adenocarcinoma is real, and that we are starting to make an impact in terms of outcome," Dr. Metz said in an interview. "I think there are limitations on how much you can learn from databases, but I think this is a good study."

Although the study had a large sample size and was from a widely validated database, the data are retrospective, there were no chemotherapy data, there is a lead-time and length-time bias, and the findings cannot be generalized to populations in other countries, said Dr. Njei.

Dr. Njei had no disclosures. Dr. Metz is on the advisory committee/review panel for Eisai; has consulted for Novartis, Solesta, Fresenius, and Abbott; and has received grant/research support from Tercica and Lutethera.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – While esophageal cancer survival rates have improved over the past four decades, the prevalence of adenocarcinoma has also increased significantly, according to an analysis of a national database.

"Our study emphasized the importance of early detection of disease and increased utilization of locoregional therapies," said Dr. Basile Njei of the University of Connecticut, Farmington. He presented his abstract, which is not published, at the annual Digestive Disease Week.

Dr. Njei said that although the rise in the incidence of esophageal cancer in the United States has been well documented, there is a lack of data on trends in long-term survival and prognostic factors associated with esophageal cancer survival.

The authors analyzed the national Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2009. The database included 18 cancer registries representing about 26% of the U.S. population.

The majority of the 93,191 patients included in the analysis were older white males. Patients diagnosed by autopsy or death certificates were excluded.

The number of patients increased from 6,700 in the 1970s to 53,000 in the 2000s. In addition, the median age of patients at baseline increased significantly, from 63 years to 68 years, as did the percentage of white patients, from 74% to 86%, and the rate of adenocarcinoma, from 35% to 61% (P for trend less than .05 for all).

Dr. Njei said that while in the 1990s squamous cell carcinoma (SCC) was the most prevalent type of esophageal cancer, after the 1990s adenocarcinoma became more prevalent. He attributed the rise and fall of the two types of cancer to etiology.

The investigators divided the study population according to histology (adenocarcinoma, AC vs. squamous cell carcinoma, SCC), and by decade of diagnosis. They also analyzed independent predictors of mortality across subgroups. These factors included age, gender, ethnicity, tumor location, stage of disease, and treatment modality.

The results showed that the overall median survival was 9 months. There was a significant increase in overall median survival between the 1970s and the 2000s, from 6 months to 10 months (P less than .001). The overall 5-year survival rate was 15.5%, and there was a significant increase in overall 5-year survival, from 8.1% to 21.3%.

There were also significant improvements in survival for local, regional, and metastatic esophageal cancer during the 40 years, the authors found.

The diagnosis of esophageal cancer at a localized stage increased significantly during the study period, from 11% to 35% (P less than .001).

In addition, there were significant increases in surgical treatment (50% to 64%; P less than .05) and adjuvant radiotherapy (47% to 53%; P less than .05) during the four decades.

Meanwhile, age, sex, tumor histology, stage at diagnosis, node status, adjuvant radiotherapy, and surgery were independently associated with overall survival, the authors reported.

"There’s not much that’s really new in terms of the overall presentation here," said Dr. David C. Metz, professor of medicine at the University of Pennsylvania, Philadelphia. "But it does cement what we’ve been thinking over time, that the shift between squamous cell carcinoma and adenocarcinoma is real, and that we are starting to make an impact in terms of outcome," Dr. Metz said in an interview. "I think there are limitations on how much you can learn from databases, but I think this is a good study."

Although the study had a large sample size and was from a widely validated database, the data are retrospective, there were no chemotherapy data, there is a lead-time and length-time bias, and the findings cannot be generalized to populations in other countries, said Dr. Njei.

Dr. Njei had no disclosures. Dr. Metz is on the advisory committee/review panel for Eisai; has consulted for Novartis, Solesta, Fresenius, and Abbott; and has received grant/research support from Tercica and Lutethera.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – While esophageal cancer survival rates have improved over the past four decades, the prevalence of adenocarcinoma has also increased significantly, according to an analysis of a national database.

"Our study emphasized the importance of early detection of disease and increased utilization of locoregional therapies," said Dr. Basile Njei of the University of Connecticut, Farmington. He presented his abstract, which is not published, at the annual Digestive Disease Week.

Dr. Njei said that although the rise in the incidence of esophageal cancer in the United States has been well documented, there is a lack of data on trends in long-term survival and prognostic factors associated with esophageal cancer survival.

The authors analyzed the national Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2009. The database included 18 cancer registries representing about 26% of the U.S. population.

The majority of the 93,191 patients included in the analysis were older white males. Patients diagnosed by autopsy or death certificates were excluded.

The number of patients increased from 6,700 in the 1970s to 53,000 in the 2000s. In addition, the median age of patients at baseline increased significantly, from 63 years to 68 years, as did the percentage of white patients, from 74% to 86%, and the rate of adenocarcinoma, from 35% to 61% (P for trend less than .05 for all).

Dr. Njei said that while in the 1990s squamous cell carcinoma (SCC) was the most prevalent type of esophageal cancer, after the 1990s adenocarcinoma became more prevalent. He attributed the rise and fall of the two types of cancer to etiology.

The investigators divided the study population according to histology (adenocarcinoma, AC vs. squamous cell carcinoma, SCC), and by decade of diagnosis. They also analyzed independent predictors of mortality across subgroups. These factors included age, gender, ethnicity, tumor location, stage of disease, and treatment modality.

The results showed that the overall median survival was 9 months. There was a significant increase in overall median survival between the 1970s and the 2000s, from 6 months to 10 months (P less than .001). The overall 5-year survival rate was 15.5%, and there was a significant increase in overall 5-year survival, from 8.1% to 21.3%.

There were also significant improvements in survival for local, regional, and metastatic esophageal cancer during the 40 years, the authors found.

The diagnosis of esophageal cancer at a localized stage increased significantly during the study period, from 11% to 35% (P less than .001).

In addition, there were significant increases in surgical treatment (50% to 64%; P less than .05) and adjuvant radiotherapy (47% to 53%; P less than .05) during the four decades.

Meanwhile, age, sex, tumor histology, stage at diagnosis, node status, adjuvant radiotherapy, and surgery were independently associated with overall survival, the authors reported.

"There’s not much that’s really new in terms of the overall presentation here," said Dr. David C. Metz, professor of medicine at the University of Pennsylvania, Philadelphia. "But it does cement what we’ve been thinking over time, that the shift between squamous cell carcinoma and adenocarcinoma is real, and that we are starting to make an impact in terms of outcome," Dr. Metz said in an interview. "I think there are limitations on how much you can learn from databases, but I think this is a good study."

Although the study had a large sample size and was from a widely validated database, the data are retrospective, there were no chemotherapy data, there is a lead-time and length-time bias, and the findings cannot be generalized to populations in other countries, said Dr. Njei.

Dr. Njei had no disclosures. Dr. Metz is on the advisory committee/review panel for Eisai; has consulted for Novartis, Solesta, Fresenius, and Abbott; and has received grant/research support from Tercica and Lutethera.

nmiller@frontlinemedcom.com

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.

nmiller@frontlinemedcom.com

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.

nmiller@frontlinemedcom.com

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.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – An investigational immunomodulator prosaically named DIMS 0150 was associated with sustained remissions in some patients with ulcerative colitis, reported investigators at the annual Digestive Disease Week.

Among patients with ulcerative colitis (UC) randomized to receive a single rectally delivered dose of DIMS 0150 or placebo, 5 of 16 patients available for 3-month follow-up had a sustained clinical response, compared with none of the eight control patients who received a placebo enema, said Dr. Thomas Knittel from InDex Pharmaceuticals in Stockholm.

The drug contains a single-stranded oligonucleotide that acts as a Toll-like receptor 9 (TLR9) agonist by activating TLR9 when the drug is administered to mucosal surfaces. TLR9 (also called CD289) encodes a protein involved in innate immunity and pathogen recognition and in mediation of anti-inflammatory cytokines, primarily interleukin 10 and interferon-alpha.

In animal studies, activation of TLR9 has been shown to promote healing of UC.

The investigators conducted a randomized, double-blind, placebo-controlled trial of the agent in patients with UC refractory to steroids. A total of 34 patients were randomized to receive on a 2:1 basis (22:12) either a single 30-mg dose of DIMS 0150 delivered via enema, or a placebo enema consisting of only water.

The patients had Disease Activity Index (DAI) scores of 6-11 pts were taking at least 5 mg steroids/day and were judged as either steroid dependent or steroid resistant.

At the end of the first follow-up week, 7 of 17 patients on DIMS 0150 had a clinical response (decrease in DAI score of at least 3 points from baseline), compared with 1 of 11 patients on placebo. By week 4, two additional patients on the TLR9 agonist had achieved a clinical response (9 of 17), as did three additional patients on placebo (4 of 11).

By week 12, 5 of 16 patients who had received DIMS 0150 and completed 12 weeks of therapy still had a clinical response, in contrast to none of the eight patients on placebo who completed 12 weeks of follow-up. However, neither the 4-week nor 12-week follow-up differences in sustained response between the active drug and placebo groups were significant.

Two of 17 patients on DIMS 0150 had a clinical remission (total DAI score of 2 points or less, with no individual subscore higher than 1) at week 1, 3 of 17 were in remission at week 4, and 6 of 16 were in remission at 12 weeks. In contrast, none of the control patients had remissions at either week 1 or week 4, but two of eight controls were in remission at week 12.

The authors also looked at histologic remission (improvement to a score of 0) at all three time points and found that at week 4, 6 of 17 patients on the TLR9 agonist had a remission, vs. 0 of 11 on placebo, a difference that teetered on the edge of statistical significance (P = .055).

Dr. Knittel did not present safety data, but said that in previous studies, the drug at the 30-mg dose has been shown to be safe and that patients tolerated it well.

In response to a question following his presentation, Dr. Knittel noted that the investigators had not measured cytokine levels to determine whether the drug was having its intended effect, but instead relied on clinical findings to determine efficacy.

The phase II study Dr. Knittel presented confirms clinical data obtained in earlier studies of this agent, and "indicates that a single dose of a TLR9 agonist can be effective, and efficacy was observed with respect to clinical response, clinical remission, and histological healing," he said.

But a gastroenterologist who was not involved in the study says that it was lacking data in several key areas, because the investigators did not measure baseline or post-treatment levels of anti-inflammatory cytokines or C-reactive protein and did not perform endoscopies to assess colonic mucosa.

"In ulcerative colitis, that’s where the rubber hits the road: whether the mucosa gets better," said Dr. Maria T. Abreu, chief of gastroenterology and professor of medicine at the University of Miami.

"I don’t expect it to completely resolve, because even in studies of anti-TNF [tumor necrosis factor–alpha], which we believe to be the most potent therapy we have now for mucosal healing, the numbers of patients that actually have the mucosa heal completely in ulcerative colitis is low – only about a quarter of patients have that happen. ... But these investigators didn’t report any change in the endoscopy," Dr. Abreu said.

The study was funded by InDex Pharmaceuticals. Dr. Knittel is chief medical officer and consultant for the company, and two of his coauthors are employees.

ORLANDO – Triple-drug therapy with the protease inhibitor telaprevir plus ribavirin and peg-interferon alpha 2a provides higher sustained virologic response than traditional dual-drug therapy in chronic hepatitis C patients on hemodialysis, according to findings from the randomized, placebo-controlled Target C Trial.

Sustained virologic response after 24 months was 63% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin and peg-IFN alpha 2a for weeks 0-24 (group A) and 50% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin for weeks 13-36 and peg-IFN alpha 2a for weeks 0-36 (group B), compared with 25% in 12 patients treated with placebo plus standard dual therapy with ribavirin and peg-IFN alpha 2a for weeks 0-24 and weeks 37-48 (group C, reference arm), Dr. Patrick Basu reported at the annual Digestive Disease Week.

Telaprevir in groups A and B was given as two 750-mg tablets three times daily for 4 days and three 750-mg tablets given twice daily for 3 days after dialysis. The ribavirin dose in group A was 200 mg for weeks 0-12 and 400 mg for weeks 13-24; for group B it was 400 mg for weeks 13-36 (with placebo given for weeks 0-12). All ribavirin doses in group C were 400 mg, and peg-IFN alpha 2a doses in all three groups were 135 mcg, said Dr. Basu of Columbia University College of Physicians and Surgeons, New York.

Patients in the study included 26 men and 10 women with a mean age of 58 years, a mean body mass index of 26.6 kg/m², and a mean viral load of 869,000 IU/mL who were treated between May 2011 and November 2012. All had end-stage renal disease and were on hemodialysis for a mean of 6 years. The groups were well balanced with respect to BMI, race, viral load, and disease genotype.

Adverse events that occurred more often in the telaprevir groups (A and/or B), compared with group C, included anemia, neutropenia less than 750 ANA, thrombocytopenia, skin rash, anorectal dysfunction, dysgeusia, depression, and constipation. Neuropathy was more common in group C.

Protease inhibitors are now part of the standard of care for treatment of chronic hepatitis C, genotype 1. Telaprevir was approved in May 2011 for this purpose.

Since the drug is primarily metabolized in the liver and excreted in the feces, thus limiting renal toxicity, it was considered a promising treatment option for the 3% of chronic hepatitis C patients with end-stage renal disease on hemodialysis – a population with progressive fibrosis and high mortality, Dr. Basu said.

The findings of this pilot study suggest that truncated triple therapy that includes telaprevir does indeed have an advantage over the standard of care for this special population, he concluded, noting that the telaprevir regimen requires further evaluation in a large prospective trial.

Dr. Basu disclosed financial relationships with Gilead Science, BMS, ROMAX, Genentech, Vertex, Otsuka, Takeda, Three Rivers, GI Pathology, and Salix.

ORLANDO – Triple-drug therapy with the protease inhibitor telaprevir plus ribavirin and peg-interferon alpha 2a provides higher sustained virologic response than traditional dual-drug therapy in chronic hepatitis C patients on hemodialysis, according to findings from the randomized, placebo-controlled Target C Trial.

Sustained virologic response after 24 months was 63% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin and peg-IFN alpha 2a for weeks 0-24 (group A) and 50% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin for weeks 13-36 and peg-IFN alpha 2a for weeks 0-36 (group B), compared with 25% in 12 patients treated with placebo plus standard dual therapy with ribavirin and peg-IFN alpha 2a for weeks 0-24 and weeks 37-48 (group C, reference arm), Dr. Patrick Basu reported at the annual Digestive Disease Week.

Telaprevir in groups A and B was given as two 750-mg tablets three times daily for 4 days and three 750-mg tablets given twice daily for 3 days after dialysis. The ribavirin dose in group A was 200 mg for weeks 0-12 and 400 mg for weeks 13-24; for group B it was 400 mg for weeks 13-36 (with placebo given for weeks 0-12). All ribavirin doses in group C were 400 mg, and peg-IFN alpha 2a doses in all three groups were 135 mcg, said Dr. Basu of Columbia University College of Physicians and Surgeons, New York.

Patients in the study included 26 men and 10 women with a mean age of 58 years, a mean body mass index of 26.6 kg/m², and a mean viral load of 869,000 IU/mL who were treated between May 2011 and November 2012. All had end-stage renal disease and were on hemodialysis for a mean of 6 years. The groups were well balanced with respect to BMI, race, viral load, and disease genotype.

Adverse events that occurred more often in the telaprevir groups (A and/or B), compared with group C, included anemia, neutropenia less than 750 ANA, thrombocytopenia, skin rash, anorectal dysfunction, dysgeusia, depression, and constipation. Neuropathy was more common in group C.

Protease inhibitors are now part of the standard of care for treatment of chronic hepatitis C, genotype 1. Telaprevir was approved in May 2011 for this purpose.

Since the drug is primarily metabolized in the liver and excreted in the feces, thus limiting renal toxicity, it was considered a promising treatment option for the 3% of chronic hepatitis C patients with end-stage renal disease on hemodialysis – a population with progressive fibrosis and high mortality, Dr. Basu said.

The findings of this pilot study suggest that truncated triple therapy that includes telaprevir does indeed have an advantage over the standard of care for this special population, he concluded, noting that the telaprevir regimen requires further evaluation in a large prospective trial.

Dr. Basu disclosed financial relationships with Gilead Science, BMS, ROMAX, Genentech, Vertex, Otsuka, Takeda, Three Rivers, GI Pathology, and Salix.

ORLANDO – Triple-drug therapy with the protease inhibitor telaprevir plus ribavirin and peg-interferon alpha 2a provides higher sustained virologic response than traditional dual-drug therapy in chronic hepatitis C patients on hemodialysis, according to findings from the randomized, placebo-controlled Target C Trial.

Sustained virologic response after 24 months was 63% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin and peg-IFN alpha 2a for weeks 0-24 (group A) and 50% in 12 patients treated with telaprevir for weeks 0-12 plus ribavirin for weeks 13-36 and peg-IFN alpha 2a for weeks 0-36 (group B), compared with 25% in 12 patients treated with placebo plus standard dual therapy with ribavirin and peg-IFN alpha 2a for weeks 0-24 and weeks 37-48 (group C, reference arm), Dr. Patrick Basu reported at the annual Digestive Disease Week.

Telaprevir in groups A and B was given as two 750-mg tablets three times daily for 4 days and three 750-mg tablets given twice daily for 3 days after dialysis. The ribavirin dose in group A was 200 mg for weeks 0-12 and 400 mg for weeks 13-24; for group B it was 400 mg for weeks 13-36 (with placebo given for weeks 0-12). All ribavirin doses in group C were 400 mg, and peg-IFN alpha 2a doses in all three groups were 135 mcg, said Dr. Basu of Columbia University College of Physicians and Surgeons, New York.

Patients in the study included 26 men and 10 women with a mean age of 58 years, a mean body mass index of 26.6 kg/m², and a mean viral load of 869,000 IU/mL who were treated between May 2011 and November 2012. All had end-stage renal disease and were on hemodialysis for a mean of 6 years. The groups were well balanced with respect to BMI, race, viral load, and disease genotype.

Adverse events that occurred more often in the telaprevir groups (A and/or B), compared with group C, included anemia, neutropenia less than 750 ANA, thrombocytopenia, skin rash, anorectal dysfunction, dysgeusia, depression, and constipation. Neuropathy was more common in group C.

Protease inhibitors are now part of the standard of care for treatment of chronic hepatitis C, genotype 1. Telaprevir was approved in May 2011 for this purpose.

Since the drug is primarily metabolized in the liver and excreted in the feces, thus limiting renal toxicity, it was considered a promising treatment option for the 3% of chronic hepatitis C patients with end-stage renal disease on hemodialysis – a population with progressive fibrosis and high mortality, Dr. Basu said.

The findings of this pilot study suggest that truncated triple therapy that includes telaprevir does indeed have an advantage over the standard of care for this special population, he concluded, noting that the telaprevir regimen requires further evaluation in a large prospective trial.

Dr. Basu disclosed financial relationships with Gilead Science, BMS, ROMAX, Genentech, Vertex, Otsuka, Takeda, Three Rivers, GI Pathology, and Salix.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.

Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.

The trial was stopped early after an interim analysis showed no benefit for mesalamine.

"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.

Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.

Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.

To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).

As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.

But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).

There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.

"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."

Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.

"Diverticular disease and diverticulitis are probably not one entity," he said.

The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.

ORLANDO – Mid- and long-term esophageal cancer-free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer-free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy. The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

ORLANDO – Mid- and long-term esophageal cancer-free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer-free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy. The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

ORLANDO – Mid- and long-term esophageal cancer-free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer-free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy. The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

ORLANDO – Nosocomial infections in cirrhotic patients are associated with acute kidney injury and prolonged hospital stay, and thus adversely affect outcomes, findings from a Swedish population-based study suggest.

Of 344 patients diagnosed with cirrhosis between 2000 and 2010, 122 experienced a total of 230 bacterial infections; 29% were community acquired, 51% were health care acquired (HCA), and 20% were nosocomial. Most (70%) occurred in decompensated patients, and most patients (64%) used proton pump inhibitors. In-hospital mortality was 18%, Dr. Konstantina Sargenti reported at the annual Digestive Disease Week.

On logistic regression analysis, nosocomial/HCA infections, compared with community-acquired infections, were independently associated with PPI use (odds ratio, 2.07) and decompensated patient status (OR, 2.12). After researchers adjusted for confounders, nosocomial/HCA infections were not found to be associated with inpatient mortality (OR, 1.78) or systemic inflammatory response syndrome (OR, 1.18), but nosocomial infections alone were independently associated with hospital length of stay (OR, 23.34 per day) and acute kidney injury (OR, 2.82), which was defined by an increase of greater than 50% in serum creatinine, said Dr. Sargenti of Skane University Hospital, University of Lund (Sweden).

Study subjects – residents of an area in Sweden with a population of about 250,000 – all were diagnosed with cirrhosis during the study period. The patients were retrospectively evaluated, with all relevant hospitalization- and infection-related data extracted from medical records. They were then followed until death, transplantation, or the end of 2011, for a median follow-up of 50 months.

The groups of patients with community-acquired, HCA, or nosocomial infections did not differ significantly with respect to patient demographics, etiology of liver cirrhosis, or the presence of comorbidities or hepatocellular carcinoma. Length of stay was longer for those with HCA and nosocomial infections, but the three groups did not differ with respect to need for intensive care unit stay, in-hospital mortality, acute kidney injury, or systemic inflammatory response syndrome occurrence.

Also, PPI use was more frequent in the HCA and nosocomial infection groups, but the groups did not differ in their use of immunosuppressive or steroid use.

The results did not change in an analysis that included only the first bacterial infection for each patient, Dr. Sargenti said.

The most common types of infections were urinary tract infections in 22% of patients, spontaneous bacterial peritonitis in 19%, pneumonia in 14%, spontaneous bacteremia in 14%, and skin infections in 10%.

Nosocomial and HCA infections occur commonly in cirrhosis, but population-based data characterizing their occurrence and potential role in mortality or length of stay have been lacking, Dr. Sargenti said, noting also that while PPIs are known to increase the risk for infections, and acute kidney injury and systemic inflammatory response syndrome during an infectious episode are known to be associated with poor prognosis, it was previously unclear whether these conditions are more common in nosocomial and HCA infections.

The current findings suggest that most infections in a cirrhotic cohort are HCA or nosocomial infections, and that PPI use is an independent predictor of such infections. Nosocomial infections are a particular concern, as they appear to increase the risk of factors associated with poor outcomes, she concluded.

Dr. Sargenti reported having no disclosures.

ginews@gastro.org

ORLANDO – Nosocomial infections in cirrhotic patients are associated with acute kidney injury and prolonged hospital stay, and thus adversely affect outcomes, findings from a Swedish population-based study suggest.

Of 344 patients diagnosed with cirrhosis between 2000 and 2010, 122 experienced a total of 230 bacterial infections; 29% were community acquired, 51% were health care acquired (HCA), and 20% were nosocomial. Most (70%) occurred in decompensated patients, and most patients (64%) used proton pump inhibitors. In-hospital mortality was 18%, Dr. Konstantina Sargenti reported at the annual Digestive Disease Week.

On logistic regression analysis, nosocomial/HCA infections, compared with community-acquired infections, were independently associated with PPI use (odds ratio, 2.07) and decompensated patient status (OR, 2.12). After researchers adjusted for confounders, nosocomial/HCA infections were not found to be associated with inpatient mortality (OR, 1.78) or systemic inflammatory response syndrome (OR, 1.18), but nosocomial infections alone were independently associated with hospital length of stay (OR, 23.34 per day) and acute kidney injury (OR, 2.82), which was defined by an increase of greater than 50% in serum creatinine, said Dr. Sargenti of Skane University Hospital, University of Lund (Sweden).

Study subjects – residents of an area in Sweden with a population of about 250,000 – all were diagnosed with cirrhosis during the study period. The patients were retrospectively evaluated, with all relevant hospitalization- and infection-related data extracted from medical records. They were then followed until death, transplantation, or the end of 2011, for a median follow-up of 50 months.

The groups of patients with community-acquired, HCA, or nosocomial infections did not differ significantly with respect to patient demographics, etiology of liver cirrhosis, or the presence of comorbidities or hepatocellular carcinoma. Length of stay was longer for those with HCA and nosocomial infections, but the three groups did not differ with respect to need for intensive care unit stay, in-hospital mortality, acute kidney injury, or systemic inflammatory response syndrome occurrence.

Also, PPI use was more frequent in the HCA and nosocomial infection groups, but the groups did not differ in their use of immunosuppressive or steroid use.

The results did not change in an analysis that included only the first bacterial infection for each patient, Dr. Sargenti said.

The most common types of infections were urinary tract infections in 22% of patients, spontaneous bacterial peritonitis in 19%, pneumonia in 14%, spontaneous bacteremia in 14%, and skin infections in 10%.

Nosocomial and HCA infections occur commonly in cirrhosis, but population-based data characterizing their occurrence and potential role in mortality or length of stay have been lacking, Dr. Sargenti said, noting also that while PPIs are known to increase the risk for infections, and acute kidney injury and systemic inflammatory response syndrome during an infectious episode are known to be associated with poor prognosis, it was previously unclear whether these conditions are more common in nosocomial and HCA infections.

The current findings suggest that most infections in a cirrhotic cohort are HCA or nosocomial infections, and that PPI use is an independent predictor of such infections. Nosocomial infections are a particular concern, as they appear to increase the risk of factors associated with poor outcomes, she concluded.

Dr. Sargenti reported having no disclosures.

ginews@gastro.org

ORLANDO – Nosocomial infections in cirrhotic patients are associated with acute kidney injury and prolonged hospital stay, and thus adversely affect outcomes, findings from a Swedish population-based study suggest.

Of 344 patients diagnosed with cirrhosis between 2000 and 2010, 122 experienced a total of 230 bacterial infections; 29% were community acquired, 51% were health care acquired (HCA), and 20% were nosocomial. Most (70%) occurred in decompensated patients, and most patients (64%) used proton pump inhibitors. In-hospital mortality was 18%, Dr. Konstantina Sargenti reported at the annual Digestive Disease Week.

On logistic regression analysis, nosocomial/HCA infections, compared with community-acquired infections, were independently associated with PPI use (odds ratio, 2.07) and decompensated patient status (OR, 2.12). After researchers adjusted for confounders, nosocomial/HCA infections were not found to be associated with inpatient mortality (OR, 1.78) or systemic inflammatory response syndrome (OR, 1.18), but nosocomial infections alone were independently associated with hospital length of stay (OR, 23.34 per day) and acute kidney injury (OR, 2.82), which was defined by an increase of greater than 50% in serum creatinine, said Dr. Sargenti of Skane University Hospital, University of Lund (Sweden).

Study subjects – residents of an area in Sweden with a population of about 250,000 – all were diagnosed with cirrhosis during the study period. The patients were retrospectively evaluated, with all relevant hospitalization- and infection-related data extracted from medical records. They were then followed until death, transplantation, or the end of 2011, for a median follow-up of 50 months.

The groups of patients with community-acquired, HCA, or nosocomial infections did not differ significantly with respect to patient demographics, etiology of liver cirrhosis, or the presence of comorbidities or hepatocellular carcinoma. Length of stay was longer for those with HCA and nosocomial infections, but the three groups did not differ with respect to need for intensive care unit stay, in-hospital mortality, acute kidney injury, or systemic inflammatory response syndrome occurrence.

Also, PPI use was more frequent in the HCA and nosocomial infection groups, but the groups did not differ in their use of immunosuppressive or steroid use.

The results did not change in an analysis that included only the first bacterial infection for each patient, Dr. Sargenti said.

The most common types of infections were urinary tract infections in 22% of patients, spontaneous bacterial peritonitis in 19%, pneumonia in 14%, spontaneous bacteremia in 14%, and skin infections in 10%.

Nosocomial and HCA infections occur commonly in cirrhosis, but population-based data characterizing their occurrence and potential role in mortality or length of stay have been lacking, Dr. Sargenti said, noting also that while PPIs are known to increase the risk for infections, and acute kidney injury and systemic inflammatory response syndrome during an infectious episode are known to be associated with poor prognosis, it was previously unclear whether these conditions are more common in nosocomial and HCA infections.

The current findings suggest that most infections in a cirrhotic cohort are HCA or nosocomial infections, and that PPI use is an independent predictor of such infections. Nosocomial infections are a particular concern, as they appear to increase the risk of factors associated with poor outcomes, she concluded.

Dr. Sargenti reported having no disclosures.

ginews@gastro.org

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.

nmiller@frontlinemedcom.com

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.

nmiller@frontlinemedcom.com

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.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Colonoscopy with or without fecal occult blood testing is associated with lower overall mortality risk in individuals with increased baseline colorectal cancer risk, findings from a large prospective cohort study suggest.

Overall mortality was 33.2% in 2,123 Veterans Administration patients aged 21-89 years who were followed for up to 16 years as part of the study. Deceased patients, compared with those still living at the end of the study period, had significantly lower odds of having undergone colonoscopy alone (18.5% vs. 23%) or colonoscopy plus fecal occult blood testing (17.4% vs. 23.9%), and significantly greater odds of having undergone neither screening modality (41.4% vs. 28%), Dr. Martin Tobi reported at the annual Digestive Disease Week.

The use of fecal occult blood testing (FOBT) alone was not associated with overall mortality; 25% and 22% of the deceased and living patients, respectively, underwent FOBT alone, said Dr. Tobi of the University of Pennsylvania, Philadelphia.

Study participants were adults seen at the outpatient primary care clinics of a VA hospital between 1995 and 2012. Some had symptoms and some did not – this was not a screening population, Dr. Tobi noted.

The subjects were followed for a mean of 8 years. Risk for colorectal cancer at baseline was assessed using a risk questionnaire and based on past neoplasia, chronic inflammatory bowel disease, symptomatology, and family history. Mortality and use of FOBT and colonoscopy were determined by a manual medical records review.

The impact of colonoscopy and FOBT on overall mortality associated with colorectal cancer has been unclear, and although large-scale randomized trials to evaluate the relationships are ongoing, definitive results are more than a decade away, Dr. Tobi said.

Though limited by missing data in a substantial number of cases, the current findings from a large VA population suggest there is indeed a relationship between colonoscopy with or without FOBT and overall mortality.

"Further analyses are needed to determine whether a true protective effect of colonoscopy is attributable to a causal relationship or due to a confounding one – mainly a healthy user effect," he concluded.

The Veterans Health Administration provided funding for this study. Dr. Tobi reported having no disclosures.

ORLANDO – Colonoscopy with or without fecal occult blood testing is associated with lower overall mortality risk in individuals with increased baseline colorectal cancer risk, findings from a large prospective cohort study suggest.

Overall mortality was 33.2% in 2,123 Veterans Administration patients aged 21-89 years who were followed for up to 16 years as part of the study. Deceased patients, compared with those still living at the end of the study period, had significantly lower odds of having undergone colonoscopy alone (18.5% vs. 23%) or colonoscopy plus fecal occult blood testing (17.4% vs. 23.9%), and significantly greater odds of having undergone neither screening modality (41.4% vs. 28%), Dr. Martin Tobi reported at the annual Digestive Disease Week.

The use of fecal occult blood testing (FOBT) alone was not associated with overall mortality; 25% and 22% of the deceased and living patients, respectively, underwent FOBT alone, said Dr. Tobi of the University of Pennsylvania, Philadelphia.

Study participants were adults seen at the outpatient primary care clinics of a VA hospital between 1995 and 2012. Some had symptoms and some did not – this was not a screening population, Dr. Tobi noted.

The subjects were followed for a mean of 8 years. Risk for colorectal cancer at baseline was assessed using a risk questionnaire and based on past neoplasia, chronic inflammatory bowel disease, symptomatology, and family history. Mortality and use of FOBT and colonoscopy were determined by a manual medical records review.

The impact of colonoscopy and FOBT on overall mortality associated with colorectal cancer has been unclear, and although large-scale randomized trials to evaluate the relationships are ongoing, definitive results are more than a decade away, Dr. Tobi said.

Though limited by missing data in a substantial number of cases, the current findings from a large VA population suggest there is indeed a relationship between colonoscopy with or without FOBT and overall mortality.

"Further analyses are needed to determine whether a true protective effect of colonoscopy is attributable to a causal relationship or due to a confounding one – mainly a healthy user effect," he concluded.

The Veterans Health Administration provided funding for this study. Dr. Tobi reported having no disclosures.

ORLANDO – Colonoscopy with or without fecal occult blood testing is associated with lower overall mortality risk in individuals with increased baseline colorectal cancer risk, findings from a large prospective cohort study suggest.

Overall mortality was 33.2% in 2,123 Veterans Administration patients aged 21-89 years who were followed for up to 16 years as part of the study. Deceased patients, compared with those still living at the end of the study period, had significantly lower odds of having undergone colonoscopy alone (18.5% vs. 23%) or colonoscopy plus fecal occult blood testing (17.4% vs. 23.9%), and significantly greater odds of having undergone neither screening modality (41.4% vs. 28%), Dr. Martin Tobi reported at the annual Digestive Disease Week.

The use of fecal occult blood testing (FOBT) alone was not associated with overall mortality; 25% and 22% of the deceased and living patients, respectively, underwent FOBT alone, said Dr. Tobi of the University of Pennsylvania, Philadelphia.

Study participants were adults seen at the outpatient primary care clinics of a VA hospital between 1995 and 2012. Some had symptoms and some did not – this was not a screening population, Dr. Tobi noted.

The subjects were followed for a mean of 8 years. Risk for colorectal cancer at baseline was assessed using a risk questionnaire and based on past neoplasia, chronic inflammatory bowel disease, symptomatology, and family history. Mortality and use of FOBT and colonoscopy were determined by a manual medical records review.

The impact of colonoscopy and FOBT on overall mortality associated with colorectal cancer has been unclear, and although large-scale randomized trials to evaluate the relationships are ongoing, definitive results are more than a decade away, Dr. Tobi said.

Though limited by missing data in a substantial number of cases, the current findings from a large VA population suggest there is indeed a relationship between colonoscopy with or without FOBT and overall mortality.

"Further analyses are needed to determine whether a true protective effect of colonoscopy is attributable to a causal relationship or due to a confounding one – mainly a healthy user effect," he concluded.

The Veterans Health Administration provided funding for this study. Dr. Tobi reported having no disclosures.