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Digestive Disease Week (DDW 2013)
After HCV treatment failure, some success with boceprevir-IFN-ribavirin
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
AT DDW 2013
Major finding: Among patients with hepatitis C infections who did not have a sustained virologic response after prior therapy, 63% had an SVR for at least 24 weeks after treatment with boceprevir, pegylated interferon, and ribavirin (intention-to-treat population).
Data source: Single-arm, open-label, nonrandomized study in 168 patients.
Disclosures: The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
Amitriptyline eases functional dyspepsia symptoms
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
AT DDW 2013
Major finding: In a clinical trial, 53% of patients with functional dyspepsia assigned to amitriptyline reported at least 5 weeks of symptom relief compared with 38% of patients on escitalopram and 40% on placebo.
Data source: A prospective, randomized, double-blind double-dummy study of 292 patients with functional dyspepsia.
Disclosures: The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he served as a consultant to the company.
Onsite cytopathology improves pancreatic biopsy quality
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
AT DDW 2013
Major finding: Onsite cytopathologists identified significantly more samples as suspicious or malignant than did pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
Data source: A randomized controlled trial conducted with 131 patients at three clinical centers.
Disclosures: The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
Drug combo curbs organ failures in acute pancreatitis patients
ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
T
ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
T
T
AT DDW 2013
Major finding: The combination of octreotide and celecoxib halved rates of organ failure and disease progression in patients with acute pancreatitis.
Data source: A randomized controlled trial of patients with severe acute pancreatitis and those at risk for it.
Disclosures: The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
Investigational noninterferon HCV treatment effective across patient groups
ORLANDO – Both 12- and 24-week regimens of an investigational interferon-free therapy for hepatitis C were associated with high sustained virological response rates at 12 weeks post treatment in a phase II study of patients with hepatitis C virus genotype 1 who had baseline characteristics associated with poor response to interferon-based therapies.
The findings of this subgroup analysis of the randomized, open-label, multicenter Aviator trial demonstrate that the high response rates recently reported for the entire cohort also apply to patients with older age, black race, Hispanic/Latino ethnicity, interleukin (IL)-28B non-cc genotype, and higher body mass index (BMI), Dr. Frederick Nunes reported at the annual Digestive Disease Week.
The Aviator trial assessed the safety and efficacy of various dosing regimens and combinations of three AbbVie investigational direct-acting antivirals (DAAs) with or without ribavirin, including the potent hepatitis C virus (HCV) protease inhibitor ABT-450 dosed with 100 mg of ritonavir (ABT-450/r, dosed at 100 or 150 mg daily), the NS5A inhibitor ABT-267 (25 mg daily), and the non-nucleoside NS5B inhibitor ABT-333 (400 mg twice daily). A total of 247 patients were included in the subanalysis, Dr. Nunes reported at the meeting.
The regimen that included all three investigational drugs and ribavirin, known as 3 DAA/RBV, was associated with sustained virological response rates of 99% and 93% at 12 weeks in treatment-naive patients and previous peg-interferon/ribavirin (peg-IFN/RBV) null responders, respectively, said Dr. Nunes, who is clinical associate professor of medicine in the University of Pennsylvania Health System, and section chief of gastroenterology at Pennsylvania Hospital, Philadelphia.
In the current analysis, high sustained virological response rates at 12 weeks (SVR12) were also achieved in the 247 patients with chronic HCV genotype 1, including 159 treatment-naive and 88 previous peg-IFN/RBV null responders, who were assigned to 12 or 24 weeks of 3 DAA/RBV. The virological response rates were 99% and 93% for the treatment-naive 12- and 24-week groups, respectively, and 93% and 98% for the null responder 12- and 24-week groups.
The high responses occurred regardless of treatment duration, age, race, ethnicity, BMI, Homeostatic Model of Assessment–Insulin Resistance (HOMA-IR), IL-28B host genotype, or baseline viral load. The rates did not differ significantly on any comparison made in treatment-naive patients or previous null responders, he said.
In the treatment-naive patients, no breakthroughs occurred, although 1% of those in the 12-week treatment arm relapsed, and 3% of the 24-week treatment group relapsed.
In the null responder group, no relapses occurred, but breakthroughs occurred in 7% of those in the 12-week treatment arm, and in 2% of the 24-week treatment arm, he said.
Treatment was safe and generally well tolerated. Four patients discontinued treatment due to drug-related adverse events, most commonly fatigue (in 32.7% and 23.9% of treatment-naive and null responders, respectively) and headache (31.4% and 30.7%, respectively).
One patient had a serious adverse event (arthralgia) considered to be possibly related to the study drug regimen.
Because ribavirin was included in the treatment regimens, it is impossible to tease out whether the adverse events were associated with that drug or with the investigational DAAs, Dr. Nunes noted.
Patients included in the study were noncirrhotic adults aged 18-70 years with a BMI between 18 and 38 kg/m2, and HCV genotype 1.
"The overall efficacy was excellent irrespective of the baseline grouping. So black race, Hispanic/Latino ethnicity, age greater than 50, BMI over 30, male gender, HOMA-IR greater than 3, IL-28B non-cc genotype, and viral load greater than 7 logs all had very high SVR12 response rates," Dr. Nunes said.
The safety and efficacy of this interferon-free 3 DAA/RBV therapy will be further explored in phase III studies, he said.
Dr. Nunes has received grant or research support from Merck, Abbott Laboratories, and Roche Pharma AG.
ORLANDO – Both 12- and 24-week regimens of an investigational interferon-free therapy for hepatitis C were associated with high sustained virological response rates at 12 weeks post treatment in a phase II study of patients with hepatitis C virus genotype 1 who had baseline characteristics associated with poor response to interferon-based therapies.
The findings of this subgroup analysis of the randomized, open-label, multicenter Aviator trial demonstrate that the high response rates recently reported for the entire cohort also apply to patients with older age, black race, Hispanic/Latino ethnicity, interleukin (IL)-28B non-cc genotype, and higher body mass index (BMI), Dr. Frederick Nunes reported at the annual Digestive Disease Week.
The Aviator trial assessed the safety and efficacy of various dosing regimens and combinations of three AbbVie investigational direct-acting antivirals (DAAs) with or without ribavirin, including the potent hepatitis C virus (HCV) protease inhibitor ABT-450 dosed with 100 mg of ritonavir (ABT-450/r, dosed at 100 or 150 mg daily), the NS5A inhibitor ABT-267 (25 mg daily), and the non-nucleoside NS5B inhibitor ABT-333 (400 mg twice daily). A total of 247 patients were included in the subanalysis, Dr. Nunes reported at the meeting.
The regimen that included all three investigational drugs and ribavirin, known as 3 DAA/RBV, was associated with sustained virological response rates of 99% and 93% at 12 weeks in treatment-naive patients and previous peg-interferon/ribavirin (peg-IFN/RBV) null responders, respectively, said Dr. Nunes, who is clinical associate professor of medicine in the University of Pennsylvania Health System, and section chief of gastroenterology at Pennsylvania Hospital, Philadelphia.
In the current analysis, high sustained virological response rates at 12 weeks (SVR12) were also achieved in the 247 patients with chronic HCV genotype 1, including 159 treatment-naive and 88 previous peg-IFN/RBV null responders, who were assigned to 12 or 24 weeks of 3 DAA/RBV. The virological response rates were 99% and 93% for the treatment-naive 12- and 24-week groups, respectively, and 93% and 98% for the null responder 12- and 24-week groups.
The high responses occurred regardless of treatment duration, age, race, ethnicity, BMI, Homeostatic Model of Assessment–Insulin Resistance (HOMA-IR), IL-28B host genotype, or baseline viral load. The rates did not differ significantly on any comparison made in treatment-naive patients or previous null responders, he said.
In the treatment-naive patients, no breakthroughs occurred, although 1% of those in the 12-week treatment arm relapsed, and 3% of the 24-week treatment group relapsed.
In the null responder group, no relapses occurred, but breakthroughs occurred in 7% of those in the 12-week treatment arm, and in 2% of the 24-week treatment arm, he said.
Treatment was safe and generally well tolerated. Four patients discontinued treatment due to drug-related adverse events, most commonly fatigue (in 32.7% and 23.9% of treatment-naive and null responders, respectively) and headache (31.4% and 30.7%, respectively).
One patient had a serious adverse event (arthralgia) considered to be possibly related to the study drug regimen.
Because ribavirin was included in the treatment regimens, it is impossible to tease out whether the adverse events were associated with that drug or with the investigational DAAs, Dr. Nunes noted.
Patients included in the study were noncirrhotic adults aged 18-70 years with a BMI between 18 and 38 kg/m2, and HCV genotype 1.
"The overall efficacy was excellent irrespective of the baseline grouping. So black race, Hispanic/Latino ethnicity, age greater than 50, BMI over 30, male gender, HOMA-IR greater than 3, IL-28B non-cc genotype, and viral load greater than 7 logs all had very high SVR12 response rates," Dr. Nunes said.
The safety and efficacy of this interferon-free 3 DAA/RBV therapy will be further explored in phase III studies, he said.
Dr. Nunes has received grant or research support from Merck, Abbott Laboratories, and Roche Pharma AG.
ORLANDO – Both 12- and 24-week regimens of an investigational interferon-free therapy for hepatitis C were associated with high sustained virological response rates at 12 weeks post treatment in a phase II study of patients with hepatitis C virus genotype 1 who had baseline characteristics associated with poor response to interferon-based therapies.
The findings of this subgroup analysis of the randomized, open-label, multicenter Aviator trial demonstrate that the high response rates recently reported for the entire cohort also apply to patients with older age, black race, Hispanic/Latino ethnicity, interleukin (IL)-28B non-cc genotype, and higher body mass index (BMI), Dr. Frederick Nunes reported at the annual Digestive Disease Week.
The Aviator trial assessed the safety and efficacy of various dosing regimens and combinations of three AbbVie investigational direct-acting antivirals (DAAs) with or without ribavirin, including the potent hepatitis C virus (HCV) protease inhibitor ABT-450 dosed with 100 mg of ritonavir (ABT-450/r, dosed at 100 or 150 mg daily), the NS5A inhibitor ABT-267 (25 mg daily), and the non-nucleoside NS5B inhibitor ABT-333 (400 mg twice daily). A total of 247 patients were included in the subanalysis, Dr. Nunes reported at the meeting.
The regimen that included all three investigational drugs and ribavirin, known as 3 DAA/RBV, was associated with sustained virological response rates of 99% and 93% at 12 weeks in treatment-naive patients and previous peg-interferon/ribavirin (peg-IFN/RBV) null responders, respectively, said Dr. Nunes, who is clinical associate professor of medicine in the University of Pennsylvania Health System, and section chief of gastroenterology at Pennsylvania Hospital, Philadelphia.
In the current analysis, high sustained virological response rates at 12 weeks (SVR12) were also achieved in the 247 patients with chronic HCV genotype 1, including 159 treatment-naive and 88 previous peg-IFN/RBV null responders, who were assigned to 12 or 24 weeks of 3 DAA/RBV. The virological response rates were 99% and 93% for the treatment-naive 12- and 24-week groups, respectively, and 93% and 98% for the null responder 12- and 24-week groups.
The high responses occurred regardless of treatment duration, age, race, ethnicity, BMI, Homeostatic Model of Assessment–Insulin Resistance (HOMA-IR), IL-28B host genotype, or baseline viral load. The rates did not differ significantly on any comparison made in treatment-naive patients or previous null responders, he said.
In the treatment-naive patients, no breakthroughs occurred, although 1% of those in the 12-week treatment arm relapsed, and 3% of the 24-week treatment group relapsed.
In the null responder group, no relapses occurred, but breakthroughs occurred in 7% of those in the 12-week treatment arm, and in 2% of the 24-week treatment arm, he said.
Treatment was safe and generally well tolerated. Four patients discontinued treatment due to drug-related adverse events, most commonly fatigue (in 32.7% and 23.9% of treatment-naive and null responders, respectively) and headache (31.4% and 30.7%, respectively).
One patient had a serious adverse event (arthralgia) considered to be possibly related to the study drug regimen.
Because ribavirin was included in the treatment regimens, it is impossible to tease out whether the adverse events were associated with that drug or with the investigational DAAs, Dr. Nunes noted.
Patients included in the study were noncirrhotic adults aged 18-70 years with a BMI between 18 and 38 kg/m2, and HCV genotype 1.
"The overall efficacy was excellent irrespective of the baseline grouping. So black race, Hispanic/Latino ethnicity, age greater than 50, BMI over 30, male gender, HOMA-IR greater than 3, IL-28B non-cc genotype, and viral load greater than 7 logs all had very high SVR12 response rates," Dr. Nunes said.
The safety and efficacy of this interferon-free 3 DAA/RBV therapy will be further explored in phase III studies, he said.
Dr. Nunes has received grant or research support from Merck, Abbott Laboratories, and Roche Pharma AG.
AT DDW 2013
Major finding: An investigational interferon-free therapy is effective in patients at risk for poor response to interferon-based therapy.
Data source: A randomized, open-label, multicenter trial (Aviator trial).
Disclosures: Dr. Nunes has received grant or research support from Merck, Abbott Laboratories, and Roche Pharma AG.
Tumor biology appears to play role in missed interval colorectal cancers
ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.
Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.
Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.
Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.
Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.
The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.
Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.
Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.
In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.
"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.
"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.
Dr. Samadder has served as a speaker and teacher for Cook.
ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.
Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.
Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.
Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.
Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.
The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.
Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.
Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.
In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.
"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.
"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.
Dr. Samadder has served as a speaker and teacher for Cook.
ORLANDO – Colorectal cancers that are identified 6 months or more after a colonoscopy due to either a missed lesion or a new cancer development occur in 3.5%-6% of patients in the United States, findings from a large population-based retrospective cohort study suggest.
Characteristics of these missed or newly developed cancers, or "missed interval" cancers, suggest that tumor biology, rather than patient or physician factors, plays an important role in their development, Dr. N. Jewel Samadder said at the annual Digestive Disease Week.
Of 129,936 patients aged 50-80 years who underwent colonoscopy in Utah between Feb. 15, 1995, and Jan. 31, 2009, 2,659 were diagnosed with colorectal cancer, and 37 cases of a missed interval cancer that occurred 6-60 months after the index colonoscopy were identified. Using a 6- to 36-month window following the index colonoscopy, the rate of missed interval cancers was 3.5%; using a 6- to 60-month window, the rate was 6%, said Dr. Samadder of Huntsman Cancer Institute, Salt Lake City.
Nearly 85% of the missed cancers occurred in patients who underwent polypectomy at a prior colonoscopy, meaning only about 15% occurred in patients with a prior clean colonoscopy. Furthermore, missed interval colorectal cancers were significantly associated with a lower stage than were those detected at the index colonoscopy (advanced-stage odds ratio, 0.70), and were significantly more likely to be proximally located (OR, 2.24), he said.
Missed interval cancers also were associated with distinctly better survival than were detected cancers, both overall (hazard ratio, 0.63), and by stage (HR: 0.77, 0.54, 0.50, and 0.48 for cancer stages 1, 2, 3, and 4, respectively), he noted.
The findings are noteworthy because while prior studies from other countries have shown similar rates of missed interval colorectal cancers, those findings weren’t necessarily generalizable to U.S. populations, and the rate in the United States has been unclear, Dr. Samadder said. The size of the current study and the use of statewide data reflect clinical practice and make the findings generalizable to the U.S. population and routine GI clinical practice, he noted.
Although colonoscopy is the preferred screening option for colorectal cancer, controversy exists about its effectiveness, particularly with respect to missed interval cancer, he said.
Several factors have been suggested as to the cause of missed interval cancers, including a low adenoma detection rate, incomplete colonoscopy, poor bowel preparation, and differences in tumor biology.
In this study, neither age nor gender was associated with missed interval versus detected cancer. Also, the cecal intubation rate was 92% in the missed interval cases, and bowel prep was rated as good or excellent in 92% of cases. All procedures were performed by a gastroenterologist.
"Thus, our study suggests that a low adenoma detection rate, incomplete colonoscopy, and poor bowel prep may not be the complete estimation of the missed interval cancer issue; tumor biology may play a greater role," Dr. Samadder said. The results are consistent with missed interval colorectal cancers developing from either microsatellite instability or the serrated pathway, he added.
"Future directions include determining molecular predictors of missed interval colorectal cancer, thus identifying patients and communities at greatest risk and needing increased surveillance," he said.
Dr. Samadder has served as a speaker and teacher for Cook.
AT DDW 2013
Major finding: At 6-36 months after colonoscopy the rate of missed interval cancers was 3.5%; at 6-60 months the rate was 6%.
Data source: A population-based retrospective cohort study of 129,936 patients.
Disclosures: Dr. Samadder has served as a speaker and teacher for Cook.
Risk factors for death in NAFLD patients remain elusive
ORLANDO – The risk factors for death in patients with nonalcoholic fatty liver disease include older age, male sex, truncal obesity, and a low HDL cholesterol level – in other words, the same factors that increase risk for death from cardiovascular disease and other causes, according to Dr. Naga P. Chalasani.
On the other hand, elevations in alanine aminotransferase (ALT) levels in patients with NAFLD are not associated with an increased risk for death or other poor outcomes, meaning that researchers may have to burrow more deeply through the available data to find risk predictors unique to NAFLD, said Dr Chalasani of Indiana University, Indianapolis.
"How do we identify someone with NAFLD who is at risk for poor outcomes? I think this is the first shot at risk mapping patients," Dr. Chalasani said at the annual Digestive Disease Week.
Dr. Keith D. Lindor, who moderated the session at which the data were presented, agreed.
"What we’re having trouble with, I think, is defining nonalcoholic fatty liver disease easily, particularly amongst the population," he said. "We saw data that ALT, which we commonly used to use, may not be telling, and there are questions about how well ultrasound detects [NAFLD], particularly given that the amount of steatosis in order to be detected by ultrasound has to be relatively dramatic."
It is still not known whether people with steatosis discovered during biopsy but not visible on ultrasound will have risk factors similar to those of people with more grossly evident steatosis, he said in an interview.
Although Dr. Chalasani and colleagues failed to find unique risk markers in this population, it was not for want of trying. The investigators pored over data from the third National Health and Nutrition Examination Survey (NHANES III) for baseline and follow-up information about patients with NAFLD.
The data were collected from 1988 through 1994, and included gallbladder ultrasound with liver images in 14,797 adults aged 20-74. The authors linked the data to the National Death Index in an attempt to determine which factors might be harbingers of early mortality in patients with NAFLD vs. controls.
They defined NAFLD by the presence of moderate to severe hepatic steatosis on ultrasonography, and by the absence of iron overload, hepatitis B or C infections, and excessive alcohol consumption. Controls were participants in the same data set who did not have underlying liver disease and had normal ultrasound and liver function tests.
There were a total of 2,441 people with NAFLD and 8,423 controls. During a median follow-up of 14.3 years, 14% of controls (1,193), and 21% of those with NAFLD (501) died, a difference that was significant in a univariate analysis (P = .0328).
But when they looked at overall mortality, cancer-related mortality, and cardiovascular mortality, they found that all three categories shared male sex, older age, and a low HDL level as independent predictors for death, with cardiovascular mortality having the added bonus of the metabolic syndrome as an additional risk factor.
The authors did not disclose a funding source. Dr. Chalasani and Dr. Lindor reported having no relevant financial disclosures.
ORLANDO – The risk factors for death in patients with nonalcoholic fatty liver disease include older age, male sex, truncal obesity, and a low HDL cholesterol level – in other words, the same factors that increase risk for death from cardiovascular disease and other causes, according to Dr. Naga P. Chalasani.
On the other hand, elevations in alanine aminotransferase (ALT) levels in patients with NAFLD are not associated with an increased risk for death or other poor outcomes, meaning that researchers may have to burrow more deeply through the available data to find risk predictors unique to NAFLD, said Dr Chalasani of Indiana University, Indianapolis.
"How do we identify someone with NAFLD who is at risk for poor outcomes? I think this is the first shot at risk mapping patients," Dr. Chalasani said at the annual Digestive Disease Week.
Dr. Keith D. Lindor, who moderated the session at which the data were presented, agreed.
"What we’re having trouble with, I think, is defining nonalcoholic fatty liver disease easily, particularly amongst the population," he said. "We saw data that ALT, which we commonly used to use, may not be telling, and there are questions about how well ultrasound detects [NAFLD], particularly given that the amount of steatosis in order to be detected by ultrasound has to be relatively dramatic."
It is still not known whether people with steatosis discovered during biopsy but not visible on ultrasound will have risk factors similar to those of people with more grossly evident steatosis, he said in an interview.
Although Dr. Chalasani and colleagues failed to find unique risk markers in this population, it was not for want of trying. The investigators pored over data from the third National Health and Nutrition Examination Survey (NHANES III) for baseline and follow-up information about patients with NAFLD.
The data were collected from 1988 through 1994, and included gallbladder ultrasound with liver images in 14,797 adults aged 20-74. The authors linked the data to the National Death Index in an attempt to determine which factors might be harbingers of early mortality in patients with NAFLD vs. controls.
They defined NAFLD by the presence of moderate to severe hepatic steatosis on ultrasonography, and by the absence of iron overload, hepatitis B or C infections, and excessive alcohol consumption. Controls were participants in the same data set who did not have underlying liver disease and had normal ultrasound and liver function tests.
There were a total of 2,441 people with NAFLD and 8,423 controls. During a median follow-up of 14.3 years, 14% of controls (1,193), and 21% of those with NAFLD (501) died, a difference that was significant in a univariate analysis (P = .0328).
But when they looked at overall mortality, cancer-related mortality, and cardiovascular mortality, they found that all three categories shared male sex, older age, and a low HDL level as independent predictors for death, with cardiovascular mortality having the added bonus of the metabolic syndrome as an additional risk factor.
The authors did not disclose a funding source. Dr. Chalasani and Dr. Lindor reported having no relevant financial disclosures.
ORLANDO – The risk factors for death in patients with nonalcoholic fatty liver disease include older age, male sex, truncal obesity, and a low HDL cholesterol level – in other words, the same factors that increase risk for death from cardiovascular disease and other causes, according to Dr. Naga P. Chalasani.
On the other hand, elevations in alanine aminotransferase (ALT) levels in patients with NAFLD are not associated with an increased risk for death or other poor outcomes, meaning that researchers may have to burrow more deeply through the available data to find risk predictors unique to NAFLD, said Dr Chalasani of Indiana University, Indianapolis.
"How do we identify someone with NAFLD who is at risk for poor outcomes? I think this is the first shot at risk mapping patients," Dr. Chalasani said at the annual Digestive Disease Week.
Dr. Keith D. Lindor, who moderated the session at which the data were presented, agreed.
"What we’re having trouble with, I think, is defining nonalcoholic fatty liver disease easily, particularly amongst the population," he said. "We saw data that ALT, which we commonly used to use, may not be telling, and there are questions about how well ultrasound detects [NAFLD], particularly given that the amount of steatosis in order to be detected by ultrasound has to be relatively dramatic."
It is still not known whether people with steatosis discovered during biopsy but not visible on ultrasound will have risk factors similar to those of people with more grossly evident steatosis, he said in an interview.
Although Dr. Chalasani and colleagues failed to find unique risk markers in this population, it was not for want of trying. The investigators pored over data from the third National Health and Nutrition Examination Survey (NHANES III) for baseline and follow-up information about patients with NAFLD.
The data were collected from 1988 through 1994, and included gallbladder ultrasound with liver images in 14,797 adults aged 20-74. The authors linked the data to the National Death Index in an attempt to determine which factors might be harbingers of early mortality in patients with NAFLD vs. controls.
They defined NAFLD by the presence of moderate to severe hepatic steatosis on ultrasonography, and by the absence of iron overload, hepatitis B or C infections, and excessive alcohol consumption. Controls were participants in the same data set who did not have underlying liver disease and had normal ultrasound and liver function tests.
There were a total of 2,441 people with NAFLD and 8,423 controls. During a median follow-up of 14.3 years, 14% of controls (1,193), and 21% of those with NAFLD (501) died, a difference that was significant in a univariate analysis (P = .0328).
But when they looked at overall mortality, cancer-related mortality, and cardiovascular mortality, they found that all three categories shared male sex, older age, and a low HDL level as independent predictors for death, with cardiovascular mortality having the added bonus of the metabolic syndrome as an additional risk factor.
The authors did not disclose a funding source. Dr. Chalasani and Dr. Lindor reported having no relevant financial disclosures.
AT DDW 2013
Major finding: Age, male sex, truncal obesity, and a low HDL level are risk factors for death in patients with NAFLD, but are common to other causes of death as well.
Data source: A review of data from the third National Health and Nutrition Examination Survey.
Disclosures: The authors did not disclose a funding source. Dr. Chalasani and Dr. Lindor reported having no relevant financial disclosures.
Serum cytokeratin fragments correlate with NASH histology
ORLANDO – Changes in serum levels of cytokeratin fragments appear to reflect changes in liver histology in patients with nonalcoholic steatohepatitis, Dr. Raj Vuppalanchi reported at the annual Digestive Disease Week.
Among 231 participants in the PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis) trial, every 100-U/L decline in serum cytokeratin fragment (CK-18) level was significantly associated with overall histological improvement (P less than .001); resolution of NASH (P = .002); and improvement of at least 1 point in steatosis grade, hepatocellular ballooning, and nonalcoholic fatty liver disease (NAFLD) score (P less than .001 for all).
"We feel that serum CK-18 is a potentially useful surrogate marker for detection of improvement in clinical trials for NASH," said Dr. Vuppalanchi from Indiana University in Indianapolis.
Dr. Keith D. Lindor, executive vice provost for health at Arizona State University in Phoenix, said in an interview that CK-18 shows promise as a marker for disease activity in NASH but offers only limited information.
"It doesn’t hold the possibility of giving as much detailed information as a biopsy. We look at the amount of fat, amount of inflammation, amount of scarring – the biopsy lets us do that, but I don’t think a single serum assay will allow that," he said.
Dr. Lindor, who was not involved in the study, moderated the session at which the data were presented.
In previous cross-sectional studies, circulating CK-18 levels were shown to be associated with steatohepatitis in people with NAFLD, but it was unclear whether longitudinal changes in CK-18 would reflect changes in liver histology, Dr. Vuppalanchi said.
The investigators looked at CK-18 levels measured at baseline and at 16, 48, and 96 months among 231 of the 247 patients enrolled in the PIVENS trial, which compared vitamin E and/or pioglitazone against placebo in nondiabetic patients with NASH. The participants had liver biopsies at baseline and after 96 weeks of treatment.
The main trial results showed that vitamin E, but not pioglitazone, was significantly better than placebo at improvement of steatohepatitis.
In this substudy, the authors found that, compared with placebo, serum CK-18 levels were significantly lower in vitamin E–treated patients (P = .02 at 16 weeks, and P = .009 at 48 and 96 weeks). Among pioglitazone-treated patients, there was a similar pattern of lower CK-18 levels vs. placebo at all three time intervals (P = .001 for all).
Reductions in CK-18 correlated strongly with disease measures. For each 100-U/L decrease in CK-18 over 96 weeks, the odds ratios (ORs) were as follows: overall histological improvement (OR, 1.41; P less than .001); resolution of NASH (OR, 1.31; P = .002); and 1 point or more improvement in steatosis grade (OR, 1.45; P less than .001), hepatocellular ballooning (OR, 1.36; P less than .001), and NAFLD (OR, 1.41; P less than .001).
The study was supported by the National Institutes of Health with additional funding from Takeda Pharmaceuticals. Dr. Vuppalanchi and Dr. Lindor reported having no financial disclosures.
ORLANDO – Changes in serum levels of cytokeratin fragments appear to reflect changes in liver histology in patients with nonalcoholic steatohepatitis, Dr. Raj Vuppalanchi reported at the annual Digestive Disease Week.
Among 231 participants in the PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis) trial, every 100-U/L decline in serum cytokeratin fragment (CK-18) level was significantly associated with overall histological improvement (P less than .001); resolution of NASH (P = .002); and improvement of at least 1 point in steatosis grade, hepatocellular ballooning, and nonalcoholic fatty liver disease (NAFLD) score (P less than .001 for all).
"We feel that serum CK-18 is a potentially useful surrogate marker for detection of improvement in clinical trials for NASH," said Dr. Vuppalanchi from Indiana University in Indianapolis.
Dr. Keith D. Lindor, executive vice provost for health at Arizona State University in Phoenix, said in an interview that CK-18 shows promise as a marker for disease activity in NASH but offers only limited information.
"It doesn’t hold the possibility of giving as much detailed information as a biopsy. We look at the amount of fat, amount of inflammation, amount of scarring – the biopsy lets us do that, but I don’t think a single serum assay will allow that," he said.
Dr. Lindor, who was not involved in the study, moderated the session at which the data were presented.
In previous cross-sectional studies, circulating CK-18 levels were shown to be associated with steatohepatitis in people with NAFLD, but it was unclear whether longitudinal changes in CK-18 would reflect changes in liver histology, Dr. Vuppalanchi said.
The investigators looked at CK-18 levels measured at baseline and at 16, 48, and 96 months among 231 of the 247 patients enrolled in the PIVENS trial, which compared vitamin E and/or pioglitazone against placebo in nondiabetic patients with NASH. The participants had liver biopsies at baseline and after 96 weeks of treatment.
The main trial results showed that vitamin E, but not pioglitazone, was significantly better than placebo at improvement of steatohepatitis.
In this substudy, the authors found that, compared with placebo, serum CK-18 levels were significantly lower in vitamin E–treated patients (P = .02 at 16 weeks, and P = .009 at 48 and 96 weeks). Among pioglitazone-treated patients, there was a similar pattern of lower CK-18 levels vs. placebo at all three time intervals (P = .001 for all).
Reductions in CK-18 correlated strongly with disease measures. For each 100-U/L decrease in CK-18 over 96 weeks, the odds ratios (ORs) were as follows: overall histological improvement (OR, 1.41; P less than .001); resolution of NASH (OR, 1.31; P = .002); and 1 point or more improvement in steatosis grade (OR, 1.45; P less than .001), hepatocellular ballooning (OR, 1.36; P less than .001), and NAFLD (OR, 1.41; P less than .001).
The study was supported by the National Institutes of Health with additional funding from Takeda Pharmaceuticals. Dr. Vuppalanchi and Dr. Lindor reported having no financial disclosures.
ORLANDO – Changes in serum levels of cytokeratin fragments appear to reflect changes in liver histology in patients with nonalcoholic steatohepatitis, Dr. Raj Vuppalanchi reported at the annual Digestive Disease Week.
Among 231 participants in the PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis) trial, every 100-U/L decline in serum cytokeratin fragment (CK-18) level was significantly associated with overall histological improvement (P less than .001); resolution of NASH (P = .002); and improvement of at least 1 point in steatosis grade, hepatocellular ballooning, and nonalcoholic fatty liver disease (NAFLD) score (P less than .001 for all).
"We feel that serum CK-18 is a potentially useful surrogate marker for detection of improvement in clinical trials for NASH," said Dr. Vuppalanchi from Indiana University in Indianapolis.
Dr. Keith D. Lindor, executive vice provost for health at Arizona State University in Phoenix, said in an interview that CK-18 shows promise as a marker for disease activity in NASH but offers only limited information.
"It doesn’t hold the possibility of giving as much detailed information as a biopsy. We look at the amount of fat, amount of inflammation, amount of scarring – the biopsy lets us do that, but I don’t think a single serum assay will allow that," he said.
Dr. Lindor, who was not involved in the study, moderated the session at which the data were presented.
In previous cross-sectional studies, circulating CK-18 levels were shown to be associated with steatohepatitis in people with NAFLD, but it was unclear whether longitudinal changes in CK-18 would reflect changes in liver histology, Dr. Vuppalanchi said.
The investigators looked at CK-18 levels measured at baseline and at 16, 48, and 96 months among 231 of the 247 patients enrolled in the PIVENS trial, which compared vitamin E and/or pioglitazone against placebo in nondiabetic patients with NASH. The participants had liver biopsies at baseline and after 96 weeks of treatment.
The main trial results showed that vitamin E, but not pioglitazone, was significantly better than placebo at improvement of steatohepatitis.
In this substudy, the authors found that, compared with placebo, serum CK-18 levels were significantly lower in vitamin E–treated patients (P = .02 at 16 weeks, and P = .009 at 48 and 96 weeks). Among pioglitazone-treated patients, there was a similar pattern of lower CK-18 levels vs. placebo at all three time intervals (P = .001 for all).
Reductions in CK-18 correlated strongly with disease measures. For each 100-U/L decrease in CK-18 over 96 weeks, the odds ratios (ORs) were as follows: overall histological improvement (OR, 1.41; P less than .001); resolution of NASH (OR, 1.31; P = .002); and 1 point or more improvement in steatosis grade (OR, 1.45; P less than .001), hepatocellular ballooning (OR, 1.36; P less than .001), and NAFLD (OR, 1.41; P less than .001).
The study was supported by the National Institutes of Health with additional funding from Takeda Pharmaceuticals. Dr. Vuppalanchi and Dr. Lindor reported having no financial disclosures.
AT DDW 2013
Major finding: Every 100-U/L decline in serum cytokeratin fragment (CK-18) levels was significantly associated with overall histological improvement of NAFLD.
Data source: Subanalysis of data from the randomized controlled PIVENS trial.
Disclosures: The study was supported by the National Institutes of Health with additional funding from Takeda Pharmaceuticals. Dr. Vuppalanchi and Dr. Lindor reported having no financial disclosures.
Physicians' adenoma detection rate predicts risk of interval colorectal cancers
ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.
Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.
The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.
The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.
Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.
Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.
After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.
A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.
Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.
Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.
Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.
Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.
Physicians' individual adenoma detection rates were proposed as a quality metric for colonoscopy some time ago by the U.S. Multi-Society Task Force on Colorectal Cancer, and while that proposal made a great deal of sense from a clinical perspective, few supportive data existed, according to Dr. Linda Rabeneck.
Dr. Corley's finding that physician adenoma detection rates are an independent risk factor for patient colorectal cancer following a negative colonoscopy, confirm findings from a Polish study published in 2010 in the New England Journal of Medicine (N. Engl. J. Med. 2010;362:1795-803), and provide the first large-scale U.S. evidence to support that proposal, Dr. Rabeneck said in an interview.
"This really is further evidence that the risk of subsequent colorectal cancer is associated with the adenoma detection rate," she said.
However, Dr. Corley's intriguing finding that there appears to be no threshold above which there is no further benefit, raises some interesting questions for future study - namely, where the bar should be set. The task force proposed a threshold rate of 25% for male patients, and 15% for women, but based on these findings it appears these rates are too low.
"What should they be for a person undergoing their first colonoscopy screening? I think some further work is needed to refine this. But this is an important study to move us forward. I don't think anybody in the field would disagree now that adenoma detection rate should be a quality measure for colonoscopy. We now have strong evidence from a large study by a well-known group of investigators to underpin this," she said.
"It's a fine study. The investigators are to be congratulated."
Physicians' individual adenoma detection rates were proposed as a quality metric for colonoscopy some time ago by the U.S. Multi-Society Task Force on Colorectal Cancer, and while that proposal made a great deal of sense from a clinical perspective, few supportive data existed, according to Dr. Linda Rabeneck.
Dr. Corley's finding that physician adenoma detection rates are an independent risk factor for patient colorectal cancer following a negative colonoscopy, confirm findings from a Polish study published in 2010 in the New England Journal of Medicine (N. Engl. J. Med. 2010;362:1795-803), and provide the first large-scale U.S. evidence to support that proposal, Dr. Rabeneck said in an interview.
"This really is further evidence that the risk of subsequent colorectal cancer is associated with the adenoma detection rate," she said.
However, Dr. Corley's intriguing finding that there appears to be no threshold above which there is no further benefit, raises some interesting questions for future study - namely, where the bar should be set. The task force proposed a threshold rate of 25% for male patients, and 15% for women, but based on these findings it appears these rates are too low.
"What should they be for a person undergoing their first colonoscopy screening? I think some further work is needed to refine this. But this is an important study to move us forward. I don't think anybody in the field would disagree now that adenoma detection rate should be a quality measure for colonoscopy. We now have strong evidence from a large study by a well-known group of investigators to underpin this," she said.
"It's a fine study. The investigators are to be congratulated."
Physicians' individual adenoma detection rates were proposed as a quality metric for colonoscopy some time ago by the U.S. Multi-Society Task Force on Colorectal Cancer, and while that proposal made a great deal of sense from a clinical perspective, few supportive data existed, according to Dr. Linda Rabeneck.
Dr. Corley's finding that physician adenoma detection rates are an independent risk factor for patient colorectal cancer following a negative colonoscopy, confirm findings from a Polish study published in 2010 in the New England Journal of Medicine (N. Engl. J. Med. 2010;362:1795-803), and provide the first large-scale U.S. evidence to support that proposal, Dr. Rabeneck said in an interview.
"This really is further evidence that the risk of subsequent colorectal cancer is associated with the adenoma detection rate," she said.
However, Dr. Corley's intriguing finding that there appears to be no threshold above which there is no further benefit, raises some interesting questions for future study - namely, where the bar should be set. The task force proposed a threshold rate of 25% for male patients, and 15% for women, but based on these findings it appears these rates are too low.
"What should they be for a person undergoing their first colonoscopy screening? I think some further work is needed to refine this. But this is an important study to move us forward. I don't think anybody in the field would disagree now that adenoma detection rate should be a quality measure for colonoscopy. We now have strong evidence from a large study by a well-known group of investigators to underpin this," she said.
"It's a fine study. The investigators are to be congratulated."
ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.
Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.
The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.
The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.
Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.
Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.
After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.
A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.
Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.
Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.
Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.
Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.
ORLANDO – The rate at which physicians detect adenomas during colonoscopy is an independent risk factor for their patients’ risk of developing colorectal cancer following a negative colonoscopy, according to findings from a large observational study.
Physicians with low rates of adenoma detection during screening colonoscopies were more likely to have patients who developed interval colorectal cancers. For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%, Dr. Douglas A. Corley reported at the annual Digestive Disease Week.
The findings suggest that adenoma detection rates – the proportion of screening colonoscopies in which a physician detects at least one adenoma – could be a useful quality metric, he said.
The findings were noted in a study of 314,872 colonoscopy exams in which 8,708 colorectal cancers were detected. Interval colorectal cancers – cancers diagnosed at examinations that took place at least 6 months after the index colonoscopy – were seen in 712 patients, said Dr. Corley, of the Kaiser Permanente Division of Research, Oakland, Calif.
Most (60%) interval cancers were proximal. In total, 34% were advanced cancers, and about 20% led to colorectal cancer–related deaths. About one-third were diagnosed in the early interval period, between 6 months and 3 years. The remaining two-thirds were diagnosed 3-10 years after an initial negative screening colonoscopy, Dr. Corley said.
Physician adenoma detection rates ranged from 7% to 52%, which are rates consistent with prior reports in the literature. There was a linear association across five quintiles of physician adenoma detection rates and subsequent patient colorectal cancer risk. "There’s no threshold effect above which increases in adenoma detection rate were without benefit," Dr. Corley said.
After adjusting for colonoscopy indication and patient age, sex, race/ethnicity, family history of colorectal cancer, and Charlson comorbidity score, the risk was about 80%-90% higher among patients of physicians whose adenoma detection rates were in the first or second quintile, as compared with patients of physicians with detection rates in the highest quintile.
A similar pattern was seen for advanced colorectal cancers, and the correlation was even stronger. The risk was increased more than twofold among patients of physicians in the bottom two quintiles of adenoma detection rates, compared with patients whose physicians were in the top quintile, he said.
Risk of death from colorectal cancer followed a similar pattern. Patients of physicians in the first and second quintiles had more than a 2.5-fold increased risk of colorectal cancer death compared with patients of physicians in the top quintile. Risk did not differ by patient status or by cancer location, Dr. Corley said.
Patients included in the study were aged 50 years or older, had been members of the Kaiser Permanente Northern California health plan for at least 2 years, and had a negative colonoscopy for any indication between 1998 and 2010. Only those colonoscopies performed by experienced endoscopists – those who had performed more than 300 colonoscopies and more than 75 screening exams during the study period – were included in the study.
Patients were followed for 10 years or until another negative colonoscopy was performed, health plan membership was terminated, a diagnosis of colorectal cancer was made, or Jan. 31, 2011 – whichever came first.
Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.
AT DDW 2013
Major finding: For every 1% decline in the physician adenoma detection rate, colorectal cancer risk increased by about 3%, and the risk of death related to colorectal cancer increased by about 4%.
Data source: An observational study of 314,872 colonoscopies in which 8,708 interval colorectal cancers occurred.
Disclosures: Dr. Corley has received grant or research support from Pfizer Pharmaceuticals.
Hint of prolonged response to vedoluzimab seen in Crohn's
ORLANDO – In patients with Crohn’s disease, a response to the investigational monoclonal antibody vedoluzimab within 6 weeks of initiating therapy was predictive of a continued response to the drug, even at lower doses.
Among patients in the GEMINI II trial with a documented response to vedoluzimab after 6 weeks, 32% of those who were then randomized to receive the drug once every 8 weeks for an additional 46 weeks had a corticosteroid-free clinical remission of Crohn’s disease (CD), as did 29% of those who continued to receive the same dose every 4 weeks and 16% of those on placebo, said Dr. William Sandborn at the annual Digestive Disease Week.
However, the rate of durable clinical remissions, defined as clinical remissions at 80% or more of study visits, was comparable for both dosing groups and the placebo group.
"Patients who had a clinical response to vedolizumab by week 6 then went on to have stable clinical remission rates throughout the maintenance phase and significantly higher clinical remission rates than placebo by week 52," said Dr. Sandborn of the University of California, San Diego.
Vedolizumab is an investigational, gut-selective monoclonal antibody targeting the alpha-4 beta-7 integrin. In GEMINI II, the drug was shown to be more effective than placebo for induction and maintenance therapy of CD.
For this analysis, the researchers dug deeper into the data from GEMINI II and looked at maintenance-phase outcomes for those patients who had a clinical response to the drug by week 6 of the trial.
Patients in the trial were adults 18-80 years old with a diagnosis of CD at least 3 months before study entry, moderate to severe CD as determined by a CD Activity Index (CDAI) score of 220-450 at screening, and either intolerance of or an inadequate response to purine antimetabolites or anti–tumor necrosis factor (anti-TNF) agents.
A clinical response to vedolizumab was defined as at least a 70-point decline in CDAI score from baseline value at week 6 following two induction doses of therapy. Patients were randomized on a 1:1:1 basis to receive vedolizumab via infusion every 8 weeks, the same dose every 4 weeks, or placebo until week 52.
Patients who did not have a clinical response by week 6 were treated with open-label vedolizumab at the 300-mg dose every 8 weeks until week 52, and were assessed with those patients who had been on placebo throughout the induction and maintenance phases.
CDAI scores among 153 patients on placebo stabilized at 26 weeks, but continued to decline through week 52 among patients on vedolizumab at both dosing frequencies (154 patients in each dosing group). Rates of clinical remission (CDAI score of 150 or lower) remained relatively stable among patients on vedolizumab, but declined among those on placebo.
A corticosteroid-free remission was seen at week 52 in 32% of patients on the 8-week schedule and in 16% of those on placebo (P = .015). The remission rate was 29% for those on the 4-week schedule (P vs. placebo = .045).
In addition, 21% of those on vedolizumab every 8 weeks had durable clinical remissions, as did 16% of those on the every-4-week dose and 14% of those on placebo. There were no statistically significant differences among the three groups.
In the question-and-answer session following presentation of the results, an attendee commented that "it’s a little disturbing that the more frequent dose seemed to be numerically inferior to the less-frequent dose at virtually every measured outcome."
Dr. Sandborn said that the investigators have extensively examined that question and determined that "there’s noise around the measurements, but you couldn’t draw any firm statistical conclusions."
The study was funded by Millennium/Takeda. Dr. Sandborn disclosed serving as a consultant and receiving grant and research support from the combined companies.
ORLANDO – In patients with Crohn’s disease, a response to the investigational monoclonal antibody vedoluzimab within 6 weeks of initiating therapy was predictive of a continued response to the drug, even at lower doses.
Among patients in the GEMINI II trial with a documented response to vedoluzimab after 6 weeks, 32% of those who were then randomized to receive the drug once every 8 weeks for an additional 46 weeks had a corticosteroid-free clinical remission of Crohn’s disease (CD), as did 29% of those who continued to receive the same dose every 4 weeks and 16% of those on placebo, said Dr. William Sandborn at the annual Digestive Disease Week.
However, the rate of durable clinical remissions, defined as clinical remissions at 80% or more of study visits, was comparable for both dosing groups and the placebo group.
"Patients who had a clinical response to vedolizumab by week 6 then went on to have stable clinical remission rates throughout the maintenance phase and significantly higher clinical remission rates than placebo by week 52," said Dr. Sandborn of the University of California, San Diego.
Vedolizumab is an investigational, gut-selective monoclonal antibody targeting the alpha-4 beta-7 integrin. In GEMINI II, the drug was shown to be more effective than placebo for induction and maintenance therapy of CD.
For this analysis, the researchers dug deeper into the data from GEMINI II and looked at maintenance-phase outcomes for those patients who had a clinical response to the drug by week 6 of the trial.
Patients in the trial were adults 18-80 years old with a diagnosis of CD at least 3 months before study entry, moderate to severe CD as determined by a CD Activity Index (CDAI) score of 220-450 at screening, and either intolerance of or an inadequate response to purine antimetabolites or anti–tumor necrosis factor (anti-TNF) agents.
A clinical response to vedolizumab was defined as at least a 70-point decline in CDAI score from baseline value at week 6 following two induction doses of therapy. Patients were randomized on a 1:1:1 basis to receive vedolizumab via infusion every 8 weeks, the same dose every 4 weeks, or placebo until week 52.
Patients who did not have a clinical response by week 6 were treated with open-label vedolizumab at the 300-mg dose every 8 weeks until week 52, and were assessed with those patients who had been on placebo throughout the induction and maintenance phases.
CDAI scores among 153 patients on placebo stabilized at 26 weeks, but continued to decline through week 52 among patients on vedolizumab at both dosing frequencies (154 patients in each dosing group). Rates of clinical remission (CDAI score of 150 or lower) remained relatively stable among patients on vedolizumab, but declined among those on placebo.
A corticosteroid-free remission was seen at week 52 in 32% of patients on the 8-week schedule and in 16% of those on placebo (P = .015). The remission rate was 29% for those on the 4-week schedule (P vs. placebo = .045).
In addition, 21% of those on vedolizumab every 8 weeks had durable clinical remissions, as did 16% of those on the every-4-week dose and 14% of those on placebo. There were no statistically significant differences among the three groups.
In the question-and-answer session following presentation of the results, an attendee commented that "it’s a little disturbing that the more frequent dose seemed to be numerically inferior to the less-frequent dose at virtually every measured outcome."
Dr. Sandborn said that the investigators have extensively examined that question and determined that "there’s noise around the measurements, but you couldn’t draw any firm statistical conclusions."
The study was funded by Millennium/Takeda. Dr. Sandborn disclosed serving as a consultant and receiving grant and research support from the combined companies.
ORLANDO – In patients with Crohn’s disease, a response to the investigational monoclonal antibody vedoluzimab within 6 weeks of initiating therapy was predictive of a continued response to the drug, even at lower doses.
Among patients in the GEMINI II trial with a documented response to vedoluzimab after 6 weeks, 32% of those who were then randomized to receive the drug once every 8 weeks for an additional 46 weeks had a corticosteroid-free clinical remission of Crohn’s disease (CD), as did 29% of those who continued to receive the same dose every 4 weeks and 16% of those on placebo, said Dr. William Sandborn at the annual Digestive Disease Week.
However, the rate of durable clinical remissions, defined as clinical remissions at 80% or more of study visits, was comparable for both dosing groups and the placebo group.
"Patients who had a clinical response to vedolizumab by week 6 then went on to have stable clinical remission rates throughout the maintenance phase and significantly higher clinical remission rates than placebo by week 52," said Dr. Sandborn of the University of California, San Diego.
Vedolizumab is an investigational, gut-selective monoclonal antibody targeting the alpha-4 beta-7 integrin. In GEMINI II, the drug was shown to be more effective than placebo for induction and maintenance therapy of CD.
For this analysis, the researchers dug deeper into the data from GEMINI II and looked at maintenance-phase outcomes for those patients who had a clinical response to the drug by week 6 of the trial.
Patients in the trial were adults 18-80 years old with a diagnosis of CD at least 3 months before study entry, moderate to severe CD as determined by a CD Activity Index (CDAI) score of 220-450 at screening, and either intolerance of or an inadequate response to purine antimetabolites or anti–tumor necrosis factor (anti-TNF) agents.
A clinical response to vedolizumab was defined as at least a 70-point decline in CDAI score from baseline value at week 6 following two induction doses of therapy. Patients were randomized on a 1:1:1 basis to receive vedolizumab via infusion every 8 weeks, the same dose every 4 weeks, or placebo until week 52.
Patients who did not have a clinical response by week 6 were treated with open-label vedolizumab at the 300-mg dose every 8 weeks until week 52, and were assessed with those patients who had been on placebo throughout the induction and maintenance phases.
CDAI scores among 153 patients on placebo stabilized at 26 weeks, but continued to decline through week 52 among patients on vedolizumab at both dosing frequencies (154 patients in each dosing group). Rates of clinical remission (CDAI score of 150 or lower) remained relatively stable among patients on vedolizumab, but declined among those on placebo.
A corticosteroid-free remission was seen at week 52 in 32% of patients on the 8-week schedule and in 16% of those on placebo (P = .015). The remission rate was 29% for those on the 4-week schedule (P vs. placebo = .045).
In addition, 21% of those on vedolizumab every 8 weeks had durable clinical remissions, as did 16% of those on the every-4-week dose and 14% of those on placebo. There were no statistically significant differences among the three groups.
In the question-and-answer session following presentation of the results, an attendee commented that "it’s a little disturbing that the more frequent dose seemed to be numerically inferior to the less-frequent dose at virtually every measured outcome."
Dr. Sandborn said that the investigators have extensively examined that question and determined that "there’s noise around the measurements, but you couldn’t draw any firm statistical conclusions."
The study was funded by Millennium/Takeda. Dr. Sandborn disclosed serving as a consultant and receiving grant and research support from the combined companies.
AT DDW 2013
Major finding: Among patients with a documented response to vedoluzimab after 6 weeks, 32% of those who received it every 8 weeks had a clinical remission at week 52, compared with 29% on an every-4-week dose and 16% of those on placebo.
Data source: Subanalysis of 461 patients in the maintenance phase of a randomized controlled trial.
Disclosures: The study was funded by Millennium/Takeda. Dr. Sandborn disclosed serving as a consultant and receiving grant and research support from the combined companies.
