From the AGA Journals

For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.

In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.

Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.

For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.

In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine₂ receptor blockers, and 24% were on antacid agents.

Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.

In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.

The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.

This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
 

SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.

For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.

In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.

Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.

For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.

In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine₂ receptor blockers, and 24% were on antacid agents.

Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.

In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.

The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.

This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
 

SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.

For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.

In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.

Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.

For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.

In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine₂ receptor blockers, and 24% were on antacid agents.

Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.

In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.

The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.

This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
 

SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.

Individuals with Lynch syndrome were significantly more likely to have a personal history of gastric cancer if they were older, male, had an affected first-degree relative, or had pathogenic variants in the MLH1 or MSH2 mismatch repair genes, researchers reported.

“These findings suggest that personalized, risk-stratified approaches to gastric cancer surveillance may be appropriate for individuals with Lynch syndrome–associated mutations,” wrote Jaihwan Kim of Seoul National University Bundang Hospital, Seongnam, South Korea, and associates. Their report is in Clinical Gastroenterology and Hepatology.

Lynch syndrome, which involves autosomal dominant germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and EPCAM, significantly increases the risk for several types of cancer. Although Lynch syndrome increases gastric cancer risk almost tenfold, more than 90% of individuals with Lynch syndrome do not develop it, the researchers noted. Given the lethality of this cancer, they sought to better characterize risk factors.

To do so, they studied cancer histories and clinical and demographic data from 51,086 individuals who were tested for gene variants associated with Lynch syndrome at a commercial laboratory between 2006 and 2013. More than 3,800 individuals had pathogenic variants, including more than 1,300 with mutations of MLH1, more than 1,600 with mutations of MSH2, 670 with mutations of MSH6, 145 with mutations in PMS2, and 28 with mutations in EPCAM. In all, 41 (1%) individuals with pathogenic mutations had a personal history of gastric cancer, while 350 (9%) had an affected first or second-degree relative.

After the researchers controlled for potential confounders, males with Lynch syndrome–associated mutations had nearly triple the odds of a personal history of gastric cancer compared with females (odds ratio, 2.82; 95% CI, 1.48 to 5.38). The odds of gastric cancer also rose approximately twofold with each 10-year increase in age — and by 2.5-fold when individuals had an affected first-degree relative. Having a second-degree relative with gastric cancer was not an independent correlate. Compared with mutations in MSH6, PMS2, and EPCAM, gastric cancer was significantly more likely among individuals with mutations of MLH1 (OR, 6.53; 95% CI, 1.5 to 28.42) or MSH2 (OR = 5.23; 95% CI, 1.21 to 22.71).

Clinicians might use these factors to risk-stratify patients with Lynch syndrome to identify those who might benefit from enhanced surveillance with more frequent esophagogastroduodenoscopy, the researchers wrote. They noted that male sex, age, and first-degree family history increase the risk for sporadic gastric cancer unassociated with Lynch syndrome–associated mutations. Thus, these “traditional risk factors” might compound the inherited risk for gastric cancer observed in Lynch syndrome carriers.

The National Institutes of Health and the Pussycat Foundation Helen Gurley Brown Presidential Initiative provided funding. One coinvestigator disclosed a consulting relationship with Myriad Genetic Laboratories and having rights to an inventor portion of licensing revenues from PREMM5, a prediction model for Lynch syndrome mutations. The other researchers reported having no conflicts of interest.

SOURCE: Kim J et al. Clin Gastroenterol Hepatol. 2019 Jul 15. doi: 1016/j.cgh.2019.07.012.

Individuals with Lynch syndrome were significantly more likely to have a personal history of gastric cancer if they were older, male, had an affected first-degree relative, or had pathogenic variants in the MLH1 or MSH2 mismatch repair genes, researchers reported.

“These findings suggest that personalized, risk-stratified approaches to gastric cancer surveillance may be appropriate for individuals with Lynch syndrome–associated mutations,” wrote Jaihwan Kim of Seoul National University Bundang Hospital, Seongnam, South Korea, and associates. Their report is in Clinical Gastroenterology and Hepatology.

Lynch syndrome, which involves autosomal dominant germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and EPCAM, significantly increases the risk for several types of cancer. Although Lynch syndrome increases gastric cancer risk almost tenfold, more than 90% of individuals with Lynch syndrome do not develop it, the researchers noted. Given the lethality of this cancer, they sought to better characterize risk factors.

To do so, they studied cancer histories and clinical and demographic data from 51,086 individuals who were tested for gene variants associated with Lynch syndrome at a commercial laboratory between 2006 and 2013. More than 3,800 individuals had pathogenic variants, including more than 1,300 with mutations of MLH1, more than 1,600 with mutations of MSH2, 670 with mutations of MSH6, 145 with mutations in PMS2, and 28 with mutations in EPCAM. In all, 41 (1%) individuals with pathogenic mutations had a personal history of gastric cancer, while 350 (9%) had an affected first or second-degree relative.

After the researchers controlled for potential confounders, males with Lynch syndrome–associated mutations had nearly triple the odds of a personal history of gastric cancer compared with females (odds ratio, 2.82; 95% CI, 1.48 to 5.38). The odds of gastric cancer also rose approximately twofold with each 10-year increase in age — and by 2.5-fold when individuals had an affected first-degree relative. Having a second-degree relative with gastric cancer was not an independent correlate. Compared with mutations in MSH6, PMS2, and EPCAM, gastric cancer was significantly more likely among individuals with mutations of MLH1 (OR, 6.53; 95% CI, 1.5 to 28.42) or MSH2 (OR = 5.23; 95% CI, 1.21 to 22.71).

Clinicians might use these factors to risk-stratify patients with Lynch syndrome to identify those who might benefit from enhanced surveillance with more frequent esophagogastroduodenoscopy, the researchers wrote. They noted that male sex, age, and first-degree family history increase the risk for sporadic gastric cancer unassociated with Lynch syndrome–associated mutations. Thus, these “traditional risk factors” might compound the inherited risk for gastric cancer observed in Lynch syndrome carriers.

The National Institutes of Health and the Pussycat Foundation Helen Gurley Brown Presidential Initiative provided funding. One coinvestigator disclosed a consulting relationship with Myriad Genetic Laboratories and having rights to an inventor portion of licensing revenues from PREMM5, a prediction model for Lynch syndrome mutations. The other researchers reported having no conflicts of interest.

SOURCE: Kim J et al. Clin Gastroenterol Hepatol. 2019 Jul 15. doi: 1016/j.cgh.2019.07.012.

Individuals with Lynch syndrome were significantly more likely to have a personal history of gastric cancer if they were older, male, had an affected first-degree relative, or had pathogenic variants in the MLH1 or MSH2 mismatch repair genes, researchers reported.

“These findings suggest that personalized, risk-stratified approaches to gastric cancer surveillance may be appropriate for individuals with Lynch syndrome–associated mutations,” wrote Jaihwan Kim of Seoul National University Bundang Hospital, Seongnam, South Korea, and associates. Their report is in Clinical Gastroenterology and Hepatology.

Lynch syndrome, which involves autosomal dominant germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and EPCAM, significantly increases the risk for several types of cancer. Although Lynch syndrome increases gastric cancer risk almost tenfold, more than 90% of individuals with Lynch syndrome do not develop it, the researchers noted. Given the lethality of this cancer, they sought to better characterize risk factors.

To do so, they studied cancer histories and clinical and demographic data from 51,086 individuals who were tested for gene variants associated with Lynch syndrome at a commercial laboratory between 2006 and 2013. More than 3,800 individuals had pathogenic variants, including more than 1,300 with mutations of MLH1, more than 1,600 with mutations of MSH2, 670 with mutations of MSH6, 145 with mutations in PMS2, and 28 with mutations in EPCAM. In all, 41 (1%) individuals with pathogenic mutations had a personal history of gastric cancer, while 350 (9%) had an affected first or second-degree relative.

After the researchers controlled for potential confounders, males with Lynch syndrome–associated mutations had nearly triple the odds of a personal history of gastric cancer compared with females (odds ratio, 2.82; 95% CI, 1.48 to 5.38). The odds of gastric cancer also rose approximately twofold with each 10-year increase in age — and by 2.5-fold when individuals had an affected first-degree relative. Having a second-degree relative with gastric cancer was not an independent correlate. Compared with mutations in MSH6, PMS2, and EPCAM, gastric cancer was significantly more likely among individuals with mutations of MLH1 (OR, 6.53; 95% CI, 1.5 to 28.42) or MSH2 (OR = 5.23; 95% CI, 1.21 to 22.71).

Clinicians might use these factors to risk-stratify patients with Lynch syndrome to identify those who might benefit from enhanced surveillance with more frequent esophagogastroduodenoscopy, the researchers wrote. They noted that male sex, age, and first-degree family history increase the risk for sporadic gastric cancer unassociated with Lynch syndrome–associated mutations. Thus, these “traditional risk factors” might compound the inherited risk for gastric cancer observed in Lynch syndrome carriers.

The National Institutes of Health and the Pussycat Foundation Helen Gurley Brown Presidential Initiative provided funding. One coinvestigator disclosed a consulting relationship with Myriad Genetic Laboratories and having rights to an inventor portion of licensing revenues from PREMM5, a prediction model for Lynch syndrome mutations. The other researchers reported having no conflicts of interest.

SOURCE: Kim J et al. Clin Gastroenterol Hepatol. 2019 Jul 15. doi: 1016/j.cgh.2019.07.012.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) recently updated recommendations for patient follow-up after colonoscopy and polypectomy.

The new guidance was based on advancements in both research and technology since the last recommendations were published in 2012, reported lead author Samir Gupta, MD, AGAF, of the University of California, San Diego, and colleagues.

“[Since 2012,] a number of articles have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes, such as incident CRC and polyps,” the investigators wrote in Gastroenterology. “Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g., adequate bowel preparation, cecal intubation, adequate adenoma detection, and complete polyp resection), and utilization of state of the art technologies (e.g., high-definition colonoscopes).”

The task force, which comprised the American College of Gastroenterology, the American Gastroenterological Association, and the American Society of Gastrointestinal Endoscopy, identified key topics using PICO (patient, intervention, comparison, and outcome) questions before conducting a comprehensive literature review that included 136 articles. Based on these findings, two task force members generated recommendations that were further refined through consensus discussion. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy.

According to Dr. Gupta and colleagues, some of the new recommendations, particularly those that advise less stringent follow-up, may encounter resistance from various stakeholders.

“Patients, primary care physicians, and colonoscopists may have concerns about lengthening a previously recommended interval, and will need to engage in shared decision making regarding whether to lengthen the follow-up interval based upon the guidance here or utilize the recommendation made at the time of the prior colonoscopy,” the task force wrote.

The most prominent recommendations of this kind concern patients who undergo removal of tubular adenomas less than 10 mm in size. For patients who have 1-2 of these adenomas removed, the task force now recommends follow-up after 7-10 years, instead of the previously recommended interval of 5-10 years.

“[This decision was] based on the growing body of evidence to support low risk for metachronous advanced neoplasia,” the task force wrote. “In this population, the risk for metachronous advanced neoplasia is similar to that for individuals with no adenoma. Importantly, the observed risk for fatal CRC among individuals with 1-10 adenomas less than 10 mm is lower than average for the general population.”

Along similar lines, patients who undergo removal of 3-4 small adenomas now have a recommended 3-5 year follow-up window, instead of the previously strict recommendation for follow-up at 3 years.

But not all of the new guidance is less stringent. While the task force previously recommended a follow-up period of less than 3 years after removal of more than 10 adenomas, they now recommend follow-up at 1 year. This change was made to simplify guidance, the investigators wrote, noting that the evidence base in this area “has not been markedly strengthened” since 2012.

Compared with the old guidance, the updated publication offers more detailed recommendations for follow-up after removal of serrated polyps. On this topic, 10 clinical scenarios are presented, with follow-up ranging from 6 months after piecemeal resection of a sessile serrated polyp greater than 20 mm to 10 years after removal of 20 or fewer hyperplastic polyps less than 10 mm that were located in the rectum or sigmoid colon. Incidentally, these two recommendations are strong and based on moderate evidence, whereas the remaining recommendations for serrated polyps are weak and based on very-low-quality evidence.

Because of such knowledge gaps, the investigators emphasized the need for more data. The publication includes extensive discussion of pressing research topics and appropriate methods of investigation.

“Our review highlights several opportunities for research to clarify risk stratification and management of patients post-polypectomy,” the task force wrote. “In order to optimize risk-reduction strategies, the mechanisms driving metachronous advanced neoplasia after baseline polypectomy and their relative frequency need to be better understood through studies that include large numbers of patients with interval cancers and/or advanced neoplasia after baseline polypectomy. Mechanisms may include new/incident growth, incomplete baseline resection, and missed neoplasia; each of these potential causes may require different interventions for improvement.”

The task force also suggested that some basic questions beyond risk stratification remain unanswered, such as the impact of surveillance on CRC incidence and mortality.

“Such evidence is needed given the increasing proportion of patients who are having adenomas detected as part of increased participation in CRC screening,” the task force wrote.

Other suggested topics of investigation include age-related analyses that incorporate procedural risk, cost-effectiveness studies, and comparisons of nonendoscopic methods of surveillance, such as fecal immunochemical testing.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs. The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Gupta S et al. Gastroenterology. 2020 Feb 7. doi: 10.1053/j.gastro.2019.10.026.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

The U.S. Multi-Society Task Force (USMSTF) on Colorectal Cancer recently published recommendations for endoscopic removal of precancerous colorectal lesions.

According to lead author Tonya Kaltenbach, MD, of the University of California, San Francisco, and fellow panelists, the publication aims to improve complete resection rates, which can vary widely between endoscopists; almost one out of four lesions (22.7%) may be incompletely removed by some practitioners, leading to higher rates of colorectal cancer.

“[A]lthough the majority (50%) of postcolonoscopy colon cancers [are] likely due to missed lesions, close to one-fifth of incident cancers [are] related to incomplete resection,” the panelists wrote in Gastroenterology, referring to a pooled analysis of eight surveillance studies.

The panelists’ recommendations, which were based on both evidence and clinical experience, range from specific polyp removal techniques to guidance for institution-wide quality assurance of polypectomies. Each statement is described by both strength of recommendation and level of evidence, the latter of which was determined by Grading of Recommendations, Assessment, Development, and Evaluation Ratings of Evidence (GRADE) criteria. Recommendations were written by a panel of nine experts and approved by the governing boards of the three societies they represented – the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The recommendations were copublished in the March issues of the American Journal of Gastroenterology, Gastroenterology, and Gastrointestinal Endoscopy. 

Central to the publication are recommended polypectomy techniques for specific types of lesions.

“Polypectomy techniques vary widely in clinical practice,” the panelists wrote. “They are often driven by physician preference based on how they were taught and on trial and error, due to the lack of standardized training and the paucity of published evidence. In the past decade, evidence has evolved on the superiority of specific methods.”

“Optimal techniques encompass effectiveness, safety, and efficiency,” they wrote. “Colorectal lesion characteristics, including location, size, morphology, and histology, influence the optimal removal method.”

For lesions up to 9 mm, the panelists recommended cold snare polypectomy “due to high complete resection rates and safety profile.” In contrast, they recommended against both cold and hot biopsy forceps, which have been associated with higher rates of incomplete resection. Furthermore, they cautioned that hot biopsy forceps may increase risks of complications and produce inadequate tissue samples for histopathology.

For nonpedunculated lesions between 10 and 19 mm, guidance is minimal. The panelists recommended cold or hot snare polypectomy, although this statement was conditional and based on low-quality evidence.

Recommendations were more extensive for large nonpedunculated lesions (at least 20 mm). For such lesions, the panelists strongly recommended endoscopic mucosal resection (EMR). They emphasized that large lesions should be removed in the fewest possible pieces by an appropriately experienced endoscopist during a single colonoscopy session. The panelists recommended the use of a viscous injection solution with a contrast agent and adjuvant thermal ablation of the post-EMR margin. They recommended against the use of tattoo as a submucosal injection solution, and ablation of residual lesion tissue that is endoscopically visible. Additional recommendations for large lesions, including prophylactic closure of resection defects and coagulation techniques, were based on low-quality evidence.

For pedunculated lesions greater than 10 mm, the panelists recommended hot snare polypectomy. For pedunculated lesions with a head greater than 20 mm or a stalk thickness greater than 5 mm, they recommended prophylactic mechanical ligation.

Beyond lesion assessment and removal, recommendations addressed lesion marking, equipment, surveillance, and quality of polypectomy.

Concerning quality, the panelists recommended that endoscopists participate in a quality assurance program that documents adverse events, and that institutions use standardized polypectomy competency assessments, such as Cold Snare Polypectomy Competency Assessment Tool and/or Direct Observation of Polypectomy Skills.

“Focused teaching is needed to ensure the optimal endoscopic management of colorectal lesions,” the panelists wrote. They went on to suggest that “development and implementation of polypectomy quality metrics may be necessary to optimize practice and outcomes.”

“For example, the type of resection method used for the colorectal lesion removal in the procedure report should be documented, and the inclusion of adequate resection technique as a quality indicator in colorectal cancer screening programs should be considered,” they wrote. “Adverse events, including bleeding, perforation, hospital admissions, and the number of benign colorectal lesions referred for surgical management, should be measured and reported. Finally, standards for pathology preparation and reporting of lesions suspicious for submucosal invasion should be in place to provide accurate staging and management.”

The investigators reported relationships with Covidien, Ironwood, Medtronic, and others.

SOURCE: Kaltenbach T et al. Gastroenterology. 2020 Jan 18. doi: 10.1053/j.gastro.2019.12.018.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

Compared with patients who have normal baseline colonoscopy findings, those with low-risk adenomas may not have elevated risks of colorectal cancer (CRC) or CRC-related death, based on a retrospective analysis of more than 64,000 patients.

In contrast, patients with high-risk adenomas at baseline had significantly elevated rates of both CRC and CRC-related death, reported lead author Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco and colleagues.

With additional research, these findings may influence colonoscopy surveillance intervals, the investigators wrote in Gastroenterology.

“Current guidelines recommend that patients with a low-risk adenoma finding ... receive surveillance colonoscopy in 5-10 years, although in practice, clinicians often use even more frequent surveillance ... in this low-risk group,” they wrote. “The rationale for continued support of shorter-than-recommended surveillance intervals for patients with low-risk adenomas is unclear, but could stem from a lack of long-term population-based studies assessing colorectal cancer incidence and related deaths following low-risk adenoma removal or randomized trials evaluating optimal postpolypectomy surveillance intervals.”

To alleviate this knowledge gap, the investigators began by screening data from 186,046 patients who underwent baseline colonoscopy between 2004 and 2010 at 21 medical centers in California. Following exclusions based on family history, confounding gastrointestinal diseases, and incomplete data, 64,422 patients remained. Among these patients, the mean age was 61.6 years, with a slight female majority (54.3%). Almost three out of four patients (71.2%) had normal colonoscopy findings, followed by smaller proportions who were diagnosed with low-risk adenoma (17.0%) or high-risk adenoma (11.7%), based on United States Multi-Society Task Force guidelines.

After a median follow-up of 8.1 years, 117 patients who had normal colonoscopy findings developed CRC, 22 of whom died from the disease. In comparison, the low-risk adenoma group had 37 cases of CRC and 3 instances of CRC-related death, whereas the high-risk adenoma group had 60 cases of CRC and 13 instances of CRC-related death.

In the no-adenoma and low-risk groups, trends in age-adjusted CRC incidence rates were similar; in both cohorts, CRC incidence increased gradually over the decade following colonoscopy, with each group reaching approximately 50 cases per 100,000 person-years by year 10. In contrast, CRC incidence climbed rapidly in the high-risk adenoma group, ultimately peaking a decade later at almost 220 cases per 100,000 person-years. Average incidence rates per 100,000 person-years were similar among patients with no adenoma (31.1) and low-risk adenoma (38.8), but markedly higher among those with high-risk adenoma (90.8). At the end of the 14-year follow-up period, absolute risks of CRC among patients with no adenoma, low-risk adenoma, and high-risk adenoma were 0.51%, 0.57%, and 2.03%, respectively.

Based on covariate-adjusted Cox regression models, patients with low-risk adenoma did not have a significantly higher risk of CRC or CRC-related death than did patients with no adenoma. In contrast, patients with high-risk adenoma had significantly higher risks of CRC (hazard ratio, 2.61) and CRC-related death (HR, 3.94).

“These findings support guideline recommendations for intensive colonoscopy surveillance in [patients with high-risk adenomas at baseline],” the investigators wrote.

Considering similar risks between patients with low-risk adenomas and those with normal findings, the investigators suggested that longer surveillance intervals may be acceptable for both of these patient populations.

“Guidelines recommending comparable follow-up for low-risk adenomas and normal examinations, such as lengthening the surveillance interval to more than 5 years and possibly 10 years, may provide comparable cancer incidence and mortality benefits for these two groups,” they wrote.

Still, the investigators noted that study limitations – such as disparate rates of subsequent colonoscopy between groups – make it difficult to draw definitive, practice-changing conclusions.

“Additional studies, potentially including randomized trials, on the natural history of low-risk adenoma and normal findings without intervening surveillance exams before 10 years are needed to help guide future surveillance practices,” they concluded.

The study was supported by the National Cancer Institute and the American Gastroenterological Association. The investigators disclosed no conflicts of interest.

SOURCE: Lee JK et al. Gastroenterology. 2019 Oct 4. doi: 10.1053/j.gastro.2019.09.039.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.

On a population level, mailed fecal immunohistochemical tests (FITs) may catch more cases of advanced neoplasia than endoscopic methods, based on a Dutch screening study that invited more than 30,000 people to participate.

The relative success of mailed FIT screening was largely due a participation rate of 73%, compared with participation rates between 24% and 31% among those invited to undergo endoscopic screening, reported lead author Esmée J. Grobbee, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues.

In addition to high participation, previous research has shown that successful FIT screening depends upon continued adherence to the screening program, the investigators wrote in Clinical Gastroenterology and Hepatology. They noted that, in the present study, just two rounds of FIT were needed to outperform endoscopic methods, and that these comparative findings are a first for the field.

“No literature is available on the comparison between endoscopic screening strategies and multiple rounds of FIT screening,” the investigators wrote. “It is of key importance for policy makers to know the impact of different screening programs over multiple rounds with long-term follow-up.”

To this end, the investigators invited 30,052 screening-naive people in the Netherlands to participate in the present study. Each invitation was for one of three groups: once-only colonoscopy, once-only flexible sigmoidoscopy, or four rounds of FIT. All individuals received an advanced notification by mail followed 2 weeks later by a more substantial information kit (and first FIT test when applicable). If these steps received no response, a reminder was sent 6 weeks later.

Participants in the FIT group received one test every 2 years. Patients who had a positive FIT (hemoglobin concentration of at least 10 mcg Hb/g feces) were scheduled for a colonoscopy. Similarly, colonoscopies were performed in patients who had concerning findings on flexible sigmoidoscopy (e.g., sessile serrated adenoma. This sequential system reduced the relative number of colonoscopies in these two groups; colonoscopy rates in the FIT group and flexible sigmoidoscopy group were 13% and 3%, respectively, compared with the 24% participation rate in the colonoscopy group.

At a population level, FIT screening had the highest advanced neoplasia detection rate, at 4.5%, compared with 2.3% and 2.2% for screening by sigmoidoscopy and colonoscopy, respectively.

“In the intention-to-screen analysis, FIT already detected significantly more advanced neoplasia and colorectal cancer (CRC) after only 2 rounds of FIT, and this difference increased over rounds,” the investigators noted.

Again in the intention-to-screen population, mailed FIT detected three times as many cases of CRC than either of the other two groups (0.6% vs. 0.2% for both). In contrast, colonoscopy and sigmoidoscopy had higher detection rates for nonadvanced adenomas, at 5.6% and 3.7%, respectively, compared with 3.2% for FIT, although the investigators noted that nonadvanced adenomas are “of uncertain clinical importance.” Sessile adenoma detection rates were similar across all three groups.

The as-screened analysis revealed higher detection rates of advanced neoplasia for colonoscopy (9.1%), compared with sigmoidoscopy (7.4%) and FIT (6.1%). In the same analysis, detection rates of colorectal cancer (CRC) were comparable across all three groups.

According to the investigators, the CRC-related findings require careful interpretation.

“Comparing CRC detection rates of FIT and endoscopic screening is complex … because CRCs detected in FIT screening could in theory have been prevented in a once-only colonoscopy by the removal of adenomas,” they wrote.

Still, the key takeaway of the study – that FIT screening was the most effective strategy – may have practical implications on a global scale, according to the investigators.

“Because many countries are considering implementing screening programs, the findings of this study aid in deciding on choice of screening strategies worldwide, which is based on expected participation rates and available colonoscopy resources,” they wrote.

The study was funded by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

SOURCE: Grobbee EJ et al. Clin Gastro Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.015.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.