Amy Karon

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

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.

For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.

Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.

EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.

In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).

In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.

Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”

The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.

SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.

For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.

Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.

EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.

In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).

In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.

Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”

The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.

SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.

For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.

Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.

EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.

In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).

In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.

Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”

The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.

SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.

After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.

High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.

The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).

During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote. 

A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.

The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.

*This story was updated on January 13, 2020.

SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018

An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.

After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.

High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.

The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).

During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote. 

A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.

The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.

*This story was updated on January 13, 2020.

SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018

An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.

After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.

High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.

The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).

During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote. 

A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.

The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.

*This story was updated on January 13, 2020.

SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018