From the AGA Journals

About 13% of U.S. veterans with hepatocellular carcinoma had no evidence of preexisting cirrhosis, according to a report published in the January issue of Clinical Gastroenterology and Hepatology.

“The main risk factors for this entity were nonalcoholic fatty liver disease [NAFLD] or metabolic syndrome” – not hepatitis C virus infection [HCV], HBV [hepatitis B virus] infection, or alcohol abuse, said Dr. Sahil Mittal of the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. Screening all patients with NAFLD for hepatocellular carcinoma [HCC] is impractical, so studies should seek “actionable risk factors” or biomarkers that reliably identify NAFLD patients who are at particular risk of HCC, wrote Dr. Mittal and his coinvestigators.

Courtesy of Wikimedia / Nephron / Creative Commons License

Researchers have debated whether chronic HCV infection or alcohol abuse can lead to HCC in the absence of cirrhosis, while at least one study has shown that NAFLD can predispose patients to this disease entity (Arch Pathol Lab Med. 2008;132:1761-6).

But few studies have systematically examined risk factors for HCC without cirrhosis in the general population, the investigators said. Therefore, they randomly selected 1,500 patients from the U.S. Veterans Affairs system who were diagnosed with HCC between 2005 and 2010 on the basis of histopathology or established imaging criteria (Hepatology 2005;42:1208-36).

They reviewed complete medical records for these patients, and classified those who did not have cirrhosis according to the quality of supporting histology, laboratory, and imaging data (Clin Gastroenterol Hepatol. 2015. doi: 0.1016/j.cgh.2015.07.019).

In all, 3% of the cohort had level 1 (“highest-quality”) evidence for not having cirrhosis, while another 10% had level 2 evidence for no cirrhosis, the investigators said. “Compared with HCC in the presence of cirrhosis, these patients were more likely to have metabolic syndrome or NAFLD or no identifiable risk factor, and less likely to have alcohol abuse or HCV infection,” they added. Only two-thirds of NAFLD patients with HCC had cirrhosis, compared with 91% of patients with chronic HCV infection, 92% of HCV-infected patients, and 88% of patients with an alcohol use disorder. Notably, the odds of HCC in the absence of cirrhosis were more than five times higher when patients had NAFLD (odds ratio [OR], 5.4; 95% confidence interval [CI], 3.4-8.5) or metabolic syndrome (OR, 5.0; 95% CI, 3.1-7.8) compared with HCV infection.

Patients with cirrhosis often go unscreened for HCC even though they are at greatest risk of this cancer. Therefore, trying to screen all patients with NAFLD for HCC would be “logistically impractical,” particularly when the absolute risk of HCC in noncirrhotic patients is unknown and no one has examined the best ways to screen this population, the investigators said. Instead, clinicians could prioritize screening and treating NAFLD patients for diabetes mellitus and obesity, both of which are associated with HCC. “There is evidence to suggest that metformin reduces the risk of HCC among diabetics,” they added. “Studies of these and other risk factors of HCC among NAFLD patients with and without cirrhosis are needed.”

Most patients in the study were male, potentially limiting the generalizability of the findings, the researchers noted.

The National Cancer Institute, the Houston Veterans Affairs Health Services Research and Development Center of Excellence, the Michael E. DeBakey Veterans Affairs Medical Center, and the Dan Duncan Cancer Center funded the study. The researchers had no disclosures.

About 13% of U.S. veterans with hepatocellular carcinoma had no evidence of preexisting cirrhosis, according to a report published in the January issue of Clinical Gastroenterology and Hepatology.

“The main risk factors for this entity were nonalcoholic fatty liver disease [NAFLD] or metabolic syndrome” – not hepatitis C virus infection [HCV], HBV [hepatitis B virus] infection, or alcohol abuse, said Dr. Sahil Mittal of the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. Screening all patients with NAFLD for hepatocellular carcinoma [HCC] is impractical, so studies should seek “actionable risk factors” or biomarkers that reliably identify NAFLD patients who are at particular risk of HCC, wrote Dr. Mittal and his coinvestigators.

Courtesy of Wikimedia / Nephron / Creative Commons License

Researchers have debated whether chronic HCV infection or alcohol abuse can lead to HCC in the absence of cirrhosis, while at least one study has shown that NAFLD can predispose patients to this disease entity (Arch Pathol Lab Med. 2008;132:1761-6).

But few studies have systematically examined risk factors for HCC without cirrhosis in the general population, the investigators said. Therefore, they randomly selected 1,500 patients from the U.S. Veterans Affairs system who were diagnosed with HCC between 2005 and 2010 on the basis of histopathology or established imaging criteria (Hepatology 2005;42:1208-36).

They reviewed complete medical records for these patients, and classified those who did not have cirrhosis according to the quality of supporting histology, laboratory, and imaging data (Clin Gastroenterol Hepatol. 2015. doi: 0.1016/j.cgh.2015.07.019).

In all, 3% of the cohort had level 1 (“highest-quality”) evidence for not having cirrhosis, while another 10% had level 2 evidence for no cirrhosis, the investigators said. “Compared with HCC in the presence of cirrhosis, these patients were more likely to have metabolic syndrome or NAFLD or no identifiable risk factor, and less likely to have alcohol abuse or HCV infection,” they added. Only two-thirds of NAFLD patients with HCC had cirrhosis, compared with 91% of patients with chronic HCV infection, 92% of HCV-infected patients, and 88% of patients with an alcohol use disorder. Notably, the odds of HCC in the absence of cirrhosis were more than five times higher when patients had NAFLD (odds ratio [OR], 5.4; 95% confidence interval [CI], 3.4-8.5) or metabolic syndrome (OR, 5.0; 95% CI, 3.1-7.8) compared with HCV infection.

Patients with cirrhosis often go unscreened for HCC even though they are at greatest risk of this cancer. Therefore, trying to screen all patients with NAFLD for HCC would be “logistically impractical,” particularly when the absolute risk of HCC in noncirrhotic patients is unknown and no one has examined the best ways to screen this population, the investigators said. Instead, clinicians could prioritize screening and treating NAFLD patients for diabetes mellitus and obesity, both of which are associated with HCC. “There is evidence to suggest that metformin reduces the risk of HCC among diabetics,” they added. “Studies of these and other risk factors of HCC among NAFLD patients with and without cirrhosis are needed.”

Most patients in the study were male, potentially limiting the generalizability of the findings, the researchers noted.

The National Cancer Institute, the Houston Veterans Affairs Health Services Research and Development Center of Excellence, the Michael E. DeBakey Veterans Affairs Medical Center, and the Dan Duncan Cancer Center funded the study. The researchers had no disclosures.

About 13% of U.S. veterans with hepatocellular carcinoma had no evidence of preexisting cirrhosis, according to a report published in the January issue of Clinical Gastroenterology and Hepatology.

“The main risk factors for this entity were nonalcoholic fatty liver disease [NAFLD] or metabolic syndrome” – not hepatitis C virus infection [HCV], HBV [hepatitis B virus] infection, or alcohol abuse, said Dr. Sahil Mittal of the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. Screening all patients with NAFLD for hepatocellular carcinoma [HCC] is impractical, so studies should seek “actionable risk factors” or biomarkers that reliably identify NAFLD patients who are at particular risk of HCC, wrote Dr. Mittal and his coinvestigators.

Courtesy of Wikimedia / Nephron / Creative Commons License

Researchers have debated whether chronic HCV infection or alcohol abuse can lead to HCC in the absence of cirrhosis, while at least one study has shown that NAFLD can predispose patients to this disease entity (Arch Pathol Lab Med. 2008;132:1761-6).

But few studies have systematically examined risk factors for HCC without cirrhosis in the general population, the investigators said. Therefore, they randomly selected 1,500 patients from the U.S. Veterans Affairs system who were diagnosed with HCC between 2005 and 2010 on the basis of histopathology or established imaging criteria (Hepatology 2005;42:1208-36).

They reviewed complete medical records for these patients, and classified those who did not have cirrhosis according to the quality of supporting histology, laboratory, and imaging data (Clin Gastroenterol Hepatol. 2015. doi: 0.1016/j.cgh.2015.07.019).

In all, 3% of the cohort had level 1 (“highest-quality”) evidence for not having cirrhosis, while another 10% had level 2 evidence for no cirrhosis, the investigators said. “Compared with HCC in the presence of cirrhosis, these patients were more likely to have metabolic syndrome or NAFLD or no identifiable risk factor, and less likely to have alcohol abuse or HCV infection,” they added. Only two-thirds of NAFLD patients with HCC had cirrhosis, compared with 91% of patients with chronic HCV infection, 92% of HCV-infected patients, and 88% of patients with an alcohol use disorder. Notably, the odds of HCC in the absence of cirrhosis were more than five times higher when patients had NAFLD (odds ratio [OR], 5.4; 95% confidence interval [CI], 3.4-8.5) or metabolic syndrome (OR, 5.0; 95% CI, 3.1-7.8) compared with HCV infection.

Patients with cirrhosis often go unscreened for HCC even though they are at greatest risk of this cancer. Therefore, trying to screen all patients with NAFLD for HCC would be “logistically impractical,” particularly when the absolute risk of HCC in noncirrhotic patients is unknown and no one has examined the best ways to screen this population, the investigators said. Instead, clinicians could prioritize screening and treating NAFLD patients for diabetes mellitus and obesity, both of which are associated with HCC. “There is evidence to suggest that metformin reduces the risk of HCC among diabetics,” they added. “Studies of these and other risk factors of HCC among NAFLD patients with and without cirrhosis are needed.”

Most patients in the study were male, potentially limiting the generalizability of the findings, the researchers noted.

The National Cancer Institute, the Houston Veterans Affairs Health Services Research and Development Center of Excellence, the Michael E. DeBakey Veterans Affairs Medical Center, and the Dan Duncan Cancer Center funded the study. The researchers had no disclosures.

Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.

The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.

Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).

For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.

Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.

The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.

The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.

Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.

The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.

Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).

For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.

Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.

The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.

The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.

Neural progenitor cells from the proximal colons of patients with Hirschsprung disease divided and formed neurons and glia in their own distal aganglionic colon tissue, according to a study published in the January issue of Cellular and Molecular Gastroenterology and Hepatology.

The approach could lead to “a promising therapeutic strategy” for Hirschsprung disease, because autologous transplantation of nerve progenitor cells would prevent immune rejection, said Dr. Benjamin Rollo of Murdoch Children’s Research Institute in Victoria, Australia, and his associates. But they cautioned against reading too much into their findings, “as there are distributional hurdles to surmount” before cell therapy can be used alone or in combination with surgery.

Hirschsprung disease is a congenital disorder in which embryonic neural crest cells fail to form the distal part of the enteric nervous system. The resulting lack of bowel motility leads to severe constipation and potentially fatal megacolon. Treatment involves surgically resecting the aganglionic distal bowel and anastomosing the normal proximal bowel to the anorectum, but this approach itself can cause constipation as well as fecal soiling, the investigators noted (Cell Molec Gastroenterol Hepatol. 2015 Oct. 22 [doi: 10.1016/j.jcmgh.2015.09.007]).

For the study, they harvested tissue from the proximal (neuronal) and distal (aneuronal) margins of resection of the colons of 31 infants and children with Hirschsprung disease. They cultured cells from the myenteric plexus of the proximal colon, and separated out nerve cells by using flow cytometry for the p75 neural crest marker. To test whether these nerve cells could colonize aganglionic colon, they co-cultured them with aneural avian embryo gut and with patients’ own aneuronal colon muscle. In addition, they co-cultured embryonic mouse enteric nernous system cells with human aneuronal colon muscle. They used quantitative reverse transcriptase PCR and several other standard laboratory techniques to detect cellular markers and mitosis.

Ganglia from the patients’ proximal colons expressed the neural crest markers p75, SOX10, and HNK1, as well as several neuronal, neurite, and glial markers, the researchers reported. The proximal colon specimens also contained ENS progenitor cells, which were SOX10-positive but lacked neuronal or glial markers. The progenitor cells comprised less than 5% of all cells from the proximal colon, but proliferated fourfold more after supplementation with CHIR-99021, a selective inhibitor of glycogen synthase kinase 3. They successfully colonized avian aneural embryonic gut and autologous postnatal aneuronal colon tissue, and the latter also was colonized successfully by mouse enteric neural crest cells.

The study “fulfilled three key requirements” for transplantation – harvesting enteric nervous system cells from the proximal colons of patients with Hirschsprung disease; confirming that postnatal aneuronal colon tissue could support an enteric nervous system; and showing that enteric nervous system–derived cells could colonize both embryonic gut and autologous postnatal colon tissue, said the researchers. More work is needed to sufficiently expand embryonic neural crest stem or progenitor cells and transplant them over a large area of colon, although supplementation with growth factors and use of elastic polymer substrates might help, they added.

The National Health and Medical Research Council, Murdoch Children’s Research Institute, Graham Burke and Yvonne Spencer, the Federation of Chinese Associations, Fonds du Service de chirurgie pédiatrique et de Perfectionnement du CHUV, Fondation SICPA, and Société Académique Vaudoise funded the study. The researchers disclosed no conflicts of interest.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

A retrospective data analysis showed that stereotactic body radiotherapy (SBRT) outperformed radiofrequency ablation (RFA) on tumors larger than 2 cm in patients with hepatocellular carcinoma.

For all tumors treated with RFA, 1- and 2-year freedom from local progression (FFLP) were 83.6% and 80.2%, and for tumors treated with SBRT, rates were 97.4% and 83.8%. On tumors smaller than 2 cm, FFLP was similar for the two methods (HR, 2.50; 95% confidence interval, 0.72-8.67; P = .15) but was significantly worse for RFA treatment of larger tumors (HR, 3.35; 95% CI, 1.17-9.62, P = .025).

“These results suggest that both SBRT and RFA are excellent choices for smaller tumors but that SBRT may be preferred for larger tumors. Prospective, randomized clinical trials are needed to compare these two modalities, especially for larger tumors, although we are unaware of any such trials,” wrote Dr. Daniel R. Wahl, radiation oncologist at the University of Michigan (J Clin Oncol. 2015 Dec. 2. doi:10.1200/JCO.2015.61.4925).

The retrospective study evaluated 224 patients with nonmetastatic hepatocellular carcinoma – 161 patients (249 tumors) who underwent RFA and 63 patients (83 tumors) who underwent SBRT at the University of Michigan from 2004 to 2012. Patients treated with RFA had higher rates of cirrhosis (95% vs. 78%; P less than .001), lower AFP levels (8.8 vs. 18.6; P = .04), and fewer prior liver-directed treatments compared with patients treated with SBRT.

To investigate the impact of fiducial use for image guidance in SBRT, the researchers examined treatment failures. Of the 21 treatments that used fiducials, none had local failure, compared with six failures in 62 treatments without fiducials.

Both methods had similar low rates of late adverse events. Acute adverse events and treatment-related deaths were nonsignificantly greater with RFA, which may suggest SBRT as a better option for medically unfit patients who may not tolerate invasive procedures such as RFA.

The study included only three tumors larger than 5 cm in diameter, so rates of local control for this size tumor cannot be estimated reliably, reported Dr. Wahl and his colleagues.

The National Institutes of Health and the Taubman Institute supported the research. Dr. Wahl reported stock or other ownership in Lycera. Several of his coauthors reported ties to industry.

A retrospective data analysis showed that stereotactic body radiotherapy (SBRT) outperformed radiofrequency ablation (RFA) on tumors larger than 2 cm in patients with hepatocellular carcinoma.

For all tumors treated with RFA, 1- and 2-year freedom from local progression (FFLP) were 83.6% and 80.2%, and for tumors treated with SBRT, rates were 97.4% and 83.8%. On tumors smaller than 2 cm, FFLP was similar for the two methods (HR, 2.50; 95% confidence interval, 0.72-8.67; P = .15) but was significantly worse for RFA treatment of larger tumors (HR, 3.35; 95% CI, 1.17-9.62, P = .025).

“These results suggest that both SBRT and RFA are excellent choices for smaller tumors but that SBRT may be preferred for larger tumors. Prospective, randomized clinical trials are needed to compare these two modalities, especially for larger tumors, although we are unaware of any such trials,” wrote Dr. Daniel R. Wahl, radiation oncologist at the University of Michigan (J Clin Oncol. 2015 Dec. 2. doi:10.1200/JCO.2015.61.4925).

The retrospective study evaluated 224 patients with nonmetastatic hepatocellular carcinoma – 161 patients (249 tumors) who underwent RFA and 63 patients (83 tumors) who underwent SBRT at the University of Michigan from 2004 to 2012. Patients treated with RFA had higher rates of cirrhosis (95% vs. 78%; P less than .001), lower AFP levels (8.8 vs. 18.6; P = .04), and fewer prior liver-directed treatments compared with patients treated with SBRT.

To investigate the impact of fiducial use for image guidance in SBRT, the researchers examined treatment failures. Of the 21 treatments that used fiducials, none had local failure, compared with six failures in 62 treatments without fiducials.

Both methods had similar low rates of late adverse events. Acute adverse events and treatment-related deaths were nonsignificantly greater with RFA, which may suggest SBRT as a better option for medically unfit patients who may not tolerate invasive procedures such as RFA.

The study included only three tumors larger than 5 cm in diameter, so rates of local control for this size tumor cannot be estimated reliably, reported Dr. Wahl and his colleagues.

The National Institutes of Health and the Taubman Institute supported the research. Dr. Wahl reported stock or other ownership in Lycera. Several of his coauthors reported ties to industry.

A retrospective data analysis showed that stereotactic body radiotherapy (SBRT) outperformed radiofrequency ablation (RFA) on tumors larger than 2 cm in patients with hepatocellular carcinoma.

For all tumors treated with RFA, 1- and 2-year freedom from local progression (FFLP) were 83.6% and 80.2%, and for tumors treated with SBRT, rates were 97.4% and 83.8%. On tumors smaller than 2 cm, FFLP was similar for the two methods (HR, 2.50; 95% confidence interval, 0.72-8.67; P = .15) but was significantly worse for RFA treatment of larger tumors (HR, 3.35; 95% CI, 1.17-9.62, P = .025).

“These results suggest that both SBRT and RFA are excellent choices for smaller tumors but that SBRT may be preferred for larger tumors. Prospective, randomized clinical trials are needed to compare these two modalities, especially for larger tumors, although we are unaware of any such trials,” wrote Dr. Daniel R. Wahl, radiation oncologist at the University of Michigan (J Clin Oncol. 2015 Dec. 2. doi:10.1200/JCO.2015.61.4925).

The retrospective study evaluated 224 patients with nonmetastatic hepatocellular carcinoma – 161 patients (249 tumors) who underwent RFA and 63 patients (83 tumors) who underwent SBRT at the University of Michigan from 2004 to 2012. Patients treated with RFA had higher rates of cirrhosis (95% vs. 78%; P less than .001), lower AFP levels (8.8 vs. 18.6; P = .04), and fewer prior liver-directed treatments compared with patients treated with SBRT.

To investigate the impact of fiducial use for image guidance in SBRT, the researchers examined treatment failures. Of the 21 treatments that used fiducials, none had local failure, compared with six failures in 62 treatments without fiducials.

Both methods had similar low rates of late adverse events. Acute adverse events and treatment-related deaths were nonsignificantly greater with RFA, which may suggest SBRT as a better option for medically unfit patients who may not tolerate invasive procedures such as RFA.

The study included only three tumors larger than 5 cm in diameter, so rates of local control for this size tumor cannot be estimated reliably, reported Dr. Wahl and his colleagues.

The National Institutes of Health and the Taubman Institute supported the research. Dr. Wahl reported stock or other ownership in Lycera. Several of his coauthors reported ties to industry.

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Baseline exposure to an immunomodulator did not improve the odds of clinical response or remission when starting anti–tumor necrosis factor (anti-TNF) therapy for Crohn’s disease (CD), said authors of a meta-analysis of 11 randomized, controlled trials. Pending better trials, patients with CD and their clinicians will need to carefully weigh the risks and benefits of continuing an immunomodulator when starting anti-TNF therapy, Dr. Jennifer Jones of Dalhousie University in Halifax, Canada and her associates wrote in the December issue of Clinical Gastroenterology and Hepatology.

Intense debate persists about whether patients with CD who have already been exposed to immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate should stay on them when starting anti-TNF agents. The landmark 2010 SONIC trial could not answer this question because it only enrolled patients who had never received an immunomodulator, and more recent studies (Clin Gastroenterol Hepatol. 2011;9:36-41) have raised concerns about the safety of immunomodulators, the researchers noted. To compare combination immunomodulators and anti-TNF treatment with anti-TNF monotherapy in luminal and fistulizing CD, they analyzed original datasets from 11 randomized, controlled trials published between 1980 and 2008. A total of 625 patients with CD had received an immunomodulator, while 976 patients had not. The investigators excluded trials in which patients were naive to both immunomodulators and anti-TNF agents (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.034]).

Nephron/Wikimedia Commons/CC BY-SA 3.0/

In the overall analysis, combination therapy was no better than anti-TNF monotherapy in terms of 6-month remission, maintenance of response, or partial or full fistula closure, Dr. Jones and her associates reported. The same was true for subgroup analyses, but the odds ratio for infliximab reached statistical significance in a sensitivity analysis that included data from the ACCENT 2 (Clin Gastroenterol Hepatol. 2004;2:912-20) trial. “For the infliximab-only analysis, adding ACCENT 2 resulted in minimal change in the point estimate but, as expected, increased the precision of the 95% CIs (the lower CI increased from 0.97 to 1.06), which led to a statistically significant difference in the comparison between infliximab monotherapy and combination therapy,” the researchers commented. While sensitivity analyses have limitations, the finding “does raise the question” of whether the benefits of staying on an immunomodulator depend on the anti-TNF agent, they said.

Combination therapy did not heighten the chances of infusion reactions, malignancies, serious infections, or death, said the investigators. In fact, baseline immunomodulator exposure was associated with fewer injection site reactions among infliximab patients (OR, 0.46; 95% CI, 0.26-0.79). The researchers did not uncover publication bias, and found significant heterogeneity among studies only for the 6-month clinical response endpoint, they added.

The findings “challenge the clinical importance of combination therapy” in the setting of baseline immunomodulator exposure, but “it is hard to ignore the preponderance of data” on anti-TNF pharmacokinetics that support combination therapy over monotherapy, the investigators emphasized. “Whether combination therapy has a greater protective effect against anti-drug antibody development and lower trough levels for all anti-TNF agents or for patients previously exposed to anti-TNF agents is still in question,” they added. They called for a well-designed, randomized, placebo-controlled trial that uses objective measures of disease activity and follow patients long enough to assess efficacy.

The investigators reported no funding sources for the study. Dr. Jones reported having been a speaker for Jansen, Merck, Schering-Plough, Abbott, and AbbVie, and having served on advisory boards for Janssen, Abbott, and Takeda. Nine co-authors reported financial and consulting relationships with Jansen, Merck, Schering-Plough, Abbott, and a number of other pharmaceutical companies.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

Researchers detected circulating tumor cells (CTCs) in the portal venous blood of all patients with pancreaticobiliary cancer (PBC), but in the peripheral blood of only 22% of patients, according to a small single-center cohort study.

“We have shown that portal venous CTCs are far more common and higher in absolute numbers than peripheral blood CTCs. We also have shown the feasibility of obtaining portal venous CTCs noninvasively via endoscopic ultrasound,” Dr. Daniel Catenacci, Dr. Christopher Chapman, and their associates from the University of Chicago Medicine wrote in the December issue of Gastroenterology. “Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue.”

Circulating tumor cells have shown promise in the minimally invasive assessment of solid tumors, but the peripheral bloodstream contains only about one CTC for every 1 billion blood cells, limiting the potential sensitivity of testing. The researchers therefore used EUS guidance to transhepatically collect portal venous blood from 18 patients with PBCs. They quantified CTCs in both their portal venous and peripheral blood by using CellSearch, a commercially available test that uses magnetic beads labeled with antibodies against epithelial cell adhesion molecules. They only counted epithelial-derived cells as CTCs if they were morphologically compatible with tumor cells, CD45-negative, and positive for cytokeratins 8, 18, or 19 and 40,6-diamidino-2-phenylindole (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.08.050]).

Patients suffered no adverse affects from portal vein sampling, the researchers reported. They detected CTCs in the portal venous blood of all 18 patients, but in the peripheral blood of only four (22%) patients. Average CTC concentrations also were significantly higher in portal venous blood (118.4 ± 36.8 CTCs per 7.5 mL) compared with peripheral blood (0.8 ± 0.4 CTCs per 7.5 mL; P less than .01).

Among nine patients with nonmetastatic, resectable, or borderline-resectable PBC, portal vein CTCs averaged 83.2 per 7.5 mL (median, 62.0), the researchers reported. Whole-genome amplification and KRAS codon sequencing in one patient also showed that CTCs had the same mutations and similar levels of P16, SMAD4, and P53 proteins as tumor cells from a metastatic lymph node.

In addition, magnetic cell sorting identified CTC clusters, which other studies have implicated in the metastatic seeding of distant organs, the researchers said. Indeed, CTCs are now known to include “a heterogeneous population of cells, including apoptotic cells, cells undergoing epithelial-to-mesenchymal transition with loss of epithelial markers, epithelial cells, and cell clusters,” they noted. This heterogeneity might make CTCs useful for studying the pathogenesis and progression of PBCs, as well as for assessing the individual chances of recurrence or metastasis, they added. “Future prospective studies will define the role of portal vein CTCs or predictive biomarkers in the perioperative setting,” the investigators concluded.

The work was funded by the Rolfe Pancreatic Cancer Foundation, officers of the Gerald O. Mann Charitable Foundation, the National Institutes of Health, the University of Chicago Comprehensive Cancer Center, the Cancer Research Foundation, the Alliance for Clinical Trials in Oncology Foundation, and the Live Like Katie Foundation. The researchers reported having no conflicts of interest.

Source: American Gastroenterological Association

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

Diseases such as Clostridium difficile infection, inflammatory bowel disease, and liver cancer continue to cost billions and cause many thousands of deaths in the United States every year, investigators reported in the December issue of Gastroenterology.

“Gastrointestinal and liver diseases are a source of substantial burden and cost,” said Dr. Anne Peery and her associates at the University of North Carolina School of Medicine and the Gillings School of Public Health, both in Chapel Hill. The Affordable Care Act has extended health insurance to more than 16 million Americans, which is “expected to change the landscape of care for GI illnesses” and intensifies the need for their comprehensive study, the researchers added.

©andegro4ka/ thinkstockphotos.com

They analyzed health care visits, costs, and deaths from GI, pancreatic, and hepatic diseases for 2007 through 2012 by using surveillance data from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Chronic hepatitis C virus infection was a leading disease burden, they found. Associated emergency department visits rose by 176% between 2006 and 2012, hospital admissions increased by 225% between 2003 and 2012, and in-hospital mortality approached 6%. These trends reflect the aging of baby boomers, who make up three-quarters of infected patients, the investigators noted. As a result, rates of new liver cancers also are rising, and end-stage liver disease is expected to keep increasing until 2030, they added (Gastroenterology. 2015 Aug 20. doi: 10.1053/j.gastro.2015.08.045). Aging boomers are increasingly seeking care for other age-related GI disorders, the investigators reported. Outpatient visits for hemorrhoids are rising, as are emergency department visits for constipation and lower-GI bleeding, and hospitalizations for acute diverticulitis and C. difficile infection. Gastrointestinal hemorrhage was the most common diagnosis at hospitalization, accounting for more than 500,000 discharges and costing almost $5 billion dollars in 2012 alone, the researchers said.

Despite better treatments, hospital admissions for Crohn’s disease and ulcerative colitis also rose from less than 60,000 in 1993 to about 100,000 in 2012, said Dr. Peery and her associates. “This is congruent with earlier trends using the National Hospital Discharge Survey. Emergency department visits [for inflammatory bowel disease] are also rising,” they added.

In contrast, cases and deaths from colorectal cancer continue to drop, partly because of intensified screening efforts, the investigators said. They called the trend “encouraging,” but noted that CRC still tops cancers of the pancreas, liver, and intrahepatic bile ducts as the leading GI cause of mortality in the United States. In 2012, more than 51,000 Americans died from CRC, and screening efforts captured only 58% of those between 50 and 75 years old. Boosting that percentage to 80% by 2018 http://nccrt.org/tools/80-percent-by-2018/ could prevent 280,000 CRC cases and 200,000 deaths within 20 years, Dr. Peery and her associates noted.

The National Institutes of Health helped fund the work. The investigators reported having no conflicts of interest.

Source: American Gastroenterological Association

Diseases such as Clostridium difficile infection, inflammatory bowel disease, and liver cancer continue to cost billions and cause many thousands of deaths in the United States every year, investigators reported in the December issue of Gastroenterology.

“Gastrointestinal and liver diseases are a source of substantial burden and cost,” said Dr. Anne Peery and her associates at the University of North Carolina School of Medicine and the Gillings School of Public Health, both in Chapel Hill. The Affordable Care Act has extended health insurance to more than 16 million Americans, which is “expected to change the landscape of care for GI illnesses” and intensifies the need for their comprehensive study, the researchers added.

©andegro4ka/ thinkstockphotos.com

They analyzed health care visits, costs, and deaths from GI, pancreatic, and hepatic diseases for 2007 through 2012 by using surveillance data from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Chronic hepatitis C virus infection was a leading disease burden, they found. Associated emergency department visits rose by 176% between 2006 and 2012, hospital admissions increased by 225% between 2003 and 2012, and in-hospital mortality approached 6%. These trends reflect the aging of baby boomers, who make up three-quarters of infected patients, the investigators noted. As a result, rates of new liver cancers also are rising, and end-stage liver disease is expected to keep increasing until 2030, they added (Gastroenterology. 2015 Aug 20. doi: 10.1053/j.gastro.2015.08.045). Aging boomers are increasingly seeking care for other age-related GI disorders, the investigators reported. Outpatient visits for hemorrhoids are rising, as are emergency department visits for constipation and lower-GI bleeding, and hospitalizations for acute diverticulitis and C. difficile infection. Gastrointestinal hemorrhage was the most common diagnosis at hospitalization, accounting for more than 500,000 discharges and costing almost $5 billion dollars in 2012 alone, the researchers said.

Despite better treatments, hospital admissions for Crohn’s disease and ulcerative colitis also rose from less than 60,000 in 1993 to about 100,000 in 2012, said Dr. Peery and her associates. “This is congruent with earlier trends using the National Hospital Discharge Survey. Emergency department visits [for inflammatory bowel disease] are also rising,” they added.

In contrast, cases and deaths from colorectal cancer continue to drop, partly because of intensified screening efforts, the investigators said. They called the trend “encouraging,” but noted that CRC still tops cancers of the pancreas, liver, and intrahepatic bile ducts as the leading GI cause of mortality in the United States. In 2012, more than 51,000 Americans died from CRC, and screening efforts captured only 58% of those between 50 and 75 years old. Boosting that percentage to 80% by 2018 http://nccrt.org/tools/80-percent-by-2018/ could prevent 280,000 CRC cases and 200,000 deaths within 20 years, Dr. Peery and her associates noted.

The National Institutes of Health helped fund the work. The investigators reported having no conflicts of interest.

Source: American Gastroenterological Association

Diseases such as Clostridium difficile infection, inflammatory bowel disease, and liver cancer continue to cost billions and cause many thousands of deaths in the United States every year, investigators reported in the December issue of Gastroenterology.

“Gastrointestinal and liver diseases are a source of substantial burden and cost,” said Dr. Anne Peery and her associates at the University of North Carolina School of Medicine and the Gillings School of Public Health, both in Chapel Hill. The Affordable Care Act has extended health insurance to more than 16 million Americans, which is “expected to change the landscape of care for GI illnesses” and intensifies the need for their comprehensive study, the researchers added.

©andegro4ka/ thinkstockphotos.com

They analyzed health care visits, costs, and deaths from GI, pancreatic, and hepatic diseases for 2007 through 2012 by using surveillance data from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. Chronic hepatitis C virus infection was a leading disease burden, they found. Associated emergency department visits rose by 176% between 2006 and 2012, hospital admissions increased by 225% between 2003 and 2012, and in-hospital mortality approached 6%. These trends reflect the aging of baby boomers, who make up three-quarters of infected patients, the investigators noted. As a result, rates of new liver cancers also are rising, and end-stage liver disease is expected to keep increasing until 2030, they added (Gastroenterology. 2015 Aug 20. doi: 10.1053/j.gastro.2015.08.045). Aging boomers are increasingly seeking care for other age-related GI disorders, the investigators reported. Outpatient visits for hemorrhoids are rising, as are emergency department visits for constipation and lower-GI bleeding, and hospitalizations for acute diverticulitis and C. difficile infection. Gastrointestinal hemorrhage was the most common diagnosis at hospitalization, accounting for more than 500,000 discharges and costing almost $5 billion dollars in 2012 alone, the researchers said.

Despite better treatments, hospital admissions for Crohn’s disease and ulcerative colitis also rose from less than 60,000 in 1993 to about 100,000 in 2012, said Dr. Peery and her associates. “This is congruent with earlier trends using the National Hospital Discharge Survey. Emergency department visits [for inflammatory bowel disease] are also rising,” they added.

In contrast, cases and deaths from colorectal cancer continue to drop, partly because of intensified screening efforts, the investigators said. They called the trend “encouraging,” but noted that CRC still tops cancers of the pancreas, liver, and intrahepatic bile ducts as the leading GI cause of mortality in the United States. In 2012, more than 51,000 Americans died from CRC, and screening efforts captured only 58% of those between 50 and 75 years old. Boosting that percentage to 80% by 2018 http://nccrt.org/tools/80-percent-by-2018/ could prevent 280,000 CRC cases and 200,000 deaths within 20 years, Dr. Peery and her associates noted.

The National Institutes of Health helped fund the work. The investigators reported having no conflicts of interest.

Source: American Gastroenterological Association

A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.

Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).

Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.

The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.

Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.

The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.

A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.

Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).

Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.

The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.

Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.

The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.

A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.

“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.

Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).

Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.

The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.

Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.

The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.