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Esophagus/Upper GI section
One highlight of the AGA Postgraduate Course was the esophageal disease session. The presentation by Dr. Michael B. Wallace summarized recent studies using advanced imaging modalities in patients with Barrett’s esophagus. Studies using chromoscopy and virtual chromoscopy techniques such as narrow-band imaging have increased the detection of dysplasia in BE patients. These are so-called red flag techniques that image large areas of mucosa to detect mucosal abnormalities suspicious for the presence of dysplasia or neoplasia.
Endomicroscopy describes the use of real-time, targeted endoscopic imaging modalities that are capable of producing histologic-like images of mucosa at depths up to 200 microns. Confocal laser endomicroscopy (CLE) uses a blue light laser (405 nm) and collimated light detection and analysis to produce 1000-fold magnified images. When used with a fluorescent contrast agent such as fluorescein or acriflavin dye, these systems produce cellular level images that are comparable to those images seen with optical microscopy. A recent study from Canto et al found that the use of CLE detected BE dysplasia at rates similar to targeted plus random biopsy protocols. Further, a multicenter study will soon begin using a tethered-capsule (nonendoscopic) form of volumetric laser endomicroscopy as a method to screen for BE.
Dr. Amitabh Chak expanded on these issues and reviewed the issues surrounding screening and surveillance of BE patients for the early detection and treatment of esophageal adenocarcinoma. This presentation suggested that necessary future improvements include cost-effective advanced imaging techniques optimized for use in clinical practice, molecular biomarker panels for prediction of which patients may progress to dysplasia and neoplasia, and high-quality intensive endoscopic surveillance for high risk BE patients.
Dr. Joe Murray’s comprehensive presentation of celiac disease described the protean clinical presentations of this disease as well as optimal use of serologic and endoscopic testing. Celiac disease is increasingly identified in middle-aged patients (median 45 years) without diarrhea. Classic malabsorption symptoms of diarrhea, weight loss, steatorrhea, and nutritional deficiencies are found in 25% of patients. Half of celiac patients will have only one symptom such as anemia, diarrhea, lactose intolerance, or weight loss. Nongastrointestinal symptoms are present in another 25% of patients such as infertility, bone disease, chronic fatigue, or abnormal liver enzyme test results.
Optimal use of serologic and endoscopic testing was reviewed, including the differential diagnosis of lymphocytic duodenosis including use of nonsteroidal anti-inflammatory agents (NSAIDs), Helicobacter pylori infection, Crohn’s disease, and Sjogren’s syndrome. Proper duodenal biopsy technique was emphasized with two forceps biopsy samples obtained from the duodenal bulb and four biopsy samples obtained from the second portion of the duodenum. Also discussed was the utility of HLA typing for DQ2/8 in patients currently using a gluten free diet, patients with negative serology results but abnormal duodenal biopsy findings, and those with negative serology results who are at increased genetic risk.
Dr. James Scheiman discussed management of the complex interaction and risks associated with the use of NSAIDs, aspirin, clopidogrel, and proton pump inhibitors in the setting of previous ulcer disease, gastrointestinal bleeding, and Helicobacter pylori infection. Results from randomized controlled studies and observational studies were the basis for the Consensus Group to recommend the use of proton pump inhibitor therapy as the GI bleeding protective strategy of choice. PPI therapy was also recommended as cost-effective treatment for aspirin-using patients, although the risks and benefits of long-term PPI treatment require patient education and individualization.
Finally, Dr. Rhonda Souza discussed eosinophilic esophagitis (EoE), a chronic immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction associated with eosinophil-predominant inflammation such as dysphagia, food impaction, chest pain, heartburn, abdominal pain, and refractory reflux dyspepsia. Endoscopic features include the ringed esophagus, white specks, linear furrows and stricture. Histologic features of EoE are eosinophilia (more than 15 intraepithelial eosinophils per high power field), basal zone hyperplasia, and dilated intercellular spaces. These eosinophils are activated via T-helper 2 immune system via interleukins-4, -5 and -13. This inflammation is mediated by the dramatic upregulation involving the eotaxin-3 gene that produces a potent chemoattractant for eosinophils. Treatment of EoE usually requires the use of proton pump inhibitors based on their acid suppression, anti-oxidant and anti-inflammatory effects. The use of topical corticosteroids and endoscopic dilation for symptomatic strictures may also be necessary. Nondrug treatment approaches such as the six food elimination diet (SFED) of the most common food allergens such as milk, soy, eggs, wheat, nuts and seafood have also been successful.
Dr. Wolfsen is in the division of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla. He moderated this session during the 2014 Digestive Diseases Week.
One highlight of the AGA Postgraduate Course was the esophageal disease session. The presentation by Dr. Michael B. Wallace summarized recent studies using advanced imaging modalities in patients with Barrett’s esophagus. Studies using chromoscopy and virtual chromoscopy techniques such as narrow-band imaging have increased the detection of dysplasia in BE patients. These are so-called red flag techniques that image large areas of mucosa to detect mucosal abnormalities suspicious for the presence of dysplasia or neoplasia.
Endomicroscopy describes the use of real-time, targeted endoscopic imaging modalities that are capable of producing histologic-like images of mucosa at depths up to 200 microns. Confocal laser endomicroscopy (CLE) uses a blue light laser (405 nm) and collimated light detection and analysis to produce 1000-fold magnified images. When used with a fluorescent contrast agent such as fluorescein or acriflavin dye, these systems produce cellular level images that are comparable to those images seen with optical microscopy. A recent study from Canto et al found that the use of CLE detected BE dysplasia at rates similar to targeted plus random biopsy protocols. Further, a multicenter study will soon begin using a tethered-capsule (nonendoscopic) form of volumetric laser endomicroscopy as a method to screen for BE.
Dr. Amitabh Chak expanded on these issues and reviewed the issues surrounding screening and surveillance of BE patients for the early detection and treatment of esophageal adenocarcinoma. This presentation suggested that necessary future improvements include cost-effective advanced imaging techniques optimized for use in clinical practice, molecular biomarker panels for prediction of which patients may progress to dysplasia and neoplasia, and high-quality intensive endoscopic surveillance for high risk BE patients.
Dr. Joe Murray’s comprehensive presentation of celiac disease described the protean clinical presentations of this disease as well as optimal use of serologic and endoscopic testing. Celiac disease is increasingly identified in middle-aged patients (median 45 years) without diarrhea. Classic malabsorption symptoms of diarrhea, weight loss, steatorrhea, and nutritional deficiencies are found in 25% of patients. Half of celiac patients will have only one symptom such as anemia, diarrhea, lactose intolerance, or weight loss. Nongastrointestinal symptoms are present in another 25% of patients such as infertility, bone disease, chronic fatigue, or abnormal liver enzyme test results.
Optimal use of serologic and endoscopic testing was reviewed, including the differential diagnosis of lymphocytic duodenosis including use of nonsteroidal anti-inflammatory agents (NSAIDs), Helicobacter pylori infection, Crohn’s disease, and Sjogren’s syndrome. Proper duodenal biopsy technique was emphasized with two forceps biopsy samples obtained from the duodenal bulb and four biopsy samples obtained from the second portion of the duodenum. Also discussed was the utility of HLA typing for DQ2/8 in patients currently using a gluten free diet, patients with negative serology results but abnormal duodenal biopsy findings, and those with negative serology results who are at increased genetic risk.
Dr. James Scheiman discussed management of the complex interaction and risks associated with the use of NSAIDs, aspirin, clopidogrel, and proton pump inhibitors in the setting of previous ulcer disease, gastrointestinal bleeding, and Helicobacter pylori infection. Results from randomized controlled studies and observational studies were the basis for the Consensus Group to recommend the use of proton pump inhibitor therapy as the GI bleeding protective strategy of choice. PPI therapy was also recommended as cost-effective treatment for aspirin-using patients, although the risks and benefits of long-term PPI treatment require patient education and individualization.
Finally, Dr. Rhonda Souza discussed eosinophilic esophagitis (EoE), a chronic immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction associated with eosinophil-predominant inflammation such as dysphagia, food impaction, chest pain, heartburn, abdominal pain, and refractory reflux dyspepsia. Endoscopic features include the ringed esophagus, white specks, linear furrows and stricture. Histologic features of EoE are eosinophilia (more than 15 intraepithelial eosinophils per high power field), basal zone hyperplasia, and dilated intercellular spaces. These eosinophils are activated via T-helper 2 immune system via interleukins-4, -5 and -13. This inflammation is mediated by the dramatic upregulation involving the eotaxin-3 gene that produces a potent chemoattractant for eosinophils. Treatment of EoE usually requires the use of proton pump inhibitors based on their acid suppression, anti-oxidant and anti-inflammatory effects. The use of topical corticosteroids and endoscopic dilation for symptomatic strictures may also be necessary. Nondrug treatment approaches such as the six food elimination diet (SFED) of the most common food allergens such as milk, soy, eggs, wheat, nuts and seafood have also been successful.
Dr. Wolfsen is in the division of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla. He moderated this session during the 2014 Digestive Diseases Week.
One highlight of the AGA Postgraduate Course was the esophageal disease session. The presentation by Dr. Michael B. Wallace summarized recent studies using advanced imaging modalities in patients with Barrett’s esophagus. Studies using chromoscopy and virtual chromoscopy techniques such as narrow-band imaging have increased the detection of dysplasia in BE patients. These are so-called red flag techniques that image large areas of mucosa to detect mucosal abnormalities suspicious for the presence of dysplasia or neoplasia.
Endomicroscopy describes the use of real-time, targeted endoscopic imaging modalities that are capable of producing histologic-like images of mucosa at depths up to 200 microns. Confocal laser endomicroscopy (CLE) uses a blue light laser (405 nm) and collimated light detection and analysis to produce 1000-fold magnified images. When used with a fluorescent contrast agent such as fluorescein or acriflavin dye, these systems produce cellular level images that are comparable to those images seen with optical microscopy. A recent study from Canto et al found that the use of CLE detected BE dysplasia at rates similar to targeted plus random biopsy protocols. Further, a multicenter study will soon begin using a tethered-capsule (nonendoscopic) form of volumetric laser endomicroscopy as a method to screen for BE.
Dr. Amitabh Chak expanded on these issues and reviewed the issues surrounding screening and surveillance of BE patients for the early detection and treatment of esophageal adenocarcinoma. This presentation suggested that necessary future improvements include cost-effective advanced imaging techniques optimized for use in clinical practice, molecular biomarker panels for prediction of which patients may progress to dysplasia and neoplasia, and high-quality intensive endoscopic surveillance for high risk BE patients.
Dr. Joe Murray’s comprehensive presentation of celiac disease described the protean clinical presentations of this disease as well as optimal use of serologic and endoscopic testing. Celiac disease is increasingly identified in middle-aged patients (median 45 years) without diarrhea. Classic malabsorption symptoms of diarrhea, weight loss, steatorrhea, and nutritional deficiencies are found in 25% of patients. Half of celiac patients will have only one symptom such as anemia, diarrhea, lactose intolerance, or weight loss. Nongastrointestinal symptoms are present in another 25% of patients such as infertility, bone disease, chronic fatigue, or abnormal liver enzyme test results.
Optimal use of serologic and endoscopic testing was reviewed, including the differential diagnosis of lymphocytic duodenosis including use of nonsteroidal anti-inflammatory agents (NSAIDs), Helicobacter pylori infection, Crohn’s disease, and Sjogren’s syndrome. Proper duodenal biopsy technique was emphasized with two forceps biopsy samples obtained from the duodenal bulb and four biopsy samples obtained from the second portion of the duodenum. Also discussed was the utility of HLA typing for DQ2/8 in patients currently using a gluten free diet, patients with negative serology results but abnormal duodenal biopsy findings, and those with negative serology results who are at increased genetic risk.
Dr. James Scheiman discussed management of the complex interaction and risks associated with the use of NSAIDs, aspirin, clopidogrel, and proton pump inhibitors in the setting of previous ulcer disease, gastrointestinal bleeding, and Helicobacter pylori infection. Results from randomized controlled studies and observational studies were the basis for the Consensus Group to recommend the use of proton pump inhibitor therapy as the GI bleeding protective strategy of choice. PPI therapy was also recommended as cost-effective treatment for aspirin-using patients, although the risks and benefits of long-term PPI treatment require patient education and individualization.
Finally, Dr. Rhonda Souza discussed eosinophilic esophagitis (EoE), a chronic immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction associated with eosinophil-predominant inflammation such as dysphagia, food impaction, chest pain, heartburn, abdominal pain, and refractory reflux dyspepsia. Endoscopic features include the ringed esophagus, white specks, linear furrows and stricture. Histologic features of EoE are eosinophilia (more than 15 intraepithelial eosinophils per high power field), basal zone hyperplasia, and dilated intercellular spaces. These eosinophils are activated via T-helper 2 immune system via interleukins-4, -5 and -13. This inflammation is mediated by the dramatic upregulation involving the eotaxin-3 gene that produces a potent chemoattractant for eosinophils. Treatment of EoE usually requires the use of proton pump inhibitors based on their acid suppression, anti-oxidant and anti-inflammatory effects. The use of topical corticosteroids and endoscopic dilation for symptomatic strictures may also be necessary. Nondrug treatment approaches such as the six food elimination diet (SFED) of the most common food allergens such as milk, soy, eggs, wheat, nuts and seafood have also been successful.
Dr. Wolfsen is in the division of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla. He moderated this session during the 2014 Digestive Diseases Week.
Role of food allergy testing in EOE unclear
The role of food allergy testing in the evaluation and treatment of patients with eosinophilic esophagitis is not yet clear, according to a study by Dr. Seema Sharma Aceves.
The report appears in the August issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2013.09.007).
Current data suggest, but do not definitively establish, that testing for food allergies is a reasonable approach for beginning to construct an elimination diet in children with EOE, but the data are inadequate to support that strategy in adults with the disorder, she said.
It is clear that food antigens function as triggers that both induce EOE in the first place and also exacerbate the condition once it is established. And removing food antigens from the diet resolves EOE, improving both endoscopic and histologic features, in more than 60% of adults and children.
But most large studies of food elimination diets have involved only children. "This type of large cohort data does not currently exist for the adult population, and smaller studies have not demonstrated success rates that mirror the pediatric data," Dr. Aceves said.
There are several reasons why an empiric elimination diet, which simply removes the six most allergenic food types from the diet, can actually be superior to testing each patient for the specific food types that trigger his or her EOE and then removing only those items from the diet.
First, simply removing these six food types – dairy, egg, soy, wheat, peanuts/tree nuts, and fish/shellfish – usually induces the same response rate as does the more complicated process of food allergy testing. It also spares patients the anxiety and discomfort of testing.
Second, testing for milk allergy notoriously yields a high rate of false-negative results.
Third, food-specific IgE can be caused by cross-reactivity with environmental allergens. For example, a patient with a respiratory allergy to grass can test positive for food allergy to wheat. In general, EOE patients are highly atopic and tend to be sensitized to multiple food and aeroallergens, she said.
And lastly, food allergy testing may reveal a food trigger but doesn’t address the need to perform endoscopy and biopsy after suspected triggers are eliminated from the diet and after they are eventually reintroduced, said Dr. Aceves of the division of allergy and immunology at Rady Children’s Hospital, San Diego.
An argument in favor of food allergy testing is that patients will not have to avoid so many foods when their own individual triggers are identified. In one study of children, those placed on an empiric elimination diet had to eliminate eight entire food groups, with numerous different foods falling under the general categories of peanuts/tree nuts and fish/shellfish. In contrast, children who eliminated only those items identified on testing had to eliminate an average of three food groups.
Food elimination diets "should be applied judiciously" because there is always the risk that patients will lose their tolerance for a food when it has been avoided for a long period of time. Sometimes patients are sensitized to a food but tolerate it because they have very low but steady exposures that allow the body to adapt to it. When that food is completely eliminated for a period of time and then reintroduced, it can trigger a severe allergic reaction and anaphylaxis.
Before reintroducing an allergenic food that has been eliminated from the diet, gastroenterologists may want to test first for a possible hypersensitivity reaction. Alternatively, the food can be reintroduced in a controlled setting such as an allergist’s office, where the staff can recognize and respond to anaphylaxis, and the necessary medications and equipment are readily available, Dr. Aceves said.
Some diagnostic tools that have recently become available for food allergy testing but have not yet been systematically assessed for identifying food triggers in EOE may eventually prove useful. These include peptide microarrays that gauge the repertoire of IgE in patient serum, component-resolved diagnostic testing that assesses which epitopes within a food antigen are recognized by patient serum, and assays that analyze either the release or the activation of basophils in the periphery.
Finally, the recent finding that food-specific, CD4-positive, IL-5-producing T cells can be found in the peripheral blood is intriguing, Dr. Aceves said. If these cells are found to exist in the esophagus as well, then assays for such peripheral T cells might also function as markers for EOE food triggers.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Aceves reported no financial conflicts of interest.
The role of food allergy testing in the evaluation and treatment of patients with eosinophilic esophagitis is not yet clear, according to a study by Dr. Seema Sharma Aceves.
The report appears in the August issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2013.09.007).
Current data suggest, but do not definitively establish, that testing for food allergies is a reasonable approach for beginning to construct an elimination diet in children with EOE, but the data are inadequate to support that strategy in adults with the disorder, she said.
It is clear that food antigens function as triggers that both induce EOE in the first place and also exacerbate the condition once it is established. And removing food antigens from the diet resolves EOE, improving both endoscopic and histologic features, in more than 60% of adults and children.
But most large studies of food elimination diets have involved only children. "This type of large cohort data does not currently exist for the adult population, and smaller studies have not demonstrated success rates that mirror the pediatric data," Dr. Aceves said.
There are several reasons why an empiric elimination diet, which simply removes the six most allergenic food types from the diet, can actually be superior to testing each patient for the specific food types that trigger his or her EOE and then removing only those items from the diet.
First, simply removing these six food types – dairy, egg, soy, wheat, peanuts/tree nuts, and fish/shellfish – usually induces the same response rate as does the more complicated process of food allergy testing. It also spares patients the anxiety and discomfort of testing.
Second, testing for milk allergy notoriously yields a high rate of false-negative results.
Third, food-specific IgE can be caused by cross-reactivity with environmental allergens. For example, a patient with a respiratory allergy to grass can test positive for food allergy to wheat. In general, EOE patients are highly atopic and tend to be sensitized to multiple food and aeroallergens, she said.
And lastly, food allergy testing may reveal a food trigger but doesn’t address the need to perform endoscopy and biopsy after suspected triggers are eliminated from the diet and after they are eventually reintroduced, said Dr. Aceves of the division of allergy and immunology at Rady Children’s Hospital, San Diego.
An argument in favor of food allergy testing is that patients will not have to avoid so many foods when their own individual triggers are identified. In one study of children, those placed on an empiric elimination diet had to eliminate eight entire food groups, with numerous different foods falling under the general categories of peanuts/tree nuts and fish/shellfish. In contrast, children who eliminated only those items identified on testing had to eliminate an average of three food groups.
Food elimination diets "should be applied judiciously" because there is always the risk that patients will lose their tolerance for a food when it has been avoided for a long period of time. Sometimes patients are sensitized to a food but tolerate it because they have very low but steady exposures that allow the body to adapt to it. When that food is completely eliminated for a period of time and then reintroduced, it can trigger a severe allergic reaction and anaphylaxis.
Before reintroducing an allergenic food that has been eliminated from the diet, gastroenterologists may want to test first for a possible hypersensitivity reaction. Alternatively, the food can be reintroduced in a controlled setting such as an allergist’s office, where the staff can recognize and respond to anaphylaxis, and the necessary medications and equipment are readily available, Dr. Aceves said.
Some diagnostic tools that have recently become available for food allergy testing but have not yet been systematically assessed for identifying food triggers in EOE may eventually prove useful. These include peptide microarrays that gauge the repertoire of IgE in patient serum, component-resolved diagnostic testing that assesses which epitopes within a food antigen are recognized by patient serum, and assays that analyze either the release or the activation of basophils in the periphery.
Finally, the recent finding that food-specific, CD4-positive, IL-5-producing T cells can be found in the peripheral blood is intriguing, Dr. Aceves said. If these cells are found to exist in the esophagus as well, then assays for such peripheral T cells might also function as markers for EOE food triggers.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Aceves reported no financial conflicts of interest.
The role of food allergy testing in the evaluation and treatment of patients with eosinophilic esophagitis is not yet clear, according to a study by Dr. Seema Sharma Aceves.
The report appears in the August issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2013.09.007).
Current data suggest, but do not definitively establish, that testing for food allergies is a reasonable approach for beginning to construct an elimination diet in children with EOE, but the data are inadequate to support that strategy in adults with the disorder, she said.
It is clear that food antigens function as triggers that both induce EOE in the first place and also exacerbate the condition once it is established. And removing food antigens from the diet resolves EOE, improving both endoscopic and histologic features, in more than 60% of adults and children.
But most large studies of food elimination diets have involved only children. "This type of large cohort data does not currently exist for the adult population, and smaller studies have not demonstrated success rates that mirror the pediatric data," Dr. Aceves said.
There are several reasons why an empiric elimination diet, which simply removes the six most allergenic food types from the diet, can actually be superior to testing each patient for the specific food types that trigger his or her EOE and then removing only those items from the diet.
First, simply removing these six food types – dairy, egg, soy, wheat, peanuts/tree nuts, and fish/shellfish – usually induces the same response rate as does the more complicated process of food allergy testing. It also spares patients the anxiety and discomfort of testing.
Second, testing for milk allergy notoriously yields a high rate of false-negative results.
Third, food-specific IgE can be caused by cross-reactivity with environmental allergens. For example, a patient with a respiratory allergy to grass can test positive for food allergy to wheat. In general, EOE patients are highly atopic and tend to be sensitized to multiple food and aeroallergens, she said.
And lastly, food allergy testing may reveal a food trigger but doesn’t address the need to perform endoscopy and biopsy after suspected triggers are eliminated from the diet and after they are eventually reintroduced, said Dr. Aceves of the division of allergy and immunology at Rady Children’s Hospital, San Diego.
An argument in favor of food allergy testing is that patients will not have to avoid so many foods when their own individual triggers are identified. In one study of children, those placed on an empiric elimination diet had to eliminate eight entire food groups, with numerous different foods falling under the general categories of peanuts/tree nuts and fish/shellfish. In contrast, children who eliminated only those items identified on testing had to eliminate an average of three food groups.
Food elimination diets "should be applied judiciously" because there is always the risk that patients will lose their tolerance for a food when it has been avoided for a long period of time. Sometimes patients are sensitized to a food but tolerate it because they have very low but steady exposures that allow the body to adapt to it. When that food is completely eliminated for a period of time and then reintroduced, it can trigger a severe allergic reaction and anaphylaxis.
Before reintroducing an allergenic food that has been eliminated from the diet, gastroenterologists may want to test first for a possible hypersensitivity reaction. Alternatively, the food can be reintroduced in a controlled setting such as an allergist’s office, where the staff can recognize and respond to anaphylaxis, and the necessary medications and equipment are readily available, Dr. Aceves said.
Some diagnostic tools that have recently become available for food allergy testing but have not yet been systematically assessed for identifying food triggers in EOE may eventually prove useful. These include peptide microarrays that gauge the repertoire of IgE in patient serum, component-resolved diagnostic testing that assesses which epitopes within a food antigen are recognized by patient serum, and assays that analyze either the release or the activation of basophils in the periphery.
Finally, the recent finding that food-specific, CD4-positive, IL-5-producing T cells can be found in the peripheral blood is intriguing, Dr. Aceves said. If these cells are found to exist in the esophagus as well, then assays for such peripheral T cells might also function as markers for EOE food triggers.
This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Aceves reported no financial conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
PPIs cut acid pocket impact in GERD
Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.
"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).
"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.
Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.
Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).
All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.
At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.
The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."
Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.
Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm2 vs. 15 cm2; P less than .01).
Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).
Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.
Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).
This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.
The authors disclosed no conflicts of interest or outside funding.
Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.
"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).
"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.
Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.
Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).
All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.
At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.
The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."
Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.
Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm2 vs. 15 cm2; P less than .01).
Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).
Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.
Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).
This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.
The authors disclosed no conflicts of interest or outside funding.
Proton pump inhibitors affect the size, relative acidity, and position of the acid pocket in gastroesophageal reflux patients, reported Dr. Wout O. Rohof and his colleagues.
"If one accepts that the acid pocket is still the source of the refluxate during PPI use, therapeutic strategies directly intervening with the acid pocket possibly may prove effective in preventing persistent symptoms on PPI," they wrote in the July issue of Clinical Gastroenterology and Hepatology News (doi.org/10.1016/j.cgh.2014.04.003-).
"This insight is of great importance because in approximately 30% of patients PPI therapy fails to resolve symptoms, either partially or completely," they added.
Dr. Rohof of the Academic Medical Center in Amsterdam and his colleagues looked at 36 patients with gastroesophageal reflux disease (GERD) confirmed by the presence of esophagitis on endoscopy and/or impedance-pH-metry with an acid exposure of more than 4.5%, plus usual GERD symptoms.
Eighteen patients were on PPIs; the remainder had been off PPIs for at least 1 week prior to the study; eight PPI cohort patients used omeprazole, five used pantoprazole, and five used esomeprazole, with dosages varying from 20 mg (one patient), to 40 mg (eight patients), to 40 mg twice daily (nine patients).
All patients were fed a standardized meal of orange juice and pancakes; afterward, concurrent scintigraphy, high-resolution manometry, and pH-impedance recordings were acquired for 105 minutes.
At the study’s conclusion, the acid pocket – a floating pool of acid on top of ingested food, visualized on scintigraphy after patients were injected with a radioisotope – was aspirated for analysis of its pH level.
The authors found that overall, while the total number of reflux episodes was similar for both PPI and non-PPI cohorts (15 vs. 14; P = .81), "As expected, the number of acid reflux episodes was lower on PPI (4.5 vs. 2.0; P = .04)."
Only two patients in the entire cohort did not demonstrate an acid pocket on scintigraphy; both were taking PPIs.
Of the remaining patients, the size of the acid pocket was significantly less among PPI patients than their counterparts (10 cm2 vs. 15 cm2; P less than .01).
Moreover, when the acid pocket was aspirated at the conclusion of the study through the manometry catheter, the pH of the aspirated acid pocket fluid was significantly higher among PPI patients, compared with those not taking the drug (3.9 vs.0.9; P less than .001).
Finally, the investigators looked at the location of the acid pocket, which has also been shown to correlate with reflux episodes.
Their data showed that PPI patients were more likely to have the pocket located below the level of the diaphragm (60%), compared with patients not on PPI therapy (40%; P = .04).
This was especially important since pockets at this level correlated with only a 7% and 15% risk of acidic reflux events in PPI and non-PPI patients, respectively; in comparison, pockets in the hiatus and higher were associated with much greater rates of acidic reflux for both PPI and non-PPI patients, though the rates were lower among the former.
The authors disclosed no conflicts of interest or outside funding.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Proton pump inhibitors have more than one beneficial action in esophagitis.
Major finding: The size, position, and acidity of the acid pocket in reflux patients are all lessened with daily PPI therapy.
Data source: A cohort of 36 esophagitis patients, half of whom took PPIs, half of whom did not.
Disclosures: The authors disclosed no conflicts of interest or outside funding.
Screen for Barrett’s in all with central obesity?
CHICAGO – The prevalence of erosive esophagitis and Barrett’s esophagus is comparable in individuals regardless of whether they have gastroesophageal reflux symptoms, according to a population-based study.
"These results directly challenge the established GERD-based Barrett’s esophagus screening paradigm and provide strong rationale for using central obesity in Caucasian males with or without symptomatic GERD as criteria for Barrett’s esophagus screening," Dr. Nicholas R. Crews said at the annual Digestive Disease Week.
"In this study, waist-hip ratio was our surrogate marker for central obesity. It’s easily obtainable and usable in clinical practice," noted Dr. Crews of the Mayo Clinic in Rochester, Minn.
Barrett’s esophagus is the precursor lesion and principal risk factor for esophageal adenocarcinoma, a malignancy whose incidence in the United States and other developed nations is increasing at an alarming rate. Improved methods of screening for esophageal adenocarcinoma are sorely needed, he added.
Dr. Crews presented a study in which a representative sample of Olmsted County, Minn., residents over age 50 with no history of endoscopy were randomized to screening for Barrett’s esophagus by one of three methods: sedated endoscopy in the GI suite, unsedated transnasal endoscopy in the clinic, or unsedated transnasal endoscopy in a Mayo mobile research van.
Participants’ mean age was 70 years, 46% were men, 206 of the 209 were white, and only one-third of subjects had GERD symptoms.
The prevalence of esophagitis grades A-C proved to be 32% in the symptomatic GERD group and similar at 29% in those without GERD symptoms. Similarly, Barrett’s esophagus was identified in 8.7% of the symptomatic GERD group and 7.9% of subjects without GERD symptoms. Dysplasia was present in 1.4% of each group. The mean length of the esophageal segment with Barrett’s esophagus was 2.4 cm in patients with GERD symptoms and not significantly different in those who were asymptomatic.
Three risk factors proved significant as predictors of esophageal injury as defined by esophagitis or Barrett’s esophagus: male sex, central obesity as defined by a waist-hip ratio greater than 0.9, and consumption of more than two alcoholic drinks per day. Age, smoking status, and body mass index were not predictive.
The mean waist-to-hip ratio was 0.89 in screened subjects with no esophagitis or Barrett’s esophagus, 0.91 in those with positive endoscopic findings and symptomatic gastroesophageal reflux, and 0.95 in those with positive findings who were asymptomatic.
Audience members expressed skepticism about the notion of routinely screening for Barrett’s esophagus in individuals with central obesity in an era of an unprecedented obesity epidemic.
For example, Dr. Joel E. Richter, who described himself as "an anti-Barrett’s person," commented that he believes gastroenterologists are already overdiagnosing and overtreating the condition, needlessly alarming many patients.
In women, particularly, it’s increasingly clear that Barrett’s esophagus only rarely develops into esophageal adenocarcinoma, he said.
"Others have said that women with Barrett’s esophagus are as likely to get esophageal cancer as men are to get breast cancer," commented Dr. Richter, professor of internal medicine and director of the center for swallowing disorders at the University of South Florida, Tampa.
Another audience member told Dr. Crews, "I totally agree with you that we miss most people with Barrett’s by our current screening process. The problem is, it’s unclear whether it’s important or not to find them. To extrapolate from your study and say that anyone with central obesity ought to be screened for [Barrett’s esophagus] is a little strong, I think."
"It’s very controversial," Dr. Crews agreed. "It’s something we continue to struggle with."
He reported having no relevant financial conflicts.
CHICAGO – The prevalence of erosive esophagitis and Barrett’s esophagus is comparable in individuals regardless of whether they have gastroesophageal reflux symptoms, according to a population-based study.
"These results directly challenge the established GERD-based Barrett’s esophagus screening paradigm and provide strong rationale for using central obesity in Caucasian males with or without symptomatic GERD as criteria for Barrett’s esophagus screening," Dr. Nicholas R. Crews said at the annual Digestive Disease Week.
"In this study, waist-hip ratio was our surrogate marker for central obesity. It’s easily obtainable and usable in clinical practice," noted Dr. Crews of the Mayo Clinic in Rochester, Minn.
Barrett’s esophagus is the precursor lesion and principal risk factor for esophageal adenocarcinoma, a malignancy whose incidence in the United States and other developed nations is increasing at an alarming rate. Improved methods of screening for esophageal adenocarcinoma are sorely needed, he added.
Dr. Crews presented a study in which a representative sample of Olmsted County, Minn., residents over age 50 with no history of endoscopy were randomized to screening for Barrett’s esophagus by one of three methods: sedated endoscopy in the GI suite, unsedated transnasal endoscopy in the clinic, or unsedated transnasal endoscopy in a Mayo mobile research van.
Participants’ mean age was 70 years, 46% were men, 206 of the 209 were white, and only one-third of subjects had GERD symptoms.
The prevalence of esophagitis grades A-C proved to be 32% in the symptomatic GERD group and similar at 29% in those without GERD symptoms. Similarly, Barrett’s esophagus was identified in 8.7% of the symptomatic GERD group and 7.9% of subjects without GERD symptoms. Dysplasia was present in 1.4% of each group. The mean length of the esophageal segment with Barrett’s esophagus was 2.4 cm in patients with GERD symptoms and not significantly different in those who were asymptomatic.
Three risk factors proved significant as predictors of esophageal injury as defined by esophagitis or Barrett’s esophagus: male sex, central obesity as defined by a waist-hip ratio greater than 0.9, and consumption of more than two alcoholic drinks per day. Age, smoking status, and body mass index were not predictive.
The mean waist-to-hip ratio was 0.89 in screened subjects with no esophagitis or Barrett’s esophagus, 0.91 in those with positive endoscopic findings and symptomatic gastroesophageal reflux, and 0.95 in those with positive findings who were asymptomatic.
Audience members expressed skepticism about the notion of routinely screening for Barrett’s esophagus in individuals with central obesity in an era of an unprecedented obesity epidemic.
For example, Dr. Joel E. Richter, who described himself as "an anti-Barrett’s person," commented that he believes gastroenterologists are already overdiagnosing and overtreating the condition, needlessly alarming many patients.
In women, particularly, it’s increasingly clear that Barrett’s esophagus only rarely develops into esophageal adenocarcinoma, he said.
"Others have said that women with Barrett’s esophagus are as likely to get esophageal cancer as men are to get breast cancer," commented Dr. Richter, professor of internal medicine and director of the center for swallowing disorders at the University of South Florida, Tampa.
Another audience member told Dr. Crews, "I totally agree with you that we miss most people with Barrett’s by our current screening process. The problem is, it’s unclear whether it’s important or not to find them. To extrapolate from your study and say that anyone with central obesity ought to be screened for [Barrett’s esophagus] is a little strong, I think."
"It’s very controversial," Dr. Crews agreed. "It’s something we continue to struggle with."
He reported having no relevant financial conflicts.
CHICAGO – The prevalence of erosive esophagitis and Barrett’s esophagus is comparable in individuals regardless of whether they have gastroesophageal reflux symptoms, according to a population-based study.
"These results directly challenge the established GERD-based Barrett’s esophagus screening paradigm and provide strong rationale for using central obesity in Caucasian males with or without symptomatic GERD as criteria for Barrett’s esophagus screening," Dr. Nicholas R. Crews said at the annual Digestive Disease Week.
"In this study, waist-hip ratio was our surrogate marker for central obesity. It’s easily obtainable and usable in clinical practice," noted Dr. Crews of the Mayo Clinic in Rochester, Minn.
Barrett’s esophagus is the precursor lesion and principal risk factor for esophageal adenocarcinoma, a malignancy whose incidence in the United States and other developed nations is increasing at an alarming rate. Improved methods of screening for esophageal adenocarcinoma are sorely needed, he added.
Dr. Crews presented a study in which a representative sample of Olmsted County, Minn., residents over age 50 with no history of endoscopy were randomized to screening for Barrett’s esophagus by one of three methods: sedated endoscopy in the GI suite, unsedated transnasal endoscopy in the clinic, or unsedated transnasal endoscopy in a Mayo mobile research van.
Participants’ mean age was 70 years, 46% were men, 206 of the 209 were white, and only one-third of subjects had GERD symptoms.
The prevalence of esophagitis grades A-C proved to be 32% in the symptomatic GERD group and similar at 29% in those without GERD symptoms. Similarly, Barrett’s esophagus was identified in 8.7% of the symptomatic GERD group and 7.9% of subjects without GERD symptoms. Dysplasia was present in 1.4% of each group. The mean length of the esophageal segment with Barrett’s esophagus was 2.4 cm in patients with GERD symptoms and not significantly different in those who were asymptomatic.
Three risk factors proved significant as predictors of esophageal injury as defined by esophagitis or Barrett’s esophagus: male sex, central obesity as defined by a waist-hip ratio greater than 0.9, and consumption of more than two alcoholic drinks per day. Age, smoking status, and body mass index were not predictive.
The mean waist-to-hip ratio was 0.89 in screened subjects with no esophagitis or Barrett’s esophagus, 0.91 in those with positive endoscopic findings and symptomatic gastroesophageal reflux, and 0.95 in those with positive findings who were asymptomatic.
Audience members expressed skepticism about the notion of routinely screening for Barrett’s esophagus in individuals with central obesity in an era of an unprecedented obesity epidemic.
For example, Dr. Joel E. Richter, who described himself as "an anti-Barrett’s person," commented that he believes gastroenterologists are already overdiagnosing and overtreating the condition, needlessly alarming many patients.
In women, particularly, it’s increasingly clear that Barrett’s esophagus only rarely develops into esophageal adenocarcinoma, he said.
"Others have said that women with Barrett’s esophagus are as likely to get esophageal cancer as men are to get breast cancer," commented Dr. Richter, professor of internal medicine and director of the center for swallowing disorders at the University of South Florida, Tampa.
Another audience member told Dr. Crews, "I totally agree with you that we miss most people with Barrett’s by our current screening process. The problem is, it’s unclear whether it’s important or not to find them. To extrapolate from your study and say that anyone with central obesity ought to be screened for [Barrett’s esophagus] is a little strong, I think."
"It’s very controversial," Dr. Crews agreed. "It’s something we continue to struggle with."
He reported having no relevant financial conflicts.
AT DDW 2014
Key clinical point: The current recommended strategy of screening for Barrett’s esophagus on the basis of symptoms of gastroesophageal reflux is called into question by a new study showing the esophageal cancer precursor lesion is just as common in screened asymptomatic individuals.
Major finding: The mean waist-to-hip ratio was 0.89 in screened subjects with no esophagitis or Barrett’s esophagus, 0.91 in those with positive endoscopic findings and symptomatic gastroesophageal reflux, and 0.95 in those with positive findings who were asymptomatic.
Data source: This was a prospective population-based study in which 209 individuals over age 50 with no history of endoscopy, two-thirds of whom had no gastroesophageal reflux symptoms, underwent screening endoscopy.
Disclosures: The presenter reported having no relevant financial conflicts.
Novel noninvasive therapy for extraesophageal reflux
CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.
"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.
Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.
EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.
The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.
Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m2. Three-quarters of patients were on PPI therapy, which they felt to be ineffective.
The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.
Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.
The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."
"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."
Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.
Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.
The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.
CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.
"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.
Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.
EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.
The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.
Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m2. Three-quarters of patients were on PPI therapy, which they felt to be ineffective.
The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.
Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.
The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."
"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."
Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.
Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.
The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.
CHICAGO – A novel, externally worn device for the treatment of extraesophageal reflux proved effective, safe, and well tolerated in a multicenter clinical trial.
"Given the poor response to PPI [proton-pump inhibitors] therapy in many patients with extraesophageal reflux, this device may be an alternative form of treating this difficult disorder," Dr. Michael F. Vaezi said in a presentation of the study findings at the annual Digestive Disease Week.
Extraesophageal reflux (EER) affects more than 15 million Americans. The cost of care is estimated to be in excess of $50 billion annually, most of which goes for PPIs, which are overused and generally not effective in treating this common disorder, observed Dr. Vaezi, professor of medicine at Vanderbilt University, Nashville, Tenn.
EER is caused by reflux of gastroduodenal contents into the laryngopharynx, resulting in a range of symptoms including chronic cough, postnasal drip, throat clearing, hoarseness, and a sensation of a lump in the throat.
The investigational device, known as the Reza-Band, is an individually fitted upper esophageal sphincter assist device to be worn at bedtime. It is designed to apply slight pressure to the cricoid cartilage area sufficient to increase the intraluminal pressure of the upper esophageal sphincter to 20 mm Hg. In earlier studies, this modest increase in pressure eliminated pharyngeal reflux without affecting normal activities such as swallowing and belching.
Dr. Vaezi reported on 47 patients with EER treated with the upper esophageal assist device at four medical centers. Their mean age was 50 years, with an average body mass index of 26.1 kg/m2. Three-quarters of patients were on PPI therapy, which they felt to be ineffective.
The primary study endpoint was the change in Reflux Symptom Index scores from baseline through week 4 of nighttime use of the assist device. The median score improved from 27 at baseline to 14 at week 2 and 12 at week 4. That translated to a mean 54% reduction. A total of 86% of subjects were deemed to have experienced treatment success as defined by at least a 25% improvement in their symptom score; 30% of participants showed a greater than 75% improvement.
Treatment side effects were few, mild, and brief, consisting chiefly of skin irritation from the device’s Velcro strap. No one withdrew from the study.
The Reza-Band device was developed by gastroenterologists at the Medical College of Wisconsin, Milwaukee. Dr. Vaezi said he and his coinvestigators decided to formally investigate the device because "we were intrigued and impressed by the fact that it has helped so many patients."
"For me, it’s a welcome development," Dr. Vaezi added. "Just anecdotally, many patients in the study wanted to know how they could purchase this device. It’s really welcome in an area [in which] we don’t have many therapeutic options."
Still, he noted, it’s probably a good idea for device users to continue to keep a couple of bricks under the head of the bed, in accord with standard medical advice.
Future plans include a sham-controlled study designed to assess the device’s true benefit over placebo therapy; this will be an important study because EER is known to have a substantial placebo response rate, he continued. Also, plans are afoot for a safety study assessing whether the device has any clinically meaningful impact upon intraocular pressure.
The study was supported by Somna Therapeutics, which is developing the device. Dr. Vaezi reported having no financial relationship with the company.
AT DDW 2014
Key clinical point: An investigational device that modestly increases intraluminal pressure at the upper esophageal sphincter shows promise as a noninvasive therapy for extraesophageal reflux, a common disorder for which no effective pharmacotherapy exists.
Major finding: Patients with extraesophageal reflux experienced a mean 54% reduction in scores on the Reflux Symptom Index after 4 weeks of nighttime use of the upper esophageal sphincter assist device.
Data source: This was a 4-week multicenter, prospective, uncontrolled study involving 47 patients.
Disclosures: The study was supported by Somna Therapeutics. The presenter reported having no financial relationship with the company.
Diet modifications highly effective in EoE
An elemental diet was more than 90% effective in inducing histologic remission in eosinophilic esophagitis patients, reported Dr. Ángel Arias and colleagues in the June issue of Gastroenterology.
The Six Food Elimination Diet was also highly efficacious, reinforcing the idea that dietary modification "should be considered as a first-line therapy in both children and adults affected by this disease," wrote the investigators (doi:10.1053/j.gastro.2014.02.006).
Dr. Arias of the Complejo Hospitalario La Mancha Centro, in Alcázar de San Juan, Spain, searched the MEDLINE, EMBASE, and SCOPUS databases for studies performed prior to June 2013 investigating the efficacy of dietary interventions in eosinophilic esophagitis (EoE).
Abstracts and other relevant material from conferences including Digestive Disease Week, the American College of Gastroenterology meeting, and European Gastroenterology Week were also included.
Overall, 33 studies were included, 23 of which were full articles with the remainder being abstracts; there were a total of 1,128 children and 189 adults included in the analysis.
Of the 13 studies that assessed the efficacy of exclusive feeding with an amino acid–based elemental diet (involving 411 children and 18 adults), 90.8% of patients achieved histologic remission of EoE, defined as fewer than 15 eosinophils per high-power field on esophageal biopsy (95% confidence interval, 84.7%-95.5%).
The next best diet, the Six Food Elimination Diet (SFED), offered a 72.1% efficacy rate (95% CI, 65.8%-78.1%) across 75 children and 122 adults and was "the only one assessed in more adults than children."
On the other hand, the strategy of eliminating foods that gave a positive result in skin allergy tests was assessed in 14 studies (594 children and 32 adults), and demonstrated an overall efficacy of just 45.5% (95% CI, 35.4%-55.7%).
Other less-studied diets included gluten-free and cow’s milk elimination diets, both of which seemed to result in histologic remission (58.7% and 68.2%, respectively).
However, "because studies assessing these dietary treatments are still scarce, making conclusions from them can be risky," wrote the authors.
"For example, although the overall efficacy of a gluten-free diet in achieving histologic remission of EoE was 58.7%, the remission rate ranged from 23.1% to 85.6%," they reported.
"Despite its obvious success, the multiple drawbacks of elemental diets, which include the need to avoid all table food, its unpleasant taste, and high cost, and the psychological effects produced by the social limitations that this diet entails, have probably contributed to the fact that this dietary intervention has been restricted almost exclusively to pediatric patients," commented Dr. Arias.
"In fact, no research on adults was available until 2013, with the reported remission rates being comparable with those documented in children."
On the other hand, the relatively high efficacy of the SFED diet, which avoids many of the disadvantages of the elemental diet, seems to make this the best choice for "children and motivated adult patients," added the researchers.
Future studies and meta-analyses should address whether diet adherence results in changes in esophageal fibrosis as well as quality of life issues brought on by diet adherence.
The authors disclosed no relevant financial conflicts.
An elemental diet was more than 90% effective in inducing histologic remission in eosinophilic esophagitis patients, reported Dr. Ángel Arias and colleagues in the June issue of Gastroenterology.
The Six Food Elimination Diet was also highly efficacious, reinforcing the idea that dietary modification "should be considered as a first-line therapy in both children and adults affected by this disease," wrote the investigators (doi:10.1053/j.gastro.2014.02.006).
Dr. Arias of the Complejo Hospitalario La Mancha Centro, in Alcázar de San Juan, Spain, searched the MEDLINE, EMBASE, and SCOPUS databases for studies performed prior to June 2013 investigating the efficacy of dietary interventions in eosinophilic esophagitis (EoE).
Abstracts and other relevant material from conferences including Digestive Disease Week, the American College of Gastroenterology meeting, and European Gastroenterology Week were also included.
Overall, 33 studies were included, 23 of which were full articles with the remainder being abstracts; there were a total of 1,128 children and 189 adults included in the analysis.
Of the 13 studies that assessed the efficacy of exclusive feeding with an amino acid–based elemental diet (involving 411 children and 18 adults), 90.8% of patients achieved histologic remission of EoE, defined as fewer than 15 eosinophils per high-power field on esophageal biopsy (95% confidence interval, 84.7%-95.5%).
The next best diet, the Six Food Elimination Diet (SFED), offered a 72.1% efficacy rate (95% CI, 65.8%-78.1%) across 75 children and 122 adults and was "the only one assessed in more adults than children."
On the other hand, the strategy of eliminating foods that gave a positive result in skin allergy tests was assessed in 14 studies (594 children and 32 adults), and demonstrated an overall efficacy of just 45.5% (95% CI, 35.4%-55.7%).
Other less-studied diets included gluten-free and cow’s milk elimination diets, both of which seemed to result in histologic remission (58.7% and 68.2%, respectively).
However, "because studies assessing these dietary treatments are still scarce, making conclusions from them can be risky," wrote the authors.
"For example, although the overall efficacy of a gluten-free diet in achieving histologic remission of EoE was 58.7%, the remission rate ranged from 23.1% to 85.6%," they reported.
"Despite its obvious success, the multiple drawbacks of elemental diets, which include the need to avoid all table food, its unpleasant taste, and high cost, and the psychological effects produced by the social limitations that this diet entails, have probably contributed to the fact that this dietary intervention has been restricted almost exclusively to pediatric patients," commented Dr. Arias.
"In fact, no research on adults was available until 2013, with the reported remission rates being comparable with those documented in children."
On the other hand, the relatively high efficacy of the SFED diet, which avoids many of the disadvantages of the elemental diet, seems to make this the best choice for "children and motivated adult patients," added the researchers.
Future studies and meta-analyses should address whether diet adherence results in changes in esophageal fibrosis as well as quality of life issues brought on by diet adherence.
The authors disclosed no relevant financial conflicts.
An elemental diet was more than 90% effective in inducing histologic remission in eosinophilic esophagitis patients, reported Dr. Ángel Arias and colleagues in the June issue of Gastroenterology.
The Six Food Elimination Diet was also highly efficacious, reinforcing the idea that dietary modification "should be considered as a first-line therapy in both children and adults affected by this disease," wrote the investigators (doi:10.1053/j.gastro.2014.02.006).
Dr. Arias of the Complejo Hospitalario La Mancha Centro, in Alcázar de San Juan, Spain, searched the MEDLINE, EMBASE, and SCOPUS databases for studies performed prior to June 2013 investigating the efficacy of dietary interventions in eosinophilic esophagitis (EoE).
Abstracts and other relevant material from conferences including Digestive Disease Week, the American College of Gastroenterology meeting, and European Gastroenterology Week were also included.
Overall, 33 studies were included, 23 of which were full articles with the remainder being abstracts; there were a total of 1,128 children and 189 adults included in the analysis.
Of the 13 studies that assessed the efficacy of exclusive feeding with an amino acid–based elemental diet (involving 411 children and 18 adults), 90.8% of patients achieved histologic remission of EoE, defined as fewer than 15 eosinophils per high-power field on esophageal biopsy (95% confidence interval, 84.7%-95.5%).
The next best diet, the Six Food Elimination Diet (SFED), offered a 72.1% efficacy rate (95% CI, 65.8%-78.1%) across 75 children and 122 adults and was "the only one assessed in more adults than children."
On the other hand, the strategy of eliminating foods that gave a positive result in skin allergy tests was assessed in 14 studies (594 children and 32 adults), and demonstrated an overall efficacy of just 45.5% (95% CI, 35.4%-55.7%).
Other less-studied diets included gluten-free and cow’s milk elimination diets, both of which seemed to result in histologic remission (58.7% and 68.2%, respectively).
However, "because studies assessing these dietary treatments are still scarce, making conclusions from them can be risky," wrote the authors.
"For example, although the overall efficacy of a gluten-free diet in achieving histologic remission of EoE was 58.7%, the remission rate ranged from 23.1% to 85.6%," they reported.
"Despite its obvious success, the multiple drawbacks of elemental diets, which include the need to avoid all table food, its unpleasant taste, and high cost, and the psychological effects produced by the social limitations that this diet entails, have probably contributed to the fact that this dietary intervention has been restricted almost exclusively to pediatric patients," commented Dr. Arias.
"In fact, no research on adults was available until 2013, with the reported remission rates being comparable with those documented in children."
On the other hand, the relatively high efficacy of the SFED diet, which avoids many of the disadvantages of the elemental diet, seems to make this the best choice for "children and motivated adult patients," added the researchers.
Future studies and meta-analyses should address whether diet adherence results in changes in esophageal fibrosis as well as quality of life issues brought on by diet adherence.
The authors disclosed no relevant financial conflicts.
FROM GASTROENTEROLOGY
Major finding: Elemental diets effectively induced histologic remission in 90.8% of eosinophilic esophagitis patients.
Data source: A meta-analysis comprising 33 studies and 1,317 patients with EoE.
Disclosures: The authors disclosed no conflicts of interest related to this study.
FISH panel may improve Barrett’s surveillance
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
CHICAGO – Fluorescence in situ hybridization testing for aneuploidy and loss of the tumor suppressor gene P16 can be useful in predicting progression to high-grade dysplasia and adenocarcinoma in patients with nondysplastic Barrett’s esophagus.
Adding these genetic biomarkers to the clinical risk factors of age and Barrett’s esophagus (BE) segment length provides for an even more robust prediction tool, Dr. Margriet R. Timmer said at the annual Digestive Disease Week.
This conclusion is based on a prospective, multicenter cohort study involving 428 patients with nondysplastic BE. The average age of the patients was 59 years and maximum BE length 3 cm.
Fluorescence in situ hybridization (FISH) analysis was used to detect genetic abnormalities on endoscopic cytology brushes from all patients. The FISH panel included probes for six candidate biomarkers: the tumor suppressor genes P16 and P53, the oncogenes MYC, HER-2/neu, and 20q, as well as aneuploidy.
After a median follow-up of 45 months, 22 patients had histologic progression after review by two expert pathologists: 13 cases of high-grade dysplasia (HGD) and 9 cases of esophageal adenocarcinoma (EAC).
The rate of progression to HGD/EAC was 1.09% per patient-year and 0.65% per patient-year for EAC, said Dr. Timmer of the Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Univariable analysis revealed that P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04) significantly predicted progression, as did increasing age (HR, 1.06; P = .008) and longer BE length (HR, 1.15; P = .017).
None of the other biomarkers or clinical factors such as male sex, body mass index, tobacco use, family history of BE or EAC, or years of BE were significant.
A prediction model was then created using the significant predictors. The C statistic, which takes into account specificity and sensitivity, was 0.68 for the basic model that included only age and BE length, but this improved significantly to 0.73 when the biomarkers were added, she said.
Based on the prediction model, 236 patients were considered high risk and 192 patients were low risk.
Importantly, 5-year progression-free survival was significantly lower in the high-risk group than in the low-risk group (93.6% vs. 98.4%; P = .001), Dr. Timmer noted.
Session cochair Roy Wong of Walter Reed Army Medical Center, Washington, said in an interview that "intellectually, the concept is terrific," but that clinicians will need a specific risk cutoff to apply the findings to an individual patient in the community setting and that overall survival data would strengthen the results.
The study authors acknowledged that FISH testing is still costly and that they have yet to use it in the clinical setting. One major advantage of FISH, however, is that it can be applied to cytology specimens that can be easily obtained during upper endoscopy by brushing the entire Barrett’s segment, thereby overcoming the potential problem of biopsy sampling error, Dr. Timmer said.
The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
AT DDW 2014
Key clinical point: Assessing aneuploidy and P16 as well as age and BE length can be useful in stratifying patients with Barrett’s esophagus into high- and low-risk disease categories to improve the efficacy of surveillance programs.
Major finding: P16 loss (hazard ratio, 2.56; P = .03) and aneuploidy (HR, 2.66; P = .04), increasing age (HR, 1.06; P = .008), and longer BE length (HR, 1.15; P = .017) predicted progression.
Data source: A prospective study of 428 patients with nondysplastic Barrett’s esophagus.
Disclosures: The study was funded by grants from KWF Kanderbestrijding (the Dutch Cancer Society), NOW (De Nederlandse Organisatie voor Wetenschappelijk Onderzoek), Fonds NutsOhra, Gut Club, and Abbott Molecular. Dr. Timmer and her coauthors reported no financial disclosures.
Early endoscopic follow-up nets dysplasia in 9.5% of Barrett’s
CHICAGO – Early endoscopic follow-up within 24 months detected dysplasia in nearly one in 10 patients with nondysplastic or low-grade Barrett’s esophagus in a retrospective study at the Mayo Clinic.
Initial endoscopy missed four cases of high-grade dysplasia or esophageal adenocarcinoma (1.9%) and 16 cases of low-grade dysplasia (7.6%) for an overall miss-rate of 9.5%.
Patients on proton pump inhibitors were less likely to have dysplasia missed than were those off PPIs (20% vs. 52.6%, P = .008).
Those with long- versus short-segment Barrett’s esophagus were more likely to have dysplasia overlooked (85% vs. 53.6%; P = .008; mean 6 mm vs. 4 mm; P = .006), Dr. Kavel Visrodia said at the annual Digestive Disease Week.
Current American College of Gastroenterology (ACG) guidelines recommend early repeat esophagogastroduodenoscopy (EGD) to exclude the presence of missed dysplasia in newly diagnosed nondysplastic Barrett’s esophagus (BE), while the ACG and American Society for Gastrointestinal Endoscopy call for repeat EGD within 6 months for those with low-grade dysplasia.
The yield for repeat EGD has not been established, and only one study exists in the literature, said Dr. Visrodia of the department of medicine, Mayo Clinic, Rochester, Minn.
That study (Dis. Esophagus 2012 Sept. 28. [doi:10.1111/j.1442-2050.2012.01431.x]) showed a miss-rate of 8.2% among 146 patients with newly diagnosed nondysplastic BE. Long-segment BE was the only significant predictor of dysplasia on follow-up (odds ratio, 9.18; P = .008).
The cohort was relatively small and had no long-term follow-up, and with an interval to follow-up of 36 months, "it’s possible that some of these were actually incident cases of dysplasia and not prevalent cases," he said.
To address these gaps, Dr. Visrodia and his colleagues identified 488 BE cases from 1977 to 2011 in the Rochester Epidemiology Project in Olmsted County, Minn. A total of 278 patients were excluded because of high-grade dysplasia (HGD) or esophageal cancer on index endoscopy or repeat endoscopy after 24 months, leaving 181 patients with nondysplastic BE and 29 with low-grade dysplasia (LGD).
Repeat endoscopy within 24 months revealed 2 cases of HGD or cancer and 16 cases of LGD in the nondysplastic BE group, and 2 cases of HGD or cancer in the LGD group, Dr. Visrodia said.
Three of the four HGD/cancer cases were in patients with long-segment BE, defined as at least 3 cm of columnar mucosa.
Biopsies were insufficient in 63% of patients with missed dysplasia, compared with 55% in the group without missed dysplasia. Biopsies were considered adequate if the number of biopsies divided by the BE length was at least 2, indicating that samples were taken every 2 cm in accordance with guidelines. This risk factor is noteworthy, although the difference between groups was not statistically significant, possibly because of the small sample size, he said.
Finally, after a median of 6.8 years of follow-up, 30 asymptomatic, prevalent HGDs or cancers were detected within 24 months, compared with 22 incident cases detected after 24 months. This suggests that "a greater number of high-grade dysplasias and cancers were detected up front rather than during long-term careful surveillance," Dr. Visrodia said.
During a discussion of the study, one attendee asked whether the results make a better case for aggressive ablation up front rather than for surveillance, while others expressed surprise at the high miss rate at an institution such as the Mayo Clinic.
Dr. Visrodia replied that the results do give them pause, and suggested that tighter early endoscopic surveillance may be warranted, particularly in those with long-segment BE.
Dr. Visrodia and his coauthors reported no financial disclosures.
CHICAGO – Early endoscopic follow-up within 24 months detected dysplasia in nearly one in 10 patients with nondysplastic or low-grade Barrett’s esophagus in a retrospective study at the Mayo Clinic.
Initial endoscopy missed four cases of high-grade dysplasia or esophageal adenocarcinoma (1.9%) and 16 cases of low-grade dysplasia (7.6%) for an overall miss-rate of 9.5%.
Patients on proton pump inhibitors were less likely to have dysplasia missed than were those off PPIs (20% vs. 52.6%, P = .008).
Those with long- versus short-segment Barrett’s esophagus were more likely to have dysplasia overlooked (85% vs. 53.6%; P = .008; mean 6 mm vs. 4 mm; P = .006), Dr. Kavel Visrodia said at the annual Digestive Disease Week.
Current American College of Gastroenterology (ACG) guidelines recommend early repeat esophagogastroduodenoscopy (EGD) to exclude the presence of missed dysplasia in newly diagnosed nondysplastic Barrett’s esophagus (BE), while the ACG and American Society for Gastrointestinal Endoscopy call for repeat EGD within 6 months for those with low-grade dysplasia.
The yield for repeat EGD has not been established, and only one study exists in the literature, said Dr. Visrodia of the department of medicine, Mayo Clinic, Rochester, Minn.
That study (Dis. Esophagus 2012 Sept. 28. [doi:10.1111/j.1442-2050.2012.01431.x]) showed a miss-rate of 8.2% among 146 patients with newly diagnosed nondysplastic BE. Long-segment BE was the only significant predictor of dysplasia on follow-up (odds ratio, 9.18; P = .008).
The cohort was relatively small and had no long-term follow-up, and with an interval to follow-up of 36 months, "it’s possible that some of these were actually incident cases of dysplasia and not prevalent cases," he said.
To address these gaps, Dr. Visrodia and his colleagues identified 488 BE cases from 1977 to 2011 in the Rochester Epidemiology Project in Olmsted County, Minn. A total of 278 patients were excluded because of high-grade dysplasia (HGD) or esophageal cancer on index endoscopy or repeat endoscopy after 24 months, leaving 181 patients with nondysplastic BE and 29 with low-grade dysplasia (LGD).
Repeat endoscopy within 24 months revealed 2 cases of HGD or cancer and 16 cases of LGD in the nondysplastic BE group, and 2 cases of HGD or cancer in the LGD group, Dr. Visrodia said.
Three of the four HGD/cancer cases were in patients with long-segment BE, defined as at least 3 cm of columnar mucosa.
Biopsies were insufficient in 63% of patients with missed dysplasia, compared with 55% in the group without missed dysplasia. Biopsies were considered adequate if the number of biopsies divided by the BE length was at least 2, indicating that samples were taken every 2 cm in accordance with guidelines. This risk factor is noteworthy, although the difference between groups was not statistically significant, possibly because of the small sample size, he said.
Finally, after a median of 6.8 years of follow-up, 30 asymptomatic, prevalent HGDs or cancers were detected within 24 months, compared with 22 incident cases detected after 24 months. This suggests that "a greater number of high-grade dysplasias and cancers were detected up front rather than during long-term careful surveillance," Dr. Visrodia said.
During a discussion of the study, one attendee asked whether the results make a better case for aggressive ablation up front rather than for surveillance, while others expressed surprise at the high miss rate at an institution such as the Mayo Clinic.
Dr. Visrodia replied that the results do give them pause, and suggested that tighter early endoscopic surveillance may be warranted, particularly in those with long-segment BE.
Dr. Visrodia and his coauthors reported no financial disclosures.
CHICAGO – Early endoscopic follow-up within 24 months detected dysplasia in nearly one in 10 patients with nondysplastic or low-grade Barrett’s esophagus in a retrospective study at the Mayo Clinic.
Initial endoscopy missed four cases of high-grade dysplasia or esophageal adenocarcinoma (1.9%) and 16 cases of low-grade dysplasia (7.6%) for an overall miss-rate of 9.5%.
Patients on proton pump inhibitors were less likely to have dysplasia missed than were those off PPIs (20% vs. 52.6%, P = .008).
Those with long- versus short-segment Barrett’s esophagus were more likely to have dysplasia overlooked (85% vs. 53.6%; P = .008; mean 6 mm vs. 4 mm; P = .006), Dr. Kavel Visrodia said at the annual Digestive Disease Week.
Current American College of Gastroenterology (ACG) guidelines recommend early repeat esophagogastroduodenoscopy (EGD) to exclude the presence of missed dysplasia in newly diagnosed nondysplastic Barrett’s esophagus (BE), while the ACG and American Society for Gastrointestinal Endoscopy call for repeat EGD within 6 months for those with low-grade dysplasia.
The yield for repeat EGD has not been established, and only one study exists in the literature, said Dr. Visrodia of the department of medicine, Mayo Clinic, Rochester, Minn.
That study (Dis. Esophagus 2012 Sept. 28. [doi:10.1111/j.1442-2050.2012.01431.x]) showed a miss-rate of 8.2% among 146 patients with newly diagnosed nondysplastic BE. Long-segment BE was the only significant predictor of dysplasia on follow-up (odds ratio, 9.18; P = .008).
The cohort was relatively small and had no long-term follow-up, and with an interval to follow-up of 36 months, "it’s possible that some of these were actually incident cases of dysplasia and not prevalent cases," he said.
To address these gaps, Dr. Visrodia and his colleagues identified 488 BE cases from 1977 to 2011 in the Rochester Epidemiology Project in Olmsted County, Minn. A total of 278 patients were excluded because of high-grade dysplasia (HGD) or esophageal cancer on index endoscopy or repeat endoscopy after 24 months, leaving 181 patients with nondysplastic BE and 29 with low-grade dysplasia (LGD).
Repeat endoscopy within 24 months revealed 2 cases of HGD or cancer and 16 cases of LGD in the nondysplastic BE group, and 2 cases of HGD or cancer in the LGD group, Dr. Visrodia said.
Three of the four HGD/cancer cases were in patients with long-segment BE, defined as at least 3 cm of columnar mucosa.
Biopsies were insufficient in 63% of patients with missed dysplasia, compared with 55% in the group without missed dysplasia. Biopsies were considered adequate if the number of biopsies divided by the BE length was at least 2, indicating that samples were taken every 2 cm in accordance with guidelines. This risk factor is noteworthy, although the difference between groups was not statistically significant, possibly because of the small sample size, he said.
Finally, after a median of 6.8 years of follow-up, 30 asymptomatic, prevalent HGDs or cancers were detected within 24 months, compared with 22 incident cases detected after 24 months. This suggests that "a greater number of high-grade dysplasias and cancers were detected up front rather than during long-term careful surveillance," Dr. Visrodia said.
During a discussion of the study, one attendee asked whether the results make a better case for aggressive ablation up front rather than for surveillance, while others expressed surprise at the high miss rate at an institution such as the Mayo Clinic.
Dr. Visrodia replied that the results do give them pause, and suggested that tighter early endoscopic surveillance may be warranted, particularly in those with long-segment BE.
Dr. Visrodia and his coauthors reported no financial disclosures.
AT DDW 2014
Key clinical point: Early endoscopic follow-up catches 9.5% of dysplasia missed on initial exam, but is not universally recommended by medical societies.
Major finding: Index endoscopy missed 1.9% of high-grade dysplasia or esophageal cancer and 7.6% of low-grade dysplasia.
Data source: A retrospective study in 181 patients with Barrett’s esophagus.
Disclosures: Dr. Visrodia and his coauthors reported no financial disclosures.
GERD may boost risk of MI
CHICAGO – Gastroesophageal reflux disease may constitute a heretofore unrecognized risk factor for coronary heart disease.
In a nationwide case-control study of prodigious proportions, endoscopically confirmed GERD in patients without known coronary or peripheral artery disease at baseline was independently associated with a 57% increased risk of having a first acute MI within the next 5 years, Dr. Ravi K. Prakash reported at the annual Digestive Disease Week.
If this novel finding is confirmed in other databases, the clinical implications would be profound. GERD is after all an extremely common problem, affecting 30%-40% of the U.S. population, noted Dr. Prakash, a gastroenterology fellow at MetroHealth Medical Center and Case Western Reserve University, Cleveland.
The good news: When Dr. Prakash and his coinvestigators divided the 316,390 study participants with GERD into those who were on proton pump inhibitor therapy and those who weren’t, they found that the PPI users weren’t at increased MI risk, compared with the more than 13.6 million similarly aged control subjects who didn’t have GERD, had never undergone an upper endoscopy, and were free of known atherosclerotic disease at baseline.
"Effective treatment of GERD appears to protect against MI," he concluded.
The study population was drawn from Explorys, a private, cloud-based health database containing the electronic health records of 35 million U.S. patients as provided by more than 200,000 physicians in 300-plus health care systems.
A first MI occurred during follow-up in 18,860 GERD patients, or 5.96%, compared with 144,140 controls, or 1.05%. This translates into an unadjusted sixfold increased risk of acute MI in patients with rigorously diagnosed GERD, compared with GERD-free controls.
The investigators then performed a multivariate logistic regression analysis adjusted for six major cardiovascular risk factors: obesity, hypertension, diabetes, tobacco use, hyperlipidemia, and sex. Many of these risk factors were substantially more prevalent in the GERD population. As a result, the unadjusted sixfold increase in MI risk associated with GERD was attenuated in this adjusted risk model; however, the adjusted 57% increased risk remained highly significant.
Moreover, the increased relative risk of GERD seen in the multivariate analysis was comparable with the risks posed by many of the established risk factors. Obesity, for example, showed a 49% increase in MI risk, smoking a 90% increase, and hypertension a 10% increased relative risk, compared with normotension. Only hyperlipidemia and diabetes were in another league, with relative risks of 9.5- and 2.2-fold, respectively, Dr. Prakash continued.
He observed that during the past decade, the research focus has shifted away from GERD as a caustic disease process causing local injury to GERD as a systemic inflammatory disease. Among the proinflammatory cytokines shown to be elevated both in the esophagus and circulation of GERD patients are interleukins-6, -8, and -1B as well as platelet-activating factor. These cytokines are well established as important players in the formation of atherosclerotic plaque in arteries. It was the shared elevations in proinflammatory cytokines that led Dr. Prakash and coworkers to hypothesize that patients with GERD might have an increased incidence of MI.
It’s only relatively recently that several other common chronic diseases have been reconceptualized as systemic inflammatory diseases associated with increased cardiovascular risk. Diabetes, for example, has been repositioned from a straightforward endocrine disease to new status as a coronary heart disease equivalent. And strong bodies of evidence link psoriasis and periodontitis to increased cardiovascular risk, Dr. Prakash noted.
Audience member Dr. Nimish B. Vakil, a Milwaukee gastroenterologist, rose to caution about the possibility of residual confounding by other factors not accounted for in the multivariate analysis, and thus the need for confirmatory studies. That being said, he added that he finds the notion of a GERD/acute MI link mechanistically quite plausible. Acid exposure from GERD might very well trigger exaggerated firing of the esophagocardiac reflex, with resultant episodes of coronary hypoperfusion. Effective PPI therapy for GERD would be expected to reduce such events.
Dr. Prakash said his literature search suggested another possible mechanism for the apparent protective effect of PPIs against MI: effective treatment of GERD, whether using PPIs or via a fundoplication procedure, has been reported to reduce levels of the inflammatory cytokines present in GERD.
Dr. Prakash reported having no financial conflicts with regard to his study, which was supported by institutional funds.
CHICAGO – Gastroesophageal reflux disease may constitute a heretofore unrecognized risk factor for coronary heart disease.
In a nationwide case-control study of prodigious proportions, endoscopically confirmed GERD in patients without known coronary or peripheral artery disease at baseline was independently associated with a 57% increased risk of having a first acute MI within the next 5 years, Dr. Ravi K. Prakash reported at the annual Digestive Disease Week.
If this novel finding is confirmed in other databases, the clinical implications would be profound. GERD is after all an extremely common problem, affecting 30%-40% of the U.S. population, noted Dr. Prakash, a gastroenterology fellow at MetroHealth Medical Center and Case Western Reserve University, Cleveland.
The good news: When Dr. Prakash and his coinvestigators divided the 316,390 study participants with GERD into those who were on proton pump inhibitor therapy and those who weren’t, they found that the PPI users weren’t at increased MI risk, compared with the more than 13.6 million similarly aged control subjects who didn’t have GERD, had never undergone an upper endoscopy, and were free of known atherosclerotic disease at baseline.
"Effective treatment of GERD appears to protect against MI," he concluded.
The study population was drawn from Explorys, a private, cloud-based health database containing the electronic health records of 35 million U.S. patients as provided by more than 200,000 physicians in 300-plus health care systems.
A first MI occurred during follow-up in 18,860 GERD patients, or 5.96%, compared with 144,140 controls, or 1.05%. This translates into an unadjusted sixfold increased risk of acute MI in patients with rigorously diagnosed GERD, compared with GERD-free controls.
The investigators then performed a multivariate logistic regression analysis adjusted for six major cardiovascular risk factors: obesity, hypertension, diabetes, tobacco use, hyperlipidemia, and sex. Many of these risk factors were substantially more prevalent in the GERD population. As a result, the unadjusted sixfold increase in MI risk associated with GERD was attenuated in this adjusted risk model; however, the adjusted 57% increased risk remained highly significant.
Moreover, the increased relative risk of GERD seen in the multivariate analysis was comparable with the risks posed by many of the established risk factors. Obesity, for example, showed a 49% increase in MI risk, smoking a 90% increase, and hypertension a 10% increased relative risk, compared with normotension. Only hyperlipidemia and diabetes were in another league, with relative risks of 9.5- and 2.2-fold, respectively, Dr. Prakash continued.
He observed that during the past decade, the research focus has shifted away from GERD as a caustic disease process causing local injury to GERD as a systemic inflammatory disease. Among the proinflammatory cytokines shown to be elevated both in the esophagus and circulation of GERD patients are interleukins-6, -8, and -1B as well as platelet-activating factor. These cytokines are well established as important players in the formation of atherosclerotic plaque in arteries. It was the shared elevations in proinflammatory cytokines that led Dr. Prakash and coworkers to hypothesize that patients with GERD might have an increased incidence of MI.
It’s only relatively recently that several other common chronic diseases have been reconceptualized as systemic inflammatory diseases associated with increased cardiovascular risk. Diabetes, for example, has been repositioned from a straightforward endocrine disease to new status as a coronary heart disease equivalent. And strong bodies of evidence link psoriasis and periodontitis to increased cardiovascular risk, Dr. Prakash noted.
Audience member Dr. Nimish B. Vakil, a Milwaukee gastroenterologist, rose to caution about the possibility of residual confounding by other factors not accounted for in the multivariate analysis, and thus the need for confirmatory studies. That being said, he added that he finds the notion of a GERD/acute MI link mechanistically quite plausible. Acid exposure from GERD might very well trigger exaggerated firing of the esophagocardiac reflex, with resultant episodes of coronary hypoperfusion. Effective PPI therapy for GERD would be expected to reduce such events.
Dr. Prakash said his literature search suggested another possible mechanism for the apparent protective effect of PPIs against MI: effective treatment of GERD, whether using PPIs or via a fundoplication procedure, has been reported to reduce levels of the inflammatory cytokines present in GERD.
Dr. Prakash reported having no financial conflicts with regard to his study, which was supported by institutional funds.
CHICAGO – Gastroesophageal reflux disease may constitute a heretofore unrecognized risk factor for coronary heart disease.
In a nationwide case-control study of prodigious proportions, endoscopically confirmed GERD in patients without known coronary or peripheral artery disease at baseline was independently associated with a 57% increased risk of having a first acute MI within the next 5 years, Dr. Ravi K. Prakash reported at the annual Digestive Disease Week.
If this novel finding is confirmed in other databases, the clinical implications would be profound. GERD is after all an extremely common problem, affecting 30%-40% of the U.S. population, noted Dr. Prakash, a gastroenterology fellow at MetroHealth Medical Center and Case Western Reserve University, Cleveland.
The good news: When Dr. Prakash and his coinvestigators divided the 316,390 study participants with GERD into those who were on proton pump inhibitor therapy and those who weren’t, they found that the PPI users weren’t at increased MI risk, compared with the more than 13.6 million similarly aged control subjects who didn’t have GERD, had never undergone an upper endoscopy, and were free of known atherosclerotic disease at baseline.
"Effective treatment of GERD appears to protect against MI," he concluded.
The study population was drawn from Explorys, a private, cloud-based health database containing the electronic health records of 35 million U.S. patients as provided by more than 200,000 physicians in 300-plus health care systems.
A first MI occurred during follow-up in 18,860 GERD patients, or 5.96%, compared with 144,140 controls, or 1.05%. This translates into an unadjusted sixfold increased risk of acute MI in patients with rigorously diagnosed GERD, compared with GERD-free controls.
The investigators then performed a multivariate logistic regression analysis adjusted for six major cardiovascular risk factors: obesity, hypertension, diabetes, tobacco use, hyperlipidemia, and sex. Many of these risk factors were substantially more prevalent in the GERD population. As a result, the unadjusted sixfold increase in MI risk associated with GERD was attenuated in this adjusted risk model; however, the adjusted 57% increased risk remained highly significant.
Moreover, the increased relative risk of GERD seen in the multivariate analysis was comparable with the risks posed by many of the established risk factors. Obesity, for example, showed a 49% increase in MI risk, smoking a 90% increase, and hypertension a 10% increased relative risk, compared with normotension. Only hyperlipidemia and diabetes were in another league, with relative risks of 9.5- and 2.2-fold, respectively, Dr. Prakash continued.
He observed that during the past decade, the research focus has shifted away from GERD as a caustic disease process causing local injury to GERD as a systemic inflammatory disease. Among the proinflammatory cytokines shown to be elevated both in the esophagus and circulation of GERD patients are interleukins-6, -8, and -1B as well as platelet-activating factor. These cytokines are well established as important players in the formation of atherosclerotic plaque in arteries. It was the shared elevations in proinflammatory cytokines that led Dr. Prakash and coworkers to hypothesize that patients with GERD might have an increased incidence of MI.
It’s only relatively recently that several other common chronic diseases have been reconceptualized as systemic inflammatory diseases associated with increased cardiovascular risk. Diabetes, for example, has been repositioned from a straightforward endocrine disease to new status as a coronary heart disease equivalent. And strong bodies of evidence link psoriasis and periodontitis to increased cardiovascular risk, Dr. Prakash noted.
Audience member Dr. Nimish B. Vakil, a Milwaukee gastroenterologist, rose to caution about the possibility of residual confounding by other factors not accounted for in the multivariate analysis, and thus the need for confirmatory studies. That being said, he added that he finds the notion of a GERD/acute MI link mechanistically quite plausible. Acid exposure from GERD might very well trigger exaggerated firing of the esophagocardiac reflex, with resultant episodes of coronary hypoperfusion. Effective PPI therapy for GERD would be expected to reduce such events.
Dr. Prakash said his literature search suggested another possible mechanism for the apparent protective effect of PPIs against MI: effective treatment of GERD, whether using PPIs or via a fundoplication procedure, has been reported to reduce levels of the inflammatory cytokines present in GERD.
Dr. Prakash reported having no financial conflicts with regard to his study, which was supported by institutional funds.
AT DDW 2014
Major finding: GERD was found to be independently associated with a 57% increased risk of acute MI.
Data source: This was a case-control study that harnessed the huge national Explorys database to compare first MI rates in 316,390 subjects with confirmed GERD to more than 13.6 million controls without GERD who’d never had an upper endoscopy.
Disclosures: This study was supported by institutional funds. The presenter reported having no financial conflicts.
Initial dilation no help in eosinophilic esophagitis
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
This is the first prospective examination of the role of esophageal dilation in eosinophilic esophagitis (EoE). The symptom-based outcomes suggest that dilation is not necessary for the initial therapy of EoE. The improvement in dysphagia was equivalent in patients treated with dilation combined with medical therapy, compared with those treated with medical therapy alone.
Dr. Ikuo Hirano |
Moreover, while all patients randomized to dilation had dysphagia, not all had endoscopically identified esophageal strictures. One would not expect therapeutic gain for esophageal dilation in the absence of an identifiable stricture. Furthermore, randomized controlled trials of medical therapy for EoE have identified a surprisingly high placebo-response rate for the outcome of dysphagia that may have made demonstration of the benefits of dilation difficult to detect, especially in patients with mild disease severity. Symptom improvement in dysphagia may occur in response to modifications in eating habits such as meticulous mastication or avoidance of highly textured foods.
Finally, the inability to discern a difference in treatment groups may reflect the use of a nonvalidated dysphagia severity assessment instrument.
Despite these shortcomings, the results support current guideline recommendations that dilation should target aspects of esophageal remodeling in EoE that are not amenable to currently available medical or diet therapies.
The data, however, do not exclude an important therapeutic benefit of esophageal dilation in EoE. The study excluded patients with significant strictures that could not be traversed with a standard adult endoscope. The findings, therefore, would not apply to EoE patients with substantial fibrostenosis.
In this study, medical therapy was highly effective at relieving symptoms, but prior studies have shown that symptoms recur in almost all patients following cessation of medications.
Dilation, on the other hand, is generally safe and provides long-lasting relief of dysphagia in adults, even in the absence of medical or diet therapy. Additional prospective studies are needed to define the most appropriate patient subgroups that would benefit from dilation.
Dr. Ikuo Hirano is professor of medicine in the division of gastroenterology at Northwestern University's Feinberg School of Medicine in Chicago. He serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
CHICAGO – Esophageal dilation combined with standard medical management of eosinophilic esophagitis doesn’t provide added benefit over medication alone in terms of dysphagia relief, according to a randomized, blinded clinical trial.
"In our group of patients with moderate endoscopic findings and without severe stricturing disease, esophageal dilation does not appear to be a necessary additional treatment strategy," Dr. Robert T. Kavitt stated at the annual Digestive Disease Week.
The study involved 31 patients newly diagnosed with eosinophilic esophagitis and baseline moderate to severe difficulty in swallowing. They were randomized to dilation or no dilation at initial endoscopy. Then all patients received standard medical management with 440 mcg of swallowed fluticasone b.i.d. and dexlansoprazole at 60 mg/day for 2 months. Patients were blinded as to their dilation status, as were the physicians who rated their change in dysphagia scores during follow-up.
Both groups experienced robust albeit equal reductions in overall dysphagia scores upon assessment at 30 and 60 days after endoscopy. At baseline, dysphagia scores averaged 6-6.5 on a 0-9 scale, indicative of moderate to severe dysphagia. At follow-up, scores in both groups had dropped to an average of 3 or less, reported Dr. Kavitt of the University of Chicago.
Complete resolution of dysphagia, defined as a dysphagia score of 0, occurred in only 23% of the dilation group and 57% of the no-dilation controls, which was not a statistically significant difference. The looser standard of "significant improvement" – meaning a dysphagia score of 3 or less – was met by 92% of the dilation group and 86% of controls.
Two patients in the dilation group and one control reported odynophagia.
Patients in the dilation group were dilated to the endpoint of mucosal tear. Three-quarters of the patients were dilated to a maximum size of 50 French or larger.
Baseline endoscopic scores assessing strictures, fissures, rings, and other abnormalities were in the moderate range on a 0-13 severity scale, so the study finding of a lack of benefit for dilation as part of an initial treatment strategy in eosinophilic esophagitis may not extend to the minority of patients having truly severe stricturing disease, according to Dr. Kavitt.
He noted that, before this study, the role of dilation in the treatment of eosinophilic esophagitis was a matter of divergent expert opinion unsupported by randomized trial evidence. The 2013 American College of Gastroenterology guidelines state that "the role of dilation as a primary monotherapy of eosinophilic esophagitis is still controversial and should be individualized."
Later during the meeting, in his state-of-the-art lecture on changing therapeutic concepts in eosinophilic esophagitis, Dr. Ikuo Hirano cited Dr. Kavitt’s randomized trial in support of his argument against dilation as primary therapy.
"Dilation does nothing to address the underlying inflammatory response that’s causing strictures to form," noted Dr. Hirano, professor of medicine at Northwestern University, Chicago. "I believe that dilation is inappropriate therapy for children and adults with a predominantly inflammatory phenotype of disease."
Medication and diet therapies not only relieve the symptoms of eosinophilic esophagitis, he continued, they also improve the histopathology.
Dilation entails considerable pain as well as a risk of perforation. Recent reassuring safety data regarding dilation for eosinophilic esophagitis come from specialized esophageal centers with an unusual amount of experience with the procedure, the gastroenterologist said.
Dr. Kavitt reported having no financial conflicts of interest with regard to the randomized trial, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.
AT DDW 2014
Key clinical point: Dilation offers no added benefit over medication alone in relieving dysphagia symptoms in eosinophilic esophagitis.
Major finding: Significant improvement in dysphagia symptoms was documented 30 and 60 days post endoscopy in 92% of eosinophilic esophagitis patients who underwent dilation plus medical therapy and in 86% who got medication alone.
Data source: This was a randomized trial involving 31 patients newly diagnosed with eosinophilic esophagitis who were assigned to dilation or no dilation at initial endoscopy, after which all participants received 2 months of medical therapy with a swallowed corticosteroid and a proton pump inhibitor. Patients as well as the physicians who rated their dysphagia symptoms 30 and 60 days post endoscopy were blinded as to dilation status.
Disclosures: Dr. Kavitt reported having no financial conflicts regarding this study, which was supported by institutional funds. Dr. Hirano serves as a consultant to Meritage Pharma, Receptos, and Aptalis.