From the AGA Journals

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.

Aerosolized fluticasone decreases esophageal eosinophilia in adults with eosinophilic esophagitis but does not relieve the symptomatic dysphagia caused by the allergic inflammatory disease, Dr. Jeffrey A. Alexander and his colleagues reported in the July issue of Clinical Gastroenterology and Hepatology.

In a double-blind, placebo-controlled trial conducted by Dr. Alexander of the Mayo Clinic, Rochester, Minn., and his coauthors, 42 adults with eosinophilic esophagitis (EoE) were randomly assigned to receive 880 mcg of aerosolized fluticasone twice daily (21) or to use a placebo inhaler twice daily (21) for 6 weeks.

The study’s primary end point was complete symptom response, and secondary end points were partial symptom response, partial and complete histologic response, and eosinophil-derived neurotoxin response to treatment using Fisher’s exact test (Clin. Gastroenterol. Hepatol. 2012 July [doi:10.1016/j.cgh.2012.03.018]).

The study subjects were recruited from the Esophageal Clinic at Mayo Clinic Rochester during 2005-2009 for management of newly diagnosed EoE. Subjects had symptomatic dysphagia, had a peak eosinophil count of at least 20 eosinophils per high-power field on esophageal biopsy, and demonstrated at least 90% compliance with the study requirement that they keep symptom logs for review by phone interview after weeks 2 and 4, and at study completion.

For symptom assessment, a complete response was defined as an answer of "no" to the question: "In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms?" on the Mayo Dysphagia Questionnaire–2 week, while an answer of "yes" along with a two-level or one-level decrease in frequency was considered a partial response. An answer of "yes" and a one-level decrease in one variable (either frequency or severity), plus an increase in the other variable, was classified as no response, the authors wrote.

A structured phone interview to assess side effects was conducted at weeks 2 and 4, and again at study completion, along with a physical exam, endoscopy, and 24-hour urine cortisol.

Six patients in the placebo group and two in the treatment group dropped out for reasons unrelated to the treatment. Of the 15 subjects who received 6 weeks of fluticasone, 11 had a complete histologic response, defined as a greater than 90% decrease in mean eosinophil count, compared with none of the 15 placebo subjects based on intention-to-treat analysis. By per-protocol analysis, "the histologic response was observed in 68% of subjects that received fluticasone [13/19], compared to none of those that received placebo," the authors wrote.

Analysis of symptom data in the treatment group showed that a complete dysphagia response occurred in 42.9% by intent-to-treat and 47.4% per protocol, neither of which was better than the respective placebo responses of 28.6% and 40.0%, according to the authors. Similarly, "the per-protocol analysis for a complete or partial response rate for fluticasone was 63.2%, versus a 46.7% response rate for placebo," representing a nonsignificant difference, they said.

The authors hypothesized that the factors contributing to the discrepancy between symptomatic and histologic responses include a possible underappreciation at endoscopy of esophageal stricture and small-caliber esophagus, and the possibility that esophageal narrowing may require dilation to relieve symptomatic dysphagia despite a histologic response.

In addition, "changes in esophageal compliance related to fibrosis may be important," they wrote, as a decrease in esophageal distensibility and compliance has been shown in EoE, which could well be a cause of dysphagia. Candida infections, which developed in 31.6% of the treatment group and none of the placebo group, could potentially lead to persistent dysphagia despite a histologic response, they said. Most likely, however, the discrepancy "reflects a waxing and waning of dysphagia in this disease," they concluded.

The study findings are limited by the relatively small sample size and the unexpectedly high dropout rate in the placebo group, which "left us somewhat underpowered for our primary end point," the authors wrote. Also, gastroesophageal reflux disease was not categorically excluded in all of the patients prior to enrollment. "While we would have liked to adjust for baseline differences in erosive esophagitis and PPI [protein pump inhibitor] use between treatment and placebo groups, this is beyond the limits of a dataset this size," they said.

The treatment was safe and well tolerated, but further study is needed to evaluate the optimal dose of therapy, length of therapy, and long-term safety of topical fluticasone, as well as other steroid medications. "Furthermore," the authors wrote, "delivery systems need to be developed that are easier to use and provide more direct drug delivery to the esophagus."

Dr. Alexander disclosed a financial relationship with Meritage Pharmacia.