Kathryn R. Byrne

Elemental diet induces histologic response in adult eosinophilic esophagitis.

OBJECTIVES:Elemental diets have not been studied in adults with eosinophilic esophagitis (EoE). The goal of this trial was to assess the efficacy of an elemental diet in adults with EoE.METHODS:A total of 18 adults with EoE were given an elemental diet for 4 weeks, or just 2 weeks if their response was complete. Symptoms and histologic findings, based on biweekly biopsies, were monitored. Six subjects were rebiopsied 2–7 days after resuming a normal diet.RESULTS:After therapy, esophageal tissue eosinophil content decreased from 54 to 10 per maximal high power field (P=0.0006). There was complete or nearly complete response (≤10 eosinophils) in 72% of subjects. Mast cell content, parabasal layer thickness, and endoscopic furrows and exudates also significantly decreased. Of the 29 qualified subjects, 11 (38%) failed to adhere to the diet. Several subjects had significant weight loss. Symptoms and endoscopic fixed strictures did not improve. After the subjects resumed a normal diet, the eosinophil content increased substantially in 3–7 days.CONCLUSIONS:While symptoms did not improve and dietary compliance was problematic, there was substantial histologic improvement after 4 weeks on the elemental diet. EoE in adults is substantially triggered by foods.

Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial

IMPORTANCE Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMES AND MEASURES The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text]. CONCLUSIONS AND RELEVANCE Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 01187901.

Retrospective Analysis of Esophageal Food Impaction: Differences in Etiology By Age and Gender

Eosinophilic Esophagitis (EE) is an emerging cause of esophageal food impaction (EFI) not accounted for in previous studies. We sought to determine the causes of EFI in a recent cohort with recognition of EE. A retrospective chart review of all patients with EFI during the past 5 years was performed. Etiology was determined by endoscopy report, pathology results, and follow-up studies. A total of 85 EFIs occurred, in 79 patients (55 men, 30 women, age 18–100). The most common etiologies of EFI were Schatzkis ring (n=18), peptic stricture (n=18), EE (n=9), esophagitis (n=9), and no underlying diagnosis (n=20). EE was significantly more frequent in men (P < .025) and those <50 years old (P < .025). There was a significant difference in the age at which men (median age=44) and women (median age=71) present with EFI (P < .001). The etiology of EFI differs significantly by age and gender. This information may be useful in evaluation and management of EFI.

Endoscopic placement of enteral feeding catheters

Purpose of review Critical to realizing increasing benefits of enteral nutrition are techniques for feeding tube placement. Feeding tubes can be placed by bedside, endoscopic, fluoroscopic, and surgical methods. This review encompasses noteworthy studies on endoscopic approaches to enteral feeding published from January 2005 to the present. Recent findings Studies involving placement of nasoenteric feeding tubes include description of new methods for endoscopic nasoenteric feeding tube placement using a push technique with a stiffened tube, a modification of the ‘drag and pull’ method using a distal suture tie, and placement using an ultrathin transnasal endoscopic technique compared with fluoroscopic placement. Recent studies involving percutaneous endoscopic gastrostomy tube placement have demonstrated equivalent outcomes of endoscopic and fluoroscopic approaches, description of unsedated placement using transnasal technique, and risk of percutaneous endoscopic gastrostomy site metastasis in head and neck cancer patients. Studies on percutaneous jejunal feeding tubes demonstrate: high complication rate and short functional duration of percutaneous endoscopic gastrojejunostomy and reported outcomes of direct percutaneous endoscopic jejunostomy placement. Summary Enteral nutrition access can be obtained by a variety of methods depending on local expertise and resources. Endoscopic approaches have equivalent or better outcomes than other methods; however, these methods may still have limitations and distinct complications.

Utility of an Elemental Diet in Adult Eosinophilic Esophagitis

Background: Data suggests that food is a primary trigger for the development of esophageal eosinophilia in children. Six food elimination diets are effective in adults, but the efficacy of an elemental diet in adult patients with eosinophilic esophagitis (EoE) has not been reported. Aims: To determine whether adult patients with EoE exhibit clinical and histologic improvement to an elemental diet compared to their normal diet. To determine the time of response of esophageal eosinophilia to elemental diet. Methods: EoE was diagnosed by esophageal obstructive symptoms (dysphagia, chest pain, food impaction, heartburn) and esophageal biopsies demonstrating >20 eosinophils/HPF in the setting of high dose acid suppression. All subjects underwent a second EGD/biopsies 2-3 weeks after their initial EGD/biopsies to confirm stability of disease while maintaining their normal diet. After the 2nd EGD/biopsies, all patients were started on an elemental diet (Elecare, Abbott Laboratories, Columbus, Ohio) and underwent a 3d EGD/biopsies after 2 weeks of Elecare. If subjects did not completely respond (eos 20/HPF at 2nd EGD) and completed at least 2 weeks of the Elecare diet. Five subjects dropped out of the trial after 2 weeks (2 due to poor tolerance of the diet, 3 for personal reasons). One patient responded completely at 2 weeks (1 eos/hpf). The remaining 20 patients completed a 4 week trial of Elecare. Eosinophil counts did not vary significantly between the 1st and 2nd EGDs (distal 44 to 43 eos/HPF, proximal 33 to 40 eos/HPF respectively, p =0.43, p=0.43). Dramatic decreases in eosinophils were seen at 2 weeks after starting Elecare (average distal 13 eos/HPF and proximal 14 eos/HPF, p <0.001 for both) and decreases correlated with an overall clinical response to therapy at 4 weeks. Response continued less profoundly between 2 and 4 weeks on Elecare (distal 11 eos/HPF and proximal 8 eos/HPF). 11/21 (52%) responded with counts less than 8 eos/HPF by week 4. Discussion: Elemental diet resulted in marked improvement in esophageal eosinophilia in a substantial number of adults with EoE. Histologic response occurs within 2 weeks of starting the elemental diet and profound decreases in eosinophilia at 2 weeks are maintained at 4 weeks on diet. Elemental diets are useful in the treatment of EoE to provide rapid relief of symptoms and tissue eosinophilia.

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial

Importance Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. Objective To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Design, Setting, and Participants Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. Interventions Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. Main Outcomes and Measurements The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. Results Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009). Conclusion and Relevance In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum. Trial Registration clinicaltrials.gov Identifier: NCT01187901

Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia

To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months (P < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy. Ten FAP patients on placebo and 10 on sulindac and erlotinib were selected for analysis. Purity of biopsied polyp tissue was calculated from RNA expression data. RNAs differentially expressed between endpoint polyp and paired baseline normal were determined for each group and mapped to biological pathways. Key genes in candidate pathways were further validated by quantitative RT-PCR. RNA expression analyses of endpoint polyp compared with paired baseline normal for patients on placebo and drug show that pathways activated in polyp growth and proliferation are blocked by this drug combination. Directly comparing polyp gene expression between patients on drug and placebo also identified innate immune response genes (IL12 and IFNγ) preferentially expressed in patients on drug. Gene expression analyses from tissue obtained at endpoint of the trial demonstrated inhibition of the cancer pathways COX2/PGE2, EGFR, and WNT. These findings provide molecular evidence that the drug combination of sulindac and erlotinib reached the intended tissue and was on target for the predicted pathways. Furthermore, activation of innate immune pathways from patients on drug may have contributed to polyp regression. Cancer Prev Res; 11(1); 4–15. ©2017 AACR. See related editorial by Shureiqi, p. 1

S1090 Celiac Sprue and Eosinophilic Esophagitis: Are Duodenal Biopsies Enough?

Allergy testing or immunotherapy treatments were not included; (4) For pts undergoing endoscopy (EGD) w/o Bx, EoE would be missed. Results: Assuming base case probabilities (Table 1), the EGD w/o Bx arm cost

Diagnosis and Management of Barrett’s Esophagus

643 and was associated with 0.953 QALYs. The EGD with Bx arm cost

Cannulation and Sphincterotomy: Beyond the Basics

853 and was associated with 0.957 QALYs. The resulting incremental cost-effectiveness ratio (ICER) was