PUBLICATIONS

2025

Carlson DA, Pandolfino JE, Yadlapati R, et al. A Standardized Approach to Performing and Interpreting FLIP Panometry for Esophageal Motility Disorders: The Dallas Consensus.. Gastroenterology. Published online 2025. doi:10.1053/j.gastro.2025.01.234

BACKGROUND AND AIMS: Functional lumen imaging probe (FLIP) Panometry provides assessment of the esophagogastric junction (EGJ) opening and esophageal body contractile activity during an endoscopic procedure and is increasing being incorporated in comprehensive esophageal motility assessments. We aimed to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme.

METHODS: A working group of 19 FLIP Panometry experts convened in a modified Delphi consensus process to produce and assess statements on the FLIP Panometry procedure and interpretation. Three rounds of voting were conducted on an agreement scale of 1-9 for appropriateness followed by face-to-face discussions and opportunity for revisions of statements. The "percent agreement" was proportion of votes with score ≥7 indicating level of agreement on appropriateness.

RESULTS: A total of 40 statements were selected for final inclusion for the Dallas Consensus, including FLIP Panometry protocol, interpretation of EGJ opening and contractile response, and motility classification scheme. Key statements included: "FLIP Panometry should be interpreted in the context of the clinical presentation, the accompanying EGD findings and other relevant complementary testing". (Median response 9.0; 100% agreement). "A major motor disorder is unlikely in the setting of a "Normal" FLIP Panometry classification (Median response 9.0; 94% agreement). "Diminished or absent contractile response with reduced esophageal opening [i.e. "non-spastic obstruction] supports the diagnosis of a disorder of EGJ outflow. (Median response 8.5; 94% agreement).

CONCLUSION: The standardized approach for performance and interpretation of the Dallas Consensus can facilitate use of FLIP Panometry in broad clinical settings.

Shah ED, Curley MA, Patel A, Lo WK, Chan WW. Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2025;23(2):263-271. doi:10.1016/j.cgh.2024.01.049

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment.

METHODS: A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported.

RESULTS: Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts.

DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

Leung R, Yeung MLC, Li Y, Muftah M, Chan WW, Leung WK. Temporal Trend of Incidence and Prevalence of Eosinophilic Esophagitis in Asia: A Systematic Review and Meta-Analysis.. The American journal of gastroenterology. 2025;120(2):320-331. doi:10.14309/ajg.0000000000003096

INTRODUCTION: There are limited epidemiological studies on eosinophilic esophagitis (EoE) in Asia. We studied the temporal trend of EoE in Asia, the presenting symptoms, and association with atopic diseases.

METHODS: Literature search on PubMed, Embase, MEDLINE, Scopus, and Web of Science was performed to retrieve studies published between 1980 and 2023 that reported the prevalence or incidence of EoE in Asia. We used a random-effects model to estimate the pooled incidence and prevalence. I2 index and Cochran Q test were used to assess heterogeneity. Subgroup analyses were conducted for study types, different regions, years of examination, and age groups. The proportion of atopic diseases among patients with EoE was presented.

RESULTS: Twenty-five studies from Asia were included. The pooled prevalence of EoE was 33.5 cases per 100,000 inhabitants in population-based studies and 11.0 cases per 1,000 patients/visitors in hospital-based studies. The incidence rate among children was 12.3 cases per 1,000 patients/visitors, whereas for adults, it was only 0.2 cases per 1,000 patients/visitors. Among population-based studies, there was an increase in prevalence from 19.8 per 100,000 individuals in 2005-2009 to 73.0 per 100,000 individuals in 2015-2019. A similar upward trend was observed in hospital-based studies conducted during the same period. Patients with EoE commonly presented with dysphagia (36.3%) and nausea and vomiting (34.6%). History of atopy was reported in 57.2% of patients with EoE in Asia.

DISCUSSION: The prevalence and incidence of EoE in Asia have been rising over the past decades. Because of the limited number of Asian studies and variations in patient sources, caution should be exercised when interpreting these results.

Muftah M, Hartnett D, Hiramoto B, et al. Yield of Esophageal Biopsy Patterns for the Diagnosis of Eosinophilic Esophagitis.. Gastrointestinal endoscopy. Published online 2025. doi:10.1016/j.gie.2025.01.018

BACKGROUND AND AIMS: The pattern of inflammation in eosinophilic esophagitis (EoE) is patchy, necessitating multiple biopsies to optimize diagnostic yield. Current consensus-based guidelines recommend 6 total biopsies at two sites: distal and either middle or proximal esophagus, although based on limited data. We aimed to determine whether this biopsy protocol sufficiently captures EoE diagnoses by evaluating the distribution of eosinophilia in a large EoE cohort.

METHODS: This was a retrospective study of consecutive, newly-diagnosed EoE patients with ≥2 esophageal segments biopsied. Demographics, clinical characteristics/history, endoscopic findings, and histologic results were manually reviewed. Distribution (proximal, middle, and/or distal) of eosinophilia (>15 eosinophils/hpf) was assessed. Predictors for non-distal disease (<15 eosinophils/hpf on distal biopsies) were evaluated using multivariable logistic regression.

RESULTS: 511 newly-diagnosed EoE patients with ≥2 segments biopsied were included. All patients had distal esophageal biopsy. Overall, 286 (56.0%) had ≥1 site with <15 eosinophils/hpf, including 51 (10%) non-distal disease. Among patients with three segments biopsied (n=60), 19 (31.7%) had eosinophilia at only one site, including 6 (10%) isolated mid esophageal disease and no isolated proximal eosinophilia. Discordant mid and proximal biopsy results were found in 18 (30%) patients, with 17/18 (94.4%) mid esophageal eosinophilia. On multivariable analysis, increasing age (OR:1.02, CI:1.002-1.04, p=0.03) and male gender (OR:1.89, CI:1.002-3.55, p=0.049) independently predict non-distal disease.

CONCLUSIONS: Isolated segmental eosinophilia is common in EoE, including up to 10% non-distal disease. Discordant mid and proximal biopsy findings are prevalent, with no isolated proximal eosinophilia. Standard protocol should include routine biopsies of both distal and middle esophagus to maximize diagnostic yield.

Elnaiem AD, Hiramoto B, Flanagan R, Muftah M, Shah ED, Chan WW. Low Utility of Routine Thyroid Function Testing for Bowel Symptoms: A Population-Based Assessment.. Digestive diseases and sciences. Published online 2025. doi:10.1007/s10620-024-08829-4

BACKGROUND: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

AIMS: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.S.

METHODS: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) in 2005-2008. Adults aged ≥ 20 with TSH, free T4 (fT4), and bowel health data were included. Multivariable logistic regression models were constructed to examine associations between thyroid function and bowel health measures, adjusting for potential confounders.

RESULTS: Among 6,552 participants, 93.6%, 4.3%, 1.7%, and 0.4% had TSH levels of 0.24-5.4, 5.4-10, < 0.24, and ≥ 10 mIU/L, respectively. There were no significant differences in prevalence of thyroid dysfunction between individuals with constipation or diarrhea and those without. In fully adjusted models, TSH was not a significant predictor of constipation, diarrhea, or FI, but higher fT4 was protective against constipation as a continuous variable (OR 0.47, CI: 0.26-0.85, p = 0.014)). Neither hypothyroid nor hyperthyroid status significantly correlated with constipation or diarrhea, although hyperthyroidism was associated with FI (OR 3.58, CI:1.51-8.49, p = 0.005).

CONCLUSION: While bowel disturbances were common in this nationally representative sample, the yield of thyroid function testing was low. Overt hypo- and hyperthyroidism were not significantly associated with constipation or diarrhea. Clinical utility of routine thyroid testing for bowel symptoms may be low in patients without systemic manifestations of severe thyroid disease.

Lodhia NA, Hiramoto B, Horton L, Goldin AH, Chan WW. Obesity Is Independently Associated With Increased Risk of Fecal Incontinence and Altered Rectal Sensitivity.. The American journal of gastroenterology. Published online 2025. doi:10.14309/ajg.0000000000003308

INTRODUCTION: Hindgut symptoms are poorly understood complications of obesity. The impact of obesity on fecal incontinence (FI) and anorectal physiology remains unclear, with inconsistent results in prior studies. We aimed to evaluate the relationship between obesity and FI, and the physiological changes in anorectal function.

METHODS: This was a retrospective cohort study of consecutive adults who underwent high-resolution anorectal manometry (HRAM) at a tertiary center for anorectal symptoms. Demographics, clinical history, surgical/obstetric history, medications, and HRAM findings were reviewed. Patients were classified as nonobese (body mass index [BMI] <25 kg/m 2 ), overweight (BMI 25-29.9 kg/m 2 ), class I obesity (30-34.9 kg/m 2 ), and class II + III obesity (>35 kg/m 2 ). The Fisher exact/Student t test for univariate analyses and logistic/general linear regression for multivariable analyses were performed.

RESULTS: A total of 552 adults were included. The mean BMI was higher among patients with FI (27.5 vs 25.9 kg/m 2 , P = 0.013). Compared with the nonobese group, FI was more prevalent in class II + III obesity (31.7% vs 13.2%, P = 0.0024), but not class I obesity or overweight groups. On multivariable analysis controlling for potential confounders, class II + III obesity (adjusted odds ratio 2.89, 95% confidence interval 1.28-6.50, P = 0.02) remained an independent risk factor of FI. Among patients with FI, both BMI (β-coefficient 1.09, P = 0.016) and class II + III obesity (β-coefficient 18.9, P = 0.027) independently predicted increased first rectal sensation volume on HRAM on multivariable regression.

DISCUSSION: Classes II + III obesity was an independent risk factor of FI. Among patients with FI, increasing BMI and class II + III obesity were associated with altered rectal sensitivity. Anorectal function testing should be considered to help guide management of FI among patients with obesity.

Hiramoto B, Falahee BE, Muftah M, Flanagan R, Shah ED, Chan WW. Size of Pelvic Outlet as a Potential Risk Factor of Fecal Incontinence: A Population-Based Exploratory Analysis.. Clinical and translational gastroenterology. 2025;16(1):e00789. doi:10.14309/ctg.0000000000000789

INTRODUCTION: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.

METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry were included.

RESULTS: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared with the third (odds ratio [OR]: 2.05, confidence interval [CI]: 1.18-3.56, P = 0.014) and fourth (OR: 1.94, CI: 1.02-3.70, P = 0.045) quartiles. Sex-stratified analyses found similar association among female patients only.

DISCUSSION: Small pelvic area on dual-energy x-ray absorptiometry is a potential risk factor of FI.

Hiramoto B, Muftah M, Flanagan R, Shah ED, Chan WW. Cost-Effectiveness Analysis of Current Treatment Options for Eosinophilic Esophagitis.. The American journal of gastroenterology. 2025;120(1):161-172. doi:10.14309/ajg.0000000000003104

INTRODUCTION: The management strategies for eosinophilic esophagitis include proton pump inhibitors (PPIs), swallowed topical corticosteroids (tCSs), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treatment. We performed cost-effectiveness analyses to compare these approaches of first-line therapy.

METHODS: A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for eosinophilic esophagitis, including PPI, tCS, and 6-food elimination diet (SFED), with crossover in treatments for primary and secondary nonresponse. The primary outcome was incremental cost-effectiveness ratio at 2 and 5-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab with tCS and PPI.

RESULTS: In the base-case scenario (5-year time horizon), the average costs were SFED: $15,296.81, PPI: $16,153.77, and tCS: $20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a 2-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both 2 and 5-year time horizons. Among pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions.

DISCUSSION: SFED was the most effective/least costly first-line therapy from the payer perspective while PPI was more cost-effective from the societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.