Introduction

Esophageal mucosal admittance (MA) is a promising diagnostic method for gastroesophageal reflux disease (GERD), however, only some studies were done and mainly in Japan.

Aims & Methods

We conducted a study to describe the esophageal MA in patients with reflux symptoms and determine its diagnostic accuracy. We recruited 92 patients with ambulatory pH-impedance monitoring, upper gastrointestinal endoscopy, and MA measured by the tissue conductance meter. MA was measured during endoscopy at 5cm (distal esophagus) and 15cm above the Z line (middle esophagus), repeated at least five times at each position, and median MA was obtained. Afterwards, two biopsies were taken 5cm above the Z line for histopathological evaluation using the Esohisto criteria. Patients were classified as GERD or non-GERD according to the 2018 Lyon consensus.

Results

The mean age was 43.2 years, and 42 patients were males. The most common symptoms were regurgitation (75.0%), belching (65.2%), and heartburn (46.7%). Twenty-three (32.3%) were diagnosed with GERD using the Lyon consensus, and 24 (26.1%) had esophagitis on histopathology. The median MA at the distal and middle esophagus was moderately correlated. The median MA at both positions was higher in the GERD group but only statistically significant in the middle esophagus. MA was not associated with pH-impedance parameters and esophagitis on histopathology. The diagnostic model developed using the logistic regression did not have good accuracy.

Conclusion

MA was not different between GERD and non-GERD patients. The diagnostic model integrating MA did not have high accuracy in diagnosing GERD.

Introduction

Developing Computer-Aided Detection (CADe) system requires a large number of videos and it is more challenging in rare condition such as gastric neoplasia. However, all neoplasia, irrespective of location, has morphological similarities. Our hypothesis is that Barrett’s CADe should also be able to detect gastric neoplasia due to shared morphological similarities.

Aims & Methods

Three experts assessed prospectively collected videos to identify the best images demonstrating gastric neoplasia and similar gastric mucosa without neoplasia while using histology as a ground truth. We used a commercially available Barrett’s CADe system¹ (WISE VISION®,, NEC, Japan) to analyse these frames for neoplasia detection.

Results

Endoscopic videos were collected from 62 patients. Cases were divided into gastro-oesophageal (GOJ) and true gastric neoplasia. In GOJ group, there were 31 neoplastic (3 LGD, 2 HGD, 20 cancer) and 40 non-neoplastic while in gastric group, there were 20 neoplastic (2 LGD, 6 HGD, 12 cancer) and 19 non-neoplastic mucosae. Sensitivity and specificity for CADe for GOJ lesions were 83.87% and 82.50% while those for gastric neoplasia were 45.00% and 68.42% respectively. Further subgroup analysis was performed based on lesion morphology (polypoidal vs non-polypoidal). Table 1 showed that sensitivity of non-polypoidal GOJ lesion is 80% while that of non-polypoidal gastric lesions is 37.50%.

Conclusion

Our data demonstrates that Barrett’s CADe can detect majority of the GOJ neoplasia and with further refinement, its performance can potentially be enhanced. Barrett’s CADe is not suitable for gastric neoplasia detection and as it seems to be analysing more features than just morphology, a dedicated CADe will need to be developed for true gastric neoplasia.

References

1. Abdelrahim M, Saiko M, Maeda N, Hossain E, Alkandari A, Subramaniam S, Parra-Blanco A, Sanchez-Yague A, Coron E, Repici A, Bhandari P. Development and Validation of Artificial Neural Networks Model for Detection of Barrett's Neoplasia, a Multicenter Pragmatic Non-Randomized Trial. Gastrointest Endosc. 2022 Oct 22:S0016-5107(22)02084-3. doi: 10.1016/j.gie.2022.10.031. Epub ahead of print. PMID: 36283443.

Introduction

This report presents the results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study (VP-VLY-686-3301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Tradipitant, a novel NK-1 receptor antagonist, previously demonstrated efficacy in diabetic and idiopathic gastroparesis in reducing gastroparesis symptoms in a phase 2 study (VP-VLY-686-2301).

Aims & Methods

N=201 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea, and at least 1 vomiting episode were included in the ITT (Intent-to-Treat) population. Subjects were randomized to receive 85 mg tradipitant twice a day (n=102) or placebo (n=99) for 12 weeks. Nausea was assessed daily using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated using the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales. Sensitivity analyses were also performed to control for confounders that may have masked the true treatment effect size.

Results

At the primary endpoint of change in nausea from baseline as measured by the GCSDD at week 12, both tradipitant and placebo showed significant and similar reductions from baseline at 1.55 and 1.49 respectively. Comparison between treatment arms did not reach statistical significance in this measure. However, in the PGI-C scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (74% v. 58%, p=0.019) and at week 12 (78% v. 66%, p=0.065). Similarly, in the OPB scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (81% v. 62%, p=0.0003) and week 12 (86% v. 71%, p=0.011).
Sensitivity analysis adjusting for rescue medication use further confirmed the ITT findings in both the PGI-C and OPB analysis at both week 2 and week 12.

Conclusion

Significant but similar improvements from baseline for tradipitant and placebo may have masked the true treatment effect size at the primary endpoint of the study of change in nausea severity as measured by daily diary at week 12 leading to no statistically significant difference between treatments. Despite this large placebo effect, tradipitant was shown to be significantly better than placebo in global measures of patient improvement including the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales.

Disclosure

Study was sponsored by Vanda Pharmaceuticals, Inc. Authors are employees of Vanda Pharmaceuticals, Inc.

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, progressive type 2 inflammatory disease. Proton-pump inhibitors (PPIs), swallowed topical corticosteroids (STCs), and elimination diets have been used as standard treatments for EoE patients. However, the real-world evidence (RWE) highlighting disease burden in Europe are limited.

Aims & Methods

To assess disease burden and treatment patterns among adolescent and adult patients with EoE in real-world practice.
Medical records were retrospectively reviewed for patients (aged ≥12 years) who were newly diagnosed with EoE between 1 January 2009 and 31 December 2019 (index) in Germany, France, Spain, and the United Kingdom. Patients with a peak eosinophil (eos) count (PEC) of ≥15 eos/hpf within 90 days of the index date and ≥1 follow-up endoscopy within 24 months of the index date were included. Demographics, clinical features, treatment patterns, and health outcomes were assessed from the 12-month pre-index period to the last medical record entry or death. Disease progression was assessed via physician-defined (based on symptoms, endoscopy findings, histology, need for dilation, and food impaction) and proxy-reported outcomes (dilation performed, strictures, dysphagia, evidence of food impaction, treatment initiation in treatment-naïve patients and switching/augmentation).

Results

Overall, 385 patients were included, with 70.1%–78.1% being male; the mean age was 27.8 to 33.9 years. At EoE diagnosis, the PEC was 35.3–46.1 eos/hpf, the endoscopic appearance of the oesophagus was abnormal in 73.7%–85.6% of patients, and dysphagia was present in 59.8%–82.8% of patients. Most of the patients across all 4 countries were treated with PPIs (61.5%–91.8%), STCs (56.7%–82.3%) and elimination diets (41.4%–55.2%) after EoE diagnosis. Of the patients with available data, abnormal histology (≥15 eos/hpf) was reported in 44.8%–72.0% of patients during the first 5 years after EoE diagnosis. The abnormal endoscopic appearance of the oesophagus was observed in 34.6%–83.3% of patients after approximately 2 years of EoE diagnosis and dysphagia was present in 10.2%–25.0% of patients after 4 years of EoE diagnosis across all 4 countries. While physician-defined disease progression occurred in 6.1%–16.1% of patients, 19.4%–35.1% of patients experienced proxy-reported outcomes of potential disease progression (including oesophageal dilation performed in 10.8%–21.7% of patients) after EoE diagnosis. An overview of patient and clinical characteristics at EoE diagnosis and treatment patterns and disease progression (physician-defined and proxy-reported) after EoE diagnosis across Germany, France, Spain, and the United Kingdom is provided in the Table.

Conclusion

Adolescent and adult patients with EoE chronically experienced substantial disease burden. A subset demonstrated disease progression, perhaps underrecognised despite treatment with PPIs, STCs, and elimination diets. Hence, successful EoE management may include proactive disease monitoring, treating underlying pathophysiology and prescribing maintenance therapies to achieve long-term clinical remission.

References

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Disclosure

Ulrike von Arnim: Consulting and/or speaker fees from Dr. Falk Pharma, Sanofi, Astra Zeneca, EsoCap, Abbvie, Janssen, Takeda, Pfizer, Bristol Myers Squibb.
Frank Zerbib: Consulting and/or speaker fees from Sanofi, Dr Falk pharma, Bristol Myers Squibb, Bioprojet, AstraZeneca.
Tiffany Pela, Juby A. Jacob-Nara, Gaelle Le-Bagousse-Bego, Sarette T. Tilton: Employees of Sanofi; may hold stocks and/or stock options in the company.
Bram P. Raphael, Amr Radwan, Ryan B. Thomas: Employees of Regeneron Pharmaceuticals, Inc.; may hold stocks and/or stock options in the company.
Rohan C. Parikh, Fareedat Bello: Employees of RTI Health Solutions, which received research funding from Sanofi to design and execute this study.
Funding: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Acknowledgement: Medical writing support was provided by Akshata Rao and Ali Nasir Siddiqui, PhD, of Sanofi.

Introduction

Computer Aided Detection (CADe) systems have the potential to enhance the detection of early neoplasia in Barrett's Esophagus (BE) patients during endoscopic procedures. In this study, we aimed to evaluate a recently developed CADe system during live endoscopic procedures.

Aims & Methods

The CADe system was developed using a large and diverse training data set from 15 international endoscopy centers, comprising 6,237 neoplastic images from 1,304 patients and 7,595 non-dysplastic images from 1,103 patients. Multiple extensive ex-vivo benchmarking studies were performed for validation. The CADe system displayed consistent and reliable performance, leading to a significant improvement in the detection rate of neoplasia by endoscopists.
During this pilot study, the CADe system was evaluated in live endoscopic procedures of BE patients with neoplastic lesions or non-dysplastic Barrett's esophagus (NDBE) in two tertiary hospitals. The protocol involved a series of white light endoscopy videos obtained by an expert endoscopist with real-time evaluation and feedback provided by the CADe system. First, the Barrett's segment was comprehensively visualized using a standardized "pullback video", spanning from the gastric folds to the maximum extent of the Barrett's segment. Subsequently, at 2 centimeter intervals, a series of 10-second "level videos" was recorded, starting from the retrograde position. Ground truth, referring to the presence or absence of visible abnormalities requiring targeted biopsy, was determined by the endoscopist prior to starting the protocol. This was followed by post-hoc histopathological confirmation through targeted biopsies, endoscopic resection, or acquisition of random biopsies. The primary outcome measure focused on the standalone performance of the CADe system, which was evaluated in terms of per-patient sensitivity and specificity.

Results

A total of 15 neoplastic patients and 15 NDBE patients were included in the study (mean age of 67 years; mean Barrett length of C7M9; 25 males; no significant differences between groups). The CADe system exhibited a 100% sensitivity on a per patient basis, correctly identifying all neoplastic lesions. 14 out of 15 visible lesions were correctly diagnosed in the pullback videos. The initially missed lesion was detected in the subsequent level video. The system incorrectly predicted neoplasia in 8 NDBE patients. If applied in a clinical setting, this would result in a maximum of one additional targeted biopsy per patient, compared to the 16 random biopsies dictated by the mean Barrett length in this study. Histopathological examination confirmed neoplasia in 13 cases, with 11 cases being adenocarcinoma and 2 cases being high-grade dysplasia. Two cases did not contain any dysplasia. Additionally, in 4 cases from the non-dysplastic group, low-grade dysplasia was found through the random biopsy protocol.

Conclusion

This study represents one of the first evaluations of a CADe system for real-time detection of neoplasia in Barrett's esophagus in the endoscopy suite. The system accurately detected all neoplastic lesions, with an acceptable number of false positive detections.

Disclosure

This study received financial and logistical support from Olympus Tokyo.