Background Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the
esophagus characterized by esophageal eosinophilia that can lead to esophageal remodeling and
stricture formation. To assess remission, upper endoscopy (EGD) with biopsies is performed.
This is an invasive procedure and contributes to cost burden for patients. It is important to
assess non-invasive techniques to sample the cells of the esophagus.
There have been a few non-invasive testing modalities suggested, including the esophageal
string test and Cytosponge. These involve swallowing a string or capsule that ultimately
collects esophageal cells. The string test study showed a significant correlation with
traditional biopsy pathology, however, limitations included the string remaining in overnight
and potential contamination from oral flora. Katzka et al showed that the Cytosponge had an
86% specificity with limitations including gelatin allergy, local esophageal abrasions and
similar potential oral contamination as the esophageal string test.
Another promising device is EsoCheck. This is an encapsulated balloon that can be easily
swallowed and collect cells from the distal esophagus. It is well tolerated and, in Barrett's
esophagus, detected metaplasia with 91.7% specificity. The primary aims of this study are to
determine the feasibility and safety of EsoCheck compared with standard endoscopy and
biopsies in the assessment of EoE. Secondary aims include specific and sensitivity of
EsoCheck as well as specificity and sensitivity of brush cytology given that EsoCheck is a
cytology device.
Detailed Description Study design This is a prospective pilot study at the University of
Pennsylvania to evaluate feasibility and safety. Inclusion criteria include patients at least
22 years of age with known EoE diagnosed in accordance with consensus guidelines previously
scheduled upper endoscopy at the University of Pennsylvania. Exclusion criteria include:
known or suspected contraindication for esophageal intubation, esophageal stricture with
inability to pass an endoscope, history of esophageal perforation, history of esophageal
resection, esophageal diverticula, esophageal fistula, pill dysphagia, pill swallowing
phobia, food impaction, esophageal varices, coagulopathy, active anticoagulation or
antithrombotics, active GI bleeding and pregnancy.
Consecutive patients will be approached for consent until a total of 20 patients are
enrolled. Patients will be approached during the same clinic visit if they meet inclusion
criteria that arranges for the EGD or via telephone up to 2 weeks prior to scheduled EGD.
Charts will be reviewed and patients will be asked medical and surgical history questions to
assess if any exclusion criteria. Written consent will be obtained on the day of endoscopy.
Charts will be reviewed and patients called at 1 week follow up to assess if any adverse
events.
EsoCheck Description The investigational product is called EsoCheck. EsoCheck is an
encapsulated, inflatable, surface-textured balloon that is pill-sized (16x9mm) attached to a
thin 2.16 mm silicone catheter. The device is swallowed with water. The catheter will be held
without any tension to facilitate easy delivery to the stomach. The balloon is then inflated
by injecting 5 cc of air through the catheter. This will be gently withdrawn until the
tension from the esophageal sphincter is felt by the endoscopist. It is then pulled slowly to
sample the esophagus. The balloon is then deflated while still in the distal esophagus using
a syringe and inverted back into the capsule.
EsoCheck Administration and Upper Endoscopy During the intervention period of the trial,
patients will arrive early for their scheduled endoscopy. This involves swallowing the
balloon device while unsedated. They will then undergo their previously scheduled endoscopy
with standard biopsies taken as well as brush cytology performed as EsoCheck is a cytology
device to best compare histology.
EsoCheck and Brush Cytology Sample Processing and Handling:
After retrieval of the capsule through the mouth, the balloon will be re-inflated, cut from
the capsule at the junction of the balloon and the holding capsule. This will be immediately
placed into a pre-labeled vial of Preservcyt transport medium. Vials will be stored on site
in locked cabinets at room temperature. They will be shipped in small batches with
de-identified patient study numbers and sent to the Cytology Department c/o Dr. Joseph
Willis, University Hospitals Cleveland Medical Center.
Specimens will be processed according to the standard operating procedures of the Department
of Pathology at the University Hospitals Cleveland Medical Center. The vial containing the
balloon is vortexed for 5 minutes, after which the balloon is then discarded. After
centrifugation, the vial is then loaded onto the ThinPrep processor along with required
assembly elements
- - including a pre-labeled slide corresponding to the received specimens.
The ThinPrep filter rotates within the specimen vial creating turbulence that is strong
enough to separate cells, debris and mucus. In cell collection, a vacuum collects cells on
the exterior of the membrane of the filter. In cell transfer, the filter is inverted and
gently pressed against the ThinPrep microscope slide. Slight positive air pressure causes the
cells to adhere to the microscope slide resulting in an even distribution of cells in a
circular area. A ThinPrep slide is then generated and is deposited in an alcohol fixative
bath. The slide is then stained with a Hematoxylin and Eosin stain and cover slipped. After
the ThinPrep slides are made, attempts will be made to prepare cell blocks from the reminder
of the material Cytology brush samples will be analyzed at the University Hospitals Cleveland
Medical Center as well with specimens processed according to the standard operating
procedures.
Histologic and cytologic assessment EsoCheck derived samples will be analyzed at the
University Hospitals Cleveland Medical Center. ThinPrep slidesare given to a trained
gastroenterology cytopathologist for review. As the ThinPrep technology smears collected
cells onto the slide in a uniform manner using a membrane-based technology, the
cytopathologist will count eosinophils in one quadrant of the ThinPrep slide. These results
will then be compared with the clinical and pathological features of the study individuals.
The cell blocks will also be reviewed and results correlated with the ThinPrep slide results.
Assessment of brush cytology specimens will be performed at the Department of Pathology at
the University Hospitals Cleveland Medical Center to include assessing eosinophil count per
high power field (hpf).
Histologic assessment of esophageal biopsies will be performed as part of standard of care at
the University of Pennsylvania Department of Pathology and will include assessing eosinophil
count/hpf.
Surveys: Endoscopists will be surveyed regarding perceived anxiety level and comfort level
during procedure. Patients will be surveyed before and afterwards regarding confidence level,
anxiety level, satisfaction, willingness to undergo it again, and preference of EsoCheck
compared with EGD. This survey will be repeated at a 1 week telephone follow up.
Statistical Plan: Baseline and demographic characteristics will be summarized by standard
descriptive statistics (including mean and standard deviation for continuous variables such
as age and standard percentages for categorical variables such as gender). The primary
endpoint will be descriptive statistics of feasibility and patient safety assessed based on
the answers to surveys as listed above. Secondary endpoints include the sensitivity and
specificity of Esocheck with EGD and biopsy as gold standard. Secondary endpoints also
include sensitivity and specificity of brush cytology with EGD and biopsy as gold standard.
All subjects entered into the study will have detailed information collected on adverse
events for the overall study safety analysis
