Introduction
Gastroesophageal reflux disease (GERD) affects up to 20 % of the population in Western
Europe and North America [1]. GERD’s typical symptoms, such as heartburn and regurgitation once per week, affect
patients’ quality of life [2]
[3]. The disease may be diagnosed by symptoms through patient history or questionnaires,
a positive response to proton-pump inhibitor (PPI), or establishing presence of pathologic
reflux on a 24-hour pH-impedance monitoring test; however, these methods have limited
sensitivity and specificity [4].
Esophagogastroduodenoscopy (EGD) with white light endoscopy (WLE) is a standard technique
for evaluating the esophagus in patients with GERD to detect GERD complications, such
as esophageal erosion. However, up to 60 % of patients with GERD who present with
symptoms such as heartburn or acid reflux have normal endoscopic findings with WLE
and are classified as non-erosive gastroesophageal reflux disease (NERD) cases, requiring
further studies to establish a final diagnosis [5].
Previous studies using virtual chromoendoscopy with I-SCAN with high-definition technology
have shown that this technique improves diagnosis of erosive reflux disease by 30 %,
allowing detection of small inflammatory changes (short erosions or short Barrett’s
esophagus) that were not previously detected by standard endoscopy [6]
[7]. Nevertheless, I-SCAN can detect minimal mucosal esophageal lesions (MMEL). However,
due to its low sensitivity, this technique should not be used to detect these lesions
[8].
Recently, an image-enhanced endoscopic technology using pre-processor band-limited
light called the Optical Enhancement system (OE system was developed by HOYA Co. (Tokyo,
Japan) and is now equipped with endoscopic video equipment. The OE system combines
digital signal processing with optical filters that limit the spectral characteristics
of the illumination light, thus improving mucosal visualization. In addition, new
scopes, called MagniView have been developed with the ability to combine high-definition
imaging with optical magnification.
In the normal esophageal mucosa, submucosal vessels that pierce the muscle layer are
connected to the arborescent vascular network. Intrapapillary capillaries arise from
the fourth branch of the arborescent vessels into the epithelial papillae and form
loops (IPCL). It has previously been reported that patients with GERD have an increased
number of vascular lesions (dilation and tortuosity of the IPCLs), a greater number
of microerosions and increased vascularity at the squamocolumnar junction relative
to the control group [9].
The aim of this study was to evaluate patients with NERD using the new OE system and
optical magnification to determine its diagnostic yield for detection of MMEL. The
latter was of particular interest because presence of MMEL can be considered an early
sign of GERD in NERD patients and is not detectable through WLE or I-SCAN technology.
In addition, we sought to compare MMEL images to 24-hour pH-impedance monitoring test
and biopsy results to determine the sensitivity and specificity of the OE system in
predicting inflammation.
Patients and methods
Study design
This was a prospective, controlled, non-randomized, single-blind study performed at
the Instituto
Ecuatoriano de Enfermedades Digestivas (IECED), Academic Tertiary Center, Ecuador,
between September 2015 and January 2016. The study protocol and consent form were
approved by the Institutional Review Board and registered at ClinicalTrials.gov (ID:
NCT02575287). The study was conducted according to the Declaration of Helsinki. Patients
provided informed consent and answered a questionnaire to provide biometric data (sex,
age, weight [kg], height [m], body mass index [kg/m2]), and information about chronic diseases, medications and main reflux symptoms.
Population selection and inclusion and exclusion criteria
NERD group and control group selection
Patients were recruited from the gastroenterology unit of the IECED. Patient selection
(including the control group) was performed after the following analysis ([Fig. 1]). All patients with troublesome typical reflux symptoms (heartburn and regurgitation)
for more than 6 months and with more than eight points on the Spanish validated version
of the GerdQ questionnaire by Zavala-González et al ([Table 1]) underwent EGD [10]. Before endoscopic examination, antisecretory therapy using PPIs was discontinued
for 3 weeks.
Fig. 1 Study flow diagram.
Table 1
GERD-Q questionnaire.
|
Questions
|
Frequency score for symptoms
|
|
0 day
|
1 day
|
2 – 3 days
|
4 – 7 days
|
|
How often did you have a burning feeling behind your breastbone (heartburn)?
|
0
|
1
|
2
|
3
|
|
How often did you have stomach contents (liquido r food) mooving upwards to your throat
or mouth (regurgitation)?
|
0
|
1
|
2
|
3
|
|
How often did you have pain in the center of the upper stomach?
|
3
|
2
|
1
|
0
|
|
How often did you have nausea?
|
3
|
2
|
1
|
0
|
|
How often did you have difficulty getting a Good night’s sleep because of your heartburn
and/or regurgitation?
|
0
|
1
|
2
|
3
|
|
How often did you take additional medication for your heartburn and/or regurgitation,
other than what the physician told you to take (such as Tums, Rolaids and Maalox?
|
0
|
1
|
2
|
3
|
|
GERD-Q Spanish Version
|
|
Preguntas
|
Nunca
|
1 día
|
2 – 3 días
|
4 – 7 días
|
|
¿Con qué frecuencia ha tenido sensación de quemadura detrás del esternón (ardor)?
|
0
|
1
|
2
|
3
|
|
¿Con qué frecuencia ha notado que el contenido del estómago (líquido o alimento) le
subía a la garganta o a la boca (regurgitación)?
|
0
|
1
|
2
|
3
|
|
¿Con qué frecuencia ha sentido dolor en la boca del estómago?
|
3
|
2
|
1
|
0
|
|
¿Con qué frecuencia ha tenido náuseas?
|
3
|
2
|
1
|
0
|
|
¿Con qué frecuencia tuvo problemas para dormir bien por la noche debido a ardor o
regurgitación?
|
0
|
1
|
2
|
3
|
|
¿Con qué frecuencia tomó otros medicamentos para el ardor y/o la regurgitación aparte
de los que recetó su médico? (gel, sal de uvas u otro antiácido)
|
0
|
1
|
2
|
3
|
The Spanish validated version of this GerdQ questionnaire from Zavala-González et
al was used, which is composed of 6 items [10]. Patients answered each question about symptom frequency during the week preceding
examination using a scale from 0 to 3 for positive predictors and from 3 to 0 for
negative predictors. The maximum score that can be obtained is 18.
We then performed a conventional complete endoscopic procedure that reached the Z-line
of the esophagus, and evaluated the entire esophagus (upper, middle and lower segments)
initially using high-definition WLE, followed by digital chromoendoscopy (I-SCAN Pentax,
Tokyo, Japan) with three different image algorithms, including I-scans 1, 2 and 3
(tone and enhancement filters), that accurately detects erosive reflux, short Barret’s
esophagus and minimal change esophagitis (MCE) [7]
[11]. Presence of reflux lesions, such as ulcerative esophagitis, esophageal strictures,
Barrett’s esophagus or any erosive sign according to the Los Angeles classification
(grade A to D) as well as MCE, was considered sufficient to classify patients as having erosive
GERD, and they patients were excluded from the protocol [12]. On the other hand, if the esophagus was normal and no abnormalities were observed,
a 24-hour pH-impedance monitoring test (VersaFlex Z, Given Imaging, Yokneam Illit,
Israel) was performed as the gold standard method to diagnose NERD [13]. Details of the technical background of the pH-impedance procedure have been described
previously [13]. GERD diagnosis was considered when there were more than 73 reflux episodes in 24
hours or when there was an abnormal acid exposure time (AET) with pH < 4 measured
more than 4.2 % of the time over 24 hours [14]. After this period, the investigators were able to discriminate between patients
with NERD (patients with reflux symptoms, no lesions on EGD and with a positive 24-hour
pH-impedance monitoring test) and patients with functional heartburn (patients with
reflux symptoms, no lesions on EGD, and a negative 24-hour pH-impedance monitoring
test). Two groups were selected: the NERD group, and the control group. The control
group included patients with functional heartburn who agreed to be part of this study.
Included patients (NERD group and control group) were older than 18 years of age,
had a history of GERD symptoms with more than eight points on the GERD questionnaire,
and agreed to participate in this study. Patients with any type of esophagitis (actinic,
caustic or eosinophilic), achalasia, esophageal varices, esophageal cancer, usage
of PPIs or non-steroidal anti-inflammatory drugs (NSAIDs) for at least 3 weeks before
the EGD, severe uncontrolled coagulopathy, gastric lesions (ulcer, polyp, cancer),
severe gastroparesis, and a history of esophageal/gastric surgery or pregnancy were
also excluded.
Endoscopic technique
All patients included in the protocol (the NERD group and the control group) were
evaluated by EGD using the OE system (EPK-i7010 processor) and MagniViewscopes (EG-2990Zi)
(Pentax Medical, Hoya Corp., Japan). This technique involved use of a distal rubber
hood (OE-A58) (Pentax Medical, Hoya Corp., Japan) at the tip of the scope. After reaching
the Z-line, the four quadrants of the three esophageal segments (upper, middle and
lower) were evaluated. First, the cup was allowed to contact the esophageal mucosa
and water was ejected from it. Optical magnification was implemented using a button
on the MagniView scope. Then, the OE system was activated using mode 1 (described
below). All of the observed abnormalities were photographically recorded (with video
and pictures) for further validation. Finally, biopsies were completed in both groups
(one targeted biopsy from any lesion detected with OE system and optical magnification).
Endoscopies were performed by three endoscopists (C.R-M, M.V, M.S-A) who were blind
to group selection and were trained on the OE system with optical magnification.
Optical Enhancement system (OE system) and Magniview scopes
OE system
This technology combines digital signal processing with optical filters that limit
spectral characteristics of the illuminated light. Earlier I-SCAN technology uses
white light alone as an illumination source. Subsequent digital post-processing of
the light’s reflection creates images yielding the virtual chromoendoscopic image.
The basic goal of OE is to overcome the darkness of narrow band imaging (NBI), which
makes it more challenging to perform useful wide-range observations in the full extent
of the gastrointestinal lumen. OE optical filters achieve higher overall transmittance
by connecting the peaks of the hemoglobin absorption spectrum (415 nm, 540 nm, and
570 nm), thereby creating a continuous wavelength spectrum. There are two modes that
can be used with different OE filters. For the purpose of this study, Mode 1 was used
exclusively given its ability to improve microvessel visualization using a sufficient
amount of light.
Magniview scopes
This scope technology combines high-definition scopes with optical magnification.
This technology magnifies images up to 136 times, leading to a more detailed image
than standard scopes without optical zoom. This feature subsequently allows better
evaluation of the superficial vascular aspects of the mucosa, identifying early suggestive
signs of inflammation or lesions not previously noted with conventional endoscopy.
Minimal mucosal esophageal lesions
All imaged esophageal segments (upper, middle and lower segments) were analyzed. Endoscopic
images collected using OE with optical magnification were considered positive for
MMEL if IPCLs (increase in number, dilatation, and/or tortuosity) were present ([Fig. 2]) [9].
Fig. 2 An OE with an optical magnification endoscopy image showing a normal intra-papillary capillary loops (IPCLs); b tortuous IPCLs; c increased number of IPCLs; d dilated IPCLs from multiple NERD patients.
For practical reasons and to reduce the time needed for the analysis, each fully magnified
image was divided into four quadrants instead of counting IPCLs by field for evaluation
of IPCL numbers. The IPCLs in each quadrant were manually counted, and the increase
in number was determined when at least one quadrant had more than 30 IPCLs, as reported
in a previous study [9]. A pilot analysis was performed with 10 patients from the NERD group and 10 from
the control group, and a significant difference in the number of IPCLs was noted between
groups. Dilatation of the IPCLs was recognized as an increase in twice the diameter
of individual IPCLs, and IPCLs were considered dilated when they could be clearly
observed at full magnification (136x magnification through the MagniView scope) [9]
[15]. Tortuosity was visually defined by presence of corkscrewing or by the twisted appearance
of individual IPCLs ([Fig. 2]) [9]
[15].OE-derived images were compared with the results of the 24-hour pH-impedance monitoring
test and histological analysis of the biopsies to determine the sensitivity and specificity
by which reflux and inflammation could be detected using OE, respectively.
Histologic inflammation criteria
For biopsy analysis, tissues were considered inflamed due to reflux if neutrophil
and eosinophil infiltration, papillary elongation, basal zone thickening (hyperplasia)
and/or dilation of the intercellular spaces (DIS) was detected [16]
[17].
Interobserver and intraobserver agreement analysis
A dataset containing 60 photographs of the three esophageal segments was presented
to three blinded endoscopists who were asked to classify the photographs as negative
or positive IPCLs (increases in IPCL number, dilatation and tortuosity) at three time
points each 1 week apart. Each time, the same photographs were shown to the endoscopists
but in a different order. The three endoscopists were trained to evaluate the three
IPCL parameters. Interobserver agreement was measured by comparing the results of
analysis of the photographs by each endoscopist (C.R-M., M.V., M.S.A.). Intraobserver
agreement was measured based on a comparison of assessment of the photographs by the
same three endoscopists at each time point.
Statistical analysis
The sample size needed to perform robust intra-rater and inter-rater analyses was
calculated using Cohen’s kappa. The required sample size was estimated by considering
a kappa value under the null hypothesis of 50 %, alpha error (type I) of 5 % and beta
error (type II) of 20 %, which corresponded to a statistical power of 80 %. We considered
the proportion of positive diagnoses per endoscopist and the previously known kappa
value from flexible spectral imaging color enhancement feasibility for NERD [18]. NERD group and control group patients’ baseline characteristics were compared using
Student’s t-test, Welch’s t-test or the Mann-Whitney U test for continuous variables and Pearson’s chi-square
test or Fisher’s exact test for categorical variables. Continuous variables are expressed
as the mean (standard deviation) or median (interquartile range) according to their
statistical distribution. Categorical variables are expressed as percentages.
Visual OE image assessments were compared with results from the gold-standard 24-hour
pH-impedance monitoring tests and the biopsies to determine overall accuracy of the
OE analysis. Diagnostic efficacy using OE was measured through sensitivity and specificity
predictive values, and accuracy to predict reflux and inflammation at the 95 % confidence
interval (95 % CI). To examine interobserver and intraobserver agreement, kappa values
were calculated [16]. Kappa coefficients below 0.4 indicate “poor agreement,” values between 0.4 and
0.8 represent “moderate to good agreement,” and values greater than 0.8 indicate “excellent
agreement”.
P < 0.05 was considered statistically significant. Data were assessed by an IECED institutional
biostatistician. Statistical analysis was performed using R v3.4.3 (R Foundation for
Statistical Computing; Vienna, Austria).
Results
Patient baseline characteristics
The estimated sample size required for robust interobserver and intraobserver analysis
was calculated to be 46 patients, and 57 patients were finally included in the protocol,
corresponding to a statistical power of 88.5 %. Of these, 36 patients (63.1 %) were
in the NERD group and 21 patients (36.8%) were in the control group ([Fig. 1]). There were no significant differences between these groups in terms of age, sex,
main symptoms, or GERD questionnaire scores. Mean age of all patients was 48 years
(14.1). Forty-six of 57 patients (81 %) were female, and the main symptom was regurgitation
in 27 of 57 cases (47.4 %). The median GERD questionnaire score was 13 (interquartile
range 8 – 18) ([Table 2]). Among groups, there were not any macroscopic lesions detected with WLE.
Table 2
Baseline characteristics of the enrolled patients.
|
Patient characteristics
|
Total
(n = 57)
|
NERD group
(n = 36)
|
Control group
(n = 21)
|
P value
|
|
Gender (Female: n, %)
|
46 (80.7)
|
29 (80.6)
|
17 (81.0)
|
0.971
|
|
Age (years) mean (SD)
|
48.18 (14.1)
|
48.11 (15.3)
|
48.29 (12.1)
|
0.962
|
|
Symptoms, n (%)
|
|
|
|
0.860
|
|
|
8 (14.04)
|
5 (13.9)
|
3 (14.3)
|
0.969
|
|
|
27 (47.4)
|
18 (50.0)
|
9 (42.9)
|
0.603
|
|
|
22 (38.6)
|
13 (36.1)
|
9 (42.9)
|
0.614
|
|
GERD Questionnaire median (interquartile range)
|
13 (8 – 18)
|
13 (9 – 18)
|
12 (8 – 16)
|
0.266
|
GERD, gastroesophageal reflux disease; SD, standard deviation.
NERD patients have higher numbers of MMEL than control patients
There was a significant difference in the number of patients with MMEL detected with
the OE
system with optical magnification between the NERD group and control group. IPCLs
were observed
in 34 of 36 cases (94.4 %) in the NERD group and 8 of 21 cases (38 %) in the control
group (P
< 0.001) ([Fig. 2] and [Video 1]).
Video 1 Minimal mucosal esophageal lesions detected during OE with optical magnification
endoscopy. Presence of tortuos and increased numbers of IPCLs.
A positive EGD was characterized by presence of IPCLs in at least one esophageal segment.
A positive EGD was observed in 42 patients (34 in the NERD group and 8 in the control
group, P < 0.001), and most patients with a positive EGD (28/42 [66.6%]) had inflammation
according to histopathological examination of biopsied esophageal tissue. These findings
suggest that presence of IPCLs could be considered an indicator of reflux and inflammation
in patients with NERD. Most patients with IPCLs had more than one esophageal segment
with lesions; however, after analysis of the IPCL distribution by segment, it was
found that the lower third of the esophagus was the most affected (P < 0.001).
NERD patients have greater IPCL numbers and dilatation compared with control patients
[Table 3] shows data for IPCL number, dilation, and tortuosity between groups. Sub-analysis
revealed that IPCL dilatation was the most commonly observed lesion in patients with
a positive UE (33/42 [78.5 %]). There was a significant difference in dilatation (P < 0.001) and numbers of IPCLs (P = 0.003), but not tortuosity (P = 0.114) between the NERD group and control group. Dilatation and increased numbers
of IPCLs were more common among patients with biopsies with histopathologically detectable
inflammation.
Table 3
Intrapapillary capillary loop characteristics in NERD group and control group patients.
|
24-hour pH-impedance monitoring test
|
Biopsy
|
|
IPCLs
|
EGD
|
Positive (NERD group)
|
Negative (Control group)
|
P value
|
Positive[1]
|
Negative
|
P value
|
|
Increase number, n (%)
|
31/42 (73.8 %)
|
25 (80.6 %)
|
6 (19.4 %)
|
0.003[1]
|
20 (64.5 %)
|
11 (35.5 %)
|
0.025[1]
|
|
Dilatation, n (%)
|
33/42 (78.5 %)
|
27 (81.8 %)
|
6 (18.2 %)
|
< 0.001[1]
|
22 (66.6 %)
|
11 (33.4 %)
|
0.005[1]
|
|
Tortuosity, n (%)
|
24/42 (57.1 %)
|
18 (75 %)
|
6 (25 %)
|
0.114[1]
|
15 (62.5 %)
|
9 (37.5 %)
|
0.134[1]
|
IPCLs, intrapapillary capillary loops
1 Positive: tissues were considered inflamed because of reflux if neutrophil and eosinophil
infiltration, papillary elongation, basal zone thickening (hyperplasia) and/or dilation
of the intercellular spaces (DIS) was detected.
OE system and Magniview scopes show high sensitivity, specificity and accuracy in
predicting reflux and inflammation
Overall calculated accuracy parameters are presented in [Table 4]. Results from the visual analysis of the images of the esophageal mucosa obtained
with the OE system and Magniview scopes were compared with the 24-hour pH-impedance
monitoring test to determine the ability of the OE system technology to predict reflux.
Sensitivity, specificity, PPV, NPV, and accuracy were 94.4 %, 61.9 %, 80.9 %, 86.6 %,
and 82.4 %, respectively, and the use of the EGD in the lower third of the esophagus
was associated with the highest sensitivity (88.9 %) and accuracy (87.7 %). Similarly,
the OE system™ results were compared with targeted biopsy histopathology findings
to determine the ability of the OE system™ to predict inflammation. The sensitivity,
specificity, positive predictive value (PPV), negative predictive value, and accuracy
were 96.5 %, 50 %, 66.6 %, 93.3 %, and 73.6 %, respectively, and use of the EGD in
the lower third of the esophagus once again was associated with the highest accuracy.
Finally, the interobserver and intraobserver agreement were calculated using a Kappa
value for interobserver agreement of 0.85 ± 0.13 (0.59 – 1.11) and intraobserver agreement
of 0.90 ± 0.13 (0.64 – 1.16).
Table 4
Contingency table comparing the esophagogastroduodenoscopy results with those of 24-hour
pH-impedance monitoring tests and histopathological targeted biopsies.
|
Sensitivity % (95 % IC)
|
Specificity % (95 % IC)
|
PPV % (95 % IC)
|
NPV % (95 % IC)
|
Accuracy %
|
|
24 hours pH-impedance monitoring test
|
|
EGD overall
|
94.4 (81.3 – 99.3)
|
61.9 (38.4 – 81.9)
|
80.9 (65.9 – 91.4)
|
86.7 (59.5 – 98.3)
|
82.5
|
|
EGD lower third of esophagus
|
88.9 (73.9 – 96.9)
|
85.7 (63.7 – 96.9)
|
91.4 (76.9 – 98.2)
|
81.8 (59.7 – 94.8)
|
87.7
|
|
EGD middle third of esophagus
|
75.0 (57.8 – 87.9)
|
71.0 (48.0 – 89.0)
|
82.0 (65.0 – 93.0)
|
62.5 (40.6 – 81.2)
|
73.7
|
|
EGD upper third of esophagus
|
80.6 (63.9 – 91.8)
|
66.7 (43.0 – 85.4)
|
80.6 (63.9 – 91.8)
|
66.7 (43.0 – 85.4)
|
75.4
|
|
Biopsy
|
|
EGD overall
|
96.5 (82.2 – 99.9)
|
50.0 (30.7 – 69.3)
|
66.7 (50.5 – 80.4)
|
93.3 (68.1 – 99.8)
|
73.7
|
|
EGD lower third of esophagus
|
92.3 (74.9 – 99.1)
|
64.5 (45.3 – 80.8)
|
68.6 (50.7 – 83.2)
|
90.9 (70.8 – 98.9)
|
77.2
|
|
EGD middle third of esophagus
|
81.8 (59.7 – 94.8)
|
57.1 (39.4 – 73.7)
|
54.6 (36.4 – 71.9)
|
83.3 (62.6 – 95.3)
|
66. 7
|
|
EGD upper third of esophagus
|
89.5 (66.9 – 98.7)
|
50.0 (33.4 – 66.6)
|
47.2 (30.4 – 64.5)
|
90.5 (69.6 – 98.8)
|
63.1
|
EGD, esophagogastroduodenoscopy; PPV, positive predict value; NPV, negative predictive
value.
Discussion
Approximately 20 % of patients with NERD showed no evidence of microscopic esophagitis
on biopsy [19]. However, it is estimated that NERD accounts for up to 60 % to 70 % of patients
with GERD. Importantly, standard endoscopic evaluation is an inaccurate test for diagnosing
reflux disease in patients with NERD, due to absence of visible lesions on endoscopy,
making it necessary to further evaluate such patients with other diagnostic tests,
such as pH-impedance monitoring [20]
[21].
Previous studies using different endoscopic technologies, such as high-definition
and Lugol chromoendoscopy, attempted to identify minimal esophageal mucosal changes,
such as erythema or the invisibility of vessels, in NERD. However, these lesions were
found in only 43 % of patients with low sensitivity and low interobserver agreement
[22]
[23].
Chromoendoscopy with or without optical magnification has been previously used to
identify subtle esophageal changes and diagnose NERD [24]
[25]
[26]. Alterations such as punctuate erythema located above the Z-line are typically classified
as caused by NERD, but the sensitivity for their detection is low (64 %), and the
interobserver consistency displays poor agreement [25]. I-scan is useful for detecting Barrett’s esophagus and reflux esophagitis [7]. Netinatsunton et al used I-scan to detect minimal change esophagitis (minute erosion,
punctuate erythema and elongated pit pattern of gastric mucosa with triangular lesions);
however, low sensitivity and PPV were described [8].
Digital chromoendoscopy with high-definition scopes using NBI has shown greater sensitivity
than WLE for detecting inflammation in patients with suspected NERD. However, histopathological
findings are more prevalent than mucosal changes detected using this imaging technique,
such that use of biopsies is still necessary [16].
Recently, Sharma et al. used optical magnification with digital chromoendoscopy (NBI)
to evaluate 80 patients with GERD. They found that these patients had increased vascularity
at the squamocolumnar junction compared with control subjects. Although interobserver
agreement for NBI was very good (increase number of IPCLs [κ = 0.80], dilation [κ = 0.75],
and tortuosity [κ = 0.89]), intra-observer agreement was only modest (increase number
of IPCLs [κ = 0.51], dilation [κ = 0.51], and tortuosity [κ = 0.39]) [9]. However, this study has the limitation of defining GERD based on results of two
validated questionnaires instead of using a 24-hour pH-impedance monitoring test to
confirm reflux. Moreover, the study was not originally designed to evaluate IPCLs
in patients with NERD. Thus, an increase in acid exposure time was not confirmed in
the subgroup of patients with NERD, and inflammation was not confirmed histologically.
The current study aimed to clarify whether digital chromoendoscopy using the OE system
and optical magnification using Magniview scopes could be used to determine whether
IPCLs can serve as an early sign of NERD. Therefore, we prospectively evaluated specific
patients with NERD after excluding minimal change esophagitis via I-scan and confirming
reflux using the 24-hour pH-impedance monitoring test with additional histological
evaluation. We found that IPCLs were observed in 94.4 % of the NERD group, and the
lower third segment of the esophagus was the most affected by these abnormalities
(P < 0.05). By contrast, only 38 % of control group patients had IPCLs. In addition,
we found that increased numbers of IPCLs and IPCL dilation were the most commonly
observed abnormalities, affecting 86.1 % and 91.6 % of patients in the NERD group,
respectively. In addition, we demonstrated that IPCLs in patients with NERD are early
microvascular inflammatory lesions in the lamina propria, which can be considered
as early signs of NERD.
The current study has the advantage of a well-founded methodological design, in which
patients with GERD and minimal change esophagitis were excluded using I-scan technology;
more accurate gold standards for defining reflux and inflammation (24-hour pH-impedance
monitoring test and histological analysis) instead of the validated questionnaires
used in previous studies were applied [8]
[9]. The study was specifically designed to evaluate IPCL characteristics in patients
with NERD; thus, it allowed us to confirm that IPCL dilation and increases in numbers
are abnormalities found in patients with NERD that might be considered as a diagnostic
method.
The study did have some limitations. It was a non-randomized, single-center and single-blind
study. Only patients with typical reflux disease (heartburn and/or regurgitation)
were included. The generalizability of these findings needs to be evaluated, considering
that MagniView scopes are not available in all endoscopic units. In addition, a practical
limitation of optical magnification is the necessity of focusing the scope tip closer
to the mucosa. Optical enhancement plus optical magnification for evaluating IPCLs
as a diagnostic marker of NERD requires a learning curve to adjust scope maneuverability.
In addition, longer time during endoscopy must be noted as a limitation.
Conclusion
In conclusion, use of the OE systemalong with Magniview scopes proved to be a useful
method for detecting MMEL and predicting reflux in NERD patients. These technologies
had high sensitivity, accuracy, and good interobserver and intraobserver agreement.
In addition, presence of IPCLs was highly correlated with a positive diagnosis using
24-hour pH-impedance monitoring test and histological inflammation, thus suggesting
that other methods may not be essential to make a NERD diagnosis.
