Flexible Spectral Imaging Color Enhancement and Probe-based Confocal Laser Endomicroscopy in Minimal Change Esophageal Reflux Disease

Rapat Pittayanon; Surasak Aumkaew; Rungsun Rerknimitr; Naruemon Wisedopas; Pinit Kullavanijaya

doi:10.4166/kjg.2016.68.1.29

Journal List > Korean J Gastroenterol > v.68(1) > 1007585

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Pittayanon, Aumkaew, Rerknimitr, Wisedopas, and Kullavanijaya: Flexible Spectral Imaging Color Enhancement and Probe-based Confocal Laser Endomicroscopy in Minimal Change Esophageal Reflux Disease

Original Article

Korean J Gastroenterol 2016;68(1):29-35.

Published online: 4 October 2016

DOI: https://doi.org/10.4166/kjg.2016.68.1.29

Flexible Spectral Imaging Color Enhancement and Probe-based Confocal Laser Endomicroscopy in Minimal Change Esophageal Reflux Disease

Rapat Pittayanon^1,³, Surasak Aumkaew^1,³, Rungsun Rerknimitr^1,³, Naruemon Wisedopas^2,³, Pinit Kullavanijaya^1,³

¹Division of Gastroenterology, Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand

²Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

³Faculty of Medicine, Chulalongkorn University, Thai Red Cross, Bangkok, Thailand

Correspondence to: Rungsun Rerknimitr, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, 1872 Phayathai Road, Pathumwan, Bangkok 10330, Thailand. Tel: +66-22564265, Fax: +66-22527839, E-mail: Cholangiogram@gmail.com

Received 14 May 2016 Revised 4 July 2016 Accepted 4 July 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Although flexible spectral imaging color enhancement (FICE) can facilitate the diagnosis of minimal change esophageal reflux disease (MERD), the complicated diagnostic criteria cause suboptimal interobserver agreement. Confocal laser endomicroscopy (CLE) yields good diagnostic results but its interobserver agreement has never been explored. This study compares the diagnostic value of magnifying FICE and probe-based CLE (pCLE) for MERD and evaluates the interobserver agreement of both techniques.

Methods

Thirty-six patients with suspected MERD and 18 asymptomatic controls were recruited. Magnifying FICE was used for evaluation of distal esophagus. pCLE counted the number of intrapapillary capillary loops (IPCLs) using more than five IPCLs in 500×500 micron area as a criterion for MERD diagnosis. The validity scores and interobserever agreement of both FICE and pCLE were assessed.

Results

For FICE vs. pCLE, the accuracy was 79% vs. 87%, sensitivity 94% vs. 97%, specificity 50% vs. 66%, positive predictive value 79% vs. 85%, and negative predictive value 82% vs. 92%. Interobserver agreement of FICE was fair to substantial, whereas pCLE had substantial to almost perfect agreement.

Conclusions

Both FICE and pCLE have good operating characteristics and can facilitate the MERD diagnosis. However, among different observers, pCLE is more consistent on MERD diagnosis.

Keywords: Minimal esophageal reflux disease, Probe-based confocal laser endoscopy, Flexible spectral imaging color enhancement

References

1. El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007; 5:17–26.

2. Ho KY, Chan YH, Kang JY. Increasing trend of reflux esophagitis and decreasing trend of Helicobacter pylori infection in patients from a multiethnic Asian country. Am J Gastroenterol. 2005; 100:1923–1928.

3. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidencebased consensus. Am J Gastroenterol. 2006; 101:1900–1920. quiz 1943.

4. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet. 2006; 367:2086–2100.

5. Dent J. Microscopic esophageal mucosal injury in nonerosive reflux disease. Clin Gastroenterol Hepatol. 2007; 5:4–16.

6. Fass R, Fennerty MB, Vakil N. Nonerosive reflux disease–current concepts and dilemmas. Am J Gastroenterol. 2001; 96:303–314.

7. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005; 54:710–717.

8. Kiesslich R, Kanzler S, Vieth M, et al. Minimal change esophagitis: prospective comparison of endoscopic and histological markers between patients with nonerosive reflux disease and normal controls using magnifying endoscopy. Dig Dis. 2004; 22:221–227.

9. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999; 45:172–180.

10. Hoshihara Y, Hashimoto M. Endoscopic classification of reflux esophagitis. Nihon Rinsho. 2000; 58:1808–1812.

11. Miwa H, Yokoyama T, Hori K, et al. Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists. Dis Esophagus. 2008; 21:355–363.

12. Savarino E, Zentilin P, Mastracci L, et al. Microscopic esophagitis distinguishes patients with nonerosive reflux disease from those with functional heartburn. J Gastroenterol. 2013; 48:473–482.

13. Falk GW. Is conventional endoscopic identification of nonerosive reflux disease adequate? Digestion. 2008; 78(Suppl 1):17–23.

14. Osawa H, Yamamoto H. Present and future status of flexible spectral imaging color enhancement and blue laser imaging technology. Dig Endosc. 2014; 26(Suppl 1):105–115.

15. Miyasaka M, Hirakawa M, Nakamura K, et al. The endoscopic diagnosis of nonerosive reflux disease using flexible spectral imaging color enhancement image: a feasibility trial. Dis Esophagus. 2011; 24:395–400.

16. Kiesslich R, Lammersdorf K, Goetz M, et al. Microscopic changes in Non Erosive Reflux Disease (NERD) can be diagnosed during ongoing endoscopy by Confocal Laser Endomicroscopy (CLE). Gastrointestinal Endoscopy. 2006; 63:AB243.

17. Chu CL, Zhen YB, Lv GP, et al. Microalterations of esophagus in patients with nonerosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012; 107:864–874.

18. Chaiteerakij R, Geratikornsupuk N, Tangmankongworakoon N, et al. Efficacy of intelligent chromo endoscopy for detection of minimal mucosal breaks in patients with typical reflux symptoms of gastroesophageal reflux disease. Gastrointestinal Endoscopy. 2008; 67:AB86.

19. Ismail-Beigi F, Horton PF, Pope CE 2nd. Histological consequences of gastroesophageal reflux in man. Gastroenterology. 1970; 58:163–174.

20. Gaddam S, Mathur SC, Singh M, et al. Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett's esophagus. Am J Gastroenterol. 2011; 106:1961–1969.

21. Yoshida Y, Matsuda K, Sumiyama K, et al. A randomized crossover open trial of the adenoma miss rate for narrow band imaging (NBI) versus flexible spectral imaging color enhancement (FICE). Int J Colorectal Dis. 2013; 28:1511–1516.

22. Quang T, Schwarz RA, Dawsey SM, et al. A tablet-interfaced high-resolution microendoscope with automated image interpretation for real-time evaluation of esophageal squamous cell neoplasia. Gastrointest Endosc. 2016. DOI: doi:10.1016/j.gie.2016.03.1472. [Epub ahead of print].

Fig. 1.

Flexible spectral imaging color enhancement criteria for minimal change esophageal reflux disease diagnosis. (A) Triangular indentation (non-magnification) (arrow). (B) Punc-tuate erythema (arrow; ×50). (C) Viliform mucosa (arrow; ×50). (D) Increased number of capillary vessel (arrow; ×100).

Fig. 2.

Probe-based confocal laser endomicroscopy criteria for minimal change esophageal reflux disease diagnosis diagnosis showed one set of the probe-based confocal laser endomicroscopy image demonstrated intrapapillary capillary loops (arrow; ×1,000).

Fig. 3.

Study flow chart. FICE, flexible spectral imaging color enhancement; pCLE, probe-based confocal laser endomicroscopy; LA, Los Angeles classification.

Table 1.

Baseline Characteristic of Study Groups

Characteristic	GerdQ positive (n=36)	Normal (n=18)	p-value
Sex (female)	72.2	66.7	0.75
Age (yr)	53.11±10.80	55.83±12.72	0.41
Height (m)	1.59±0.08	1.61±0.07	0.41
Body weight (kg)	60.78±16.14	58.31±8.86	0.47
BMI (kg/m²)	23.92±5.64	22.48±2.81	0.31
Alcohol consumption	5.6	16.7	0.32
Smoking	0	0	1
Duration of up-right position after meal (hr)	2.86±1.35	2.89±1.18	0.94

Values are presented as % only or mean±SD.

Table 2.

Endoscopic Findings and Pathology of GerdQ Positive Patients with MERD or NERD and Normal Control

Endoscopic findings/pathology	Presence of GerdQ with MERD or NERD by endoscopy (n=36)	Normal control (n=18)
White light endoscopy
Normal	19	17
Minimal change	17	1
Erythema without sharp demarcation	13	1
Whitish turbidity	4	0
Invisible of vessles	0	0
FICE
Positive	34	9
Triagular indentation	20	6
Increased IPCLs	31	3
Punctate erythema	10	3
Villous mucosa	8	1
Negative	2	9
Confocal (pCLE)
Positive (ICPLs >5/500 μ m²)	34	6
Mean±SE	9.47±3.18	4.72±1.41
Median (range)	8 (3–16)	4 (3–8)
Negative	2	12
Pathology
Reflux esophagitis	11	2
No reflux esophagitis	25	16

Values are presented as n only, mean±standard error (SE), or median (range).

MERD, minimal change esophageal reflux disease; NERD, non-erosive reflux disease; pCLE, probe-based confocal laser endomicroscopy; IPCLs, intrapapillary capillary loops.

Table 3.

Sensitivity, Specificity, PPV, NPV and Accuracy of pCLE, FICE and Pathology in MERD Diagnosis

Instrument	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
FICE	94	50	79	82	79
pCLE	97	66	85	92	87
Pathology	33	88	84	41	52

PPV, positive predictive value; NPV, negative predictive value; FICE, flexible spectral imaging color enhancement; pCLE, probe-based confocal laser endomicroscopy; MERD, minimal change esophageal reflux disease.

Table 4.

Sensitivity, Specificity, PPV, NPV and Accuracy of Off-line and Real-time pCLE in MERD Diagnosis

Diagnostic value	Off-line reading	Real-time reading	p-value
Sensitivity (%)	97	95	>0.10
Specificity (%)	66	63	>0.10
PPV (%)	85	83	>0.10
NPP (%)	92	94	>0.10
Accuracy (%)	87	83	>0.10

PPV, positive predictive value; NPV, negative predictive value; pCLE, probe-based confocal laser endomicroscopy; MERD, minimal change esophageal reflux disease.

Table 5.

Reading Skill and Interobserver Agreement in MERD Diagnosis by FICE and pCLE

MERD reading skill	First test		Second test		Third test		Fourth test
MERD reading skill	FICE	pCLE	FICE	pCLE	FICE	pCLE	FICE	pCLE
Sensitivity	71.4	86.1	83.3	100	92.5	97.5	91.2	83.3
	(57.1–100)	(50–100)	(55.6–100)		(75–100)	(75–100)	(75–100)	(33.3–100)
Specificity	70	88.3	100	94.4	70	98.8	35	93.3
	(33.3–100)	(66.7–100)		(77.8–100)	(50–100)	(87.5–100)	(0–50)	(77.8–100)
PPV	84.7	86.9	100	100	92.5	97.5	84.8	94.4
	(57.1–100)	(66.7–100)			(85.7–100)	(88.9–100)	(75–88.9)	(81.8–100)
NPV	51.2	88.1	40	85.7	70	98.8	50	80.6
	(25–100)	(66.7–100)	(20–100)	(60–100)	(33.3–100)	(80–100)	(0–100)	(60–100)
Accuracy	71	88.3	85	95.8	88	98.3	80	90.8
	(60–90)	(66.7–100)	(60–100)	(83.3–100)	(70–100)	(91.7–100)	(60–90)	(83.3–100)
Inter-observer	0.37	0.75	0.50	0.89	0.62	0.96	0.29	0.75
agreement (κ)	(fair)	(substantial)	(moderate)	(almost perfect)	(substantial)	(almost perfect)	(fair)	(substantial)

Values are presented as % (range).

MERD, minimal change esophageal reflux disease; FICE, flexible spectral imaging color enhancement; pCLE, probe-based confocal laser endomicroscopy; PPV, positive predictive value; NPV, negative predictive value.

TOOLS

Similar articles