1. Los Angeles Classification: Development, validation and accumulated experience
John Dent
Chair, International Working Group for the Classification of Oesophagitis

2. Important challenges addressed during development of a novel severity grading system for reflux esophagitis
The name of the classification?
How to develop and validate?
How many grades of severity?
What endoscopic findings are reliable indicators of reflux esophagitis?
Criteria and methods for severity assessment?
How to make it simple and memorable?

3. The name of the classification?

4. Why the Los Angeles Classification?
First presented at a symposium at the 1994 Los Angeles World Congress

5. How to develop and validate?

6. Development of criteria (1)
Discussion, discussion, discussion on multiple occasions by a small international working group
Testing of approaches on a bank of still endoscopic pictures of esophagitis

7. Development of criteria (2)
The first publication from the group describes the development of the Los Angeles Classification criteria by assessment of stored still images
1996 – The endoscopic assessment of esophagitis – A progress report on observer agreement. Armstrong D, Bennett JR, Blum AL, Dent J, de Dombal FT, Galmiche J-P, Lundell L, Margulies M, Richter JE, Spechler SJ, Tytgat GNJ, Wallin L. Gastroenterology 111:

8. Limited image quality handicapped the development of the Los Angeles Classification
Still photographs from fibre optic endoscopes were the only option for the first study
Images had very limited resolution and brightness
Could not capture all relevant findings in a single frame

9. Major outcomes of development study (1)
Assessment of radial extent of mucosal breaks shown to be more reliable and so adopted as the main severity criterion
Endoscopic judgment of length of mucosal breaks greater than a few mm shown to be unreliable
1 cm
D Armstrong et al., Gastroenterology 1996;111:85-92

10. Major outcomes of development study (2)
Folds best demonstrated by partial deflation of the esophagus
Mucosal folds were found to be the best landmarks for determination of radial extent
1 cm
D Armstrong et al., Gastroenterology 1996;111:85-92

11. How many grades of severity?

12. Three or four severity grades?
Hotly debated within the group
Majority of members eventually supported four grades believing:
these would be clinically relevant
criteria for four grades possible

13. What endoscopic findings are reliable indicators of reflux esophagitis?

14. Minimal endoscopic changes for the diagnosis of reflux esophagitis?
Literature review and the working group’s assessments indicate minimal changes cannot be scored reliably with standard endoscopes

15. Minimal endoscopic changes for the diagnosis of reflux esophagitis?
The working group is currently investigating the utility of newer endoscopic technologies for recognition of minimal changes

16. How to handle use of the words “erosion” and “ulceration”?
Still on the topic of minimum endoscopic criteria for reflux esophagitis
How to handle use of the words “erosion” and “ulceration”?
The Los Angeles Group eventually decided to avoid them, using “mucosal break” to include erosion and ulceration, and not to use ulceration as measure of severity
Why? – because the group’s studies showed that endoscopic differentiation of erosion and ulceration could not be made with consistent reliability

17. Definition of a mucosal break
“An area of slough or erythema with a sharp line of demarcation from adjacent normal mucosa”

18. Criteria and methods for severity assessment?

19. The Los Angeles Classification was designed to only grade severity of esophagitis
Thus, the only logical criterion is an estimation of extent of mucosal breaks
Complications of esophagitis such as stricture and Barrett’s Esophagus are not reliable measures of severity of esophagitis, so should not be used for assessment of its severity

20. Final approach to grading the extent of esophagitis
Rely primarily on radial extent, using mucosal folds as landmarks
The two milder grades are distinguished by:
mucosal breaks not extending between two or more mucosal folds
axial extent of mucosal breaks differentiates between these grades
The two most severe grades are defined by:
mucosal breaks extending between two or more mucosal folds
radial extent of mucosal folds differentiates between these grades

21. Los Angeles Classification of reflux esophagitis
LA grade A
LA grade B
One (or more) mucosal break no longer than 5 mm, that does not extend between the tops of two mucosal folds
One (or more) mucosal break more than 5 mm long, that does not extend between the tops of two mucosal folds
1 cm
1 cm
LA grade C
LA grade D
One (or more) mucosal break that is continuous between the tops of two or more mucosal folds,
but which involves less than 75% of the circumference
One (or more) mucosal break which involves at least 75% of the esophageal circumference
1 cm
1 cm
Lundell et al., Gut 45: (1999)

22. How to make it simple and memorable?

23. Keeping it simple and memorable
This was helped by:
Building criteria around longitudinal mucosal folds
Minimizing numerical judgments on axial and radial extent
Giving the four grades the letters A-D as a code for severity grade

24. Validation study of criteria

25. Validation of criteria through grading of endoscopic video clips by external assessors and by pathophysiological correlates
The second publication from the group is the definitive description of the Los Angeles Classification
1999 – Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles Classification Lundell LR, Dent J, Bennett JR, Armstrong D, Galmiche J-P, Johnson F, Hongo, M, Richter JE, Spechler SJ, Tytgat GNJ, Wallin L. Gut 45:

26. Inter-observer agreement on presence of individual measures of severity of esophagitis
Kappa value is measure of agreement: 0.0 = only chance agreement; 0.4 = just acceptable; 1.0 = perfect agreement
The level of agreement was probably reduced by endoscopic image degradation through recording & copying of video clips
0.6
0.5
Kappa value median and interquartile range
0.4
0.3
0.2
0.1
Mucosal break present
≥2 mucosal breaks continued to the top of mucosal folds
Mucosal break involving ≥2 folds being continuous between folds
Radial extension (0-25%) of the circumference
0.0
Lundell et al., Gut 45: (1999)

27. Correlates with measurements of gastro-esophageal reflux

28. 24 hour esophageal acid exposure according to LA grade
Gradation of acid exposure by LA grade 20
n=10
% Time Esophageal pH<4.0 16
n=50
n=9 12
n=50 8
n=40 4
Non-erosive reflux disease A B C D
LA grade
Johnsson et al., Scand J Gastroenterol 33:15-20 (1998)

29. LA grades C and D predict high levels of nocturnal acid exposure
Day-time
LA grades C and D identify patients with high levels of nocturnal acid reflux
Night-time 70
n=8
n=7 60 50
% Time Esophageal pH<4.0
(median) 40 30 20
n=10
n=12 10
n=20
Normal A B C D
LA grade
Adachi et al., J Gastroenterol & Hepatol 16: (2001)

30. Other methodological evaluations outside the IWGCO

31. Levels of interobserver agreement on endoscopic grading of reflux esophagitis with three grading systems
Nine endoscopists scored video recordings of the esophagus in 60 patients with and without reflux esophagitis according to the 3 systems
1.0
Excellent
Endoscopist experience
0.8
High (n=3)
Good
Moderate (n=3)
0.6
Kappa
Value
Minimal (n=3)
Moderate
0.4
Fair
0.2
Poor
Random
* Two severity grades for both erosions and ulcer
Los Angeles
Muse Erosions*
Muse Ulcer*
Savary- Miller
Agreement Level
Rath et al., Gastrointest Endosc 60; (2004)

32. Additional methodological research into the Los Angeles Classification
Pandolfino et al. Comparison of inter- and intraobserver consistency for grading of esophagitis by expert and trainee endoscopists. Gastrointest Endosc 56: (2002)
Kusano et al. Numerical modification of the Los Angeles Classification of gastroesophageal reflux disease fails to decrease observer variation. Dig Endosc 16:9-11 (2004)

33. Patterns of adoption of the LA Classification in recent years

34. The LA Classification is now used most widely
A review of all relevant publications (n=306) in which reflux esophagitis was formally graded from 2003–2006 inclusive
Others 2%
More than one 1%
Hetzel-Dent 5%
Savary Miller
Los Angeles
36%
56%
Savary-Miller and Hetzel-Dent classifications include modifications

35. % studies using LA Classification
The uptake of the LA Classification has been greatest outside Europe and North America
Data for published studies 2003–2006 inclusive
100 80
79% 60
% studies using LA Classification
46% 40
40% 20
Year of publication
Europe (n=139)
North America (n=50)
Rest of World (n=117)
Number of published studies

36. Adoption of the LA Classification is increasing
100 80
73%
62% 60
% studies using LA Classification
52% 40
38% 20
Year of publication
2003 (n=86)
2004 (n=67)
2005 (n=89)
2006 (n=64)
Number of published studies

37. Other studies in which use of the Los Angeles Classification has been important
Nakase et al. Relationship between asthma and gastro-oesophageal reflux: significance of endoscopic grade… J Gastroenterol & Hepatol 14:715–722 (1999)
Inamori et al. Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification. J Gastroenterol & Hepatol 17:172–176 (2003)
Okamoto et al. Clinical Symptoms in endoscopic reflux esophagitis: evaluation in 8031 patients. Dig Dis Sci 48: (2003)
Sasaki et al. Long-term observation of reflux oesophagitis developing after Helicobacter pylori eradication therapy. Aliment Pharmacol Ther 17:1529–1534 (2003)
Lin et al. Limited value of typical gastro-esophageal reflux disease symptoms to screen for erosive esophagitis in Taiwanese. J Formos Med Assoc 102: (2003)
El-Serag et al. Gastro-esophageal reflux among different racial groups in the United States. Gastroenterology 126: (2004)
Ishiki et al. Helicobacter pylori eradication improves pre-existing reflux esophagitis in patients with duodenal ulcer disease. Clin Gastroenterol & Hepatol 2: (2004)
Johnson and Fennerty. Heartburn severity underestimates erosive esophagitis severity in elderly patients with gastro-esophageal reflux disease. Gastroenterology 126: (2004)

38. The Los Angeles Classification since 1994
A now huge experience indicates that this is the best system available for diagnosis and grading of the severity of reflux esophagitis
J Dent, on behalf of IWGCO Members, on basis of literature review and survey data in process of publication

39. Conclusions – The Los Angeles Classification
The subgrouping of patients into LA grades A-D is clinically relevant
Hundreds of endoscopists around the world have shown that they can learn and use the classification
Outcomes from multiple studies can now be pooled to explore factors possibly relevant to reflux esophagitis severity
LA grading should be useful for guiding clinical management strategies, but this needs more formal research