los angeles classification: development, validation and accumulated experience john dent chair,...
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Los Angeles Classification: Development, validation
and accumulated experience
Los Angeles Classification: Development, validation
and accumulated experience
John DentChair, International Working Group for the
Classification of Oesophagitis
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?
The name of the classification?The name of the classification?
Why the Los Angeles Classification?
First presented at a symposium at the 1994 Los Angeles World Congress
First presented at a symposium at the 1994 Los Angeles World Congress
How to develop and validate?How to develop and validate?
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
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 111:85-92 1996
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
D Armstrong et al., Gastroenterology 1996;111:85-92
Major outcomes of development study (1)
1 cm
Endoscopic judgment of length of mucosal breaks
greater than a few mm shown to be unreliable
Assessment of radial extent of mucosal breaks shown to be more reliable and so adopted as the main severity criterion
D Armstrong et al., Gastroenterology 1996;111:85-92
Major outcomes of development study (2)
1 cm
Folds best demonstrated by partial deflation of the esophagus
Mucosal folds were found to be the best landmarks for
determination of radial extent
How many grades of severity?How many grades of severity?
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
What endoscopic findings are reliable indicators of reflux esophagitis?
What endoscopic findings are reliable indicators of reflux esophagitis?
Literature review and the working group’s assessments Literature review and the working group’s assessments indicate minimal changes cannot be scored reliably indicate minimal changes cannot be scored reliably
with standard endoscopeswith standard endoscopes
Literature review and the working group’s assessments Literature review and the working group’s assessments indicate minimal changes cannot be scored reliably indicate minimal changes cannot be scored reliably
with standard endoscopeswith standard endoscopes
Minimal endoscopic changes for the diagnosis of reflux esophagitis?
Minimal endoscopic changes for the diagnosis of reflux esophagitis?
The working group is currently investigating the utility of The working group is currently investigating the utility of newer endoscopic technologies for recognition of newer endoscopic technologies for recognition of
minimal changesminimal changes
The working group is currently investigating the utility of The working group is currently investigating the utility of newer endoscopic technologies for recognition of newer endoscopic technologies for recognition of
minimal changesminimal changes
Still on the topic of minimum endoscopic criteria for reflux esophagitis
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
How to handle use of the words “erosion” and “ulceration”?
““An area of slough or erythema with a sharp line of An area of slough or erythema with a sharp line of demarcation from adjacent normal mucosa”demarcation from adjacent normal mucosa”
““An area of slough or erythema with a sharp line of An area of slough or erythema with a sharp line of demarcation from adjacent normal mucosa”demarcation from adjacent normal mucosa”
Definition of a mucosal break
Criteria and methods for severity assessment?
Criteria and methods for severity assessment?
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
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
Lundell et al., Gut 45:172-180 (1999)
Los Angeles Classification of reflux esophagitis
1 cm
One (or more) mucosal break no longer than 5 mm, that does not extend between the tops of two mucosal folds
1 cm
One (or more) mucosalbreak more than 5 mm long, that does not extend between the tops of two mucosal folds
1 cm
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
1 cm
One (or more) mucosalbreak which involves atleast 75% of the esophageal circumference
LA grade A LA grade B
LA grade C LA grade D
How to make it simple and memorable?
How to make it simple and memorable?
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
Validation study of criteriaValidation study of criteria
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 45:172-180 1999
Inter-observer agreement on presence of individual measures of severity of esophagitis
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
Lundell et al., Gut 45:172-180 (1999)
Kappa value
median and interquartile
range
The level of agreement was probably reduced by endoscopic The level of agreement was probably reduced by endoscopic image degradation through recording & copying of video clipsimage degradation through recording & copying of video clipsThe level of agreement was probably reduced by endoscopic The level of agreement was probably reduced by endoscopic
image degradation through recording & copying of video clipsimage degradation through recording & copying of video clips
Kappa value is measure of agreement: 0.0 = only chance agreement; 0.4 = just acceptable; 1.0 = perfect agreement
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Correlates with measurements of gastro-esophageal reflux
Correlates with measurements of gastro-esophageal reflux
Johnsson et al., Scand J Gastroenterol 33:15-20 (1998)
24 hour esophageal acid exposure according to LA grade
Gradation of acid exposure by LA gradeGradation of acid exposure by LA gradeGradation of acid exposure by LA gradeGradation of acid exposure by LA grade
Non-erosive reflux disease
n=40
A
n=50
B
n=50
C
n=9
D
n=1020
16
12
8
4
0
LA grade
% TimeEsophageal
pH<4.0
Adachi et al., J Gastroenterol & Hepatol 16:1191-1196 (2001)
LA grades C and D predict high levels of nocturnal acid exposure
Day-time
Night-time
n=20
n=12n=10
n=8
n=7
Normal
LA grades C and D LA grades C and D identify patients with identify patients with
high levels of high levels of nocturnal acid refluxnocturnal acid reflux
LA grades C and D LA grades C and D identify patients with identify patients with
high levels of high levels of nocturnal acid refluxnocturnal acid reflux
50
40
30
20
10
0
70
60
% TimeEsophageal
pH<4.0(median)
A B C D
LA grade
Other methodological evaluations outside the IWGCO
Other methodological evaluations outside the IWGCO
Rath et al., Gastrointest Endosc 60; 44-49 (2004)
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 Nine endoscopists scored video recordings of the esophagus in 60 patients with and without reflux esophagitis according to the 3 systems without reflux esophagitis according to the 3 systems
Nine endoscopists scored video recordings of the esophagus in 60 patients with and Nine endoscopists scored video recordings of the esophagus in 60 patients with and without reflux esophagitis according to the 3 systems without reflux esophagitis according to the 3 systems
KappaValue
Los Angeles
Muse Erosions*
Muse Ulcer*
Savary- Miller
Agreement Level
Endoscopist experienceExcellent
Good
Moderate
Fair
Poor
1.0
0.8
0.6
0.4
0.2
0 * Two severity grades for both erosions and ulcer
High (n=3)
Moderate (n=3)
Minimal (n=3)
Random
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 56:639-643 (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)
Patterns of adoption of the LA Classification in recent years
Patterns of adoption of the LA Classification in recent years
Los Angeles56%
Savary Miller36%
Others2%
More than one 1%Hetzel-Dent 5%
Savary-Miller and Hetzel-Dent classifications include modifications
The LA Classification is now used most widelyA review of all relevant publications (n=306) in which reflux esophagitis was formally graded
from 2003–2006 inclusive
40%46%
79%
Europe(n=139)
North America(n=50)
Rest of World(n=117)
% 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
60
40
20
0Year of publication
Number of published studies
38%
52%
62%
73%
Adoption of the LA Classification is increasing
2003(n=86)
2004(n=67)
2005(n=89)
2006(n=64)
Year of publication
100
80
60
40
20
0
Number of published studies
% studies using LA Classification
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 48:2237-2241 (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 102:299-304 (2003)
• El-Serag et al. Gastro-esophageal reflux among different racial groups in the United States. Gastroenterology 126:1692-1699 (2004)
• Ishiki et al. Helicobacter pylori eradication improves pre-existing reflux esophagitis in patients with duodenal ulcer disease. Clin Gastroenterol & Hepatol 2:474-479 (2004)
• Johnson and Fennerty. Heartburn severity underestimates erosive esophagitis severity in elderly patients with gastro-esophageal reflux disease. Gastroenterology 126:660-664 (2004)
The Los Angeles Classification since 1994
A now huge experience indicates that this isthe 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
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