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