A study on histological chronic gastritis in A study on histological chronic gastritis in the East Coast of Peninsular Malaysia – the East Coast of Peninsular Malaysia – correlation with endoscopic findings, causes correlation with endoscopic findings, causes

and helicobacter pyloriand helicobacter pyloriYeong Yeh Lee

MD MRCP(UK) MMED

ORAL PRESENTATION APDW 2007

INTRODUCTIONINTRODUCTIONThe prevalence of chronic atrophic gastritis (CAG) varied inThe prevalence of chronic atrophic gastritis (CAG) varied in

different geographical areas of the world with the Japanesedifferent geographical areas of the world with the Japanese

and Chinese among the highestand Chinese among the highest11..

Chronic atrophic gastritis was associated with 5 folds increasedChronic atrophic gastritis was associated with 5 folds increased

risk of gastric cancerrisk of gastric cancer22. . Helicobacter pyloriHelicobacter pylori infection was associated infection was associated

with 2.9 times higher risk for gastric cancerwith 2.9 times higher risk for gastric cancer33..

1 Melanie NW, Hermann B; Prevalence of CAG in different parts of the world; Ca Epid Biomarkers Prev 20062 Kato I et al. A prospective study of atrophic gastritis and stomach cancer risk; Jpn J Cancer Res 19923 Uemura N et al. H pylori infection and development of gastric cancer; N Eng J Med 2001

INTRODUCTIONINTRODUCTION

The incidence for gastric cancer in Malaysia was 4.3/100,000The incidence for gastric cancer in Malaysia was 4.3/100,000in 2003in 200344. A higher incidence was seen in older age >60 years,. A higher incidence was seen in older age >60 years,Chinese and males.Chinese and males.

The prevalence rate for The prevalence rate for helicobacter pylorihelicobacter pylori infection in the east infection in the eastcoast of peninsular Malaysia was one of the lowest reportedcoast of peninsular Malaysia was one of the lowest reportedin the literature (4.2% among 496 blood donors and 4.8%in the literature (4.2% among 496 blood donors and 4.8%among 921 subjects who attended health screening clinicsamong 921 subjects who attended health screening clinics55).).

4Second Report of National Cancer Registry, Malaysia 20035 Uyub AM, Raj SM. Helicobacter pylori infection in north-eastern peninsular Malaysia. Evidence for an unusually low prevalence, Scand J Gastroenterol 1994

OBJECTIVESOBJECTIVES11.. To determine the prevalence of chronic atrophic To determine the prevalence of chronic atrophic

(CAG) and non-atrophic (CNAG) antral gastritis (CAG) and non-atrophic (CNAG) antral gastritis

2.2. To determine the association of chronic atrophic To determine the association of chronic atrophic antral gastritis with the risk of metaplasia and antral gastritis with the risk of metaplasia and dysplasiadysplasia

3.3. To determine the association between patient To determine the association between patient demographics, causes of gastritis and demographics, causes of gastritis and helicobacter helicobacter pylori pylori with the risk of metaplasia and dysplasia in with the risk of metaplasia and dysplasia in CAGCAG

4.4. To correlate the endoscopic findings with To correlate the endoscopic findings with histological gastritishistological gastritis

METHODOLOGYMETHODOLOGY

A total of 234 consecutive histological reports of biopsiesA total of 234 consecutive histological reports of biopsies

taken from endoscopic antral gastritis were reviewed andtaken from endoscopic antral gastritis were reviewed and

analyzed from January until December 2006.analyzed from January until December 2006.

METHODOLOGYMETHODOLOGY

A total of 4 biopsies were taken from the antrum or incisuraA total of 4 biopsies were taken from the antrum or incisura

with endoscopic gastritis.with endoscopic gastritis.

Histological gastritis was classified into atrophic and non-Histological gastritis was classified into atrophic and non-

atrophic gastritis based on Sydney system and Atrophy Clubatrophic gastritis based on Sydney system and Atrophy Club

definitions.definitions.

Helicobacter pylori Helicobacter pylori was detected using CLO test and histology. was detected using CLO test and histology.

METHODOLOGYMETHODOLOGY

Data was analyzed using SPSS software version 12.0.1.Data was analyzed using SPSS software version 12.0.1.

P-value of 0.05 was considered significant and a kappa valueP-value of 0.05 was considered significant and a kappa valuebetween 0.4 to 1.0 was considered good agreement.between 0.4 to 1.0 was considered good agreement.

Univariate analysis was carried out using Fischer-Exact orUnivariate analysis was carried out using Fischer-Exact orChi-Square test. Multivariate analysis was carried out usingChi-Square test. Multivariate analysis was carried out usingmultiple logistic regression (forward LR).multiple logistic regression (forward LR).

0 20 40 60 80 100

Age

0

10

20

30

40

Fre

que

ncy

Mean = 53.09Std. Dev. = 15.541N = 234

Histogram

RESULTSRESULTS

Figure 1Figure 1: The mean age was 53 ± 15 : The mean age was 53 ± 15 years old (range 15 to 94 years old).years old (range 15 to 94 years old).

Statistics

Age234

0

53.09

1.016

54.00

15.541

241.516

-.135

.159

79

15

94

Valid

Missing

N

Mean

Std. Error of Mean

Median

Std. Deviation

Variance

Skewness

Std. Error of Skewness

Range

Minimum

Maximum

635758

364241

73

87

79

22

8

17

5 4 4

4137

100

0

10

20

30

40

50

60

70

80

90

100

Percentage

Male

Fem

ale

Malay

Chine

se

Oth

ers

Sex Race Total

Demographics

Demographics Vs Histology Findings

atrophic

non-atrophic

Total

Figure 2:Figure 2: There were no differences in the prevalence of both atrophic and non- There were no differences in the prevalence of both atrophic and non-atrophic gastritis between the two genders . The Chinese had more atrophic atrophic gastritis between the two genders . The Chinese had more atrophic gastritis (22%). The Malays had more non-atrophic gastritis (87%). The gastritis (22%). The Malays had more non-atrophic gastritis (87%). The prevalence of CAG was 41%. prevalence of CAG was 41%.

Table 1Table 1: Indications of endoscopy, causes of gastritis and : Indications of endoscopy, causes of gastritis and medications before endoscopymedications before endoscopy

155 (66)

14 (6)

58 (67)

4 (5)

61 (63)

7 (7)

PPI

H2RA

Medications

20 (22)

18 (20)

18 (20)

8 (25)

7 (22)

4 (12.5)

6 (15)

5 (12.5)

11 (27)

NSAID

Antiplatelet

Previous gastric ulcers

Causes

149 (64)

37 (16)

54 (63)

15 (17)

57 (59)

20 (21)

Dyspepsia

Malaena

Indications

Total

N (%)

Non-atrophic

N (%)

Atrophic

N (%)

Variables

Legend: N=number, %=percentage, NSAID=non-steroidal inflammatory drugs, PPI=proton pump inhibitor, H2RA=histamine receptor blocker

Dyspepsia was the commonest symptom in both CAG and non-CAG. Chemical gastritis Dyspepsia was the commonest symptom in both CAG and non-CAG. Chemical gastritis (NSAID and antiplatelet) was more common in non-atrophic gastritis (47% VS 27.5%). (NSAID and antiplatelet) was more common in non-atrophic gastritis (47% VS 27.5%). Proton pump inhibitors were used in 66% of chronic gastritis prior to endoscopy.Proton pump inhibitors were used in 66% of chronic gastritis prior to endoscopy.

Figure 2:Figure 2: The prevalence of The prevalence of helicobacter pylorihelicobacter pylori was n=16 (7%). The was n=16 (7%). The histology test for histology test for helicobacter pylori helicobacter pylori appeared more sensitive than CLO test appeared more sensitive than CLO test in atrophic gastritis (n=7 VS n=1). in atrophic gastritis (n=7 VS n=1).

1

78

4 4

8

5

11

16

0

2

4

6

8

10

12

14

16

No of Patients

Atrophic Non-atrophic Total

Histology Findings

Helicobacter pylori Vs Histology Findings

H pylori CLOH pylori HistologyH pylori Both

RESULTS

Figure 3: There was a significant association between moderate atrophy with : There was a significant association between moderate atrophy with the risk of metaplasia (p=0.006). This was tested with multiple comparisons the risk of metaplasia (p=0.006). This was tested with multiple comparisons between different degree of atrophy and Bonferroni adjustment of p-value. between different degree of atrophy and Bonferroni adjustment of p-value. Moderate atrophy increased the risk of metaplasia by 21%.Moderate atrophy increased the risk of metaplasia by 21%.

93 7

97 3

79 21

0% 20% 40% 60% 80% 100%

Percentage

No

Mild

ModerateA

tro

ph

y

Deg

ree o

f

Atr

op

hy

Association between Atrophic Gastritis and risk of Metaplasia

Metaplasia NoMetaplasia Yes

0.0060.002Mild Vs Moderate

0.0690.023No Vs Moderate

0.5430.181No Vs Mild

Bonferroni AdjustmentP valueComparisons

Figure 4Figure 4: There was significant association between moderate atrophy with : There was significant association between moderate atrophy with the risk of dysplasia (p=0.003). the risk of dysplasia (p=0.003). This was tested with multiple comparisons This was tested with multiple comparisons between different degree of atrophy and Bonferroni adjustment of p-value. between different degree of atrophy and Bonferroni adjustment of p-value. Moderate atrophy increased the risk of dysplasia by 18%.Moderate atrophy increased the risk of dysplasia by 18%.

97 3

99 1

82 18

0% 20% 40% 60% 80% 100%

Percentage

No

Mild

Moderate

Atr

op

hy

Deg

ree o

f A

tro

ph

yAssociation between Atrophic Gastritis and

risk of Dysplasia

Dysplasia No

Dysplasia Yes

<0.003<0.001Mild Vs Moderate

<0.003<0.001No Vs Moderate

1.00.687No Vs Mild

Bonferroni AdjustmentP valueComparisons

LOGISTIC REGRESSION ANALYSISLOGISTIC REGRESSION ANALYSIS

Variables in the Equation

-2.872 1.163 6.099 1 .014 .057 .006 .553

-.405 .913 .197 1 .657 .667

Hpylori(1)

Constant

Step1

a

B S.E. Wald df Sig. Exp(B) Lower Upper

95.0% C.I.for EXP(B)

Variable(s) entered on step 1: Hpylori.a.

Table 3: Logistic regression analysis (Forward LR) of factors (age, sex, race, causes, helicobacter pylori and atrophy) associated with the risk of Metaplasia

Variables in the Equation

-3.258 1.089 8.951 1 .003 .038 .005 .325

.405 .913 .197 1 .657 1.500

Hpylori(1)

Constant

Step1

a

B S.E. Wald df Sig. Exp(B) Lower Upper

95.0% C.I.for EXP(B)

Variable(s) entered on step 1: Hpylori.a.

Table 4: Logistic regression analysis (Forward LR) of factors (age, sex, race, causes, helicobacter pylori and atrophy) associated with the risk of Dysplasia

Symmetric Measures

-.056 .019 -1.418 .156

234

KappaMeasure of Agreement

N of Valid Cases

ValueAsymp.

Std. Errora

Approx. Tb

Approx. Sig.

Not assuming the null hypothesis.a.

Using the asymptotic standard error assuming the null hypothesis.b.

234183 (78)51 (22)Total

227176 (77)51 (22)Abnormal

77(100)0 (0)Normal

TotalAbnormalNormalN (%)

Endosocopic

findings

Histology Findings

Table 2: Correlation between histological gastritis and endoscopic findings

Normal histology was seen in 22% of abnormal endoscopic findings. The agreement between histological gastritis and endoscopic findings was poor.

05 2 0

30

60

19

1

19

48

31

1 49

3 1

0

10

20

30

40

50

60

No

of P

atie

nts

No Mild Moderate Severe

Endoscopic severity

Endoscopic severity VS histological severity

No

Mild

Moderate

Severe

Figure 6Figure 6: Most endoscopic and histological gastritis were mild to moderate in : Most endoscopic and histological gastritis were mild to moderate in severity. The agreement was however poor with kappa=0.06.severity. The agreement was however poor with kappa=0.06.

Symmetric Measures

.061 .042 1.478 .140

233

KappaMeasure of Agreement

N of Valid Cases

ValueAsymp.

Std. Errora

Approx. Tb

Approx. Sig.

Not assuming the null hypothesis.a.

Using the asymptotic standard error assuming the null hypothesis.b.

CONCLUSIONCONCLUSION

The prevalence for chronic atrophic gastritis in theThe prevalence for chronic atrophic gastritis in the

East coast of peninsular Malaysia was 41%. East coast of peninsular Malaysia was 41%.

Moderate atrophy was significantly related to the riskModerate atrophy was significantly related to the risk

of intestinal metaplasia and dysplasia. of intestinal metaplasia and dysplasia.

CONCLUSIONCONCLUSION

Despite the low prevalence of Despite the low prevalence of Helicobacter pylori Helicobacter pylori inin

this regionthis region, , it was the most important risk forit was the most important risk for

metaplasia and dysplasia in chronic atrophicmetaplasia and dysplasia in chronic atrophic

gastritis. gastritis.

- “ No - “ No helicobacter pylori helicobacter pylori No Cancer” No Cancer”

CONCLUSIONCONCLUSION

There was a poor agreement between the severity ofThere was a poor agreement between the severity of

endoscopic and histological gastritis.endoscopic and histological gastritis.

Follow-up should be recommended for chronicFollow-up should be recommended for chronic

gastritis with moderate atrophy and gastritis with moderate atrophy and helicobacter pylorihelicobacter pylori

using a standardized protocol for biopsy.using a standardized protocol for biopsy.