Gastric Cancer, Gastritis and the Role of H. pylori Prof. Anthony Axon 1 The screen versions of these slides have full details of copyright and acknowledgements Gastric Cancer, Gastritis and the Role of H. pylori 1 Prof. Anthony Axon Centre for Digestive Diseases The General Infirmary Leeds World Organisation of Digestive Endoscopy 1 • Honorary Professor of Gastroenterology University of Leeds UK Professor Anthony Axon 2 • Past President BSG, ESGE, UEGF, OMED 2 Gastric cancer mortality is second only to lung cancer 3 3
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Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
1The screen versions of these slides have full details of copyright and acknowledgements
Gastric Cancer, Gastritis and the Role of H. pylori
11
Prof. Anthony AxonCentre for Digestive Diseases
The General InfirmaryLeeds
World Organisation of Digestive Endoscopy
1
• Honorary Professor of Gastroenterology University of Leeds UK
Professor Anthony Axon
22
• Past PresidentBSG, ESGE, UEGF, OMED
2
Gastric cancer mortality is second only to lung cancer
333
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
2The screen versions of these slides have full details of copyright and acknowledgements
Scanning EM of Helicobacter pylori colonising the gastric mucosa
444
Aims of this presentation
• Understand the natural history of Hp gastritis
• Review the evidence showing Hp to be an essential risk factor for gastric cancer
55
• Discuss the mechanisms involved in gastric carcinogenesis
• Appreciate why gastric cancer incidence varies
5
Transmission EM of Helicobacter pyloricolonising the gastric mucosa
66h- H. pylori on the apical and intracellular junctions of epithelial layer (arrowhead) L- gastric lumen
6
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
3The screen versions of these slides have full details of copyright and acknowledgements
Acute infection with H. pylori
• Usually occurs in childhood
• 7-10 day incubation
• Epigastric pain, flatulence and halitosis
77
• Anorexia with mucous vomiting
• Achlorhydria
• Symptoms resolve but the infection often persists
• Transmission unknown
7
Acute gastric inflammation immediately after infection with Helicobacter pylori
88Sobala et al., Gut (1991) 32(11) 1415-1418 8
Chronic gastritis with “activity” in the antrum some years following infection
99
Infected antrumNormal, healthy antrum
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
4The screen versions of these slides have full details of copyright and acknowledgements
Helicobacter gastritis before and one month after treatment
1010
Before treatment After treatment
Dixon, Current Diagnostic Pathology (1994) 1, 80-89
H. pylori gastric mucosa interactions
1111Cover and Blaser, Gastroenterology (2009) 136:1863-73
11
Development of atrophy and intestinal metaplasia after many years of infection
1212
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
5The screen versions of these slides have full details of copyright and acknowledgements
H. pylori, gastric atrophy and IM a multicentre study of 2455 patients
1313Asaka et al., Helicobacter (2001) 6 294-29913
Natural history of Hp Gastritis
• Acute infection (days)
• Chronic inflammation (years)
• Atrophy and intestinal metaplasia (severity and time)
1414
• Hypochlorhydria (loss of parietal cells)
• Overgrowth of oral and intestinal bacteria
• Hp disappears and serology reverts
14
Aims of this presentation
• Understand the natural history of Hp gastritis
• Review the evidence showing Hp to be an essential risk factor for gastric cancer
• Discuss the mechanisms involved
1515
• Discuss the mechanisms involved in gastric carcinogenesis
• Appreciate why gastric cancer incidence varies
15
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
6The screen versions of these slides have full details of copyright and acknowledgements
Meta analysis of nested studies showing association between Hp and gastric cancer
1616Helicobacter and cancer collaborative group; Gut (2001) 49: 347-353
Non Cardia (OR; 2.97) Cardia (OR; 0.99)
16
Gastric cancer and infection with H. pylori using IgG ELISA serology
76%
55%• Odds ratio of 3 is not high enough to draw the conclusion that Hp is a necessary factor
• All the nested studies used standard anti Hp ELISA serology80100120140160180200
er o
f pat
ient
s
1717
Cancer cases Normal controls
Odds ratio 2.2 (95% confidence interval 1.4-3.6)
Ekstrom et al., Gastroenterology (2001) 121: 784-791
• The studies may have underestimated the odds ratio
0204060
Hp - Hp + Hp - Hp +
Num
be
17
Gastric cancer and infection with H. pylori (corrected for CagA serology)
96%
57%
80100120140160180200
er o
f pat
ient
s
1818
Cancer cases Normal controls
Odds ratio 21.0 (95% confidence interval 8.3-53.4) Ekstrom et al., Gastroenterology (2001) 121: 784-791
020406080
Hp - Hp + Hp - Hp +
No. of patientsNum
be
18
Gastric Cancer, Gastritis and the Role of H. pylori
Prof. Anthony Axon
7The screen versions of these slides have full details of copyright and acknowledgements
Helicobacter gastritis and gastric acidity
High acid Low acid
191919
Type of gastritis and cancer risk, an 8 year prospective study of 1526 patients
Gastritis Relative riskAtrophy
None or mild 1.0Moderate 1.7 (0.8-3.7)Severe 4.9 (2.8 - 19.2)