Gastritis, peptic ulcer, and gastric cancer

1
Gastritis, peptic ulcer, and gastric cancer

• Roger Thomas MD PhD CCFP MRCGP
• Professor of Family Medicine
• Cochrane Collaboration Coordinator
• University of Calgary

2
Outline

• H pylori and NSAIDS are two key causes of stomach
  ulcers others are tobacco and alcohol, and
  medical/surgical stress
• Two types of gastric cancer
• Epidemiology of H pylori
• Role of H pylori in stomach cancer
• Eradication of H pylori
• Treatment of dyspepsia

3
What are the causes of stomach cancer?

• 2nd cause of cancer deaths for males for 4th for
  females worldwide
• 10-fold variation world wide, highest rates Japan
  and Korea
• Incidence of gastric cancer has fallen last 30
  years many Western countries
• Multifactorial causes H pylori, diet high in
  salt and N-nitroso compounds and low in fruit and
  vegetables, tobacco (OR 2.0), (and reflux and
  obesity for cardiac tumours)
• WHO classifies H pylori as Class I carcinogen
  

4
What are the 2 types of stomach cancer?

• Proximal cardia tumours
• related to pangastritis without atrophy
• more common in developed countries and
  individuals with higher socio-economic status
• Gastroesophageal reflux and obesity are important
  causes also H pylori

5
Two types of stomach cancer

• Distal gastric cancer
• related to gastric atrophy and intestinal
  metaplasia
• predominates in developing countries and
  individuals with lower socieconomic status
• Main risk factor is H pylori

6
What is the epidemiology of H pylori (Malatys
review)

• Prevalence varies by country 80 India, Saudi
  Arabia, Vietnam, Canada 30
• Acquired in childhood from family. Low childhood
  socioeconomic status is key determinant (Russian
  children 30, French 10)
• Transmission bodily fluids, vomit, water, food
• Increasing prevalence with age
• St. Petersburg and Japanese studies show
  individuals lose H pylori as socio-economic
  status and crowding improve

7
What are the effects of H pylori on the stomach?
(Reviews by Thomas)

• H pylori increase odds of stomach cancer by 2.1
  to 16.7 in various studies (average 5.9)
• 3 of individuals with H pylori progress to
  gastric cancer
• in distal gastric cancer progression over 30
  years is
• chronic superficial gastritis
• atrophic gastritis
• intestinal metaplasia
• dysplasia

8
What factors increase the risk of gastric cancer
from H pylori? (review by Thomas)

• Patient polymorphisms that express higher levels
  of cytokine IL-1ß
• Higher level of TNF-? (suppresses gastric acid
  production)
• Histocompatibility genotypes upregulated by H
  pylori that affect how epithelium responds to
  infection
• H pylori with gene sequencs cag (allows bacterial
  proteins to enter host cells) and vacA and babA2
  (permit adhesion of bacteria to cell surfaces)

9
What factors decrease the risk of non-cardia
gastric cancer?

• OR 95
  CI
• NSAIDS 0.72 0.58 to 0.89
• Aspirin 0.64 0.51 to 0.80
• Hypothesis use reduces production of Cox-1 and
  Cox 2
• Note There is more use of NSAIDS by H pylori
  patients

10
Treatment of H pylori reduces intestinal
metaplasia

• Wong randomised 1,630 patients with H pylori to
  eradication (0 gastric cancer after 7.5 years) ad
  placebo (6 gastric cancers)
• Leung randomised 587 patients to eradication or
  placebo and progression to intestinal hyperplasia
  was related to persistent H pylori infection, age
  gt 45 years, alcohol abuse and drinking well water

11
How sensitive and specific is Screening for H
pylori? (Review by Thomas)
Sensitivity specificityUrea
breath tests 97 95Stool tests
93 93

• Treatment
• Clarithromycin 500 mg Amoxicillin 1 g PPI bid
• Duration of therapy 7 days vs. 10 - 14 days

12
What is the effect of treating H pylori on
duodenal ulcers? (Cochrane review by Ford)

• H pylori is implicated in 90-95 of duodenal and
  70 of gastric ulcers
• Risk of persisting duodenal ulcer
• RR
  95CI
• H pylori eradication 0.66 0.58 to
  0.76
• ulcer healing drug vs. NNT 14 11 to 20
• ulcer-healing drug

13
What is the effect of treating H pylori on
gastric ulcers? (Cochrane review by Ford)

• Risk of persisting gastric ulcer
• RR
  95CI
• H pylori eradication 1.25 0.88 to
  1.76
• ulcer healing drug vs.
• ulcer-healing drug
• MODERATOR ANALYSIS Intention to treat analysis,
  difference in loss from treatment arms lt 10,
  blinding, not being a multicentre study, all
  reduced this RR
• HOWEVER we are interested in eradication of H
  pylori not just ulcer treatment so go ahead and
  treat

14
What are the costs and benefits of screening for
H pylori?

• A UK study showed that screening for H pylori in
  individuals who consulted for dyspepsia over two
  years reduced the costs of GI consultations
  enough to pay for the gastric cancer screening
  aspects of the H pylori screening

15
Nonaspirin NSAIDS and upper GI bleeding and
perforation (Hernández-Díaz review)

• Risk of upper GI bleed or perforation with NSAIDS
• RR
  95CI
• 3.8
  3.6 to 4.1
• Men 3.5
  3.1 to 4.0
• Women 5.1 4.6
  to 5.7

16
Risk of upper GI bleed or perforation with NSAIDS
(Hernández-Díaz review)

• By age (25-49 is reference group, RR 1)
• Age 50-59 1.8 1.5
  to 2.1
• 60-69 2.4
  2.2 to 2.7
• 70-80 4.5
  4.0 to 4.9
• gt80 9.2
  7.6 to 11.1

17
Risk of upper GI bleeding and perforation of with
low to medium doses nonaspirin NSAIDS
(Hernández-Díaz review)

• 
  RR 95CI
• Ibuprofen 1500 to 2400mg 2.1 1.6
  to 2.7
• Indomethacin 75 to 100 mg 3.0 2.2
  to 4.2
• Diclofenac 75 to 100 mg 3.1
  2.0 to 4.7
• Naproxen 500 to 1000mg 3.5 2.8
  to 4.3
• Piroxicam 20 mg 5.6
  4.7 to 6.7
• Risks are similar across NSAIDS when daily
  equivalent doses are equalised except for
  piroxicam

18
Conclusions

• H pylori and NSAIDS are the key causes of stomach
  ulcers. Other causes are alcohol, tobacco and
  stress ulcers
• H pylori is acquired in childhood from family
  members in situations of crowding (up to 80
  incidence in some developing countries)
• In 3 of individuals with H pylori there is
  progression to stomach cancer (particularly
  distal non-cardia)
• H pylori should be treated with clarithromycin
  500 mg and amoxicillin 1000 mg bid a PPI x 7
  days
• Reduction in the costs of treating dyspepsia over
  two years pays for H pylori screening programmmes
• NSAIDS should be given in low-intermediate doses
  and with caution in older individuals. (A stomach
  protector misprostol 200 mcg qid reduces risks of
  bleeding but 17 will complain of diarrhea)