Peptic Ulcer Disease

Question 1

Peptic Ulcer Disease?

Answer 1

An excoriated segment of
the GI mucosa, typically in
the stomach (gastric
ulcer) or first few cm of
the duodenum (duodenal
ulcer), which penetrates
through the muscularis
mucosae

Question 2

What are possible causes of PUD

Answer 2

H. pylori infection
 found in the majority of cases
 over 90% of duodenal ulcer patients and 70% of
gastric ulcer patients infected (O’Connor, 1994)
Drug use
 oral corticosteroids (Messer et al, 1983)
 aspirin (Lanas et al, 1992)
 NSAIDs (Langman et al, 1994)
Lifestyle Factors
 stress (Levenstein et al, 1999)
 smoking (Kurata and Haile, 1984)
 alcohol abuse (Zelickson et al, 2011)
 low dietary fibre intake

Question 3

PUD - Prevalence?

Answer 3

Meta-analysis looking at US data (Sobieraj et al, 2011)
◦ prevalence of PUD 3.3%
◦ lifetime prevalence 13.8%
Prevalence appears to be decreasing
worldwide
- Colonises ~50% of the world’s inhabitants!

Question 4

Helicobacter pylori
What is it?

Answer 4

◦ Gram-negative, microaerophilic
bacterium
◦ colonises the gastric mucosa and
sometimes the duodenal mucosa
 generally lives in mucus layer
 more rarely attaches to mucosal cells
Identified and linked as a cause
of active gastritis in 1983

Question 5

Helicobacter pylori
Presence associated with:?

Answer 5

 dyspepsia symptoms (Ford et al, 2022)
 gastritis (Yang & Hu, 2022)
 duodenal ulcer (Cekin et al, 2012)
 gastric ulcer (Uyanikoğlu et al, 2012)
 increased risk of gastric
adenocarcinoma (Correa & Piazuelo, 2011)
 increased risk of gastric B-cell
lymphoma (Hu et al, 2016)
◦ Virulence of strains differs

Question 6

Helicobacter pylori – Diagnosis, how?

Answer 6

Test Sensitivity Specificity Advantages Disadvantages
Serology 85–92% 79–83% Only test not influenced by PPI or antibiotic use Cannot confirm cure
Urea Breath Test 95% 96% Confirms cure Accuracy affected by PPI and antibiotic use
Fecal antigen testing 95% 94% Confirms cure Accuracy affected by PPI and antibiotic use
Rapid urease test 98% 99% Inexpensive, confirms cure Requires endoscopy, less accurate after treatment or after PPI use
Histology >95% >95% Permits visualization, confirms cure Requires endoscopy, affected by PPI and antibiotic use
Culture 70–90% 100% Allows determination of antimicrobial sensitivity, confirms cure Requires endoscopy, result takes several days, affected by PPI and antibiotic use

Question 7

Helicobacter pylori
Problems with Conventional Treatment:??

Answer 7

 Increasing AB resistance and decreasing efficacy (Graham & Fischback,
2010)(Zou et al, 2020)
 Significant short-term side effects (Wong et al, 2006)
 >33% of subjects experience se
 dizziness; nausea/vomiting; loose stools/diarrhoea
 Potential long-term consequences of AB use
 ↑ risk of a range of cancers (Petrelli et al, 2019)
 ↑ risk of depression (Lurie et al, 2015)
 ↑ risk of cognitive decline & dementia (Mehta et al, 2022)(Kim et al, 2022)
 Substantial short-term & long-term alterations to the
microbiota (Chen et al, 2022)(Liou et al, 2019)
 extinction of Oxalobacter formigenes from microbiota
——–key oxalate eating bacteria in colon; problems if incr oxalate absorption

Question 8

Helicobacter pylori – To treat or not
to treat?

Answer 8

Given H. pylori’s potential protective effect
in GORD, should we eradicate it when
found upon testing?

Question 9

Helicobacter pylori – Eradication
using Natural Medicines list

Answer 9

 Foods & Drinks
 Probiotics
 Herbal medicines
 Nutritional Agents

Question 10

Treating Helicobacter pylori – Foods & Drinks

Answer 10

1. Green tea: inhibits growth, prevents adhesion of H. pylori to mucoseal cells
2. Cranberries: inhibits growth, inhibits attachment to gastric cells
3. Cark grapes
4. Berries
   ◦ Strongest
    Elderberries - most
    Bilberries
    Blueberries
    Cranberries - least
   ◦ Weaker
    Strawberries
    Raspberries

Question 11

The main cause of gastrooesophageal reflux is:

High gastric acid output
Low gastric acid output
Lower esophageal sphincter incompetence
Cigarette smoking

Answer 11

Lower esophageal sphincter incompetence Correct!

Question 12

Melatonin helps in GERD by:

Inhibiting gastric acid output
Inhibiting nitric oxide biosynthesis; thereby reducing the
rate of transient
relaxations in the LES
Strengthening the LES
All of the above
None of the above

Answer 12

All of the above

Question 13

Helicobacter pylori – Mucus layer
Can we decrease the viscosity of the
mucous layer to facilitate greater contact
between the antimicrobial agents and HP?

Answer 13

N-acetyl cysteine (NAC)
 Mucolytic agent (Zala et al, 1994)
 reduces gastric barrier mucus thickness by ~75%
 reduces mucus viscoelasticity
 600 mg NAC bid (concurrent with AB)
 improved AB eradication rate from 41% vs 71% (Zala et al, 1994)
 400 mg tds (concurrent with AB)
 improved AB eradication rate from 23% to 50% (Gurbuz et al, 2005

Question 14

Helicobacter pylori – Probiotics?

Answer 14

IN ISOLATION
1. Lactobacillus acidophilus NAS strain (Mrda et al, 1998)
 open-label trial
 daily ingestion over a 2-month period resulted in
eradication of H. pylori in 43% of subjects
2.Lactobacillus reuteri MM53
-  treatment with omeprazole + MM53 eradicated H.
pylori in 60% of subjects after 30 days compared to
none in the placebo + omeprazole group
3. Lactobacillus acidophilus LA5 & Bifidobacterium
lactis Bb12
 daily ingestion for 6 weeks resulted in:
 decreased H. pylori density (P=0.006) and gastritis (P=0.015)
on the antrum, as well as decreased urea breath test values
compared to baseline (P<0.05)
 decreased urease activity (P<0.0001)
4. Saccharomyces cerevesiae var boulardii Biocodex
strain
 daily ingestion over an 8-week period resulted in
eradication of H. pylori in 12% of subjects

Pre-Antibiotic therapy
1. ◦ Lactobacillus acidophilus LA5 & Bifidobacterium
lactis Bb12
4 weeks pretreatment with probiotics improved H.
pylori eradication rates from 71 to 85% (P<0.05)
after quadruple therapy in subjects in which triple
therapy had failed
 side effects also reduced

With Antibiotic therapy:
1. Lactobacillus reuteri MM53
-  concurrent administration for 10 days and taken for
another 10 days following AB
 reduction in GI symptom scores in MM53 grp
 4.1 vs 6.2 (P<0.01) during eradication therapy
 3.2 vs 5.8 (P<0.009) at end of follow-up

Question 15

In human clinical trials, which agent(s) appears to be the most effective in
eradicating H. pylori when used without antibiotics?
Mastic gum (Pistacia lentiscus var Chia)
Rhubarb root (Rheum emodi)
Black seed (Nigella sativa)
Vitamin C
Vitamin E and C

Answer 15

Black seed (Nigella sativa)

Question 16

Herbs/nutritional agents used to fight H. pylori that have been tested in humans:

Answer 16

1. Nigella sativa (ground seeds)
   grp 1 - Triple therapy for 7 days
    grp 2 – omeprazole + 1g NS caps (500 mg bd; after meals;40 d)
    grp 3 – omeprazole + 2g NS caps (1000 mg bd; after meals; 40 d)
    grp 4 - omeprazole + 3g NS caps (1500 mg bd; after meals; 40d)
    Eradication rates at 40 days
    grp 1 – 83%
    grp 2 – 48%
    grp 3 – 67% (not sig. diff than triple therapy)
    grp 4 – 48%
   all groups showed significant improvements in GI S&S
2. Broccoli sprouts
   - subjects randomly assigned to receive:
    either 14g, 28g, or 56g of fresh broccoli sprouts twice daily on
   an empty stomach for 7 days
   -Day 8 –
    7/9 patients (78%) were H. pylori –ve on stool antigen
    Day 35 -
    6/9 patients (67%) were H. pylori –ve on stool antigen
    on breath testing:
    2 were –ve, 2 were +ve & 2 were indeterminate (gastric
   biopsy showed –ve) = 44% confirmed eradication rate
3. Mastic Gum (Pistacia lentiscus var Chia)
   Dabos et al, 2010
    RCT ; n=52
    350 mg tid for 14 days – 31% eradication
    1000 mg tid for 14 days - 39% eradication
    Triple therapy for 10 days - 77% eradication
    Bebb et al, 2003
    OL; n=9
    1000 mg 4x/day for 14 days – no effect on H. pylori status of
   any subject
4. vitamin C
   R, OL; n=312 (Zojaji et al, 2009)
    Quadruple therapy alone for 14 days – 49% eradication
    Quadruple therapy + vitamin C (500 mg/day) for 14 days – 78%
   eradication (P<0.0001)
    R, OL; n=60 (Jarosz et al, 1998)
    5g/day ascorbic acid or antacids for 4 weeks – 30% eradication
   rate in vit C grp vs 0% in antacid group (P=0.01)
    vitamin C administered in 4 divided doses (2g, 1g, 1g, 1g)
5. Vitamin C plus E
    R, OL; n=120 (Sezikli et al, 2011)
    Triple therapy alone for 14 days – 43% eradication rate
    Triple therapy + vitamin C (500 mg bid) and vitamin E (200 IU bid)
   for 14 days – 64% eradication rate (P<0.005)
    R, OL; n=200 (Sezikli et al, 2012)
    Triple therapy alone for 14 days – 45% eradication rate
    Triple therapy for 14 days + vitamin C (500 mg bid) and vitamin E
   (200 IU bid) for 30 days – 83% eradication rate (P<0.005)
6. Zinc Carnosine
    R,OL; n=66
    Triple therapy for 7 days – 77% eradication
    Triple therapy + zinc carnosine (150 mg bid) for 7 days – 94%
   eradication (P<0.05)
7. Lactoferrin
    Meta-analysis of 9 trials (n=1343)
    all of which examined the efficacy of bovine lactoferrin in
   combination with AB therapy (triple or quadruple therapy)
    all used 200 mg lactoferrin bid
    Pooled H. pylori eradication rates were 86.6% in the
   +lactoferrin group vs 74.4% in the AB only group
    Occurrence of total side effects was 9.1% in +lactoferrin
   group vs 16.3% in the AB only group

Question 17

Supplements/agents that can promote Ulcer healing (gastric/duodenal)

Answer 17

1. Melatonin - 21 days
2. L-tryptophan - 21 days
3. Zinc carnosine - only animal studies
4. Cabbage juice 7 (gastric) to 10 (duodenal) days
5. Mastic gum
    1000 mg bid or placebo for 14 days in patients with duodenal
   ulcer
    symptomatic relief obtained by 80% of subjects in mastic grp vs 50% in
   control grp (P<0.01)
    endoscopically-proven healing in 70% of subjects in mastic grp vs 22%
   in placebo (P<0.01)
6. Licorice (Glycyrrhiza glabra)

Question 18

Herbal vulneraries for peptic ulcer disease?

Answer 18

◦ Symphytum officinale
◦ Althaea officinalis root
◦ Calendula officinalis flowers
◦ Achillea millefolium aerial parts

Question 19

Potential exaerbatin ggactor