Peptic Ulcer Disease Flashcards
Peptic Ulcer Disease?
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
What are possible causes of PUD
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
PUD - Prevalence?
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!
Helicobacter pylori
What is it?
◦ 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
Helicobacter pylori
Presence associated with:?
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
Helicobacter pylori – Diagnosis, how?
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
Helicobacter pylori
Problems with Conventional Treatment:??
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
Helicobacter pylori – To treat or not
to treat?
Given H. pylori’s potential protective effect
in GORD, should we eradicate it when
found upon testing?
Helicobacter pylori – Eradication
using Natural Medicines list
Foods & Drinks
Probiotics
Herbal medicines
Nutritional Agents
Treating Helicobacter pylori – Foods & Drinks
- Green tea: inhibits growth, prevents adhesion of H. pylori to mucoseal cells
- Cranberries: inhibits growth, inhibits attachment to gastric cells
- Cark grapes
- Berries
◦ Strongest
Elderberries - most
Bilberries
Blueberries
Cranberries - least
◦ Weaker
Strawberries
Raspberries
The main cause of gastrooesophageal reflux is:
High gastric acid output
Low gastric acid output
Lower esophageal sphincter incompetence
Cigarette smoking
Lower esophageal sphincter incompetence Correct!
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
All of the above
Helicobacter pylori – Mucus layer
Can we decrease the viscosity of the
mucous layer to facilitate greater contact
between the antimicrobial agents and HP?
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
Helicobacter pylori – Probiotics?
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
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
Black seed (Nigella sativa)
Herbs/nutritional agents used to fight H. pylori that have been tested in humans:
- 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 - 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 - 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 - 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) - 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) - 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) - 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
Supplements/agents that can promote Ulcer healing (gastric/duodenal)
- Melatonin - 21 days
- L-tryptophan - 21 days
- Zinc carnosine - only animal studies
- Cabbage juice 7 (gastric) to 10 (duodenal) days
- 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) - Licorice (Glycyrrhiza glabra)
Herbal vulneraries for peptic ulcer disease?
◦ Symphytum officinale
◦ Althaea officinalis root
◦ Calendula officinalis flowers
◦ Achillea millefolium aerial parts
Potential exaerbatin ggactor
