An Effective Management

of Peptic Ulcer Disease

Somchai Leelakusolvong, M.D.

Gi Division, Siriraj Medical School
Siriraj Endoscopy Center
02-02-2017
 An Effective Management
of Peptic Ulcer Disease (PUD)
Objective:
Tell the current management of
peptic ulcer disease (PUD)
Role of PPIs for management of PUD
Current recommendations of H pylori
eradication
 An Effective Management
of Peptic Ulcer Disease (PUD)
A 65-year-old male underlying DM, HT and old CVA
presented with acute abdominal pain in the epigastric
region for 2 weeks following the intermittent pain for
months after taking baby ASA
The pain was reported as extreme, remitting, sharp and
cramping, and radiating to back.
He denied fever or chills, and reported that eating
influenced the pain.
He had vomited once but denied the appearance of blood
with black stool but no hematochezia.
He drunk 3-4 glasses of beer per night with a 10 pack-year
tobacco.
 An Effective Management
of Peptic Ulcer Disease (PUD)
PE: mild anemia
Abd: mild tender at epigastric
region

Dx: Peptic ulcer bleeding

 Causes of UGIB
526 consecutive patients with overt UGIB admitted to Siriraj Hospital during 2007-2009

ulcer46% gastritis24% varices20% PHG 7%

MWT 3% cancer2% Dieulafoys 1% Angiodysplasia 0.2%

Charatcharoenwitthaya P, Pausawasdi N, Leelakusolvong S, et al. World J Gastro 2011

 An Effective Management
of Peptic Ulcer Disease (PUD)
The EGD was underwent with
finding as following picture:

Dx: Gastric ulcer

Rx: Biospy was done with positive UBT for H pylori testing
 Management of PUD:
INITIAL MANAGEMENT
Eradication of Helicobacter pylori
is associated with higher healing rates
Withdrawal of offending or contributing
factors
avoid NSAIDs
Avoid contributing factors (eg, treating
medical comorbidities, poor nutritional
status, ischemia)
smoking cessation
limit alcohol intake
Malfertheiner P, et al. Maastricht V Gut 2016
 Management of PUD:
Antisecretory therapy
Choice and duration of therapy
varies based on the
ulcer characteristics
risk factors for recurrent peptic ulcer
disease (continued NSAID use, failure to
eradicate H. pylori)
The presence of ulcer complications
(bleeding, gastric outlet obstruction,
ulcer penetration, perforation)
Malfertheiner P, et al. Maastricht V Gut 2016
PPI for Healing NSAID-associated
Gastric Ulcers
 PPI for Gastric ulcer
Overall healing rate of different PPIs for GU
Meta-analysis in 2002

Omeprazole 20 mg
Lansoprazole 30 mg
Rabeprazole 20 mg
Pantoprazole 40 mg

Salas M, et al. BMC Gastroenterol. 2002;2:17.

 PPI for Duodenal ulcer
DU healing at 4 weeks head-to-head trials

McDonagh MS, Carson S, Thakurta S. Drug class review:

Proton pump inhibitors. Update 5. 2009.
 Choice and Duration of PPI
for GU and DU
H pylori-positive ulcer
-Uncomplicated DUs
PPI 10-14 D (with ATB for Hp)
No additional PPI if they are asymptomatic
Eradication of H. pylori even without concurrent acid
suppression therapy heals >90% of DUs
-Complicated DUs
PPI for 4-8 weeks
-GUs
PPI for 8-12 weeks
Discontinue PPI only after ulcer healing has been confirmed by
upper endoscopy
Lam SK, et al. Gut. 1997;41(1):43
Sung JJ, et al. N Engl J Med. 1995;332(3):139
Buckley M, et al. Ir J Med Sci. 1996;165 Suppl 5:1
Gisbert JP, et al. Aliment Pharmacol Ther. 2004;19(6):617
 Choice and Duration of PPI
for GU and DU
-Confirm cure of H. pylori infection after > 4 wks of
eradication therapy
-NSAID-induced ulcer
PPI for > 8 wks
In patients with peptic ulcers who need to remain on
NSAIDs or ASA, maintenance PPI should be considered
-Non-H. pylori, non-NSAID ulcers
suggest PPI 4-8 wks based on the ulcer location (gastric
or duodenal) and the presence of complications

Lam SK, et al. Gut. 1997;41(1):43

Sung JJ, et al. N Engl J Med. 1995;332(3):139
Buckley M, et al. Ir J Med Sci. 1996;165 Suppl 5:1
Gisbert JP, et al. Aliment Pharmacol Ther. 2004;19(6):617
 Management of PUD: Efficacy

PPIs > H2RA

PPIs + H2RAs adds to cost without

enhancing healing

Antacids and sucralfate

not routinely recommended to treat
peptic ulcers

Yeomans ND, et al. N Engl J Med. 1998;338(11):719.

 Management of PUD:
ENDOSCOPY AFTER INITIAL THERAPY
Duodenal ulcers
low risk of malignancy
Not routinely recommend to repeat upper
endoscopy
Gastric ulcers
The decision to repeat endoscopy should be
individualized

Eckardt VF, et al. Cancer. 1992;69(2):301.

Stephens MR, et al. Br J Surg. 2005;92(7):840.
 Management of PUD:
ENDOSCOPY AFTER INITIAL THERAPY
Gastric ulcers
Suggest a surveillance endoscopy after 12 wks of PPI in
GUs with one of the following:
Symptoms despite PPI Rx
Unclear etiology
Giant ulcer (>2 cm)
Not performed or inadequate sampling on the index upper endoscopy
(total of <4 biopsies obtained from 4 quadrants of the ulcer and
additional biopsies of the edges with jumbo forceps if there are
endoscopic features of a malignant GU)
Suspicious for malignancy on index upper endoscopy (mass lesion,
elevated irregular ulcer borders, or abnormal adjacent mucosal folds)
Initial endoscopy was performed for bleeding
Risks factors for gastric cancer

Hosokawa O, et al. Endoscopy. 2001;33(4):301.

Eckardt VF, et al. Cancer. 1992;69(2):301.
Stephens MR, et al. Br J Surg. 2005;92(7):840.
 Management of PUD:
REFRACTORY ULCERS
A refractory PUD is defined = an
endoscopically proven ulcer > 5 mm in
diameter that does not heal after 12 wks of PPI

Approximately 5-10% are refractory to initial

PPI therapy

Gisbert JP, et al.Aliment Pharmacol Ther. 2005 Apr;21(7):795-804.

Dammann HG, et al. Aliment Pharmacol Ther. 1993;7 Suppl 2:17
Bianchi Porro G, et al. Drugs. 1991;41(1):38. .
 Preventing Gastric Ulcer
Recurrence while on Aspirin

Lai KC, et al. N Engl J Med 2002;346:2033

 Management of PUD:
MAINTENANCE THERAPY
To continue maintenance with a PPI in the
following high-risk subgroups of patients
Giant (>2 cm) ulcer and age >50 years or multiple co-
morbidities
H. pylori-negative, non-NSAID ulcer disease
Refractory peptic ulcer
Failure to eradicate H. pylori
Frequently recurrent peptic ulcers (>2 recurrences a
year)
Continued NSAID use

Gisbert JP, et al.Aliment Pharmacol Ther. 2005 Apr;21(7):795-804.

Dammann HG, et al. Aliment Pharmacol Ther. 1993;7 Suppl 2:17
Bianchi Porro G, et al. Drugs. 1991;41(1):38. .
Management of H pylori
 Maastricht V
Statement 1
H. pylori gastritis is an infectious disease
irrespective of symptoms and complications

Level of Evidence: 1B
Grade of Recommendation: A

Malfertheiner P, et al. Maastricht V Gut 2016

 H pylori and NSAIDs
Statement 7: H pylori infection is associated with an increased
risk of uncomplicated and complicated gastroduodenal ulcers
in NSAID and low-dose aspirin (acetosalicylic acid (ASA))
users.
Evidence level: 2a Grade of recommendation: B
Statement 8: H pylori eradication is beneficial before starting
NSAID treatment. It is mandatory in patients with a peptic
ulcer history
Evidence level: 1b Grade of recommendation: A
However, H pylori eradication alone does not reduce the
incidence of gastroduodenal ulcers in patients already
receiving long-term NSAID treatment. They require continued
PPI treatment as well as eradication treatment.
Evidence level: 1b Grade of recommendation: A
Malfertheiner P, et al. GUT 2012:61;646-664
Thailand Consensus on
Helicobactor pylori
Management 2015
 Diagnosis statements
Statement 1: Helicobacter pylori test was
recommended in patients who were
Peptic ulcer diseases and gastric erosions
Chronic NSAIDs/ASA users with history of peptic ulcer
diseases or multiple risk factors of upper GI bleeding
Marginal zone B-cell lymphoma (MALT type)
Dyspeptic patients who do not response to anti-secretory
drug
Family history of gastric cancer in 1st degree relative
Gastric cancer

Level of evidence 1b
Grade of recommendation A
Agreement 87%
 Diagnosis statements
Statement 2:
-Pretreatment diagnosis of active H.pylori can be
made by an endoscopy-based diagnosis, UBT or
stool Ag test.
-PPI should be discontinued at least 2 weeks
before the test.
-Urease test is the most practical test in Thailand.

Level of evidence 2b
Grade of recommendation B
Agreement 100%
 Diagnosis statements
Statement 3: Serology test is not
recommended to detect active H.
pylori infection.

Evidence level 1C
Grade of recommendation: A
Agreement 100%
 Treatment statements
Statement 1: 10-14 days triple therapy results
in 80% eradication rate. Either 10 days
sequential therapy or 10 days concomitant
therapy is alternative first-line H pylori
eradication in Thailand.

Evidence level 2b
Grade of recommendation B
Agreement 100%
 Eradication rate of H.Pylori is decreasing due to Antimicrobial resistance especially

Clarithromycin.

Therapeutic Regimen

Prevacid 30 mg. + Amoxicillin 1 g. BID for 5 days

Prevacid 30 mg. + Metronidazole 500 mg. BID + Clarithromycin 1 g. for 5 days

Eradication rate is 95% (97.2% in Clarithromycin-sensitive and 57.1% in Clarithromycin-resistance)

31
 Clarithromycin resistance rate in Thailand
from 5 teaching hospitals is vary from 5-
29.20% (median=13.8%)1
7-day PPI- based triple therapy ER in
Thailand is < 80%
Recent study in Thailand, 14- day PPI-
based triple therapy provided ER of 85%.
10-day sequential therapy achieved ER
>90%.
10-day concomitant achieved ER = 96.4%.
Mahachai V, Vilaichone RK. Helicobacter research 2011, Pittayanon R, et al. DDW 2015,
Sirimontaporn N, Am J Gastro 2010, Mahachai V, et al. JGH 2011, Konchayanun C, et al.
Helicobacter 2012
 Treatment statements
Statement 2: After failure of first-line therapy,
- either
bismuth-containing quadruple therapy
should be used as second-line treatment
or
Triple therapy (PPI + levofloxacin +
amoxicillin) x 14 D
Evidence level: 1a
Grade of recommendation: A
Agreement 100%
 Recent meta-analysis of RCTs confirmed
10-day levofloxacin-containing triple
therapy as a second-line therapy

Bismuth-containing quadruple therapy

has advantage of using bismuth which
rarely resistance reported.

Di Caro S, et al. WJG 2012, Chung JW, et al. Helicobacter 2011

 Quadruple therapy
Bismuth-containing quadruple therapy
PPI + bismuth subsalicylate (524 mg QID) + two
antibiotics (eg, metronidazole 250 mg QID
and tetracycline 500 mg QID) x 14 days.
If tetracycline is not available, doxycycline (100 mg
twice daily) may be substituted.
Quadruple non-bismuth therapy = Concomitant
therapy
PPI + amoxicillin + metronidazole + clarithromycinx14 D
FOR
used as initial if clarithromycin resistance is 15%, or in patients with
recent or repeated exposure to clarithromycin or metronidazole
as a second-line treatment in patients who fail initial triple therapy

McColl KE, et al. NEJM 2010;362:1597

 Maastricht V
Statement 4
In areas of high (>15%) clarithomycin
resistance
bismuth quadruple or
non-bismuth quadruple concomitant
(PPI + amoxicillin +clarithromycin + a nitroimidazole)
In areas of high dual clarithromycin and
metronidazole resistance,
bismuth quadruple therapy is the recommended first-line
treatment
Level of Evidence: 2b (moderate)
Grade of Recommendation: B (strong)

Malfertheiner P, et al. Maastricht V Gut 2016

Treatment statements
Statement 3: After failure of second-line
therapy, if possible, antimicrobial
susceptibility testing should be done
for appropriate regimen.

Evidence level: 2c
Grade of recommendation: B
Agreement 87%
 Antibiotic resistant H. pylori in SEA and
South Asian countries (n=682): 2010-2013
Thailand Laos Bhutan Myanmar
Antibiotics
(n=400) (n=119) (n=111) (n=52)
Amoxicillin
(MIC 0.25 g/ml ) 5.2% - 0% 0%
Clarithromycin
(MIC 1 g/ml) 3.7-15% 12.6% 0% 0%
Metronidazole
(MIC 8 g/ml ) 36% - 82.9% 36.5%
Tetracycline
(MIC 1 g/ml ) 1.7% - 0% 0%
Ciprofloxacin
(MIC 1 g/ml ) 7.7% 13.4% 2.7% 5.8%
Levofloxacin
(MIC 1 g/ml ) 7.2% 13.4% 2.7% 5.8%
V. Mahachai, T. Ratanachu-ek, T. Myint3, R. Pittayanon, Y. Yamaoka5,, L. Tshering, S. Vannarath, R. Vilaichone. EHSG 2014,
Rome, Italy
H. pylori antibiotic resistance in Europe
(2008-2009)
ATB No. of Resistant % Resistant
Clarithromycin 332 17.5%

Amoxycillin 14 0.7%

Levofloxacin 267 14.1%

Tetracyclin 17 0.9%

Rifabutin 22 1.1%

Metronidazole 661 34.9%

Megraud F, et al. GUT 2013

Treatment after Multiple Failures
Furazolidone 100 mg TID +
Tetracycline 500 mg QID + Bismuth 2
tabs QID + PPI BID x 14 days (ER -80%)

Rifabutin 150 mg BID + Amoxy 1,000

mg BID and PPI BID x 14 days (ER=60-
70%)
 Maastricht V
Statement 10
The use of high dose PPI twice daily increases
the efficacy of triple therapy.

Level of Evidence: 1a (moderate) Grade of

Recommendation: A (strong)
*Level of Evidence: 2a (low) *Grade of
Recommendation: B (weak)

Malfertheiner P, et al. Maastricht V Gut 2016

 Algorithm for Management of
H. pylori in Thailand 2015
10-14 days STT: ER=80%

10-day Sequential or Concomitant regimens

14-day Quadruple Therapy 14-day Levo based triple therapy

Susceptibility testing (E-Test or Molecular test)

(Not to use Resistant antibiotics)

STT = standard triple therapy

 Eradication of H pylori
1st Line
Triple therapy 14 days
Sequential 10-14 days
Concomitant 10-14 days
2nd Line
Quadruple therapy (Bismuth or non-
bismuth base)
3rd Line
Need culture or molecular testing
Maastricht V: Hp 1st line eradication
in high CLR resistance (>15%)

Malfertheiner P, et al. Maastricht V Gut 2016

Thank you for your attention!!