1. De rol van de MDL-arts bij een bloedend ulcus
Ernst J. Kuipers
Afd. MDL
Erasmus MC Rotterdam

2. PUB; the role of the gastroenterologist
Endoscopic diagnosis and treatment
Stop ulcer bleeding
Reduce rebleeding risk
Risk assessment – rebleeding, mortality
Drug treatment
Determine the disease etiology
Causal treatment to prevent recurrence

4. Forrest classification
endoscopic Forrest class prevalence recurrent bleeding
appearance % (range) % (range)
active bleeding I (4-26) 55 (17-100)
non-bleeding
visible vessel IIa (4-35) 43 (0-81)
adherent clot IIb (0-49) 22 (14-36)
flat spot IIc (0-42) 10 (0-13)
clean base III (19-52) 5 (0-10)
Laine et al New Engl J Med 1994;331:717-27

6. Injectietherapie ulcera
injecties
adrenaline opl. 1:10 000
4 kwadranten rond
bloedingsplek +
ter plaatse bloedingsplek
geen
sclerosantia
alcohol X

8. Increasing the injected volume reduces the risk of rebleeding
Lin et al Gastrointest Endosc 2002;55:615-9
RCT n =155
epineprine 1:10, ml ml
recurrent bleeding % % (p<0.03)
Park et al Gastrointest Endosc 2004;60:875-80
RCT n = 72
epinephrine 10, ml ml
recurrent bleeding % % (p<0.05)

9. Does a second procedure improve outcome after epinephrine injection ??
Clavet et al Gastroenterology 2004;126:441-50
16 studies patients
epinephrine injection + thrombin (2)
sclerosant (5)
ethanol (3)
hemoclip (2)
fibrin glue (1)
heat probe (1)
bipolar coag. (1)
NYAG laser (1)

10. co-aptive thermocoagulation
gold probe

11. Conclusion additional endoscopic treatment after epinephrine injection
reduces
further bleeding (18 % > 11 %)
need for surgery (11 % > 8 %)
mortality ( 5 % > 3 %)
remarks
optimal additional method remains unknown
variable criteria for rebleeding
epinephrine volumes
policy second look endoscopy
more perforations combined therapy (6/558 vs 1/560; n.s.)

12. PUB; the role of the gastroenterologist
Endoscopic diagnosis and treatment
Stop ulcer bleeding
Reduce rebleeding risk
Risk assessment – rebleeding, mortality
Drug treatment
Determine the disease etiology
Causal treatment to prevent recurrence

13. Effect on rebleeding for IV PPIs1,2, but…
PPIs: Meta-analyses
Effect on rebleeding for IV PPIs1,2, but…
endoscopic treatment not standardised
differing patient populations (Asian vs non-Asian)
various PPIs and dosing regimens pooled
no reduction of mortality
publication bias3?
Leontiadis et al, BMJ 2005;330:568-70
Leontiadis et al, Aliment Pharmacol Ther 2005;21:
van Rensburg et al, Canadian DDW 2004, Abstract 147

14. Asian vs non-Asian populations
Clinical effects of PPIs in PUB studies from
Asia: positive1, 2
Europe/N America/S Africa: variable3, 4, 5
Different intragastric pH response to PPI therapy6:
H. pylori prevalence
Parietal cell mass
Drug metabolism
Khuroo et al, NEJM 1997;336:1054-8
Lau et al, NEJM 2000;343:310-6
Hasselgren et al, Scand J Gastroenterol 1997;32:328-33
van Rensburg et al, Canadian DDW 2004, Abstract 147
Jensen et al, Am J Gastroenterol 2004;99:S296, Abstract 903
Leontiadis et al, Aliment Pharmacol Ther 2005;21:

15. Recent Clinical Studies in PUB
Two large studies with i.v. pantoprazole
US1 – not completed
Non-US2 – inconclusive
No clarification as to role of IV PPI in PUB
Both randomized, controlled trials, comparing after successful endoscopic haemostasis:
high-dose i.v. infusion of pantoprazole vs ranitidine
study population: pts at high risk for rebleeding
primary variable: rebleeding during 72 h
Jensen et al, Am J Gastroenterol 2004;99:S296
van Rensburg et al, Canadian DDW 2004, Abstract 147

16. Non-US high dose pantoprazole iv study
Ranitidine
n (ITT)
618
626
Primary variable
11%
14%
p=0.083
- Forrest Ia
35%
p=0.0059
- Gastric ulcers
5.3%
10.6%
p=0.051
van Rensburg et al, Canadian DDW 2004, Abstract 147

17. 2nd look endoscopy ??
Idea
2nd assessment and therapy in patients with persistent
stigmata of recent bleeding in order to prevent rebleeding
randomized controlled trials
Villanueva 1994 n = 104 epinephrine
Saeed n= heat probe
Rutgeerts 1997 n = 536 fibrin glue
Messmann 1998 n = 105 epinephrine/thrombin-fibrin
Chiu n = 194 epinephrine/heat probe
meta-analyses
Marmo
Romagnuolo

18. Conclusion Second look endoscopy reduces rebleeding risk
No effect on risk of surgery and mortality
remarks
relatively small trials
to demonstrate effect on mortality trial size ~ !
NNT to prevent one rebleed: 16

19. PUB; the role of the gastroenterologist
Endoscopic diagnosis and treatment
Stop ulcer bleeding
Reduce rebleeding risk
Risk assessment – rebleeding, mortality
Drug treatment
Determine the disease etiology
Causal treatment to prevent recurrence

20. Etiology of ulcer disease
H. pylori infection
NSAID use
Idiopathic ulcer disease

21. The proportion of idiopathic ulcer disease among patients with PUB and the risk of recurrent bleeding in Hong Kong
Hung et al. Gastroenterology 2005; 129:

22. Idiopathic ulcer disease; etiologic considerations
Microbes
Drug use
Malignancy
Gastritis syndromes
Hyperacidic syndromes
Ischemia
Specific ulcer types
Systemic inflammation
Other conditions

23. Idiopathic ulcer disease; diagnostic considerations
Microbes - histology
Drug use - medical history
Malignancy - histology
Gastritis syndromes - histology + duodenal bx
Hyperacidic syndromes - gastrin, secretin test
Ischemia - vascular assessment
Specific ulcer types - endoscopy
Systemic inflammation - histology, colonoscopy
Other conditions - medical history

24. Persistence of PPI use by indication in a Dutch primary care population
Based on Erasmus Primary Care Cohort, N =
van Soest et al. Submitted

25. Conclusions Gastroenterologists have the primary role in PUB:
Initial diagnosis and treatment
Injection therapy
Multimodality treatment
PPI treatment
efficacy of high-dose continuous PPI remains to be proven in Caucasian populations
2nd look endoscopy not useful, unless perhaps in high-risk patients
Adequate diagnosis and treatment of underlying cause of ulcer disease mandatory