de rol van de mdl-arts bij een bloedend ulcus ernst j. kuipers afd. mdl erasmus mc rotterdam
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De rol van de MDL-arts bij een bloedend ulcus
Ernst J. Kuipers
Afd. MDL
Erasmus MC Rotterdam
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16-10-2001
1. Endoscopic diagnosis and treatment
• Stop ulcer bleeding
• Reduce rebleeding risk
2. Risk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
PUB; the role of the gastroenterologist
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Forrest classificationForrest classificationendoscopicendoscopic Forrest class prevalence recurrent bleeding Forrest class prevalence recurrent bleedingappearanceappearance % (range) % (range) % (range) % (range)
active bleedingactive bleeding I 18 (4-26) 55 (17-100)
non-bleedingnon-bleeding visible vesselvisible vessel IIa 17 (4-35) 43 (0-81)
adherent clotadherent clot IIb 17 (0-49) 22 (14-36)
flat spotflat spot IIc 20 (0-42) 10 (0-13)
clean baseclean base III 42 (19-52) 5 (0-10)
Laine et al New Engl J Med 1994;331:717-27
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injectiesadrenaline opl. 1:10 0004 kwadranten rondbloedingsplek + ter plaatse bloedingsplek
geensclerosantiaalcohol
X
XX
Injectietherapie ulcera
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Lin et al Gastrointest Endosc 2002;55:615-9RCT n =155epineprine 1:10,000 5-10 ml 13-20 mlrecurrent bleeding 31 % 15 % (p<0.03)
Park et al Gastrointest Endosc 2004;60:875-80RCT n = 72epinephrine 10,000 15-25 ml 35- 45 mlrecurrent bleeding 17 % 0 % (p<0.05)
Increasing the injected volume reduces the risk of rebleeding
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Does a second procedure improve outcomeafter epinephrine injection ??
Clavet et al Gastroenterology 2004;126:441-50
16 studies 1673 patientsepinephrine injection + thrombin (2)
sclerosant (5) ethanol (3) hemoclip (2) fibrin glue (1) heat probe (1) bipolar coag. (1) NYAG laser (1)
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gold probe
co-aptive thermocoagulation
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ConclusionConclusionadditional endoscopic treatment after epinephrine injectionreduces
further bleeding (18 % > 11 %) need for surgery (11 % > 8 %) mortality ( 5 % > 3 %)
remarksoptimal additional method remains unknown variable criteria for rebleeding epinephrine volumes policy second look endoscopymore perforations combined therapy (6/558 vs 1/560; n.s.)
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16-10-2001
1. Endoscopic diagnosis and treatmentEndoscopic diagnosis and treatment
• Stop ulcer bleedingStop ulcer bleeding
• Reduce rebleeding riskReduce rebleeding risk
2. Risk assessment – rebleeding, mortalityRisk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiologyDetermine the disease etiology
5. Causal treatment to prevent recurrenceCausal treatment to prevent recurrence
PUB; the role of the gastroenterologist
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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?
1. Leontiadis et al, BMJ 2005;330:568-702. Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-613. van Rensburg et al, Canadian DDW 2004, Abstract 147
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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
1. Khuroo et al, NEJM 1997;336:1054-82. Lau et al, NEJM 2000;343:310-63. Hasselgren et al, Scand J Gastroenterol 1997;32:328-334. van Rensburg et al, Canadian DDW 2004, Abstract 1475. Jensen et al, Am J Gastroenterol 2004;99:S296, Abstract 9036. Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-61
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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
1. Jensen et al, Am J Gastroenterol 2004;99:S2962. van Rensburg et al, Canadian DDW 2004, Abstract 147
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Non-US high dose pantoprazole iv study
Pantoprazole Ranitidine
n (ITT) 618 626
Primary variable 11% 14% p=0.083
- Forrest Ia 11% 35% p=0.0059
- Gastric ulcers 5.3% 10.6% p=0.051
van Rensburg et al, Canadian DDW 2004, Abstract 147
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2nd look endoscopy ??2nd look endoscopy ??
Idea2nd assessment and therapy in patients with persistent stigmata of recent bleeding in order to prevent rebleeding
randomized controlled trialsVillanueva 1994 n = 104 epinephrineSaeed 1996 n= 40 heat probeRutgeerts 1997 n = 536 fibrin glueMessmann 1998 n = 105 epinephrine/thrombin-fibrinChiu 2003 n = 194 epinephrine/heat probe
meta-analyses Marmo Romagnuolo
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ConclusionConclusion
Second look endoscopy reduces rebleeding riskNo effect on risk of surgery and mortality
remarksrelatively small trialsto demonstrate effect on mortality trial size ~ 14000 !NNT to prevent one rebleed: 16
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16-10-2001
1. Endoscopic diagnosis and treatmentEndoscopic diagnosis and treatment
• Stop ulcer bleedingStop ulcer bleeding
• Reduce rebleeding riskReduce rebleeding risk
2. Risk assessment – rebleeding, mortalityRisk assessment – rebleeding, mortality
3. Drug treatmentDrug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
PUB; the role of the gastroenterologist
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16-10-2001
H. pylori infection
NSAID use
Idiopathic ulcer disease
Etiology of ulcer disease
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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: 1845-50
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16-10-2001
Microbes
Drug use
Malignancy
Gastritis syndromes
Hyperacidic syndromes
Ischemia
Specific ulcer types
Systemic inflammation
Other conditions
Idiopathic ulcer disease; etiologic considerations
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16-10-2001
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
Idiopathic ulcer disease; diagnostic considerations
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Persistence of PPI use by indication in a Dutch primary care population
Based on Erasmus Primary Care Cohort, N = 600.000van Soest et al. Submitted
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 92 182 272 366 488 648
Treatment time (days)
Pro
po
rtio
n o
f p
ersi
sten
t u
sers
GERD Non-reflux dyspepsia H. pylori ass.diseases With NSAIDs With aspirin
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16-10-2001
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