De rol van de MDL-arts bij een bloedend ulcus

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 18 (4-26) 55 (17-100) non-bleeding visible vessel IIa 17 (4-35) 43 (0-81) adherent clot IIb 17 (0-49) 22 (14-36) flat spot IIc 20 (0-42) 10 (0-13) clean base III 42 (19-52) 5 (0-10) Laine et al New Engl J Med 1994;331:717-27

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

8. Increasing the injected volume reduces the risk of rebleeding Lin et al Gastrointest Endosc 2002;55:615-9 RCT n =155 epineprine 1:10,000 5-10 ml 13-20 ml recurrent bleeding 31 % 15 % (p<0.03) Park et al Gastrointest Endosc 2004;60:875-80 RCT n = 72 epinephrine 10,000 15-25 ml 35- 45 ml recurrent bleeding 17 % 0 % (p<0.05)

9. Does a second procedure improve outcome after epinephrine injection ?? Clavet et al Gastroenterology 2004;126:441-50 16 studies 1673 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. 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;21:1055-61 • 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;21:1055-61

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 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 1996 n= 40 heat probe Rutgeerts 1997 n = 536 fibrin glue Messmann 1998 n = 105 epinephrine/thrombin-fibrin Chiu 2003 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 ~ 14000 ! 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: 1845-50

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 = 600.000 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