Treatment and prognosis in peptic ulcer bleeding.

Peptic ulcer bleeding is a frequent cause of admission. Despite several advances in treatment the 30-day mortality seems unchanged at a level around 11%. Use of risk scoring systems is shown to be advantageous in the primary assessment of patients presenting with symptoms of peptic ulcer bleeding. Studies performed outside Denmark have demonstrated that use of risk scoring systems facilitates identification of low-risk patients suitable for outpatient management. Nevertheless, these systems have not been implemented for routine use in Denmark. This is mainly explained by concerns about the external validity due to considerable inter-country variation in patients' characteristics. In recent years, transcatheter arterial embolization (TAE) has become increasingly used for achievement of hemostasis in patients with peptic ulcer bleeding not responding to endoscopic therapy. As rebleeding is associated with poor outcome TAE could, in theory, also be beneficial as a supplementary treatment in patients with ulcer bleeding responding to endoscopic therapy. This has not been examined previously. Several studies have concluded that peptic ulcer bleeding is associated with excess long-term mortality. These findings are, however, questioned as the studies were based on life-table analysis, unmatched control groups, or did not perform adequate adjustment for comorbidity. Treatment with blood transfusion is, among patients undergoing cardiac bypass surgery, shown to increase the long-term mortality. Despite frequent use of blood transfusion in treatment of peptic ulcer bleeding a possible adverse effect of on long-term survival has not been examined in these patients. The aims of the present thesis were: 1. To examine which risk scoring system is best at predicting need of hospital-based intervention, rebleeding, and mortality in patients presenting with upper gastrointestinal bleeding (Study I) 2. To evaluate if supplementary transcatheter arterial embolization (STAE) after successful endoscopic haemostasis improves outcome in patients with PUB with active bleeding, a non-bleeding visible vessel, or an adherent clot (Study II) 3. To examine the short- and long-term mortality in PUB compared to a matched control group including identification of predictive factors for adverse outcome, identification of underlying causes of death, and investigation of a possible association between treatment with blood transfusion and long-term mortality (Study III). Study I was conducted as a prospective validation study. During a two-year period 831 patients presenting with upper gastrointestinal haemorrhage were included. The study demonstrated that the Glasgow Blatchford Score (GBS) was superior to the other risk scoring systems at predicting need for hospital-based intervention. The GBS was found to be favourable for the assessment of Danish patients presenting with symptoms of upper gastrointestinal haemorrhage. According to the findings of Study 1 implementation of the GBS at a 1000-bed hospital would be associated with a 90.000 EUR annual saving through avoidance of admission of patients in very low risk of needing hospital-based intervention. None of the examined risk scoring systems were suitable for predicting risk of rebleeding or 30-day mortality. Study II was designed as a non-blinded, stratified, parallel group, randomized controlled trial. Patients were randomized in a 1:1 ratio to receive STAE within 24 hours from therapeutic endoscopy or to continue standard treatment. A total of 105 patients were included. After adjustment for possible imbalances STAE was associated with a clear trend of reduced rate of rebleeding (P=.079). Numbers needed to treat in order to avoid one case of rebleeding was 10. Study III was conducted as a prospective cohort study. The long-term survival of 455 patients admitted with peptic ulcer bleeding was compared to an age- and sex-matched control group consisting of 2224 individuals selected from the same geographical area. Long-term mortality was adjusted for differences in comorbidity using the Charlson comorbidity index. The study demonstrated that peptic ulcer bleeding is associated with long-lasting excess mortality. Age, recurrent bleeding, and comorbidity were predictors for 30-day mortality. The underlying cause of 30-day mortality was in the majority of patients related to comorbidity. The main predictors for long-term mortality were old age, comorbidity, male sex, severe anaemia and tobacco use. Although severe anaemia predicted long-term mortality treatment with blood transfusion was not associated with long-term mortality per se.