Complicated peptic ulcer disease : prevention and treatment

Peptic ulcer is a common disease worldwide and its complications can cause serious clinical problems. While the incidence of uncomplicated peptic ulcer disease is decreasing, the incidence of more complex ulcer disease is not. The most common complication is bleeding. Endoscopic intervention achieves haemostasis in most patients. The remaining part face a substantial risk of mortality and these patients have typically undergone more or less radical surgery. Transcatheter arterial embolisation (TAE) has emerged as a less invasive alternative to surgery, but there is limited scientific evidence supporting its role. The increased use of gastric bypass surgery for obesity has resulted in an increase in marginal ulcer, a complication of uncertain aetiology which is often difficult to heal. Helicobacter pylori (H. pylori) is the main risk factor for peptic ulcer, and eradication of this bacterium is an important part of the treatment. Yet, eradication after peptic ulcer is often delayed, with uncertain clinical consequences.

This thesis aimed to help improve the treatment of peptic ulcer bleeding (Study I and II), identify risk factors for marginal ulcer (Study III), and clarify consequences of delayed H. pylori eradication after peptic ulcer diagnosis (Study IV). Study I compared mortality after a more radical with a minimal surgical approach for ulcer bleeding in a population-based cohort study using data from the Swedish Patient Registry in 1987-2008. The overall all-cause 5-year mortality was similar (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.95-1.16), but was possibly higher following radical surgery from the year 2000 onwards (HR 1.27, 95% CI 0.99-1.63). Study II compared outcomes after TAE with surgery for ulcer bleeding in a cohort study in Stockholm County in 2000-2014, using data from medical records and the Swedish Patient Registry. Compared to the surgery group, the overall all-cause mortality was decreased in the TAE group (HR 0.66, 95% CI 0.46-0.96) as was the risk of complications (8.3% versus 32.2%), and the median length of hospital stay (8 versus 16 days, adjusted acceleration factor 0.59, 95% CI 0.45-0.77). The risk of re-bleeding (HR 2.48, 95%CI 1.33-4.62) and re-intervention (HR 5.41, 95% CI 2.49-11.76) was higher in the TAE group. Study III examined potential risk factors for marginal ulcer after gastric bypass surgery in a nationwide population-based cohort study using data from the Swedish Patient Registry in 2006-2011. Diabetes (HR 1.26, 95% CI 1.03-1.55) and peptic ulcer history (2.70, 95% CI 1.81-4.03) were associated with increased risk, while hyperlipidaemia, hypertension and chronic obstructive pulmonary disease were not. Use of aspirin and non-steroid anti-inflammatory drugs (NSAIDs) below the median dose decreased the risk, while use of aspirin above the median dose entailed increased risk of marginal ulcer. Use of NSAID above the median did not influence the risk of marginal ulcer. Serotonin re-uptake inhibitor use below the median dose was associated with a decreased risk, while use above the median increased this risk. Study IV tested how various lengths of delays in H. pylori eradication after peptic ulcer diagnosis influenced outcomes in a population-based cohort study based on data from nationwide Swedish registries. Delays in eradication time-dependently increased the risk of ulcer recurrence, which was evident already after 8-30 days delay (HR 1.17, 95% CI 1.08-1.25) and so was the risk of complicated ulcer (HR 1.55, 95% CI 1.35-1.78). Longer delays (61-365 days) also seemed to increase gastric cancer risk (HR 3.64, 95%CI 1.55-8.56).

In conclusion: A less radical approach seems sufficient in the surgical treatment of ulcer bleedings. TAE could be recommended as a first-line therapy of peptic ulcer bleeding after failed endoscopic intervention. Diabetes, peptic ulcer history, and higher doses of anti-inflammatory drugs seem to be risk factors for marginal ulcer. Delays in H. pylori eradication after peptic ulcer diagnosis must be avoided, since these might time-dependently increase the risk of ulcer recurrence, ulcer complications and gastric cancer.

List of scientific papers

I. Sverdén E, Sondén A, Leinsköld T, Lagergren J, Lu Y. Minimal versus definitive surgery in managing peptic ulcer bleeding : a population-based cohort study. Digestive Surgery. 2014;31(4-5):276-82.
https://doi.org/10.1159/000365336

II. Sverdén E, Mattsson F, Lindström D, Sondén A, Lu Y, Lagergren J. Transcatheter arterial embolisation (TAE) compared to surgery for uncontrolled peptic ulcer bleeding. [Manuscript]

III. Sverdén E, Mattsson F, Sondén A, Leinsköld T, Tao W, Lu Y, Lagergren J. Risk factors for marginal ulcer after gastric bypass surgery for obesity: a population-based cohort study. Annals of Surgery. 2016;263(4):733-7.
https://doi.org/10.1097/SLA.0000000000001300

IV. Sverdén E, Brusselaers N, Wahlin K, Lagergren J. Ulcer and cancer risk following delays in Helicobacter pylori eradication in a population-based cohort study. [Manuscript]