Peptic Ulcer Disease
A peptic ulcer is a break in the lining of the gastointestinal tract, extending through to the muscularis mucosae of the bowel wall.
Whilst they may technically appear anywhere in the gastrointestinal tract, they are most often located on the lesser curvature of the proximal stomach or the first part of the duodenum.
The incidence of peptic ulcers is estimated to be 0.1-0.19% of the population per annum, with duodenal ulcers typically presenting earlier than gastric ulcers by around 20 years. A recent systematic review revealed patients are 13 times more likely to bleed from an ulcer if they are over age 70 compared to those under the age of 40
In this article, we shall look at the clinical features, investigations and management of peptic ulcer disease.
The normal gastrointestinal mucosa is protected by numerous defensive mechanisms, such as surface mucous secretion and HCO3- ion release. Ulceration occurs when there is an overwhelming presence of a noxious substance or when these natural barriers are impaired.
Most commonly, this is through the presence of Helicobacter pylori (H. pylori) or Non-Steroidal Anti-Inflammatory Drugs* (NSAIDs), however less common causes include high alcohol intake, steroid use, foreign body ingestion e.g batteries, or Zollinger-Ellison syndrome (rare).
*NSAIDs can cause peptic ulcer formation by their action in inhibiting prostaglandin synthesis. This results in a reduced secretion of glycoprotein, mucous, and phospholipids by the gastric epithelial cells, which would otherwise normally contribute to the barrier protecting the gastric mucosa.
H. pylori is a Gram negative spiral-shaped bacillus, found in the mucous layer of those with duodenal ulcers (90%) or gastric ulcers (70%). It survives in the stomach by producing an alkaline micro-environment and induces an inflammatory response in the mucosa, leading to eventual ulceration, by:
- Invoking an cytokine and interleukin-driven inflammatory response
- Increasing gastric acid secretion in both the acute and chronic phases of infection, increasing the release of histamine which acts on parietal cells
- Damaging host mucous secretion by degrading surface glycoproteins and down-regulating bicarbonate production
The two main risk factors for peptic ulcers are H. pylori infection and prolonged NSAID use. Other risk factors include alcohol excess, smoking, chemotherapy or radiotherapy, and steroid use
Up to 70% of peptic ulcers are asymptomatic. Moreover, significant pathological processes, such as malignancy, pancreatitis, and mesenteric angina can all mimic the symptoms of an ulcer. Less commonly, patients may present with complications of their peptic ulcer disease, such as bleeding, perforation, or gastric outlet obstruction.
- Epigastric pain
- Typically exacerbated by eating
- Nausea and anorexia
- Weight loss
- Epigastric pain
- Worse around 2-5 hours after consuming after a meal
- Worse when fasting and can often be alleviated by eating
The ALARMS mnemonic (Anaemia / Lost weight / Anorexia / Recent rapid onset / Meleana / Swallowing difficulties) has historically been used as a basis for referral for urgent endoscopy to assess for any malignancy. However NICE guidelines now suggest that a referral for urgent OGD should be done for patients presenting with either:
- New-onset dysphagia
- Aged >55 years with weight loss and either upper abdominal pain, reflux, or dyspepsia
Any condition that causes dyspepsia, chest pain, or abdominal pain can be considered a differential for peptic ulcer disease. However, those most important to rule out when assessing the patient include gastric malignancy, pancreatitis, acute coronary syndrome, gastro-oesphageal reflux, and gallstone disease.
Zollinger-Ellison Syndrome refers to a triad of (i) severe peptic ulcer disease; (ii) gastric acid hypersecretion; and (iii) gastrinoma. The characteristic finding is a fasting gastrin level of >1000 pg/ml. A third of these cases are discovered as part of Multiple Endocrine Neoplasia Type 1 syndrome (Pancreas/Pituitary/Parathyroid tumours), so further investigations for MEN are often warranted.
Patients with any red-flag symptoms should be referred for upper GI endoscopy (OGD). An OGD that identifies peptic ulceration (Fig. 2) will also allow for biopsies to be taken, which will be sent for histology and rapid urease “CLO” test (histological test used for determining presence of H. pylori). A full blood count is often warranted in suspected cases to assess for anaemia present.
For those patients who do not need an OGD but are not responding to initial conservative management (as discussed below), non-invasive H. pylori testing* is required, which will be either as:
- Carbon-13 urea breath test
- Serum antibodies to H. pylori
- Stool antigen test
*Importantly, prior to any H. pylori test, patients should stop any current medical therapy for 2 weeks prior to investigation to reduce the risk of false negatives. Once H. pylori is identified, no further investigations are warranted prior to starting eradication therapy.
Any patient with dyspepsia should be given lifestyle advice to reduce symptoms, such as smoking cessation, weight loss, and reduction in alcohol consumption. There should also be an avoidance/cessation of NSAIDs where possible.
Any patient who fails initial conservative management and has a negative H. pylori testing can be stared on a Proton Pump Inhibitor (such as omeprazole or lansoprazole) for 8 weeks to reduce acid production. Those patients with a positive H. pylori test should be started on triple therapy*.
NICE guidance recommends gastric ulcers to be biopsied at presentation due to malignant potential and a repeat endoscopy performed towards the end of PPI therapy to check for resolution. Persistence of symptoms post-PPI therapy should lead the clinician to suspect failure of H. pylori eradication, malignancy, or rare causes such as Zollinger-Ellison Syndrome.
*Any patient with positive H. pylori testing requires eradication therapy (also termed triple therapy), which commonly consists of a PPI with oral amoxicllin and clarithromycin or metronidazole for 7 days.
Surgery for peptic ulcer disease is now rare, except in emergencies (such as perforation) or in the management of Zollinger-Ellison Syndrome.
However, in severe or relapsing disease, the following procedures can be considered:
- Partial gastrectomy – removes the ulcer along with the G-cells contained in the antrum which secrete gastrin, which is followed by either a Bilroth I (end to side gastroduodenostomy) or Bilroth II (side to side gastrojejunostomy) anastamosis
- Selective vagotomy – removal of branches of the vagus nerve to decrease acid secretion, often used in combination with either gastroenterostomy or pyloroplasty (as the vagotomy frequently impairs the ability of the pylorus to relax leading to delayed emptying of the stomach)
The main complications of these procedures include diarrhoea (due to an increased bowel transit time), dumping syndrome (rapid gastric emptying of hyperosmotic chyme into the small bowel resulting in fluid shift and bowel distension), and alkaline reflux gastritis (reflux of duodenal contents into the stomach following Bilroth I or II procedure (can potentially be relieved by conversion to Roux-en-y anastamosis)).
The main complications of peptic ulcer disease are perforation, haemorrhage, and pyloric stenosis.
- H. pylori and NSAIDs are the most common causes for peptic ulcer disease
- Any patient with red-flag symptoms or not responding to conservative management should be referred for urgent upper GI endscopy
- Surgical management of uncomplicated peptic ulcer disease is rare, yet partial gastrectomies or selective vagotomies are occasionally indicated