In people who have stomach or upper small intestinal ulcers (peptic ulcers) that do not heal after eight to 12 weeks of medical treatment (refractory peptic ulcers) or comes back after healing (recurrent peptic ulcers), is medical or surgical treatment better?
Approximately 1 in 100 to 1 in 800 people have peptic ulcers. The major causes of peptic ulcer are Helicobacter pylori infection, non-steroidal anti-inflammatory drug (NSAID) use, and smoking. People who have peptic ulcer have upper abdominal pain, which is sometimes accompanied by dyspepsia (that is fullness, bloating, loss of appetite after eating a small amount of food, or nausea). The most serious complications of peptic ulcers are bleeding from the ulcer and perforation of the peptic ulcer, which results in stomach or upper small intestinal contents or both leaking into the tummy. About 1 in 10 people with bleeding peptic ulcer and 1 in 4 people with perforated peptic ulcer die. Peptic ulcers cause approximately 3000 to 4500 deaths per year in the US.
Currently, medical management, usually with a group of drugs called proton pump inhibitors (such as omeprazole and lansoprazole), is the mainstay treatment for uncomplicated peptic ulcers. Recently concerns have arisen about the risk of fractures with long-term use of proton pump inhibitors. The alternative to medical treatment for refractory and recurrent peptic ulcer is surgical treatment to decrease the acid secretion in the stomach with the goal of curing the peptic ulcer. It is not known whether medical or surgical management is a better option for people with a refractory or recurrent peptic ulcer. We attempted to resolve this issue by searching the medical literature for studies comparing medical and surgical treatment in people with refractory or recurrent peptic ulcers.
We found no randomised controlled trials, and identified only one non-randomised study published 30 years ago, on this topic. This study included 77 participants who had stomach ulcer and in whom medical therapy had failed after an average treatment duration of 29 months. Medical therapy included histamine H2 receptor blockers (medicines that block the action of the chemical histamine, resulting in a decreased production of stomach acid, such as ranitidine), antacids, and diet. It must be highlighted that this form of medical treatment is not considered to be as effective as treatment with proton pump inhibitors. The authors do not state whether these were recurrent or refractory ulcers. Of the 77 included participants, 37 participants continued to have medical therapy, while 40 participants received surgical therapy. Whether to use medical or surgical treatment was determined by participant's or treating physician's preference. The evidence is current to September 2015.
The study authors reported that two participants in the medical treatment group (5%) had stomach cancer, which was identified after repeated examinations using a camera to look inside the body (an endoscope), in this case, the stomach and small intestine. They did not report the percentage of participants who had stomach cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of stomach cancer in the medical treatment group. They did not report any other outcomes of interest (measures by which one treatment can be considered better than another) for this review (that is health-related quality of life, treatment-related complications, peptic ulcer-related complications, abdominal pain, and long-term deaths). There is thus no study that provides the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies on this topic are urgently required.
Quality of the evidence
Since the only study that compared medical and surgical treatment in people with refractory or recurrent ulcers did not report any of the outcomes in a sufficiently detailed manner, we were not able to assess the quality of evidence in a formal way.
We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the incidence of complications and gastric cancer (in gastric ulcers only) in recurrent and refractory peptic ulcers. In addition to complications related to treatment and disease, health-related quality of life and loss of productivity should also be measured.
Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers.
To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer.
We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies.
We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review.
Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis.
We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.
The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality).