Barrett: the annual cancer risk is 0.12%, not 0.5%

The Barrett risk, broken down

The gap between the two cohorts has an explanation and should not be hidden: Denmark includes patients without intestinal metaplasia in its definition, which dilutes the risk. With confirmed metaplasia the figure is 0.38% a year, still below the assumed 0.5%.

What that means in practice: a patient without dysplasia has about a 99% chance of not developing cancer in the year, and a cumulative ten-year risk of the order of 1% to 1.3%. The relative risk against the general population stays high, with a standardised ratio of 11.3, but an elevenfold relative risk on a very low base is still a very low base.

Drugs or surgery: what the trials measured

The LOTUS trial (JAMA, 2011), 554 patients across eleven countries, is the best five-year comparison between a proton pump inhibitor and antireflux surgery.

Surgery controls regurgitation better, the drug avoids dysphagia and digestive symptoms better. Objective reflux control is better after surgery: acid exposure falls from 8.6% to 0.7% of the time, and stays there at five years.

The question patients actually ask is this: after the operation, will I still need medication? The figures vary with what is counted, and that has to be said.

The American authors write that antireflux surgery should not be offered in the expectation that the patient will no longer need acid suppression, nor that the operation will prevent cancer in people with Barrett’s oesophagus. In the Nordic study at twelve years, 38% of those operated on had to change treatment strategy against 15% on medication.

Side effects of PPIs: what is demonstrated and what is not

This is a subject where the gap between what circulates and what is measured is considerable, and one trial settles it.

COMPASS (Gastroenterology, 2019) randomised 17,598 participants between pantoprazole and placebo, double-blind, with a median follow-up of three years and six-monthly collection of thirteen categories of event: pneumonia, Clostridium difficile infection, fractures, gastric atrophy, chronic kidney disease, diabetes, dementia, cancer, mortality.

One signal is significant: enteric infections, 1.4% against 1.0%, odds ratio 1.33 with an interval from 1.01 to 1.75. No difference for any other outcome, including fractures, kidney failure, dementia, pneumonia and cancer.

The dementia case is worth setting out, because it illustrates the mechanism.

The association appears in administrative databases, disappears in the two best-designed studies, and is not significant in meta-analysis with 99% heterogeneity. That is the profile of indication bias and residual confounding, not of a causal effect.

One honest caveat, which has to be written: COMPASS ran for a median of three years, in a cardiovascular population. It cannot rule out an effect appearing after ten or twenty years, or in another population.

What the studies do not allow us to claim

That the annual cancer risk in Barrett’s oesophagus is 0.5% has no primary source, and the Danish cohort authors say so explicitly.

That 50% of patients have gas-bloat after fundoplication is an upper bound from heterogeneous series. The randomised comparative figure is 40% bloating after surgery against 28% on medication.

That long-term PPIs raise the risk of dementia, kidney failure or fracture is, on today’s data, non-causal association.

In practice, if this concerns you

Three questions structure the discussion. Are your dominant symptoms regurgitation or heartburn, since surgery is clearly better on the former. Do you accept the trade, dysphagia and bloating against regurgitation. And if Barrett’s oesophagus has been found, is there intestinal metaplasia and is there dysplasia, since the risk runs from 0.07% to 1.40% a year depending on the answer.

Noria Health arranges a full digestive work-up near Brussels within 24 to 48 hours: upper endoscopy with systematic biopsies, pH-impedance and oesophageal manometry where the examination justifies it, and a second read of the histology. The report is issued within 24 hours, follow-up is structured at D14, D30 and D90, and surgery is considered only around day 10 if it is needed.

What Noria Health does not do: offer antireflux surgery on a promise of stopping medication for good. Rapidly developing difficulty swallowing, unexplained weight loss, vomiting blood or black stools are matters for the emergency services in your country, immediately, not for an appointment.

Further reading

• Hernia, gallbladder, reflux: when to operate and when to wait
• Gallstones: 37% of those operated on still have pain five years later
• Colonoscopy: 19% fewer cancers

Sources

1. Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med, 2011;365:1375-1383. https://pubmed.ncbi.nlm.nih.gov/21995385/
2. Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett’s esophagus patients. J Natl Cancer Inst, 2011;103:1049-1057. https://pubmed.ncbi.nlm.nih.gov/21680910/
3. Galmiche JP, Hatlebakk J, Attwood S, et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD, LOTUS. JAMA, 2011;305:1969-1977. https://pubmed.ncbi.nlm.nih.gov/21586712/
4. Hatlebakk JG, Zerbib F, Bruley des Varannes S, et al. Gastroesophageal acid reflux control 5 years after antireflux surgery. Clin Gastroenterol Hepatol, 2016;14:678-685. https://pubmed.ncbi.nlm.nih.gov/26226096/
5. Grant AM, Wileman SM, Ramsay CR, et al. Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease, REFLUX. BMJ, 2008;337:a2664. https://pubmed.ncbi.nlm.nih.gov/19074946/
6. Grant AM, Cotton SC, Boachie C, et al. Minimal access surgery compared with medical management for gastro-oesophageal reflux disease, five year follow-up. BMJ, 2013;346:f1908. https://pubmed.ncbi.nlm.nih.gov/23599318/
7. Lundell L, Miettinen P, Myrvold HE, et al. Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy. Clin Gastroenterol Hepatol, 2009;7:1292-1298. https://pubmed.ncbi.nlm.nih.gov/19490952/
8. Spechler SJ, Lee E, Ahnen D, et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease. JAMA, 2001;285:2331-2338. https://pubmed.ncbi.nlm.nih.gov/11343480/
9. Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial, COMPASS. Gastroenterology, 2019;157:682-691. https://pubmed.ncbi.nlm.nih.gov/31152740/
10. Mehta RS, Kochar BD, Zhou Z, et al. Association of proton pump inhibitor use with incident dementia and cognitive decline, ASPREE. Gastroenterology, 2023;165:564-572. https://pubmed.ncbi.nlm.nih.gov/37315867/
11. Zhang P, Li Z, Chen P, et al. Regular proton pump inhibitor use and incident dementia, UK Biobank. BMC Med, 2022;20:271. https://pubmed.ncbi.nlm.nih.gov/36045363/
12. Peng TR, et al. Proton pump inhibitors and dementia risk, a systematic review and meta-analysis. Brain Sci, 2026;16:159. https://pubmed.ncbi.nlm.nih.gov/41750160/
13. Varma S, Krishnareddy S, Lewis SK, Freedberg DE. Proton pump inhibitors and enteric infections, a self-controlled case series. Inflamm Bowel Dis, 2024;30:38-44. https://pubmed.ncbi.nlm.nih.gov/36917215/

See also: all our articles on digestive surgery.

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