AT THE 2016 JAMES W. FRESTON CONFERENCE

CHICAGO (FRONTLINE MEDICAL NEWS) Severe intestinal metaplasia can progress to adenocarcinoma in a small number of patients over 10 years, whether it’s in the esophagus or in the stomach.

Studies emerging from around the world find the same patterns and similar rates of progression in both diseases: 2% for esophageal and 3%-5% for gastric cancers over 10 years, no matter where the studies are conducted, Ernst Kuipers, MD, PhD, said at the meeting sponsored by the American Gastroenterological Association.

“It doesn’t matter if you’re in an area with a high rate or a low rate,” of gastroesophageal cancer, said Dr. Kuipers, professor of gastroenterology and hepatology at Erasmus University Medical Center, Rotterdam, the Netherlands. “The risk is about the same.”

On the flip side, global data also confirm that surveillance and treatment mitigate the risks. Following at-risk patients endoscopically means tumors are found earlier. And when a severely dysplastic lesion is removed, the risk of recurrence is very low – less than 1%.

These findings of a relatively constant rate of progression from gastroesophageal dysplasia to adenocarcinomas somewhat contradict the idea that the cancers are more of a concern in Asian countries, and fading away in Western countries. There has indeed been a dramatic decrease in stomach cancer in the last century – in the early 1900s, Dr. Kuipers said, up to 40% of cancers reported in Germany were gastric. The reasons for the decrease are many: improved diet, improved hygiene, and widespread use of antibiotics are factors. But the disease does still exist, especially among some ethnic/racial groups.

“The U.S. Surveillance, Epidemiology, and End Results (SEER) database shows that there is still a lot of it out there, and there’s huge disparity within groups, so we have to look at this from a broader perspective.”

Overall, the U.S. rates of esophageal and gastric cancer are about 8 and 10/100,000, respectively. In whites, those rates are about 8 and 9/100,000, but much higher in blacks, Asians, Native Americans, and Hispanics, with gastric cancer hovering around 14/100,000.

A 2010 meta-analysis found that Barrett’s metaplasia progressed to esophageal adenocarcinoma at a rate of 6.3/1,000 patients per year, but that number in particular came from analysis of tertiary care cohorts (Clin Gastroenterol Hepatol. 2010. doi: 10.1016/j.cgh.2009.10.010 ).

A 2015 analysis found lower rates of progression – about 2/1,000 patients per year in patients with short-segment Barrett’s, and about 3/1,000 patients per year in long-segment Barrett’s patients that have no dysplasia. “That means if you’re following 300 patients, one of these will convert to cancer every year,” Dr. Kuipers said (Gut. 2015. doi: 10.1136/gutjnl-2013-305506 ).

The risk appears much higher for patients with dysplastic Barrett’s, although the data vary widely. “Some report low progression rates, but some report these patients have a 50% or higher risk of progression within a few years. This variation depends on how selective one is in diagnosing low-grade dysplasia.”

A Dutch nationwide study of 42,200 patients with Barrett’s found that 4% progressed to adenocarcinoma over 10 years, for an annual progression rate of 0.4%. But among the small group of those with low-grade dysplasia, more than 10% had progressed by 10 years – a 1% annual progression rate (Gut. 2010. doi: 10.1136/gut.2009.176701 ).

An Irish national study found strikingly similar results. The annual progression risk in patients with metaplasia was 1.6/1,000 patients per year overall, but 2.7/1,000 per year in those with intestinal metaplasia (J Natl Cancer Inst. 2011. doi: 10.1093/jnci/djr203 ).

“So, if we have some idea of progression rate, is there evidence that we could identify and treat these cancers earlier if our patients are under surveillance?” Dr. Kuipers said. “Well the answer is ‘yes.’ ”

He cited a very recent study by his colleagues at Erasmus University (Gut. 2016. doi: 10.1136/gutjnl-2014-308802 ). Investigators determined that in Barrett’s patients who were followed endoscopically, esophageal cancers were identified at much earlier stages than among the general population; 66% of the neoplasias were identified at the high-grade dysplasia stage, 26% at stage 1. The remainder were stage 2; there were no stage 3 or 4 cancers. In the general population, numbers were reversed: 45% were stage 4 when identified, 25% stage 3, 18% stage 2, and only a few at stages 1 or high-grade dysplasia.

Gastric cancer shows the same consistency of incidence and relation to baseline premalignant severity. A Dutch study with 98,000 cases found the annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild to moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis (Gastroenterology. 2008. doi: 10.1053/j.gastro.2008.01.071 ).

A Swedish study last year found a progression rate of 3% over 10 years for patients with extensive intestinal metaplasia. (BMJ. 2015. doi: 10.1136/bmj.h3867 ).

“And this year, from Los Angeles, we saw a study of 4,300 patients with extensive intestinal metaplasia and a very similar progression rate of close to 5% in 10 years (Am J Gastro. 2016. doi: 10.1038/ajg.2016.188 ). It’s the same findings, everywhere,” he said, adding that a team from Iran presented almost identical numbers for gastric cancer incidence at this year’s Digestive Disease Week.

Again, follow-up improves outcomes. A gastric cancer endoscopy screening program for high-risk people improved survival of gastric cancer significantly over community-identified patients (80% vs. 60% at 60 months after diagnosis) (J Gastro Hepatol. 2014. doi: 10.1111/jgh.12387 ).

These data contribute strongly to recent guidelines for managing patients with premalignant stomach conditions. The European Society for Gastroenterological Endoscopy recommends that those with extensive intestinal metaplasia undergo endoscopy every 3 years (Endoscopy. 2012. doi: 10.1055/s-0031-1291491 ). Last year, the Kyoto global consensus report on Helicobacter pylori gastritis (Gut. 2015. doi: 10.1136/gutjnl-2015-309252 ) recommended that patients with extensive gastric atrophy be offered endoscopic surveillance.

There is no place for general population screening, Dr. Kuipers said in an interview. “I would not advocate actual population screening – i.e., offer the general population or risk groups a first screening endoscopy. There is at present no indication [for] this. This is different, however, from surveillance of patients who happen to be diagnosed with advanced intestinal metaplasia of the stomach, or long-segment Barrett’s esophagus, because this allows us to early detect development of neoplasia (high-grade dysplasia and cancer), which then allows for less invasive treatment, and better outcomes.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

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