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Non-Erosive GERD May Not Increase Risk Of Esophageal Cancer

Patients with non-erosive gastroesophageal reflux disease (GERD) appear to have a similar incidence of esophageal adenocarcinoma as the general population, according to a large Nordic population-based cohort study with up to 31 years of follow-up.

In nearly 500,000 adults who underwent an endoscopy in Denmark, Finland, and Sweden, the incidence rate of esophageal adenocarcinoma was 11 per 100,000 person-years among those with non-erosive GERD, which was similar to that of the general population (standardized incidence ratio [SIR] 1.04, 95% CI 0.91-1.18), and did not increase with longer follow-up (SIR 1.07, 95% CI 0.65-1.65 for 15-31 years of follow-up), reported Jesper Lagergren, MD, PhD, of the Karolinska Institutet and Karolinska University Hospital in Stockholm, and colleagues.

In contrast, people with erosive GERD had an incidence rate of esophageal adenocarcinoma of 31 per 100,00 person-years, showing an overall SIR of 2.36 (95% CI 2.17-2.57), which became more pronounced with longer follow-up, they noted in The BMJ.

"Thus, this study suggests that physicians do not need to consider referring patients with GERD with a previous normal upper endoscopy for repeat endoscopy unless they develop warning symptoms of esophageal adenocarcinoma, mainly dysphagia, as recommended for all individuals," the authors wrote. "This message contrasts with today's clinical practice, in which many patients with diagnosed non-erosive GERD undergo repeated upper endoscopies, which might be both costly and ineffective."

GERD is the main risk factor for esophageal adenocarcinoma, and patients with GERD symptoms are often referred for upper endoscopy to look for mucosal abnormalities, including erosive esophagitis and metaplasia (Barrett's esophagus), the precursor conditions to esophageal adenocarcinoma, Lagergren and team said. While the link between esophagitis and esophageal adenocarcinoma is well established, no previous research has reliably examined the risk of developing esophageal adenocarcinoma in patients with endoscopically confirmed non-erosive GERD.

"Non-erosive reflux disease has distinguishing pathogenic features including low mucosal permeability, heightened visceral sensitivity, and psychological comorbidities," noted Jerry Zhou, PhD, and Vincent Ho, PhD, of Western Sydney University in New South Wales, Australia, in an accompanying editorial. "A nuanced diagnostic approach is needed encompassing symptom severity, oesophageal pH monitoring, and response to treatment with proton pump inhibitors."

This study "prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease," they added. "The changing progression of gastroesophageal reflux disease, the complex influence of proton pump inhibitors, and the potential for a range of underlying pathophysiological causes requires a more comprehensive diagnostic perspective."

For this study, Lagergren and colleagues used data from healthcare records in Denmark from 1995 to 2019, Finland from 1987 to 2018, and Sweden from 2006 to 2019. The 486,556 patients included in the study were diagnosed with GERD and had undergone at least one upper endoscopy; 285,811 had non-erosive GERD (median age 59, 58.7% women) and 200,745 had erosive GERD and were included in the validation cohort (median age 58, 55.4% men).

Follow-up started 12 months after the index endoscopy and ended either with esophageal cancer diagnosis, death, or the end of the study period, whichever came first.

Over 2,081,051 person-years of follow-up (median follow-time 6.3 years) in the non-erosive GERD cohort, 228 patients developed esophageal adenocarcinomas, 21.2% underwent a follow-up endoscopy, and 1.1% underwent anti-reflux surgery.

Women were found to have a slightly increased standardized incidence ratio of esophageal adenocarcinoma (1.38, 95% CI 1.08-1.73), but no major differences were noted for age.

Over 1,750,249 person-years of follow-up (median follow-up time 7.8 years) in the erosive GERD validation cohort, 542 patients developed esophageal adenocarcinomas, 26.9% underwent follow-up endoscopy, and 1.9% underwent anti-reflux surgery. Standardized incidence ratios were increased in all analyses stratified by age and sex.

Disclosures

This study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Nordic Cancer Union.

The study authors and editorialists reported no competing interests.

Primary Source

The BMJ

Source Reference: Holmberg D, et al "Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study" BMJ 2023; DOI: 10.1136/bmj-2023-076017.

Secondary Source

The BMJ

Source Reference: Zhou J, Ho V "Non-erosive reflux disease and oesophageal carcinoma" BMJ 2023; DOI: 10.1136/bmj.P1979.

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Doctor's Tip: How To Prevent Cancer Of The Esophagus

The esophagus is the tube-like structure that carries food from your mouth to your stomach. About 18,000 new cases of esophageal cancer are diagnosed in the U.S. Annually, resulting in some 15,000 deaths. Once diagnosed, the prognosis is grim: the five-year survival rate is only 20 percent, with most people dying within the first year.

There are two types of esophageal cancer: Squamous cell carcinoma makes up 90 percent of cases in Eastern and Southeast Asia and sub-Saharan Africa. Today's column is about adenocarcinoma, that makes up most of the cases in the U.S. And Northern and Western Europe. Risk factors for adenocarcinoma of the esophagus include age (50-70); obesity; tobacco; and particularly chronic GERD (gastroesophageal reflux disease, a.K.A. Acid reflux).

According to Dr. Michael Greger in "How Not to Die," the incidence of esophageal cancer in America has increased six-fold over the past three decades, primarily due to an increase in GERD. It's interesting that 28% of Americans suffer from acid reflux at least weekly, whereas in Asia only 5% of the population is affected. The difference is not genetic, because when Asians move here and eat the typical meat, dairy-based, and processed food American diet they suffer the same rate of GERD as the rest of us. The difference is in what they eat in their native countries.

The most consistent factor associated with esophageal cancer is the consumption of meat and fat. A few minutes after eating a fatty meal, the sphincter muscle between the lower end of the esophagus and stomach relaxes, allowing acid to backflow into the esophagus, where it doesn't belong. This reflux of stomach acid often causes a burning sensation in the chest ("heartburn"). Over the years, the chronic irritation and inflammation from acid reflux leads to Barrett's esophagus, which is a pre-cancerous abnormality of the lower esophagus. Eventually, cancer can ensure. (Scarring of the lower esophagus can also occur, resulting in difficulty swallowing food).

Fiber—which is found in plant but not animal products—decreases reflux and reduces risk of esophageal cancer by at least a third. Fiber also prevents constipation. Increased abdominal pressure due to straining to have a bowel movement can cause a hiatal hernia, where part of the stomach is pushed up through the diaphragm, which separates the chest and abdominal cavities. Hiatal hernias are often the cause of cancer-causing acid reflux. Furthermore, fiber also binds to and "flushes out" cancer-causing environmental toxins.

Plant foods not only contain fiber, but they also contain antioxidants and other cancer-killing micronutrients. Dr. Greger notes that "the most protective foods for esophageal cancer are red, orange, and dark-green leafy vegetables, berries, apples, and citrus fruits." In a randomized study, patients with mild to moderate precancerous esophageal lesions were given large quantities of powdered strawberries daily for six months, and progression of disease was reversed in 80% of participants; in 50% the disease totally resolved.

Bottom line: To avoid this often-fatal cancer, maintain ideal body weight, don't use tobacco, eat a high fiber diet, and eat intensely-colored fruits and vegetables ("eat the rainbow"). If food gets stuck when you swallow it, or if you have more than occasional heartburn, don't just pop acid-reducing pills like Prilosec, but see your primary care provider. An upper endoscopy by a gastroenterologist can determine if you have pre-cancerous Barrett's esophagitis. In many patients with mild to moderate reflux, the problem resolves with healthier eating; avoiding aspirin, ibuprofen, and other irritating anti-inflammatory agents; raising the head of the bed on 4-6-inch blocks (or use of a foam wedge); avoiding alcohol and caffeine; and waiting at least two hours between eating and going to bed.

Dr. Feinsinger is a retired family physician with special interest in disease prevention and reversal through nutrition. Free services through Center For Prevention and The People's Clinic include: one-hour consultations, shop-with-a-doc at Carbondale City Market and cooking classes. Call 970-379-5718 for appointment or email gfeinsinger@comcast.Net.

No Increase In Cancer Risk For Most Patients With Reflux Disease

Reflux disease manifests as acid regurgitation and heartburn and is a known risk factor for oesophageal cancer. However, a new study published in The BMJ by researchers at Karolinska Institutet now reports that the majority of patients do not have a higher risk of cancer. A large-scale study from three Nordic countries shows that the cancer risk is only elevated in patients whom gastroscopy reveals to have changes in the oesophageal mucosa.

"This is a gratifying result since reflux disease is a very common condition and most patients are found to have a completely normal mucus membrane on gastroscopic examination," says the study's first author Dag Holmberg, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet and resident doctor of surgery at Karolinska University Hospital in Sweden.

In reflux disease, acidic stomach contents leak into the oesophagus. This can sometimes cause inflammation in the oesophageal mucus membrane (oesophagitis), which is diagnosed via gastroscopy. It is common knowledge that reflux disease increases the risk of oesophageal cancer, but what the cancer risk is for patients with normal mucosa has remained unknown.

The symptoms of reflux disease can come and go but generally persist, which means that many patients frequently seek medical attention and often undergo repeated gastroscopies to detect mucosal lesions or prodromal cancer.

"Our study suggests that these repeated gastroscopies are probably unnecessary for people with reflux disease who have a normal oesophageal mucosa," says Dr Holmberg. "These findings should be reassuring for this large patient group and can guide GPs who often treat them."

The present study is based on national health data registries in Sweden, Denmark and Finland, and included over 285,000 individuals with reflux disease and no gastroscopic evidence of oesophagitis. The patients were followed for up to 31 years and the researchers registered all cases of oesophageal cancer.

The cancer risk was then compared with that for individuals from the general population matched by age and sex and at the same period in the three countries. No increased risk of oesophageal cancer was observed in patients with reflux disease and a normal mucus membrane.

By way of comparison, the researchers also analysed the cancer risk in over 200,000 individuals with reflux disease and oesophagitis. These people were at a clearly increased relative risk of developing oesophageal cancer.

"We now intend to examine what factors other than oesophagitis can be linked to tumour growth in people with reflux disease," says the study's last author Jesper Lagergren, professor of surgery at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and consultant surgeon at Karolinska University Hospital.

The study was a collaboration between researchers at Karolinska Institutet and Karolinska University Hospital in Sweden, the University of Copenhagen in Denmark, and the universities of Helsinki and Oulu in Finland. It was financed by the Swedish Research Council, the Swedish Cancer Society and the Nordic Cancer Union. There are no reported conflicts of interest.

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