ACG Roundup: Young-Onset Barrett’s Esophagus on the Rise

Research presented at the annual American College of Gastroenterology (ACG) meeting in Philadelphia included studies on the increasing incidence of young-onset Barrett’s esophagus in the U.S., an association between hormone therapy in postmenopausal women and risk for irritable bowel syndrome (IBS), and a calcium release-activated channel (CRAC) inhibitor showed some promise for patients with acute pancreatitis.

Young-Onset Barrett’s Esophagus Incidence on the Rise

The incidence of Barrett’s esophagus has steadily increased over the past decade, according to an analysis of a large national medical records database.

The annual percent change in incident Barrett’s esophagus was 4.9% (P<0.05) from 2014 through 2023, reported Anila Vasireddy, MD, of the University of Pennsylvania Health System in Philadelphia.

One in five incident cases identified in the database were young-onset, and 3.6% of those under age 50 had esophageal adenocarcinoma.

“Our study validates that conventional risk-factors of Barrett’s esophagus in older patients also predict young-onset Barrett’s esophagus,” Vasireddy said. “Screening for Barrett’s esophagus before the age of 50 may have a significant impact on early detection of esophageal adenocarcinoma.”

The researchers analyzed the records of 2,670,143 patients in the TriNetX database — an electronic health record network with data from 88 U.S. healthcare organizations — from its inception in 2013 through November 2023. Among the 102,598 patients with Barrett’s esophagus (3.8%), about one-fifth occurred in patients younger than 50. There was not a significant difference between incidence in those ages 45-49 and those ages 50-54 (2.3% vs 2.6%, respectively).

While 94% of the young-onset patients had non-dysplastic Barrett’s esophagus at initial diagnosis, “an alarming” 6% had Barrett’s esophagus-related neoplasia, Vasireddy told attendees.

Risk factors with the greatest effect sizes in patients under age 50 included:

• Hiatal hernia: OR 2.57 (95% CI 2.41-2.73)
• History of smoking: OR 2.31 (95% CI 1.72-3.09)
• White race: OR 2.29, (95% CI 2.13-2.45)
• Obstructive sleep apnea: OR 2.27 (95% CI 1.50-3.27)
• Male sex: OR 1.98 (95% CI 1.88-2.08)

Other risk factors included gastroesophageal reflux disease (OR 1.19 95% CI 1.13-1.25) and change in BMI (OR 1.05, 95% CI 1.05-1.06).

Menopausal Hormone Therapy Linked to IBS Risk

Postmenopausal women taking hormone therapy had an increased risk of developing IBS, according to a retrospective analysis of medical records data.

Starting at least 30 days after initiating hormone therapy, 2.1% of women taking hormone therapy developed IBS, compared with 1.2% of women not taking it (OR 1.75, 95% CI 1.58-1.94), reported Jacqueline Khalil, DO, MS, of Case Western Reserve University and Metro Health Medical Center in Cleveland.

“Our study reveals a compelling association between hormone replacement therapy and an increased risk of developing IBS which persists over time” and “is correlated with elevated gastrointestinal symptoms, medication utilization, and diagnostic testing,” Khalil said. “These findings emphasize the importance of considering the potential consequences of hormone replacement therapy in postmenopausal women, particularly with regard to IBS.”

The researchers analyzed data from TriNetX for 1,362,976 women age 50 and older, including 51,395 prescribed hormone therapy and 1,311,581 not prescribed it. They excluded women with functional dyspepsia, gastroparesis, cyclic vomiting syndrome, lactose intolerance, small intestinal bacterial overgrowth, cannabis or opioid use, colonic malignant neoplasms, or a history of bariatric or gastrointestinal surgery.

After using propensity score matching to adjust for age, race, ethnicity, inflammatory bowel disease, and celiac disease, the researchers compared 46,627 women taking hormone therapy and an identical number of women not taking it.

After at least 30 days of starting hormone therapy, women’s odds of developing IBS with constipation doubled (OR 2.27, 95% CI 1.76-2.95, P<0.0001). And their odds were also significantly higher of developing IBS with diarrhea (OR 1.44, 95% CI 1.18-1.76, P=0.0003) and IBS with mixed bowel habits (OR 1.63, 95% CI 1.26-2.12, P=0.0002).

The analysis revealed that the association between hormone therapy and developing any form of IBS remained at 1 year (OR 1.69), 3 years (OR 1.66) and 5 years (OR 1.88, P<0.0001 for all) after starting the therapy. Women were also more likely to develop abdominal distension (OR 1.44, 95% CI 1.32-1.57) and flatulence (OR 1.86, 95% CI 1.58-2.20; P<0.0001 for both).

Researchers also found greater odds of being prescribed gastrointestinal medications after starting hormone therapy. Odds of starting plecanatide more than doubled (OR 2.73), and ORs ranged from 1.46 to 1.90 for dicyclomine, linaclotide, lubiprostone, rifaximin, and tricyclic antidepressants (P<0.0001 for all).

Odds were similarly higher after initiating hormone therapy for undergoing a diagnostic colonoscopy (OR 2.08, P<0.0001), esophagogastroduodenoscopy (OR 1.21, P=0.0002) or a hydrogen/methane breath test (OR 2.46, P=0.0002).

Zegocractin in Acute Pancreatitis

An investigational CRAC inhibitor decreased the time to solid food tolerance while also reducing rates of respiratory failure and necrotizing pancreatitis in patients with acute pancreatitis who met at least two of the criteria for systemic inflammatory response syndrome (SIRS), according to the dose-ranging phase IIb CARPO trial.

In the subgroup with a high hematocrit, time to solid food tolerance was 114 hours in those who received placebo compared with 64 hours with a 1 mg/kg dose of zegocractin (P<0.05), reported Robert Sutton, MBBS, DPhil, of the University of Liverpool and Liverpool University Hospitals NHS Foundation Trust in England.

Acute pancreatitis accounts for more than 300,000 annual hospitalizations in the U.S. and costs the nation over $3 billion annually, Sutton told attendees. An estimated 20-30% of all acute pancreatitis patients experience pancreatic necrosis, and up to a quarter of patients may experience organ failure, which increases the risk for death by as much as 50%.

“The reduction in respiratory failure will reduce mortality, the reduction in necrotizing pancreatitis will reduce morbidity, and the reduction in hospital stays will reduce the economic burden,” Sutton said.

The study enrolled 216 participants who were assessed for SIRS and had any of the following: abdominal guarding or tenderness, high hematocrit, or peripancreatic fluid. The patients were randomly assigned to one of four groups: placebo or 0.5 mg/kg, 1 mg/kg, or 2 mg/kg of zegocractin, administered three times daily by IV. The patients were assessed daily until day 30 or discharge and then had an in-person visit with contrast-enhanced CT/MRI at day 30.

Average age ranged from 42 to 48 years across the groups, and 61% of participants were male. The etiology was alcohol in 43% of participants. At baseline, 43% had high hematocrit, 7.9% had any respiratory failure, and 5.7% had readable necrotizing pancreatitis.

Respiratory failure occurred in 7.5% of placebo patients and 9.6% of low-dose zegocractin patients, as compared with 3.6% of middle-dose and 3.8% of high-dose zegocractin patients. None of the patients in the middle- or high-dose zegocractin groups experienced new-onset respiratory failure compared with 8.5% of placebo patients and 8.3% of low-dose zegocractin patients (P=0.0027).

Any severe organ failure occurred in 9.4% of placebo patients and 9.6% of low-dose zegocractin patients compared with 3.6% of middle-dose and 3.8% of high-dose patients.

At 7 days, 31% of patients who received placebo or low-dose zegocractin remained in the hospital compared to 18% of middle- and high-dose zegocractin recipients. Similarly, 10% of placebo/low-dose zegocractin and 5% of middle/high-dose zegocractin patients remained in the hospital at 14 days, and the proportion remaining was 6% and 1%, respectively, at 21 days.

New onset necrotizing pancreatitis occurred in 8% fewer high-dose zegocractin patients than placebo recipients, and only the high-dose group had a substantially earlier time to medically indicated discharge (89 vs 104 hours in the placebo group).

Rates of treatment-emergent adverse events were similar across groups, with at least one occurring in 47.2% of placebo patients, 53.8% of low-dose zegocractin patients, 64.3% of middle-dose patients, and 43.4% of high-dose zegocractin patients. Treatment-emergent adverse events led to one death in the placebo group and one in the middle-dose zegocractin group.

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