Toupet fundoplication to prevent progression of scleroderma-associated interstitial lung damage: a study protocol

Systemic sclerosis (SSc) is a rare autoimmune and multiorgan disorder. Hallmarks of the disease include inflammation, endothelial dysfunction, and dysregulation of fibroblasts leading to fibrosis of the skin and internal organs. The esophagus is often involved, with up to 80% of patients developing gastroesophageal reflux disease (GERD). Reflux can be associated with hiatal hernia and several complications such as erosive esophagitis, peptic stricture, Barrett’s esophagus, aspiration pneumonia, and chronic microaspiration. Silent aspiration can lead to interstitial lung disease (ILD) in up to 50% of patients with scleroderma and accounts for up to 40% of mortality. Treatment of GERD in patients with SSc is challenging. Proton pump inhibitors (PPI) have been shown effective in relieving typical GERD symptoms, but up to 40% of patients are non-responders. Various antireflux surgical procedures have been proposed to treat GERD and to modify the natural course of the disease by preventing lung damage in these patients. However, current algorithms consider only the degree of esophageal dilation as a marker of disease severity/progression, and results of antireflux surgery remain controversial.

We propose a feasibility, observational, multicenter, single-arm trial including adult patients diagnosed with SSc. Criteria for inclusion are individuals with GERD symptoms refractory to PPI, absence of peptic stricture at baseline endoscopy, high-resolution computed tomography (HRCT) scan showing no or less than 10% lung fibrosis, forced vital capacity at least 40% of the predicted value, and diffusing capacity of lung for carbon monoxide 30–89% of the predicted value. A laparoscopic partial posterior fundoplication according to the Toupet technique will be performed. Primary study outcome is the efficacy of fundoplication to reduce reflux exposure measured with a pH-impedance study or 4‑day wireless pH recording. Secondary outcomes include endoscopic, HRCT, and respiratory function tests findings as well as quality of life at 12-month follow-up.

The expected reduction of reflux burden in SSc patients selected for Toupet fundoplication may improve GERD symptoms/complications, pulmonary function, and quality of life, and may be associated with a reduced risk for lung transplant.