The Study Of N-acetylcysteine Relieving Esophageal Symptoms Caused By Lugol’s Iodine Chromoendoscopy

Background:Esophageal cancer as one of common malignant tumors ranks sixth in the mortality of malignant tumors in the world.Esophageal squamous cell carcinoma accounts for about90%.The progress of the diagnosis and treatment in gastrointestinal endoscopy effectively improves detection of early esophageal cancer and the prognosis of patients.The 5-year survival rate of paitents with early esophageal squamous cell carcinoma is more than 90%,which is only 20% for patients with the advanced.Lugol’s iodine chromoendoscopy is an important method to detect esophageal squamous cell carcinoma,but can induce some gastrointestinal discomfort.Sodium thiosulfate solution(STS)spray after Lugol’s chromoendoscopy is a validated approach to attenuate discomforts caused by iodine staining,however it is not accessible in many medical centers because of difficulty to obtain.As a well-known,safe,and easily accessible mucolytic reagent,N-acetylcysteine can theoretically neutralize free iodine.Object:1.to verify the effectiveness of N-acetylcysteine in neutralizing Lugol’s iodine in vitro.2.to assess the efficacy of N-acetylcysteine solution(NAC)for relieving esophagus discomfort caused by Lugol’s iodine chromoendoscopy in clinical trial.Methods:1.An in vitro trial about 96 holes plate and an ex vivo trial about esophageal tissue from pig were performed to contrast the neutralizing effect of NAC or STS to Lugol’s solution.2.In the clinical trial,patients recruited according to inclusion and exclusion criteria were dynamically randomized to study group(NAC group)and control group(STS group).Patients receive 20 m L of 5% STS or 20 m L of 3% NAC after Lugol’s iodine chromoendoscopy(10 m L of 1.5% Lugol’s iodine solution).The picture before and after spraying neutralization reagent in esophagus and gastric mucus pool and the discomfort after chromoendoscopy were recorded to assess neutrializing effect.The primary endpoint was the intensity of retrosternal pain and heartburn measured by a Visual Analogue Scale(VAS)score 30 min after chromoendoscopy.The secondary endpoints were the rate of patients with any adverse symptom,the rate of moderate to severe retrosternal discomfort occurring,and the heart rate variability before and after chromoendoscopy.Results:1.In the in vitro trial,Lugol’s iodine solution was effectively neutrialized by highdose NAC or STS.The neutralizing effect of STS was positively correlated with the dose.An unsatisfactory neutralizing effect was shown at low doses of NAC,and the color of Lugol’s iodine solution darkened instead.In the ex vivo trial of pig esophageal tissue,both NAC and STS effectively neutralize Lugol’s iodine solution.2.In the clinical trial,of all 144 participants recruited,three patients in the STS group(1 patient for severe esophageal stricture and 2 patents for withdrawing from the study)and1 patient in the NAC group(with incomplete data acquisition)were excluded during dynamic randomization,resulting in 140 patients were determined to be eligible with 68 cases in the STS group and 72 cases in the NAC group.The neutralization rates for residual iodine in the esophagus and stomach between the NAC and STS groups were not significantly different(P > 0.999).The difference of median VAS scores between the NAC and STS groups 30 minutes after chromoendoscopy was 0.0(P = 0.719;95% confidence interval,0.0-0.0),and the 95% confidence interval higher limit was 0.0,which was less than our prespecified margin of 0.5,concluding a noninferiority of NAC with regard to STS.There was no significant difference between the two groups regarding the rate of patients with any adverse symptom,rate of moderate to severe retrosternal discomfort,or heart rate variability at 5 minutes [NAC vs.STS = 7.3%(0.0%,12.9%)vs.11.0%(2.5%,21.1%),P = 0.070] or 30 minutes [0.0%(-5.0%,4.5%)vs.1.5%(-4%,9.3%),P = 0.310]after chromoendoscopy.Conclusion:As a very easily accessible reagent in clinical circumstances,NAC can also alleviate mucosal irritation symptoms induced by Lugol’s chromoendoscopy at similar efficacy as STS and can be routinely recommended as an alternative to STS.