Lower Concentration Of Lugol’s Solution In The Diagnosis And Treatment Of Early Esophageal Squamous Cell Carcinoma

Background and AimsColorectal cancer is one of the third most commonly diagnosed malignancy and the leading cause of cancer death globally.There are two main histologic types of esophageal cancer,including squamous cell carcinoma(SCC)and Barrett’s esophagus related adenocarcinoma.North-central China is one of geographic belts of higher incidence of SCC,and SCC is the predominant histological type.The prognosis of the esophageal squamous cell carcinoma is still poor,with a low survival rate.The prognosis would be better if the diagnosis is made at an early stage.In particular,superficial cancer limited within the mucosal layer is a good candidate for minimally invasive treatment by endoscopic resection.Lugol chromoendoscopy is the standard method for detecting and identifying the esophageal SCC.However,it may cause retrosternal pain and discomfort due to mucosal irritation.The conventional concentration of Lugol’s solution is in the range of 1.2%to 2.5%.However,it’s has been reported that this range of Lugol’s solution may lead to retrosternal pain and discomfort,and can even induce erosion or ulceration in the esophagus and stomach.Moreover,the increase of esophageal spasm and friction caused by iodine staining will further affect the observation of lesions.This study was to explore whether a lower concentration of Lugol’s solution,which has little mucosal irritation,can provide satisfied image quality by a randomized blinded controlled trial.The first part of this study was to investigate whether low concentration of Lugol’s solution in screening population for early esophageal SCC and precancerous lesions could reduce endoscopic resistance and adverse reactions after iodine staining of the esophagus.The purpose of the second part of this study was to investigate the effect of low concentration of Lugol’s solution on image quality in patients underwent endoscopic mucosal dissection(ESD)for esophageal mucosal lesions.MethodsPart ⅠFrom September 2017 to November 2018,we selected patients who underwent confocal endoscopy in the digestive outpatient department of Qilu Hospital,Shandong University.Patients with contraindication of iodine staining and endoscopy were excluded.The basic information of patients was recorded.All patients who met the criteria for admission were examined by white-light endoscopy and confocal laser endomicropy under intravenous anesthesia.The patients with no obvious lesions(acute erosive hemorrhagic gastritis,chronic atrophic gastritis,Helicobacter pylori infection and severe bile reflux gastritis)were randomly divided into five groups.10 mL Lugol’s solution with the concentration of 1.2%(group A),and 1.0%(Group B),0.8%(Group C),0.6%(Group D)and 0.4%(Group E)were used to observe the esophagus.All suspicious lesions would be recorded in detail including the location(distance from the central incisor),size and endoscopic type.After Lugol’s staining,histological biopsy will be took under endoscope to identify the pathological types of the suspected lesions.Lugol’s solution concentration was blinded of patients,endoscopists and data collectors.Endoscopists’ endoscopy operation satisfaction score and image quality score were recorded.Patients were followed up by telephone 24 hours after endoscopy operation.Iodine staining related adverse reaction score and serious adverse reaction events were recorded.SPSS 24.0 was used for data analysis.The measurement data are described by means,standard deviation,median and quartile.Nonparametric test(Kruskal-Wallis test,K-W test)was used to test the significance.The counting data were described by rate and composition ratio,and chi-square test was used to test the significance.Part ⅡFrom December 2018 to March 2019,we selected patients with early esophageal cancer or precancerous lesions underwent endoscopic mucosal dissection in the Department of Gastroenterology,Qilu Hospital,Shandong University.After eliminating the contraindications,all patients who met the criteria of admission were examined by white light endoscopy under intravenous anesthesia.The patients were randomly divided into four groups.The concentration of Lugol’s solution was 1.2%(Group A),1.0%(Group B),0.8%(Group C)and 0.6%(Group D),respectively.The esophagus in iodine-unstained area was observed.All lesions in iodine-unstained area were recorded in detail,including the distance from the central incisor,size,endoscopic type.Lugol’s solution concentration was blinded of patients,endoscopists and data collectors.Image quality scores and operation satisfaction scores of endoscopists after iodine staining were recorded.Pathological histological types and complete resection rate of esophageal mucosal lesions were collected after dissection of esophageal mucosal lesions.SPSS 24.0 Chinese version was used for data analysis.The measurement data are described by means,standard deviation,median and quartile.Nonparametric test(Kruskal-Wallis test,K-W test)was used to test the significance.The counting data were described by rate and composition ratio,and chi-square test was used to test the significance.ResultsPart I:A total of 200 patients were enrolled in this part of the study,with 40 patients in each group.There were significant differences in endoscopic operation satisfaction scores among the five groups(P<0.05).The average rank of endoscopic operation satisfaction scores in group D,C,E,B and A decreased in turn.The average rank of endoscopic operation satisfaction scores in group A was the lowest in comparison with that in group C,D and E(P<0.05).There were significant differences in image quality scores between the five groups(P<0.05).There were significant differences in group A,B and C(P<0.05).The average rank of image quality score of group A,group D and group E decreased in turn,and the average rank of image quality score of group E was the lowest in two comparisons.There were statistical differences between group A,group B,group C and group D(P<0.05).A total of 32 patients had adverse reactions 24 hours after iodine exposure,including post-sternal pain(n = 3),post-sternal discomfort(n = 7),nausea(n = 2),post-sternal cold feeling(n = 2),and abdominal pain or discomfort(n = 18),the incidence of adverse reactions among groups had no statistical difference(P>0.05).19 cases of suspected lesions after iodine staining were detected,only 2 cases of early esophageal cancer confirmed bypathology.Part II:A total of 40 patients were enrolled in this study,with 10 patients in each group.There was no significant difference in endoscopic operation satisfaction score and image quality score between the four groups(P>0.05).There was no significant difference in the rate of complete endoscopic resection of esophageal mucosal lesions between the four groups(P>0.05).ConclusionsThe concentration of 1.0%-0.6%Lugol’s solution do not reduce the imaging quality of Lugol’s solution staining endoscopy for esophageal lesions,but reduce the resistance of endoscopy operation after iodine staining of esophagus,improve the efficiency and quality of endoscopy,so it should be used in the diagnosis and treatment of early ESCC and precancerous lesions.Significance of the studyThis is the first study to explore the efficacy and safety of low concentration Lugol’s solution in detecting early esophageal squamous cell carcinoma and precancerous lesions.In the first part,the pilot test found that Lugol’s solution with a concentration of 1.0%-0.6%could effectively reduce the unsatisfactory degree of endoscopic surgeons after iodine staining without reducing the image quality of iodine staining in the screening population for early esophageal cancer.The second part of the validation test confirmed the feasibility of Lugol’s solution with concentration of 1.0%-0.6%to define the lesion range of early esophageal cancer and precancerous lesions.This study focused on the high-quality Lugol’s solution esophageal staining method.The quality and adverse reactions of Lugol’s solution staining were included in the analysis.The patients were followed up 24 hours after operation,which accorded with the concept of precise medicine and filled the gap of evidence for screening and diagnosing esophageal cancer with different concentrations of Lugol’s solution.It has a strong clinical significance.