The Endoscopic Findings,pathological And Prognosis Analysis Of Superficial Esophageal Squamous Cell Carcinoma And Precancerous Lesions

BackgroundChina,as a high-risk area for esophageal cancer,accounted for about 50%of morbidity and mortality in the world.Squamous cell carcinoma is the main pathological type in China.Esophageal squamous cancer limited to the mucosal or submucosal layer is called superficial squamous esophageal cancer(SESC),which has a good prognosis of patients with a 5-year survival of 85-95%.Iodine staining combined with biopsy is a common method used to screen SESC and precancerous lesions,but there existd problems such as strong irritant of iodine,strong post-sternal burning sensation,and no application to allergic patients.Narrow band imaging(NBI)has been widely used,but domestic studies on the value of different IPCL types in predicting lesion depth and the analysis of related factors are still scarce.Endoscopy submucosal resection(ESD)is the standard treatment for SESC without lymph node metastasis.Though it has the advantages of en-bloc resection,there exist shortcomings such as difficulty in operation and more complications.As for SESC with invasion to mucosal muscle or superficial submucosal layer(M3-SM1)which have the high risk of lymph node metastasis,it is controversial whether ESD is the first line treatment.Basal layer type squamous cell carcinoma(Basal layer type SCC)is a special subtype of ESCC,whose dysplasia cells are only confined to subepithelial 1/2,highly similar to LGIN.So far,only a few case reports have been published which involved the endoscopic and pathological features of basal layer type SCC.Most Chinese pathologists make a pathological diagnosis according to WHO criteria and have a limited understanding of basal layer type SCC proposed by Japanese pathologists.The development of ESCC is a multi-stage process accompanying a series of abnormal gene and protein expression.The specific proteins on the cancerous pathway are expected to provide an objective basis to determine the nature and infiltration depth of intractable esophageal lesions.Chapter 1 The diagnostic value of endoscopy and pathological biopsy in superficial esophageal squamous cell carcinoma and precancerous lesionsObjectiveTo evaluate the diagnostic value of LCE,NBI and pathological biopsy in SESC and precancerous lesions,and identify the related factors.MethodsFrom January 2010 to January 2018,we retrospectively reviewed the clinical data of patients with SESC or precancerous lesions who received ESD treatment at Nanfang Hospital.We used consistency test and chi-square analysis to compare the effectiveness of NBI-BC and LCE-PS signs in identifying SESC from precancerous lesions.We compared the value of Ione's and JES classification on SESC depth prediction,then analyzed the related factors affecting JES classification.Differences between biopsy and postoperative pathology were also analyzed.Results112 patients containing 120 lesions were included.Consistency between PS,BC and postoperative pathology were relatively strong and moderate,respectively(Kappa=0.721vs 0.521).The negative predictive value of PS in distinguishing SESC from precancerous lesions was significantly higher than BC(73.7%vs 57.9%),but there were no significant differences in sensitivity,specificity,positive predictive value,and overall accuracy.There were no differences in sensitivity,specificity,positive predictive value,negative predictive value and overall accuracy between Inoue's and JES classification in predicting SESC depth.Univariate analysis showed the length and circumference of the lesion combined the Paris classification were related to inadequate depth prediction of the JES classification(P<0.05).Multivariate analysis revealed that shallow depression of lesion(OR=4.740,P=0.007)was independent risk factor of inadequate depth prediction of the JES classification.The overall underdiagnosis rate of SESC and precancerous lesions reached 43.3%(52/120)via preoperative biopsy method.ConclusionThe diagnostic efficacy of LCE-PS in distinguishing SESC from precancerous lesions is superior to that of NBI-BC.The ability of JES classification to predict the infiltration depth of lesion is not different from Inoue's classification.The shallow depression of lesions is the factor that affects the prediction of the infiltration depth by JES classification.The coincidence rate between biopsy and postoperative pathology is low,especially for LGIN or chronic inflammation lesions suggested by biopsy.Chapter 2 The effectiveness and safety of ESD in the treatment of superficial esophageal squamous cell carcinoma and precancerous lesions and analysis of related factorsObjectiveTo evaluate the safety and effectiveness of ESD on SESC and precancerous lesions,and explore the relevant factors of postoperative esophageal stenosis.MethodsFrom January 201 0 to January 2018,we retrospectively reviewed clinical data of patients with SESC or precancerous lesions who received ESD treatment at Nanfang Hospital.The effectiveness and safety of ESD treatment were analyzed,especially M3SM1 lesions.Besides,univariate and multivariate analysis were performed to explore the independent risk factor of esophageal stenosis.Results147 patients containing 160 lesions were included.The rate of en-bloc resection and R0 resection,the incidence of bleeding and perforation were 97.5%,88.13%,0.63%,and 6.25%,respectively.The R0 resection rate of M3-SM1 was significantly lower than that of M1-M2(75%vs 92.6%,P=0.026),and the incidence of postoperative stenosis was significantly higher than that of M1-M2(35.7%vs 12.8%,P=0.006).The two group showed no statistical differences between R1 resection rate and complications.The 1-year recurrence free survival(RFS)of SESC were 94.9%.The 2year RFS was 88.1%in patients followed up for more than 2 years.The 6-,12-and 24months RFS of the M3-SM1 group were significantly lower than those of the M1-M2 group(LogRank P<0.05)Univariate analysis showed that body mass index(BMI),mucosal defect circumference>3/4,erosion or ulcer in lesions,muscularis propria injury and depth of invasion?M3 were correlated with post-ESD stenosis(P<0.05).Multivariate analysis revealed that BMI<18.5(OR=12.043,P=0.014)erosion or ulcer in lesions(OR=7.2,P=0.033)and mucosal defect circumference>3/4(OR=56.361,P<0.001)were independent risk factors for stenosis.ConclusionESD is a safe and effective way to treat SESC and precancerous lesions with mild ESD-related complications and satisfactory short-term results.The short-term relapsefree survival rate of M3-SM1 SESC is lower than that of M1-M2,so the follow-up should be strictly conducted.Mucosal defect circumference>3/4,thin body(BMI<18.5)and erosion or ulceration of the lesion were independent risk factors for stenosis.Chapter 3 The endoscopic and pathological findings of a special type of superficial esophageal cell carcinoma-Basal layer type squamous cell carcinomaObjectiveThe clinical endoscopic and pathological characteristics of patients with basal layer type SCC were analyzed to provide a reference to the early detection and diagnosis of such lesions.MethodsThis study collected endoscopic pathology data of patients who received ESD in Nanfang Hospital due to suspected SESC or precancerous lesions from January 2010 to January 2018.The HE slides of ESD specimen were digitally scanned and observed.Thus,the lesions were divided into the "basal layer type SCC" group and the"traditional SCC" group according to whether the lesions containing basal layer type SCC components.The distinctive endoscopic findings and infiltration patterns of the"basal layer type SCC" group were explored.The cumulative recurrence rate(CRS)of the two groups were compared.ResultsA total of 96 patients were included.Except 8 ESD defined LGIN,the basal layer type SCC group had 32 patients containing 55 independent basal layer type SCC lesions,and the traditional SCC group had 56 patients.Univariate analysis showed that multiple deep stained small foci in the iodine-free area and irregular iodine-free boundary were correlated with the presence of basal layer type SCC component(P<0.05).Multivariate analysis revealed that multiple deeply stained small foci(?5)in the iodine-free area were independent risk factors of basal layer type SCC(OR=4.680 P=0.005).The recurrence rate of basal layer type SCC group and traditional group were 13.79%(4/29)and 4%(2/50),respectively.There were no statistical difference in the cumulative recurrence rates between the two groups at 12 months and 24 months(P>0.05).ConclusionBasal layer type SCC is an invasive malignant tumor with marked cellular atypia.When the lesions present multiple scattered deep stained foci in the iodine-free area,the presence of basal squamous cell carcinoma should be fully warned.ESD has a good therapeutic effect on basal layer type SCC,similaring to traditional squamous cell carcinoma.But the former is suggested to conduct closer endoscopic follow-up.Chapter 4 The value of TRIP13 in the identification of the nature and invasion depth of superficial esophageal lesionsObjectiveTo explore the genes with different expression through bioinformatics analysis,so as to assist the pathological diagnosis of different degrees of SESC and precancerous lesions.MethodsThe gene expression chip dataset GSE 38129 with samples of Human esophageal squamous cell carcinoma tissue and normal tissues was downloaded from the GEO platform.The differentially expressed genes(|log2FC|?and P<0.05)were identified by R packages.The GO and pathway enrichment analysis of differentially expressed genes were analysed by DAVID.Thyroid hormone receptor interactor 13(TRIP 13),a coding gene with significant expression,was elected for immunohistochemistry to analyze its differential expression in SESC with different invasion depths and precancerous lesions.ResultsThrough the analysis of GSE 38129,a total of 801 significantly differentially expressed genes were obtained with 433 up-regulated genes and 369 down-regulated genes.Differential genes were mainly enrichment in cell differentiation,collagen catabolism and extracellular matrix G1/S phase transformation etc,and involved in 35 signal pathways,such as DNA replication,extracellular matrix receptor interaction,P53 signaling pathway,and mismatch repairs etc.TRIP 13,as one of the first 15 differentially expressed genes,differentially expressed in SESC with different invasion depths.The sensitivity and specificity of its positive expression in identifying LGIN and HGIN or above lesions were 90.48%and 91.67%,respectively.The sensitivity and specificity of strong positive expression in the differential diagnosis of HGIN-M2 and M3-SM1 lesions were 85.71%and 74.07%,respectively.ConclusionTRIP 13 showed good sensitivity and specificity in the identification of esophageal lesions,and its positive expression is highly suggestive of HGIN or above.The strong positive expression of TRIP 13 also has a good sensitivity and specificity for the differentiation between M3-SM1 and HGIN-M2,which could provide an objective basis to identify SESC lesions with difficulty in diagnosis of infiltration depth.