Prediction of the Outcome of Esophageal Epithelium Dysplasia by High Resolution Image Analysis

Objective: To predict the outcome of dysplasia of esophageal epithelium by means of high resolution image analysis (HRIA). Methods: Asymptomatic adults were examined for balloon cytology of the esophagus in 1983 from Heshun Commune of Linxian County. 93 severe dysplasias and 122 mild dysplasias of the esophagus were selected. By means of an Axiomat-microscope equipped with TV-camera, 100 normal nuclei of well-preserved cells in the intermediate layer of Pap-stained squamous epithelium were randomly examined. Results: Of the 93 cytologically diagnosed severe dysplasia cases, 24, 14 and 7 progressed to carcinoma in 3, 5 and 9 years, respectively. In the other 48 cases, dysplasia remained stable or regressed to normal. The other cases were used as the control. According to chromatin features, correct diagnosis of cases was achieved by HRIA in 75.0% (18/24), 85.7% (12/14) and 85.7% (6/7) of the cases examined, respectively (P<0.001). Of the 122 cytologically diagnosed mild dysplasia, 16, 13 and 12 cases progressed to carcinoma in 3, 5 and 9 years, respectively. The other 81 cases remained stable or regressed to normal. Correct diagnosis was made by HRIA in 93.8% (15/16), 76.9% (10/13) and 83.3% (10/12) of the cases examined, respective1y (P<0.001). Conclusion: Chromatin nuclear features examined by HRIA can predict the outcome of precancerous lesions and discriminate progressor from non-progressor ones. It can be used as surrogate endpoint biomarkers for the evaluation of efficiency of chemo-prevention trial.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia

AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.

Management of esophageal mucosa with high-grade dysplasia

Objective:Early detection and treatment in patients with esophageal cancer is the most effective way to improve the prognosis. Patients with high-grade dysplasia(HGD) in esophageal mucosa might be involved with early esophageal cancer,but the management of the disease is controversial. The purpose of our study was to explore the management of esophageal mucosa with HGD. Methods:We retrospectively analyzed 10 patients with HGD in esophageal mucosa,who underwent esophagectomy in Cancer Hospital of Fudan University from 1999 to 2006. The surgical approach,postoperative morbidity,in-hospital complications and pathological results of the patients were analyzed. Basing on our data together with other studies,we aimed at looking for an appropriate management for patients with HGD. Results:Of the 10 patients who received esophagectomy,the pathological results showed that 2(20%) cases were in situ carcinoma and 8(80%) cases were invasive cancer with no regional lymph nodes involved. 30-day mortality was 0. One patient experienced cervical anastomotic leakage,but healed in 2 weeks. There was no pulmonary complication. Conclusion:Most patients with HGD actually have occult carcinoma. High percentage of patients with HGD would develop into cancer during their lifetime. Esophagectomy is now a selective approach for the treatment of the patients with HGD.

Genomic characterization and risk stratification of esophageal squamous dysplasia

Objectives:The majority of esophageal squamous dysplasia(ESD)patients progress slowly,while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment.However,the molecular mechanisms underlying these clinical observations are still largely unknown.Methods:By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma(ESCC)patients,we demonstrated lower somatic mutation and copy number alteration(CNA)burden in ESD compared with ESCC.Results:Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression.Furthermore,we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD.Conclusions:These findings largely expanded our understanding of ESD genetics and tumorigenesis,which possessed promising significance for improving early diagnosis,reducing overtreatment,and identifying high-risk ESD patients.

Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

AIM To determine the association of p53, carcinoembryonic antigen(CEA) and CA19-9 protein expression with esophageal carcinogenesis.METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia(BCH), 247 with low-grade dysplasia(LGD), 51 with high-grade dysplasia(HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROCcurve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

Assessment of the diagnostic performance and interobserver variability of endocytoscopy in Barrett's esophagus:A pilot ex-vivo study

AIM: To investigate a classification of endocytoscopy (ECS) images in Barrett&#x02019;s esophagus (BE) and evaluate its diagnostic performance and interobserver variability.

Diagnosis and therapy of esophageal squamous cell dysplasia and early esophageal squamous cell cancer

Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC)comprise the majority of esophageal cancers,and they differ from each other in several aspects.While the incidence of EAC is increasing in the West,ESCC is still the predominant cancer type worldwide.Squamous dysplasia is considered to be a premalignant lesion to ESCC;however,the exact probability and timeline of malignant transformation are not known,hence the lack of guidelines for management of such lesions.ESCC carries a poor prognosis if not detected early,so there has been a trend towards early detection and treatment.Diagnostic modalities include endoscopic ultrasound,white light endoscopy,non-endoscopic methods such as biomarkers,etc.Early diagnosis can identify a subset of patients who could benefit from less invasive endoscopic eradication therapies.This review aims to discuss the different modalities for diagnosis and treatment of early esophageal squamous lesions,including the newer endoscopic therapies,and comparison of different techniques.