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.

Application of convolutional neural network-based endoscopic imaging in esophageal cancer or high-grade dysplasia: A systematic review and meta-analysis

BACKGROUND Esophageal cancer is the seventh-most common cancer type worldwide,accounting for 5%of death from malignancy.Development of novel diagnostic techniques has facilitated screening,early detection,and improved prognosis.Convolutional neural network(CNN)-based image analysis promises great potential for diagnosing and determining the prognosis of esophageal cancer,enabling even early detection of dysplasia.METHODS PubMed,EMBASE,Web of Science and Cochrane Library databases were searched for articles published up to November 30,2022.We evaluated the diagnostic accuracy of using the CNN model with still image-based analysis and with video-based analysis for esophageal cancer or HGD,as well as for the invasion depth of esophageal cancer.The pooled sensitivity,pooled specificity,positive likelihood ratio(PLR),negative likelihood ratio(NLR),diagnostic odds ratio(DOR)and area under the curve(AUC)were estimated,together with the 95%confidence intervals(CI).A bivariate method and hierarchical summary receiver operating characteristic method were used to calculate the diagnostic test accuracy of the CNN model.Meta-regression and subgroup analyses were used to identify sources of hetero-geneity.RESULTS A total of 28 studies were included in this systematic review and meta-analysis.Using still image-based analysis for the diagnosis of esophageal cancer or HGD provided a pooled sensitivity of 0.95(95%CI:0.92-0.97),pooled specificity of 0.92(0.89-0.94),PLR of 11.5(8.3-16.0),NLR of 0.06(0.04-0.09),DOR of 205(115-365),and AUC of 0.98(0.96-0.99).When video-based analysis was used,a pooled sensitivity of 0.85(0.77-0.91),pooled specificity of 0.73(0.59-0.83),PLR of 3.1(1.9-5.0),NLR of 0.20(0.12-0.34),DOR of 15(6-38)and AUC of 0.87(0.84-0.90)were found.Prediction of invasion depth resulted in a pooled sensitivity of 0.90(0.87-0.92),pooled specificity of 0.83(95%CI:0.76-0.88),PLR of 7.8(1.9-32.0),NLR of 0.10(0.41-0.25),DOR of 118(11-1305),and AUC of 0.95(0.92-0.96).CONCLUSION CNN-based image analysis in diagnosing esophageal cancer and HGD is an excellent diagnostic method with high sensitivity and specificity that merits further investigation in large,multicenter clinical trials.

HPV16型-E6、E7在食管鳞癌组织与非癌组织中的表达

背景与目的:越来越多的证据表明高危型人乳头状瘤病毒(humanpapillomavirus,HPV),特别是HPV16型与多种肿瘤发生、发展密切相关。本研究旨在分析人乳头状瘤病毒HPV16型E6、E7在食管正常组织、不典型增生组织和癌组织中的表达,以探讨HPV16型在食管鳞癌发生、发展中的生物学意义。方法:采用PicTureTM免疫组织化学方法对70例食管癌切除标本上、下切缘的正常粘膜上皮组织、43例不典型增生组织以及18例癌组织中的HPV16型E6、E7蛋白表达情况进行研究。结果:E6蛋白阳性率在正常食管粘膜上皮组织中为59.3%,在上皮不典型增生组织中为88.4%,在癌组织中为83.3%;E7蛋白在上述3种组织中的阳性率分别为62.1%、90.7%和88.9%。与正常食管粘膜上皮相比,上皮不典型增生组织和癌组织中E6、E7蛋白表达均有显著性差异(P<0.05)。HPV16型E6、E7蛋白在正常食管粘膜组织中同时表达即同步率为25.7%,而在上皮不典型增生组织和癌组织中二者同步率分别为88.3%和83.3%。结论:HPV16型E6、E7蛋白与食管鳞癌发生、发展密切相关,二者协同作用可能是食管鳞癌发生、发展的重要因素之一。

食管上皮高度不典型增生的处理

背景与目的：改善食管癌患者预后的最有效方法是早期诊断、早期治疗。食管上皮高度不典型增生患者可能存在早期癌变，处理方法存在争议。本研究探讨对内镜活检病理诊断为食管上皮高度不典型增生患者的处理。方法：对我院1999-2006年间10例术前内镜活检病理诊断为食管上皮高度不典型增生患者的术式、手术后并发症和疗效的分析，结合文献报道食管上皮高度不典型增生的处理方法，以探讨内镜活检病理诊断为食管上皮高度不典型增生病例的合适的处理措施。结果：10例内镜活检病理诊断为食管上皮高度不典型增生的患者经食管切除术后，病理证实原位癌2例（20％），浸润性癌8例（80％），区域淋巴结转移率为零，手术后30d内死亡率为零，围手术期颈部吻合口漏1例，经处理后2周漏口愈合。1例术后因非肿瘤疾患死亡，其余患者均长期无瘤生存（术后存活时间3～66个月）。结论：根据我们的临床资料，结合文献报道，认为大部分食管上皮高度不典型增生患者已经存在原位癌或浸润性癌，且相当部分高度不典型增生患者会转变成浸润性癌。外科切除食管目前是胸外科较成型术式，手术风险小，术后患者预后好，是食管内镜活检病理诊断为高度不典型增生患者的合适的治疗方法。

Clinical characteristics of young patients with early Barrett’s neoplasia

BACKGROUND Esophageal adenocarcinoma(EAC)and high-grade dysplasia(HGD)may appear in young patients with Barrett's esophagus(BE).However,characteristics of Barrett's-related neoplasia in this younger population remain unknown.AIM To identify clinical characteristics that differ between young and old patients with early-stage Barrett's-related neoplasia.METHODS We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early-stage EAC(pT1)and HGD at a tertiary-referral center between 2001 and 2017.Baseline characteristics,drug and risk factor exposures,clinicopathological staging of EAC/HGD and treatment outcomes[complete eradication of neoplasia(CE-N),complete eradication of intestinal metaplasia(CE-IM),recurrence of neoplasia and recurrence of intestinal metaplasia]were retrieved.Multivariate analyses were performed to identify factors that differed significantly between older and younger(≤50 years)patients.RESULTS We identified 450 patients with T1 EAC and HGD(74%and 26%,respectively);45(10%)were≤50 years.Compared to the older group,young patients were more likely to present with ongoing gastroesophageal reflux disease(GERD)symptoms(55%vs 38%,P=0.04)and to be obese(body mass index>30,48%vs 32%,P=0.04).Multivariate logistic regression analysis showed that young patients were significantly more likely to have ongoing GERD symptoms[odds ratio(OR)2.00,95%confidence interval(CI)1.04-3.85,P=0.04]and to be obese(OR 2.06,95%CI 1.07-3.98,P=0.03)whereas the young group was less likely to have a smoking history(OR 0.39,95%CI 0.20-0.75,P<0.01)compared to the old group.However,there were no significant differences regarding tumor histology,CE-N,CE-IM,recurrence of neoplasia and recurrence of intestinal metaplasia(mean follow-up,44.3 mo).CONCLUSION While guidelines recommend BE screening in patients>50 years of age,younger patients should be considered for screening endoscopy if they suffer from obesity and GERD symptoms.

Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcinoma

Gastric cardia adenocarcinoma(GCA)and esophageal squamous cell carcinoma(ESCC)present significant health challenges in China,often diagnosed at advanced stages with poor prognoses.However,effective biomarkers for early detection remain elusive.This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC.In the discovery stage,we conducted Infinium Methylation EPIC array analysis on 36 paired GCA and non-tumor adjacent tissues(NAT),identifying differentially methylated Cp G sites(DMCs)between GCA/ESCC and NAT through combined analyses of in-house and publicly available data.In the validation stage,targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50GCA and 50 ESCC patients.In the application stage,an independent set of 438 samples,including GCA,ESCC,high-and low-grade dysplasia(HGD/LGD),and normal controls,was tested for selected DMCs using pyrosequencing.Our analysis validated three GCA-specific,two ESCCspecific,and one tumor-shared DMCs,exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT.Leveraging these DMCs,we developed a GCA-specific 4-marker panel(cg27284428,cg11798358,cg07880787,and cg00585116)with an area under the receiver operating characteristic curve(AUC)of 0.917,effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls.Similarly,an ESCC-specific 3-marker panel(cg14633892,cg04415798,and cg00585116)achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases.Furthermore,integrating cg00585116,age,and alcohol consumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD(AUC,0.767;95%confidence interval,0.720–0.813).The mean AUC of the model after 5-fold cross-validation was 0.764.In summary,our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls.These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

DIGESTIVE TRACT

10.1 Esophagus2003217 The changes of immunologic function of lymphocyte and erythrocyte in esophageal carcinoma patients before and after operation. LIU Lihong(刘丽宏), et al. Dept Hematol, 4th Affili Hosp, Hebei Med U-niv, Shijiazhuang, 050011. Chin J Clin Oncol 2003; 20 (2)