Predicting preoperative lymph node metastasis in esophageal cancer:Advancement and challenges

Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer.In this letter,we present our insights and opinions on a new nomogram proposed by Xu et al.Although this research has great potential,there are still concerns re-garding the small sample size,limited consideration of biological complexity,subjective image segmentation,incomplete image feature extraction and statistical analyses.Furthermore,we discuss how to achieve more robust and accurate predictive performance in future research.

Prediction of lymph node metastasis in early esophageal cancer

BACKGROUND Given the poor prognosis of patients with lymph node metastasis,estimating the lymph node status in patients with early esophageal cancer is crucial.Indicators that could be used to predict lymph node metastasis in early esophageal cancer have been reported in many recent studies,but no recent studies have included a review of this subject.AIM To review indicators predicting lymph node metastasis in early esophageal squamous cell carcinoma(ESCC)and early esophageal adenocarcinoma(EAC).METHODS We searched PubMed with“[early esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[early esophageal carcinoma(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[superficial esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)].”A total of 29 studies were eligible for analysis.RESULTS Preoperative imaging(size),serum markers(microRNA-218),postoperative pathology and immunohistochemical analysis(depth of invasion,tumor size,differentiation grade,lymphovascular invasion,neural invasion,expression of PIM-1<30%)were predictive factors for lymph node metastasis in both early ESCC and EAC.Serum markers(thymidine kinase 1≥3.38 pmol/L;cytokeratin 19 fragment antigen 21-1>3.30 ng/mL;stathmin-1)and postoperative pathology and immunohistochemical analysis(overexpression of cortactin,mixed-lineage leukaemia 2,and stanniocalcin-1)were predictive for lymph node metastasis in early ESCC.Transcription of CD69,myeloid differentiation protein 88 and toll-like receptor 4 and low expression of olfactomedin 4 were predictive of lymph node metastasis in early EAC.A total of 6 comprehensive models for early ESCC,including logistic regression model,nomogram,and artificial neural network(ANN),were reviewed.The areas under the receiver operating characteristic curve of these models reached 0.789-0.938,and the ANN performed best.As all these models relied on postoperative pathology,further models focusing on serum markers,imaging and immunohistochemical indicators are still needed.CONCLUSION Various factors were predictive of lymph node metastasis in early esophageal cancer,and present comprehensive models predicting lymph node metastasis in early ESCC mainly relied on postoperative pathology.Further studies focusing on serum markers,imaging and immunohistochemical indicators are still in need.

Clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer

Objective To investigate the clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer. Methods One hundred and twenty-four patients who had undergone thoracic esophageal resection with recurrent laryngealnerve lymph node dissection in our hospital from March 2007 to February 2010. All clinical data were retrospectively analysed. Results Recurrent laryngeal

Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer

Accurate preoperative prediction of lymph node metastasis(LNM)in esophageal cancer(EC)patients is of crucial clinical significance for treatment planning and prognosis.AIM To develop a clinical radiomics nomogram that can predict the preoperative lymph node(LN)status in EC patients.METHODS A total of 32 EC patients confirmed by clinical pathology(who underwent surgical treatment)were included.Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy,and its correlation with LNM was analyzed.Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python.Feature extraction,data dimensionality reduction,and feature selection were performed using XGBoost model and leave-one-out cross-validation.Multivariable logistic regression analysis was used to establish the prediction model,which included radiomics features,LN status from computed tomography(CT)reports,and B7-H3 mRNA expression,represented by a radiomics nomogram.Receiver operating characteristic area under the curve(AUC)and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical application value of the model.RESULTS The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis,and the difference was statistically significant(P<0.05).The AUC value in the receiver operating characteristic(ROC)curve was 0.718(95%CI:0.528-0.907),with a sensitivity of 0.733 and specificity of 0.706,indicating good diagnostic performance.The individualized clinical prediction nomogram included radiomics features,LN status from CT reports,and B7-H3 mRNA expression.The ROC curve demonstrated good diagnostic value,with an AUC value of 0.765(95%CI:0.598-0.931),sensitivity of 0.800,and specificity of 0.706.DCA indicated the practical value of the radiomics nomogram in clinical practice.CONCLUSION This study developed a radiomics nomogram that includes radiomics features,LN status from CT reports,and B7-H3 mRNA expression,enabling convenient preoperative individualized prediction of LNM in EC patients.

Neoadjuvant chemoradiotherapy for esophageal cancer:Impact on extracapsular lymph node involvement

AIM:To assess the effects of neoadjuvant chemoradiotherapy(CRT) on the presence of extracapsular lymph node involvement(LNI) and its prognostic value in patients with resected esophageal cancer.METHODS:Two hundred and ninety-eight patients with advanced esophageal cancer underwent esophagectomy between 1997 and 2006.One hundred and ninety patients(63.8%) were treated with neoadjuvant CRT prior to resection.A total of 986 metastatic LNs were examined.Survival of the patients was analyzed according to intra-and extra-capsular LNI.RESULTS:Five-year survival rate was 22.5% for the entire patient population.Patients with extracapsular LNI had a 5-year survival rate of 16.7%,which was comparable to the 15.8% in patients with infiltrated nodes of the celiac trunk(pM1lymph).In contrast to patients treated with surgery alone,neoadjuvant therapy resulted in signif icantly(P = 0.001) more patients with pN0/M0(51.6% vs 25.0%).In 17.6% of the patients with surgery alone vs 16.8% with neoadjuvant CRT,extracapsular LNI was detected.Neoadjuvant therapy does not reduce the occurrence of extracapsular LNI.CONCLUSION:Extracapsular LNI is an independent negative prognostic factor not influenced by neoadjuvant CRT.In a revised staging system for esophageal cancer,extracapsular LNI should be considered.

A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Superficial esophageal squamous cell carcinoma(SESCC)is defined as carcinoma with mucosal or submucosal invasion,regardless of regional lymph node metastasis(LNM).The lymph node status is not only a key factor to determine the training strategy,but also the most important prognostic factor in esophageal cancer.In this study,we establish a clinical nomogram for predicting LNM in patients with SESCC.A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018.A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation.Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed(concordance index[C-index],0.860;95%confidence interval[CI],0.825-0.894)through internal validation.The external validation cohort presented good discrimination(C-index,0.916;95%CI,0.860-0.971).This model may facilitate the prediction of LNM in patients with SESCCs.

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma.Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma.The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas.Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies.In human papillomavirus driven cancers,e.g.cervical,anogenital,head and neck cancers,associated lymph nodes with a high viral load suggest metastatic lymph node involvement.Thus,human papillomavirus could potentially be useful as a marker of micro-metastases.To date,there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma.This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.

Lymphatic spreading and lymphadenectomy for esophageal carcinoma

Esophageal carcinoma(EC) is a highly lethal malignancywith a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influences the outcome of surgical treatment for EC. However, the lymphatic drainage system of the esophagus, including an abundant lymph-capillary network in the lamina propria and muscularis mucosa, is very complex with cervical, mediastinal and celiac node spreading. The extent of lymphadenectomy for EC has always been controversial because of the very complex pattern of lymph node spreading. In this article, published literature regarding lymphatic spreading was reviewed and the current lymphadenectomy trends for EC are discussed.

Comparison of mini-probe endoscopic ultrasonography with computed tomography scan in preoperative staging of esophageal cancer

Objective:To compare mini-probe endoscopic ultrasonography(MCUS)with computed tomography(CT)in pre-operative T and N staging of esophageal cancer,and to find out the MCUS parameters to judge lymph nodes metastasis for esophageal cancer.Methods:Thirty-five patients received both MCUS and CT preoperatively,on both of which the T and N stages were determined.The accuracy,sensitivity,specificity,positive predicting value and negative predicting value were compared with the postoperative pathological results.Results:The accuracy of MCUS was 85.7% in T staging and 85.7% and 80.0% in N staging by two different methods,which were 45.7% and 74.3%,respectively,by CT.Conclusion:MCUS is better than CT in preoperative staging for esophageal cancer.The ratio of short to long axis(S/L)combined with short axis is a useful way to determine lymph nodes metastasis.

Value of serum VEGFC content detection for evaluating the clinical pathological characteristics and malignant degree of esophageal cancer

Objective:To analyze serum VEGF-C content in patients with esophageal cancer and its correlation with tumor stage, lymph node metastasis and cancer cell viability.Methods:A total of 112 patients with esophageal cancer treated in our hospital were selected as observation group, healthy subjects receiving physical examination in our hospital during the same time were selected as control group, serum VEGF-C content was compared between two groups of patients, and the correlation between VEGF-C level and tumor stage, lymph node metastasis as well as cancer cell viability was analyzed.Results:Serum VEGF-C level of observation group was higher than that of normal control group;serum tumor markers SCC, CEA, CA199, CA125 and CA50 levels were higher than those of normal control group;serum VEGF-C level of patients with esophageal cancer was positively correlated with tumor stage, lymph node metastasis and cancer cell viability.Conclusion: Serum VEGF-C content in patients with esophageal cancer is well correlated with tumor stage, lymph node metastasis and cancer cell viability, and regular detection of VEGF-C level can be the effective means to evaluate the therapeutic effect and predict treatment outcome.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Thoracic para-aortic lymph node recurrence in patients with esophageal squamous cell carcinoma:A propensity score-matching analysis

BACKGROUND Thoracic para-aortic lymph node(TPLN)recurrence in esophageal squamous cell carcinoma(ESCC)is rare and its impact on survival is unknown.We studied survival in patients with ESCC who developed TPLN recurrence.AIM To study the survival in patients with ESCC who developed TPLNs recurrence.METHODS Data were collected retrospectively for 219 patients who had undergone curative surgery for ESCC during January 2012 to November 2017 and who developed recurrences(36.29%of 604 patients who had undergone curative surgeries for ESCC).The patients were classified into positive(+)and negative(-)TPLN metastasis subgroups.We also investigated TPLN recurrence in 223 patients with ESCC following definitive chemoradiotherapy during 2012-2013.Following propensity score matching(PSM)and survival estimation,factors predictive of overall survival(OS)were explored using a Cox proportional hazards model.RESULTS Among the patients with confirmed recurrence,18 were TPLN(+)and 13 developed synchronous distant metastases.Before PSM,TPLN(+)was associated with worse recurrence-free(P=0.00049)and OS[vs TPLN(-);P=0.0027],whereas only the intergroup difference in recurrence-free survival remained significant after PSM(P=0.013).The Cox analysis yielded similar results.Among the patients who had received definitive chemoradiotherapy,3(1.35%)had preoperative TPLN enlargement and none had developed recurrences.CONCLUSION TPLN metastasis is rare but may be associated with poor survival.

Endoscopic submucosal dissection and surgical treatment for gastrointestinal cancer

Endoscopic submucosal dissection (ESD) is widely usedin Japan as a minimally invasive treatment for earlygastric cancer. The application of ESD has expanded tothe esophagus and colorectum. The indication criteriafor endoscopic resection (ER) are established for eachorgan in Japan. Additional treatment, including surgery with lymph node dissection, is recommended when pathological examinations of resected specimens donot meet the criteria. Repeat ER for locally recurrent gastrointestinal tumors may be difficult because of submucosal fibrosis, and surgical resection is required inthese cases. However, ESD enables complete resectionin 82%-100% of locally recurrent tumors. Transanal endoscopic microsurgery (TEM) is a well-developed sur-gical procedure for the local excision of rectal tumors.ESD may be superior to TEM alone for superficial rectaltumors. Perforation is a major complication of ESD,and it is traditionally treated using salvage laparotomy.However, immediate endoscopic closure followed byadequate intensive treatment may avoid the need forsurgical treatment for perforations that occur during ESD. A second primary tumor in the remnant stomach after gastrectomy or a tumor in the reconstructedorgan after esophageal resection has traditionally required surgical treatment because of the technical difficulty of ER. However, ESD enables complete resectionin 74%-92% of these lesions. Trials of a combination ofESD and laparoscopic surgery for the resection of gastric submucosal tumors or the performance of sentinellymph node biopsy after ESD have been reported, butthe latter procedure requires a careful evaluation of itsclinical feasibility.

芪贞归脾汤辅助治疗对食管癌伴锁骨上淋巴结转移患者细胞E-cadherin表达的影响

目的探讨芪贞归脾汤辅助治疗对食管癌伴锁骨上淋巴结转移患者细胞钙黏素(E-cadherin)表达的影响。方法选取2016年1月—2021年1月食管癌伴锁骨上淋巴结转移病例96例,随机编号方法分两组,各48例,对照组采用常规放疗;在此基础上,观察组采用芪贞归脾汤辅助治疗,持续治疗8周。治疗前后评价中医证候积分、匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)、免疫功能、细胞角蛋白19片段(cytokeratin 19 fragment,CYFRA21-1)、癌胚抗原(carcinoembryonic antigen,CEA)、癌抗原(cancer antigen 125,CA125)、E-cadherin和不良反应情况。结果观察组治疗后咽下困难、胸闷不舒、形体消瘦、气短乏力等积分低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后睡眠质量、入睡时间、睡眠时间、睡眠效率、睡眠障碍、催眠药物、日间功能障碍等评分低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后CD^(+)_(3)、CD^(+)_(4)、CD^(+)_(4)/CD^(+)_(8)高于对照组,CD^(+)_(8)低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后血清CYFRA21-1、CEA、CA125低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后E-cadherin阳性率72.92%高于对照组54.17%,差异有统计学意义(P<0.05)。两组放射性皮炎、恶心呕吐、白细胞减少、肝功能异常、神经毒性等不良反应比较,差异无统计学意义(均P>0.05)。结论芪贞归脾汤辅助治疗可以提高食管癌伴锁骨上淋巴结转移患者的免疫功能和睡眠质量,降低肿瘤标志物及E-cadherin的表达,安全性高。

基于右胸径路完全两野/三野清扫的胸段食管癌术后治疗失败模式分析

目的:观察胸腹完全两野清扫或颈胸腹三野清扫条件下,胸段食管癌术后复发率及复发模式,筛选术后高危复发人群,为辅助治疗合理策略制定提供依据。方法:对接受右胸径路根治性手术的胸段食管行回顾性分析,采用Kaplan-Meier法推算生存率,Binary Logistic回归模型筛选肿瘤复发风险因素。结果:共235例符合入排条件者纳入分析,基于术后病理的淋巴结转移率为51.9%,其中胸上段癌上纵隔区淋巴结转移率最高(44.1%),胸中段癌下纵隔区淋巴结转移率最高(35.3%),胸下段癌腹区淋巴结转移率最高(41.2%),同时任何部位食管癌都具有较高的上纵隔淋巴结转移率(25.5%~44.1%)。235例患者中有163例随访出具体治疗失败模式,疾病总复发率为47.9%(78/163)。区域性淋巴结转移是最常见的疾病复发模式,其次为远处转移(22.7%),吻合口和瘤床复发少见(6.7%)。在区域性淋巴结转移中,以颈区+上纵隔区淋巴结转移率较高(28.2%)。Logistic回归分析显示,男性、pT3-4期、pN+期及淋巴结清扫术式均是治疗失败的危险因素。结论:在右胸径路手术条件下,胸段食管癌仍然具有较高的术后高总复发率,区域性淋巴结转移和血行转移是最常见的治疗失败模式,在区域性复发中,仍以颈区+上纵隔区淋巴结转移率居高,对合并高危因素者(男性、胸上段癌、pT3-4期及pN+期),建议系统性系治疗联合辅助放疗。

VEGF、P53表达与食管癌淋巴结转移及其预后的相关性分析

目的分析血管内皮生长因子(VEGF)、P53表达与食管癌淋巴结转移与预后的关系。方法选取120例食管癌患者,采集其癌组织(观察组)与癌旁正常组织(对照组)标本,应用免疫组织化学法测定两组VEGF、P53表达差异;并收集患者资料,分析VEGF、P53阳性表达与食管癌临床病理特征的关系;另外随访3年,分析VEGF、P53阳性表达与食管癌患者预后的关系。结果观察组VEGF阳性率为69.17%(83/120)、P53阳性率为75.00%(90/120),均高于对照组的33.33%(40/120)、31.67%(38/120),差异有统计学意义(P<0.05);VEGF、P53阳性表达与淋巴结转移、TNM分期、分化程度、肿瘤最大径相关(P<0.05);VEGF、P53阳性表达患者的生存率低于阴性表达患者,差异有统计学意义(P<0.05)。结论VEGF、P53在食管癌组织内呈高表达,表达水平与患者的淋巴结转移、TNM分期、分化程度、肿瘤最大径等临床病理特征相关,且阳性表达患者预后更差。

食管鳞癌组织中BARD1的表达及与淋巴结转移的关系

目的分析食管鳞癌(ESCC)中乳腺癌易感基因1相关环指结构域蛋白1(BARD1)的表达及与淋巴结转移的关系。方法纳入2018年1月至2021年12月本院收治且经组织病理学检查确诊的114例ESCC患者,免疫组化EnVision两步法检测癌组织与癌旁组织中BARD1的表达情况并比较BARD1阳性率,分析BARD1表达与ESCC临床病理特征的关系,建立Logistic回归模型分析BARD1表达对ESCC淋巴结转移的影响,绘制受试者工作特征(ROC)曲线分析BARD1表达对ES⁃CC淋巴结转移的预测价值。结果114例ESCC组织中BARD1阳性78例、阴性36例,对应癌旁组织中BARD1阳性23例、阴性91例,ESCC组织的BARD1阳性率为68.42%,高于癌旁组织的20.18%(χ^(2)=53.769,P<0.001)。BARD1表达与ESCC患者的T分期、分化程度和淋巴结转移有关(P<0.05),其中淋巴结转移组织的BARD1阳性率为80.36%(45/56),高于未转移组织的56.90%(33/58)。经Phi系数分析发现,BARD1表达与ESCC淋巴结转移呈正相关(r=0.276,P=0.003)。BARD1阳性是ESCC患者淋巴结转移的独立危险因素(OR=3.099,95%CI:1.339~7.175,P=0.008),且BARD1表达对ESCC患者淋巴结转移具有一定预测价值(AUC=0.636,P=0.020)。结论BARD1在ESCC中高表达,其与ESCC淋巴结转移密切相关,BARD1阳性会增加淋巴结转移风险,在评估ESCC淋巴结转移上有一定价值。

2023年ESMO会议食管癌外科治疗相关研究热点

2023年欧洲肿瘤内科学会(European Society for Medical Oncology,ESMO)大会上食管癌外科治疗相关的研究有14项,涵盖新辅助免疫治疗的不同方案以及新辅助治疗的疗效评价方法和安全性等。同时,对于新辅助治疗后达到临床完全缓解的患者是否可以避免手术治疗,来自荷兰的一项研究也报道了中期随访结果。在食管癌淋巴结转移机制、吻合口瘘预测因子及新辅助免疫治疗疗效的分子机制研究方面也取得一定的进展。本次大会也有涉及针对接受食管癌手术治疗的患者围手术期营养支持的价值的相关研究。本文拟对这些研究进行概述,以勾勒出本次大会上食管癌外科相关的研究热点。

食管癌伴巨大颈部淋巴结转移1例

多种良恶性肿瘤均可能出现颈部肿物,在既没有其他系统症状又没有病理活组织检查的情况下难以做出正确诊断,容易贻误最佳治疗时机。以巨大颈部淋巴结转移伴疼痛为首发症状的食管癌患者较为少见。该文报道1例以巨大颈部淋巴结转移为首发表现的食管癌患者,患者接受多线治疗方案,病情虽反复进展,但仍达到了33个月的较长生存期。该文对食管癌伴巨大颈部淋巴结转移患者的临床表现、诊疗过程及预后进行报道,以期提高临床医师对食管癌淋巴结转移的认识水平,提高该病首诊率并及早治疗,使患者获得较高生活质量及更长生存期。

食管癌组织中E钙粘素、原黏蛋白α3的表达水平及临床意义

目的分析E钙粘素、原黏蛋白α3(PCDHA3)在食管癌组织内的表达及意义。方法选取90例食管癌患者,术中取其癌组织与癌旁正常组织,以免疫组织化学法检测PCDHA3表达。另收集患者年龄、性别等资料,探究PCDHA3表达与患者各项临床病理特征间的联系。结果癌组织中E钙粘素阳性表达率为12.22%(11/90)、PCDHA3阳性表达率为17.78%(16/90),低于癌旁组织中的64.44%(58/90)、47.78%(43/60),有统计学差异(P<0.05)。E钙粘素、PCDHA3表达与患者的TNM分期、分化程度、淋巴结转移有关(P<0.05)。结论E钙粘素、PCDHA3在食管癌组织内呈异常低表达,两者参与疾病的发生与发展。