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Xue L, Wang J, Kuang D, Yun J, Li Y, Jiang L, Wu D, Duan P, Lu S, Jin Y, He D, Qian J, Tang W, Wang Y, Li J, Ying J. The prevalence of PD-L1 expression in patients with advanced oesophageal cancer: the EXCEED observational study. J Clin Pathol 2025:jcp-2024-209721. [PMID: 39875188 DOI: 10.1136/jcp-2024-209721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 01/06/2025] [Indexed: 01/30/2025]
Abstract
AIMS There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in patients with advanced OC. METHODS The EXCEED study was a multicentre, retrospective analysis of data from six tertiary hospitals that evaluated PD-L1 expression in adults with advanced OC or advanced head and neck squamous cell carcinoma. PD-L1 expression was evaluated at each site according to a standardised protocol. The primary outcome was the prevalence of high PD-L1 expression (Combined Positive Score (CPS) ≥10) in surgical or tumour biopsy samples. Low PD-L1 expression was defined as CPS <10. Patient demographic and baseline factors associated with high PD-L1 expression were also investigated. This report presents the results for the OC cohort only. RESULTS Overall, 482 patients were included, the majority were male (87.6%) and the mean age at diagnosis was 63.3 years; 207 had high PD-L1 expression (42.9%; 95% CI 38.5, 47.5) and 275 had low expression (57.1%; 95% CI 52.5, 61.5). There were significant differences in high PD-L1 expression prevalence between subgroups by sex (p=0.044), number of distant metastases (p=0.020), and if chemotherapy (p=0.004) was received prior to the collection of biological samples (ie, biopsy or surgery). CONCLUSIONS These real-world data provide a robust estimate of the prevalence of high PD-L1 expression in patients with advanced OC and identify clinicopathological and treatment features related to PD-L1 expression that can inform treatment selection.
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Affiliation(s)
- Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jiaqi Wang
- Department of Pathology, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Dong Kuang
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
| | - Jingping Yun
- Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yuan Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lili Jiang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Daoyuan Wu
- Department of Pathology, Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Pei Duan
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
| | - Shixun Lu
- Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yan Jin
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Du He
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jing Qian
- Value & Implementation, Global Medical & Scientific Affairs, Merck Sharp & Dohme (MSD) China, Shanghai, China
| | - Wenmin Tang
- Value & Implementation, Global Medical & Scientific Affairs, Merck Sharp & Dohme (MSD) China, Shanghai, China
| | - Yan Wang
- Value & Implementation, Global Medical & Scientific Affairs, Merck Sharp & Dohme (MSD) China, Shanghai, China
| | - Jielin Li
- Value & Implementation, Global Medical & Scientific Affairs, Merck Sharp & Dohme (MSD) China, Shanghai, China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Min Q, Zhang M, Lin D, Zhang W, Li X, Zhao L, Teng H, He T, Sun W, Fan J, Yu X, Chen J, Li J, Gao X, Dong B, Liu R, Liu X, Song Y, Cui Y, Lu SH, Li R, Guo M, Wang Y, Zhan Q. Genomic characterization and risk stratification of esophageal squamous dysplasia. MEDICAL REVIEW (2021) 2024; 4:244-256. [PMID: 38919397 PMCID: PMC11195426 DOI: 10.1515/mr-2024-0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 04/15/2024] [Indexed: 06/27/2024]
Abstract
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.
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Affiliation(s)
- Qingjie Min
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Dongmei Lin
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Weimin Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xianfeng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Department of Gastroenterology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lianmei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Huajing Teng
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Tao He
- Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China
- Department of Pathology, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, China
| | - Wei Sun
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jiawen Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiying Yu
- Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jinting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaohan Gao
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bin Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, China
| | - Rui Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xuefeng Liu
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Yongmei Song
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongping Cui
- Shenzhen Peking University-The Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Shih-Hsin Lu
- Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | | | - Mingzhou Guo
- Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China
| | - Yan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Qimin Zhan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Peking University International Cancer Institute, Peking University, Beijing, China
- Soochow University Cancer Institute, Suzhou, China
- State Key Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing, China
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Liu L, Lin H, Shen G, Liu Y, Qin X, Yuan Y, Wang B, Xue L. Prognostic significance of lymphovascular invasion in patients with pT1b esophageal squamous cell carcinoma. BMC Cancer 2023; 23:370. [PMID: 37087442 PMCID: PMC10122816 DOI: 10.1186/s12885-023-10858-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 04/18/2023] [Indexed: 04/24/2023] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) is a crucial predictor of lymph node metastasis (LNM). However, few studies have investigated the LVI positivity rate and its clinical significance in pT1b esophageal squamous cell carcinoma (ESCC) using immunohistochemistry and elastin staining. METHODS We collected data from158 patients with pT1b ESCC who had undergone radical esophagectomy. All paraffin blocks of invasive carcinoma from each patient were subjected to HE staining, elastin staining + CK (AE1/AE3) immunohistochemistry (E&IHC), and CD31/D2-40 + CK (AE1/AE3) double immunohistochemistry (D-IHC). The LVI was classified into types, i.e., vascular invasion (VI) and lymphatic vessel invasion (LI), and its location, quantity, and clinical significance were explored. RESULTS The positivity rates of VI by E&IHC (E-VI), VI by CD31D-IHC (CD31-VI), and LI by D2-40 D-IHC (D2-40-LI) were significantly higher than those obtained by HE staining (P < 0.001, respectively). CD31-VI and E-VI were independent adverse prognostic factors for recurrence-free survival (RFS), and they were significantly associated with poor distant metastasis-free survival and overall survival in pT1b ESCC. Intratumoral LVI was also crucial in pT1b ESCC, and L2 (the count of D2-40-LI was 5 or more) was the strongest predictor for LNM and RFS in pT1b ESCC. CONCLUSION E&IHC and D-IHC can dramatically improve the detection rate of LVI in pT1b ESCC, and the classification and grading of LVI can help to improve the prediction of LNM and prognosis.
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Affiliation(s)
- Linxiu Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hua Lin
- Department of Medical Record, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Guihua Shen
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Liu
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiumin Qin
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanling Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Chen L, Peng K, Han Z, Yu S, Huang Z, Xu H, Kang M. Development and validation of a nomogram for preoperative prediction of lymph node metastasis in pathological T1 esophageal squamous cell carcinoma. Medicine (Baltimore) 2022; 101:e29299. [PMID: 35608431 PMCID: PMC9276106 DOI: 10.1097/md.0000000000029299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 03/28/2022] [Indexed: 01/04/2023] Open
Abstract
Endoscopic resection is increasingly used to treat patients with pathological T1 (pT1) esophageal squamous cell carcinoma (ESCC) because of its small surgical trauma. However, reports of the risk factors for lymph node metastasis (LNM) have been controversial. Therefore, we aim to build a nomogram to individually predict the risk of LNM in pT1 ESCC patients, to make an optimal balance between surgical trauma and surgical income.One hundred seventy patients with pT1 esophageal cancer in our hospital were analyzed retrospectively. Logistic proportional hazards models were conducted to find out the risk factor associated with LNM independently, and those were imported into R library "RMS" for analysis. A nomogram is generated based on the contribution weights of variables. Finally, decision analysis and clinical impact curve were used to determine the optimal decision point.Twenty-five (14.7%) of the 170 patients with pT1 ESCC exhibited LNM. Multivariable logistic regression analysis showed that smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree were independent risk factors for LNM. The nomogram had relatively high accuracy (C index of 0.869, 95% confidence interval: 0.794-0.914, P < .0001). The decision curve analysis provided the most significant clinical benefit for the entire included population, with scores falling just above the total score of 85 in the nomogram.Smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree may predict the risk of LNM in tumor 1 ESCC. The risk of LNM can be predicted by the nomogram.
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Affiliation(s)
- Ling Chen
- Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Kaiming Peng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ziyan Han
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Shaobin Yu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhixin Huang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Hui Xu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
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Zhang W, Chen H, Zhang G, Jin G. A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma. J Biomed Res 2021; 35:361-370. [PMID: 34628403 PMCID: PMC8502689 DOI: 10.7555/jbr.35.20210034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 11/04/2022] Open
Abstract
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.
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Affiliation(s)
- Weifeng Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210000, China
| | - Han Chen
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210000, China
| | - Guoxin Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210000, China
| | - Guangfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China
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Jiang KY, Huang H, Chen WY, Yan HJ, Wei ZT, Wang XW, Li HX, Zheng XY, Tian D. Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma: A systematic review and meta-analysis. World J Gastroenterol 2021; 27:737-750. [PMID: 33716451 PMCID: PMC7934003 DOI: 10.3748/wjg.v27.i8.737] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/20/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial.
AIM To evaluate risk factors for LNM in T1 ESCC.
METHODS We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model.
RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, P < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, P < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, P < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, P < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, P < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, P < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM.
CONCLUSION A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.
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Affiliation(s)
- Kai-Yuan Jiang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Heng Huang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Wei-Yang Chen
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Hao-Ji Yan
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Zhen-Ting Wei
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Wen Wang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Hao-Xuan Li
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiang-Yun Zheng
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Dong Tian
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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Xu W, Liu XB, Li SB, Yang ZH, Tong Q. Prediction of lymph node metastasis in superficial esophageal squamous cell carcinoma in Asia: a systematic review and meta-analysis. Dis Esophagus 2020; 33:5836484. [PMID: 32399558 DOI: 10.1093/dote/doaa032] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/15/2019] [Accepted: 01/17/2020] [Indexed: 12/11/2022]
Abstract
A less invasive endoscopic therapy has been used as a routine treatment for superficial esophageal squamous cell carcinoma (SESCC). However, lymph node metastasis (LNM) in SESCC limits the effectiveness of this medical procedure. This meta-analysis aimed to screen the risk factors for LNM in SESCC in Asia to provide evidence for clinicians in selecting treatment. We searched the main reference databases for research involving patients who received esophagectomy (open or minimally invasive) with lymph node dissection for SESCC. Meta-analysis was performed using RevMan 5.3 software. Twenty studies including 3983 patients were obtained in this analysis. The meta-analysis showed that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular involvement are risk factors of LNM in SESCC, whereas age, sex, and tumor location showed no association with LNM. Five variables were screened as predictive factors for LNM in SESCC. The incidence of LNM in SESCC is not rare, and the physicians must be careful when making clinical decisions.
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Affiliation(s)
- Wen Xu
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Xiao-Bo Liu
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Sheng-Bao Li
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Zhi-Hao Yang
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Qiang Tong
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
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Min BH, Yang JW, Min YW, Baek SY, Kim S, Kim HK, Choi YS, Shim YM, Choi YL, Zo JI. Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma. J Gastroenterol Hepatol 2020; 35:1009-1015. [PMID: 31674067 DOI: 10.1111/jgh.14915] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 10/10/2019] [Accepted: 10/22/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Knowledge of lymph node metastasis (LNM) status is crucial to determine whether patients with superficial esophageal squamous cell carcinoma (ESCC) can be cured with endoscopic resection alone, without the need for additional esophagectomy. The present study aimed to identify predictive factors and develop a prediction model for LNM in patients with superficial ESCC. METHODS Clinicopathologic data from 501 patients with superficial ESCC treated with radical esophagectomy were reviewed. Stepwise logistic regression analysis determined the predictors of LNM. Using these predictors, a nomogram for predicting the risk of LNM was constructed and internally validated using a bootstrap resampling method. RESULTS LNM rates of tumors invading the lamina propria, muscularis mucosa, and SM1 layers were 3.7%, 15.5%, and 40.7%, respectively. Deep tumor invasion depth, moderately or poorly differentiated histology, and lymphovascular invasion were independent predictors of LNM. ESCC with muscularis mucosa and SM1 invasion had odds ratios of 3.635 and 11.834, respectively, compared with that for ESCC confined to the lamina propria. Large tumor size (>2.0 cm) and presence of tumor budding showed borderline significance for LNM prediction. These five variables were incorporated into a nomogram. A constructed nomogram showed good calibration and good discrimination with an area under the receiver-operating characteristic curve (area under the curve [AUC]) of 0.812. After bootstrapping, AUC was 0.811. CONCLUSIONS We developed a nomogram that can facilitate individualized prediction of risk of LNM in patients with superficial ESCC. This model can aid in decision-making for the need for additional esophagectomy after endoscopic resection for superficial ESCC.
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Affiliation(s)
- Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung Wook Yang
- Department of Pathology, Gyeongsang National University Hospital, Jinju, South Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sun-Young Baek
- Statistics and Data Center, Samsung Medical Center, Seoul, South Korea
| | - Seonwoo Kim
- Statistics and Data Center, Samsung Medical Center, Seoul, South Korea
| | - Hong Kwan Kim
- Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong Soo Choi
- Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young Mog Shim
- Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yoon-La Choi
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jae Ill Zo
- Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Yang J, Lu Z, Li L, Li Y, Tan Y, Zhang D, Wang A. Relationship of lymphovascular invasion with lymph node metastasis and prognosis in superficial esophageal carcinoma: systematic review and meta-analysis. BMC Cancer 2020; 20:176. [PMID: 32131772 PMCID: PMC7057611 DOI: 10.1186/s12885-020-6656-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 02/18/2020] [Indexed: 12/19/2022] Open
Abstract
Background The development of tumor cells inside the lymphatics or blood vessels is known as lymphovascular invasion (LVI). The correlation between LVI, lymph node metastasis (LNM), and the diagnosis of superficial esophageal carcinoma (SEC) remains unclear. Methods We searched Embase, PubMed, Web of Science, and Cochrane Library databases for prospective articles to better understand the relationship between LVI, LNM, and SEC diagnosis. Results We included 23 articles containing data for 4749 patients (range: 54–598) in our meta-analysis. The hazard ratio between LVI and overall survival (OS) was 1.85 with 95% confidence interval (CI) (1.10–3.11, P = 0.02). LNM rate was higher in SEC patients with LVI than SEC patients without LVI (univariate: OR = 4.94, 95% CI: 3.74–6.53, P < 0.0001; multivariate: OR = 5.72, 95%CI: 4.38–7.4, P < 0.0001). No obvious publication was found. Conclusions The results indicate that LVI plays a dominant role in the prognosis of LNM in SEC and in the prognostic prediction for SEC.
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Affiliation(s)
- Jinxin Yang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Zhouyi Lu
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Lintao Li
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yong Li
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Yulong Tan
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Dekang Zhang
- Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
| | - An Wang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.
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10
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Wang A, Tan Y, Zhang Y, Xu D, Fang Y, Chen X, Wang S. The prognostic role of angiolymphatic invasion in N0 esophageal carcinoma: a meta-analysis and systematic review. J Thorac Dis 2019; 11:3276-3283. [PMID: 31559030 DOI: 10.21037/jtd.2019.08.50] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background Angiolymphatic invasion (ALI) plays an important role in lymph node metastasis. The presence of an ALI predicts a high risk for lymph node metastasis and a poor prognosis in patients with lymph node negative esophageal carcinoma. The independent prognostic value of ALI in node-negative patients remains controversial. A meta-analysis was conducted to investigate the relationship between ALI and prognosis in cases of lymph node negative esophageal carcinoma. Methods We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for studies on the relationship between ALI and the prognosis of patients with esophageal carcinoma. Studies with N0 patients' survival data related to ALI were included. The effect size (ES) was the hazard ratio (HR) with 95% confidence intervals (CI) for cancer-specific survival (CSS), overall survival (OS) and recurrence-free survival (RFS). Results A total of 9 studies with 2,154 patients were included after applying the inclusion and exclusion criteria. The pooled HR showed that patients with ALI have a poor cancer specific survival (HR =2.54; 95% CI, 1.84-3.51; P<0.001), a poor overall survival (HR =2.84; 95% CI, 2.17-3.72; P<0.001) and a short disease free survival (HR =2.84; 95% CI: 1.85-4.37; P<0.001). Conclusions ALI could be used as an indicator for identifying high-risk patients with lymph node-negative esophageal carcinoma and can be used as an indicator for sub-stages in further stage classification.
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Affiliation(s)
- An Wang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
| | - Yulong Tan
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
| | - Yuyan Zhang
- Suzhou Center for Disease Prevention and Control, Suzhou 215008, China
| | - Dong Xu
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
| | - Yuchao Fang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
| | - Xiaofeng Chen
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
| | - Shaohua Wang
- Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200400, China
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Lee JY, Kim YH, Park YJ, Park SB, Chung HW, Zo JI, Shim YM, Lee KS, Choi JY. Improved detection of metastatic lymph nodes in oesophageal squamous cell carcinoma by combined interpretation of fluorine-18-fluorodeoxyglucose positron-emission tomography/computed tomography. Cancer Imaging 2019; 19:40. [PMID: 31227017 PMCID: PMC6588863 DOI: 10.1186/s40644-019-0225-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 06/13/2019] [Indexed: 12/19/2022] Open
Abstract
Background We sought to evaluate the diagnostic performance of fluorine-18-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in the detection of metastatic lymph nodes by combined interpretation of PET/CT images in patients with oesophageal squamous cell carcinoma. Methods Two hundred three patients with oesophageal squamous cell carcinoma underwent 18F-FDG PET/CT before oesophagectomy and lymph node dissection. Maximum standardized uptake value (SUVmax), mean Hounsfield unit (HU), short axis diameter (size), and visual CT attenuation (high, iso-, low) were evaluated on noncontrast CT and PET images following PET/CT scan. In this combined interpretation protocol, the high attenuated lymph nodes were considered benign, even if the SUVmax value was high. The diagnostic accuracy of each method was compared using the postoperative histologic result as a reference standard. Results A total of 1099 nodal stations were dissected and 949 nodal stations were proven to demonstrate metastasis. SUVmax and size of the malignant lymph nodes were higher than those of the benign nodes, and visual CT attenuation was significantly different among the two groups (P < 0.001). Using cutoff values of 2.6 for SUVmax and 10.2 mm for size, the combined interpretation of an SUVmax of more than 2.6 with iso- or low CT attenuation [area under the curve (AUC): 0.846, 95% confidence interval (CI): 0.824–0.867] showed significantly better diagnostic performance for detecting malignant lymph nodes than SUVmax only (AUC: 0.791, 95% CI: 0.766–0.815) and size (AUC: 0.693, 95% CI: 0.665–0.720) methods (P < 0.001) in a receiver operating characteristic curve analysis. Conclusions The diagnostic accuracy of PET/CT for nodal metastasis in oesophageal squamous cell carcinoma was improved by the combined interpretation of 18F-FDG uptake and visual CT attenuation pattern.
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Affiliation(s)
- Ji Young Lee
- Department of Nuclear Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Young Hwan Kim
- Department of Nuclear Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yong-Jin Park
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Soo Bin Park
- Department of Radiology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Hyun Woo Chung
- Department of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Jae Il Zo
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Mog Shim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyung Soo Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
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Zhou Y, Du J, Wang Y, Li H, Ping G, Luo J, Chen L, Zhang S, Wang W. Prediction of lymph node metastatic status in superficial esophageal squamous cell carcinoma using an assessment model combining clinical characteristics and pathologic results: A retrospective cohort study. Int J Surg 2019; 66:53-61. [DOI: 10.1016/j.ijsu.2019.04.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 03/13/2019] [Accepted: 04/22/2019] [Indexed: 01/02/2023]
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Mei X, Zhu X, Zuo L, Wu H, Guo M, Liu C. Predictive significance of CYFRA21-1, squamous cell carcinoma antigen and carcinoembryonic antigen for lymph node metastasis in patients with esophageal squamous cancer. Int J Biol Markers 2019; 34:200-204. [PMID: 31088185 DOI: 10.1177/1724600819847999] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
From January 2018 to May 2018, 108 patients with thoracic esophageal cancer underwent esophagectomy with two- to three-field lymph node dissection. Serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen, and carcinoembryonic antigen levels were detected before surgery. Preoperative serum levels of CYFRA21-1 and squamous cell carcinoma antigen were correlated closely with pN stage ( P = 0.000 and P = 0.045). CYFRA21-1 and pathological T status were independent predictors of lymph node metastasis ( P = 0.000). The area under the curve values of CYFRA21-1 and squamous cell carcinoma antigen for predicting lymph node metastasis were 0.731 ( P =0.000) and 0.650 ( P =0.007), respectively. Our study demonstrated that serum CYFRA21-1 and squamous cell carcinoma antigen levels were associated with lymph node metastasis in esophageal squamous cell carcinoma, especially in patients at the early T stage. The preoperative serum CYFRA21-1 level was an independent predictor of lymph node metastasis.
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Affiliation(s)
- Xinyu Mei
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
| | - Xiaodong Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
| | - Lei Zuo
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
| | - Hanran Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
| | - Mingfa Guo
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
| | - Changqing Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
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Wu M, Wang Y, Yang D, Gong Y, Rao F, Liu R, Danna Y, Li J, Fan J, Chen J, Zhang W, Zhan Q. A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma. EBioMedicine 2019; 41:244-255. [PMID: 30876762 PMCID: PMC6442225 DOI: 10.1016/j.ebiom.2019.02.012] [Citation(s) in RCA: 189] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/06/2019] [Accepted: 02/06/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Targeting PLK1 has recently been proven as a viable therapeutic strategy against oesophageal squamous cell carcinom (ESCC). Therefore, this study aimed to explore whether the PLK1 inhibitor BI2536 is able to sensitize ESCC cells to cisplatin (DDP) and determine the underlying mechanisms. METHODS Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in ESCC cells treated with BI2536 or DDP alone or in combination. Checkpoint activation was examined by immunoblotting and immunohistochemistry. Xenograft model was used to assess the efficacy of the co-treatment. The expression level of GSDME in tissue samples were examined by immunohistochemistry. FINDINGS We found that the combination of BI2536 and DDP was synergistic in ESCC cells, which induced pyroptosis in ESCC cells at low doses. Mechanistic studies revealed that BI2536 significantly induced DNA damage and impaired the DNA damage repair pathway in DDP-treated cells both in vitro and in vivo. Interestingly, we found that co-treatment with BI2536 and DDP induced pyroptosis in ESCC cells depending on the caspase-3/GSDME pathway. Importantly, our study found that GSDME was more highly expressed in tumour tissue than that in normal adjacent tissues, and could serve as a prognostic factor. INTERPRETATION BI2536 sensitizes ESCC cells to DDP by inhibiting the DNA damage repair pathway and inducing pyroptosis, which provides new information for understanding pyroptosis. Our study also reveals that the PLK1 inhibitor BI2536 may be an attractive candidate for ESCC targeted therapy, especially when combined with DDP for treating the GSDME overexpression subtype. FUND: National 973 Program and National Natural Science Fundation of China.
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Affiliation(s)
- Mengjiao Wu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yan Wang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Di Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ying Gong
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Feng Rao
- Department of Orthopedics and Trauma, Peking University People's Hospital, Beijing, China
| | - Rui Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yeerken Danna
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jinting Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jiawen Fan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jie Chen
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Weimin Zhang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Qimin Zhan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
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15
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Xue LY, Qin XM, Liu Y, Liang J, Lin H, Xue XM, Zou SM, Zhang MY, Zhang BH, Hui ZG, Zhao ZT, Ren LQ, Zhang YM, Liu XY, Yuan YL, Ying JM, Gao SG, Song YM, Wang GQ, Dawsey SM, Lu N. Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma. World J Gastroenterol 2018; 24:5154-5166. [PMID: 30568392 PMCID: PMC6288646 DOI: 10.3748/wjg.v24.i45.5154] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/22/2018] [Accepted: 11/13/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To identify the clinicopathological characteristics of pT1N0 esophageal squamous cell carcinoma (ESCC) that are associated with tumor recurrence. METHODS We reviewed 216 pT1N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrence-free survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence (≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models. RESULTS Forty-seven (24%) patients had a recurrence at 3 to 178 (median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence (Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence. CONCLUSION These results should be useful for designing optimal individual follow-up and therapy for patients with T1N0 ESCC.
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Affiliation(s)
- Li-Yan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Center for Cancer Precision Medicine, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiu-Min Qin
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong Liu
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jun Liang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hua Lin
- Department of Medical Record, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xue-Min Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shuang-Mei Zou
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Mo-Yan Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bai-Hua Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- The 2nd Department of Thoracic Surgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, CSU, Changsha 410006, Hunan Province, China
| | - Zhou-Guang Hui
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zi-Tong Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Li-Qun Ren
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Pathology, Chengde Medical College, Chengde 067000, Hebei Province, China
| | - Yue-Ming Zhang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiu-Yun Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Ling Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jian-Ming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shu-Geng Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong-Mei Song
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Gui-Qi Wang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Sanford M Dawsey
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, United States
| | - Ning Lu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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16
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Wang M, Smith JS, Wei WQ. Tissue protein biomarker candidates to predict progression of esophageal squamous cell carcinoma and precancerous lesions. Ann N Y Acad Sci 2018; 1434:59-69. [PMID: 29882970 DOI: 10.1111/nyas.13863] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 04/16/2018] [Accepted: 05/01/2018] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most predominant malignancies worldwide. The 5-year survival rate is still relatively low due to few symptoms presenting with the early disease, diagnosis at middle to late stage, and high risk of recurrence after therapy. Novel protein biomarkers for early detection and treatment of ESCC have the potential to reduce incidence and mortality rates, and significantly prolong the 5-year survival rate. To date, several ESCC biomarkers are being investigated for screening, diagnosis, and treatment to decrease the disease burden. This review summarizes recent developments in candidate protein biomarkers for early diagnosis, predictors for precancerous disease progression, and prognosis of ESCC. Protein biomarkers that enable identification of the different pathologic grades of ESCC will need to be identified. ESCC biomarkers have the potential to improve screening and treatment strategies; multicenter prospective studies with large sample sizes will be required to confirm the usefulness of these candidate biomarkers.
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Affiliation(s)
- Meng Wang
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jennifer S Smith
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Wen-Qiang Wei
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Wang S, Xi J, Lin Z, Hao J, Yao C, Zhan C, Jiang W, Shi Y, Wang Q. Clinical values of Ku80 upregulation in superficial esophageal squamous cell carcinoma. Cancer Med 2018. [PMID: 29532618 PMCID: PMC5911598 DOI: 10.1002/cam4.1314] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Ku80 is an important DNA repair protein. Here, this study sought to investigate clinical impacts of Ku80 expression for patients with superficial esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis of Ku80 expression was carried out in normal esophageal mucosa, squamous epithelial dysplasia, carcinoma in situ, and superficial ESCC. Its relationships with clinicopathological features and survival of superficial ESCC patients were further clarified. Lentivirus-mediated RNA interference was used to silence Ku80 gene in ECA109 and KYSE150 cells. Both quantitative real-time PCR and Western blot were employed to evaluate Ku80 levels. CCK-8 assay, clone formation assay, flow cytometry, and tumorigenesis experiment were performed to evaluate the malignant phenotype of ECA109 and KYSE150 cells. Increased Ku80 expression was observed in dysplastic esophageal mucosa and carcinoma in situ compared to normal esophageal mucosa (P < 0.001, P < 0.001). Ku80 expression was further increased in superficial ESCC in comparison with dysplastic esophageal mucosa and carcinoma in situ (P < 0.001, P = 0.034). In superficial ESCC, Ku80 overexpression was related to tumor differentiation (P = 0.017), T status (P = 0.011), nodal involvement (P = 0.005), TNM stage (P = 0.004), and postoperative recurrence (P = 0.008). Cox proportional hazards regression showed tumor differentiation, T status, nodal involvement, TNM stage, and Ku80 expression were both independent predictors of patients' overall survival and disease-free survival. Ku80 shRNA effectively reduced Ku80 expression, which significantly inhibited proliferation, clone formation, and induced apoptosis in ECA109 and KYSE150 cells. The tumor growth of xenografts was significantly reduced by Ku80 silencing in ECA109 and KYSE150 cells. Ku80 overexpression associates with unfavorable prognosis of superficial ESCC patients, and silencing of Ku80 could inhibit the malignant behavior of ESCC cells. We provide evidence that Ku80 has unrecognized roles in carcinogenesis and development of ESCC.
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Affiliation(s)
- Shuai Wang
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Junjie Xi
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Zongwu Lin
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Jiatao Hao
- General Practice DepartmentZhongshan HospitalFudan UniversityShanghaiChina
| | - Can Yao
- Department of GastroenterologyZhongshan HospitalFudan UniversityShanghaiChina
| | - Cheng Zhan
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Wei Jiang
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Yu Shi
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Qun Wang
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
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18
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Wang P, Shan L, Xue L, Zheng B, Ying J, Lu N. Genome wide copy number analyses of superficial esophageal squamous cell carcinoma with and without metastasis. Oncotarget 2018; 8:5069-5080. [PMID: 27974698 PMCID: PMC5354893 DOI: 10.18632/oncotarget.13847] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 11/21/2016] [Indexed: 01/08/2023] Open
Abstract
Superficial esophageal squamous cell carcinoma (ESCC) is generally considered a subtype of less invasive ESCC. Yet a subset of these superficial ESCC would have metastasis after esophagostomy or endoscopic resection and lead to poor prognosis. The objective of this study is to determine biomarkers that can identify such subset of superficial ESCC that would have metastasis after surgery using genome wide copy number alteration (CNA) analyses. The CNAs of 38 cases of superficial ESCCs originated from radical surgery, including 19 without metastasis and 19 with metastasis within 5 years’ post-surgery, were analyzed using Affymetrix OncoScan™ FFPE Assay. A 39-gene signature was identified which characterized the subset of superficial ESCC with high risk of metastasis after surgery. In addition, recurrent CNAs of superficial ESCC were also investigated in the study. Amplification of 11q13.3 (FGF4) and deletion of 9p21.3 (CDKN2A) were found to be recurrent in all 38 superficial ESCCs analyzed. Notably amplifications of 3p26.33 (SOX2OT), 8q24.21 (MYC), 14q21.1 (FOXA1) and deletion of 3p12.1 (GBE1) were only found to be recurrent in metastaic superficial ESCCs. In conclusion, using CNAs analyses, we identify a 39-gene signature which characterizes the high risk metastatic superficial ESCCs and discover several recurrent CNAs that might be the driver alterations in metastasis among superficial ESCCs.
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Affiliation(s)
- Pengjiao Wang
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Ling Shan
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Bo Zheng
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Ning Lu
- Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
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19
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Kadota T, Yano T, Fujita T, Daiko H, Fujii S. Submucosal Invasive Depth Predicts Lymph Node Metastasis and Poor Prognosis in Submucosal Invasive Esophageal Squamous Cell Carcinoma. Am J Clin Pathol 2017; 148:416-426. [PMID: 29069275 DOI: 10.1093/ajcp/aqx093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVES Lymph node metastasis (LNM) in submucosal invasive esophageal squamous cell carcinoma (SM-ESCC) is a prognostic factor. The aim of this study was to identify a histopathologic predictor of LNM in SM-ESCC. METHODS In total, 108 patients who underwent an esophagectomy and lymph node dissection without preoperative therapy and who were pathologically diagnosed with SM-ESCC were enrolled in this study. Relationships between several clinicopathologic factors and LNM were examined. RESULTS A multivariate analysis revealed that a tumor size of 35 mm or more (P = .0025), submucosal invasive depth (SID) of 2,000 μm or more (P = .013), and lymphatic infiltration (P < .0001) were significant independent predictors of LNM. In addition, there were significant differences in recurrence-free survival curves between patients with SID less than 2,000 μm or not (P = .029) and tumor size less than 35 mm or not (P = .049). CONCLUSIONS This study suggests that SID may predict not only LNM but also poor prognosis.
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Affiliation(s)
| | | | - Takeo Fujita
- Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hiroyuki Daiko
- Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Satoshi Fujii
- Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan
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20
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Zhang W, Hong R, Xue L, Ou Y, Liu X, Zhao Z, Xiao W, Dong D, Dong L, Fu M, Ma L, Lu N, Chen H, Song Y, Zhan Q. Piccolo mediates EGFR signaling and acts as a prognostic biomarker in esophageal squamous cell carcinoma. Oncogene 2017; 36:3890-3902. [PMID: 28263981 DOI: 10.1038/onc.2017.15] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 01/19/2017] [Accepted: 01/20/2017] [Indexed: 02/07/2023]
Abstract
The presynaptic cytomatrix protein Piccolo, encoded by PCLO, is frequently mutated and amplified in esophageal squamous cell carcinoma (ESCC), but its exact roles in ESCC remain unclear. Here we report that Piccolo expression correlates significantly with clinical stage, patient survival and tumor embolus. Functional studies demonstrate that PCLO knockdown remarkably attenuates ESCC malignancy in vitro and in vivo, and ectopic EGFR expression partially compensates for Piccolo loss. PCLO knockdown promotes ubiquitination and degradation of EGFR, which is associated with the negative regulatory effect of Piccolo on E3 ligase Siah1. An anti-Piccolo monoclonal antibody inhibited tumor proliferation in a mouse model of ESCC. These results demonstrate that Piccolo contributes to tumor aggressiveness in ESCC, likely by stabilizing EGFR and promoting EGFR-dependent signaling. Our results further suggest that Piccolo may represent a novel prognostic biomarker and therapeutic target for patients with ESCC.
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Affiliation(s)
- W Zhang
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China.,Guangdong Koheala Precision Medicine Institute, Guangzhou, China
| | - R Hong
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - L Xue
- Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Y Ou
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China
| | - X Liu
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China
| | - Z Zhao
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - W Xiao
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - D Dong
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - L Dong
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - M Fu
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - L Ma
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - N Lu
- Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - H Chen
- Guangdong Koheala Precision Medicine Institute, Guangzhou, China
| | - Y Song
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Q Zhan
- State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Sichuan, China.,Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital &Institute, Beijing, China
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21
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Qi X, Li M, Zhao S, Luo J, Shao Y, Zhang Z, Chen Y. Prevalence of metastasis in T1b esophageal squamous cell carcinoma: a retrospective analysis of 258 Chinese patients. J Thorac Dis 2016; 8:966-76. [PMID: 27162673 PMCID: PMC4842799 DOI: 10.21037/jtd.2016.03.69] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 03/01/2016] [Indexed: 01/02/2023]
Abstract
BACKGROUND There is controversy regarding the impact of different depths of submucosal invasion on lymph node metastasis (LNM) and overall survival (OS). We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in a Chinese population with esophageal squamous cell carcinoma (ESCC). METHODS A total of 258 patients who underwent esophagectomy from November 2009 to March 2014 were studied. Demographics of patients, tumor characteristics, and surgical information were retrospectively collected through medical records. Submucosal invasion was equally categorized into inner one-third (sm1), middle one-third (sm2), and deep one-third (sm3) invasion by pathologists. The patients were observed at the outpatient department in accordance with appointed time and recurrence, and deaths were recorded. The median follow-up duration was 26 months and the deadline was April 2015. Cancer characteristics and its association with LNM and OS were analyzed. RESULTS The study included 75 (29.1%) sm1, 73 (28.3%) sm2, and 110 (42.6%) sm3 patients, and the rates of LNM were 12% (9/75), 11% (8/73), and 20.9% (23/110), respectively. sm3 might be associated with regional LNM (univariate analysis, P=0.041). Tumor volume >1.856 cm(3) (P=0.022) and lymphovascular invasion (LVI) (P=0.004) predicted LNM using multivariate analysis. No significant differences in distant metastases were observed according to the depth of invasion. Only metastatic lymph nodes predicted OS (P<0.001) rather than the depth of invasion. CONCLUSIONS Submucosal ESCC showed a substantial rate of LNM. In T1b ESCC, after adjusting for possible covariates, depth of invasion does not predict LNM or OS.
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22
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Nason KS. Minimal or maximal surgery for esophageal cancer? J Thorac Cardiovasc Surg 2016; 151:633-635. [DOI: 10.1016/j.jtcvs.2015.09.118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 09/29/2015] [Indexed: 02/07/2023]
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23
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Jansen M, Schölvinck DW, Kushima R, Sekine S, Weusten BL, Wang GQ, Fleischer DE, Yoshinaga S, Dawsey SM, Meijer SL, Bergman JJ, Oda I. Is it justified to ablate flat-type esophageal squamous cancer? An analysis of endoscopic submucosal dissection specimens of lesions meeting the selection criteria of radiofrequency studies. Gastrointest Endosc 2014; 80:995-1002. [PMID: 25434658 PMCID: PMC5763499 DOI: 10.1016/j.gie.2014.09.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Accepted: 09/01/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endoscopic radiofrequency ablation (RFA) appears to be a safe and effective treatment for flat-type noninvasive squamous neoplasia of the esophagus. However, if RFA is applied to lesions containing invasive cancer (esophageal squamous cell carcinoma [ESCC]), histological features associated with lymph node metastases may remain undetected. In addition, extension of neoplasia down the ducts of esophageal submucosal glands (SMGs) may create a sheltered "niche" beyond the reach of ablation. OBJECTIVE To determine the RFA eligibility of flat-type ESCC. DESIGN Retrospective analysis of prospectively collected data of ESCC patients. SETTING National Cancer Center Hospital, Tokyo, Japan. PATIENTS Patients with flat-type ESCC larger than 3 cm removed by endoscopic submucosal dissection (ESD). INTERVENTIONS Three endoscopists involved in RFA studies in China reviewed endoscopic images to select lesions eligible for RFA. Corresponding ESD resection specimens were histologically examined. MAIN OUTCOME MEASUREMENTS The presence of poor histological features (ie, invasion in m3 or deeper, poor tumor differentiation, or lymphovascular invasion) and the number of involved esophageal SMGs and ducts. RESULTS Sixty-five lesions were included, 17 (26%) of which qualified as RFA eligible by RFA endoscopists. Interobserver agreement for this assessment was poor (κ = 0.09). Six of the 17 specimens (35%) showed relevant disease: 4 lesions invaded in the muscularis mucosae, 1 of which also showed lymphovascular invasion; 2 lesions showed extension of neoplasia into SMGs. LIMITATIONS Limited number of cases. RFA eligibility status was based on analysis of still images. CONCLUSIONS One third of flat-type ESCC, deemed eligible for RFA, demonstrated histological features that are considered (relative) contraindications to endoscopic treatment. Because it appears difficult for endoscopists to identify low-risk ESCC, conservative use of RFA for flat-type ESCC is advocated until long-term follow-up data are available.
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Affiliation(s)
- Marnix Jansen
- Department of Pathology, Academic Medical Center, Amsterdam
| | - Dirk W. Schölvinck
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Ryoji Kushima
- Pathology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Shigeki Sekine
- Pathology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Bas L.A.M. Weusten
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Guiqi Q. Wang
- Department of Endoscopy, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - David E. Fleischer
- Department of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | | | - Sanford M. Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | | | | | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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24
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Qin X, He S, Zhang Y, Xue L, Lu N, Wang G. Diagnosis and staging of superficial esophageal precursor based on pre-endoscopic resection system comparable to endoscopic resection. BMC Cancer 2014; 14:774. [PMID: 25330811 PMCID: PMC4213488 DOI: 10.1186/1471-2407-14-774] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 10/11/2014] [Indexed: 01/13/2023] Open
Abstract
Background Endoscopic treatments for early esophageal squamous cell carcinoma and the esophageal neoplasm are two types: endoscopic resection (ER) and ablation. Resection enables evaluation of the lesion in the ER specimens, while ablation cannot. We sought to establish a pre-ER evaluated system with a diagnostic and staging accuracy similar to ER for the development of ablation therapy. Methods In our study, we collected data pertaining to early esophageal cancer and esophageal neoplasm treated with ER, analyzed the pre- and post-ER data of the lesions and evaluated the diagnostic accuracy of pre-ER system compared with the gold standard. Results The diagnostic accuracy rate was 91% based on the pre-ER system compared with the gold standard, and 93% based on the ER diagnosis. The AUC of the pre-ER system was 0.964, while the ER examination was 0.971. Conclusion These results suggest that the accuracy of pre-ER system was comparable to ER. The pre-ER system enables prediction of histological diagnosis and stage of the lesions, and the choice of treatment for superficial esophageal neoplasm.
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Affiliation(s)
| | | | | | | | | | - Guiqi Wang
- Department of Endoscopy, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
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25
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Moon SH, Kim HS, Hyun SH, Choi YS, Zo JI, Shim YM, Lee KH, Kim BT, Choi JY. Prediction of occult lymph node metastasis by metabolic parameters in patients with clinically N0 esophageal squamous cell carcinoma. J Nucl Med 2014; 55:743-8. [PMID: 24700884 DOI: 10.2967/jnumed.113.130716] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED The aim of this study was to investigate the value of (18)F-FDG parameters of the primary tumor in predicting occult lymph node metastasis in patients with clinically N0 esophageal squamous cell carcinoma. METHODS The study comprised 143 consecutive patients (mean age ± SD, 63.9 ± 8.6 y; range, 31.8-81.2 y) from May 2003 to January 2010 who had clinically N0 esophageal squamous cell carcinoma based on preoperative imaging studies including chest CT, (18)F-FDG PET/CT, and endoscopic ultrasound. We measured maximum standardized uptake value (SUV max), mean SUV (SUV mean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) of the primary tumor and analyzed the relationship between clinicopathologic variables including PET parameters and occult lymph node metastasis using a logistic regression model. RESULTS Univariate analysis indicated that clinical T classification, SUV max, SUV mean, MTV, TLG, and longitudinal diameter of tumor were significant risk factors associated with occult lymph node metastasis. Optimal thresholds were cT2-4, SUV max ≥ 4.8, SUV mean ≥ 3.2, MTV ≥ 5.5 cm(3), TLG ≥ 220, and diameter ≥ 3.8 cm. After multivariate analysis, the logistic regression model revealed that clinical T classification (hazard ratio [HR], 4.6; 95% confidence interval [CI], 1.7-12.4; P = 0.003) and SUV max (HR, 3.5; 95% CI, 1.3-9.2; P = 0.012) were independent risk factors. The combination of SUV max and clinical T classification (HR, 13.2; 95% CI, 5.4-31.9; P < 0.001) was a significantly better powerful risk factor for occult lymph node metastasis than SUV max or clinical T classification alone. Sensitivity, specificity, positive predictive value, and negative predictive value of the combination of clinical T classification and SUV max were 73.0%, 81.5%, 60.0%, and 89.7%, respectively. CONCLUSION SUV max, combined with clinical T classification, may be useful for predicting occult lymph node metastasis in patients with clinically N0 squamous cell carcinoma of the esophagus.
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Affiliation(s)
- Seung Hwan Moon
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; and
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