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Wang XM, Liu CT, Huang JT, Zhang ZH, Xu YW, Wu FC, Peng YH. Development and validation of a prognostic model for patients with cT1-4N1-3M1 esophageal squamous cell carcinoma: based on the SEER database and the Chinese cohort study. Front Oncol 2025; 15:1547462. [PMID: 40356748 PMCID: PMC12066260 DOI: 10.3389/fonc.2025.1547462] [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: 12/18/2024] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
Objective The purpose of this study was to investigate the impact of clinicopathological factors on the overall survival (OS) of advanced esophageal squamous cell carcinoma (ESCC) patients with both lymph node and distant metastasis and build a nomogram for OS prediction. Method We selected 621 ESCC patients with cT1-4N1-3M1 stage without surgical treatment from the Surveillance, Epidemiology, and End Results (SEER) database and randomized (in a 7:3 ratio) to the training cohort and internal validation cohort. Another 159 patients were enrolled from the Cancer Hospital of Shantou University Medical College as the external validation cohort. A nomogram was developed based on independent risk factors that resulted from a multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the discriminative ability and calibration curves were constructed to evaluate the calibration ability. Kaplan-Meier survival analysis and log-rank tests were then used to predict the further OS status of these patients. Results The multivariate Cox regression analysis revealed that sex, T stage, radiotherapy, and chemotherapy were independent prognostic factors for ESCC patients with cT1-4N1-3M1 stage. All these factors were incorporated to construct a nomogram. The prognostic nomogram in training cohort exhibited the AUCs of 0.784, 0.746, and 0.735 for predicting 6-, 9-, and 12-month OS, respectively. Calibration curves exhibited that the nomogram-predicted OS were insistent with the actual OS. In validation cohorts, the nomogram still showed acceptable discrimination ability and calibration. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort. The OS of the high-risk group was shorter than that of the low-risk group in three cohorts. Conclusion We developed and validated an individualized survival prediction nomogram for predicting OS in ESCC patients with cT1-4N1-3M1 stage, which may help clinicians to assess the situation of advanced ESCC patients and implement further treatment.
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Affiliation(s)
- Xiao-Mei Wang
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
| | - Jia-Tao Huang
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Zhi-Han Zhang
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
| | - Fang-Cai Wu
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
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Nguyen CL, Tovmassian D, Isaacs A, Falk GL. Risk of lymph node metastasis in T1 esophageal adenocarcinoma: a meta-analysis. Dis Esophagus 2024; 37:doae012. [PMID: 38391209 DOI: 10.1093/dote/doae012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 06/29/2023] [Accepted: 02/02/2024] [Indexed: 02/24/2024]
Abstract
Patients with early (T1) esophageal adenocarcinoma (EAC) are increasingly having definitive local therapy endoscopically. Endoscopic resection is not able to pathologically stage or treat lymph node metastasis (LNM). Accurate identification of patients having nodal metastasis is critical to select endoscopic therapy over surgery. This study aimed to define the risk of LNM in T1 EAC. A meta-analysis of studies of patients who underwent surgery and lymphadenectomy with assessment of LNM was performed according to PRISMA. Main outcome was probability of LNM in T1a and T1b disease. Secondary outcomes were risk factors for LNM and rate of LNM in submucosal T1b (SM1, SM2, and SM3) disease. Registered with PROSPERO (CRD42022341794). Twenty cohort studies involving 2264 patients with T1 EAC met inclusion criteria: T1a (857 patients) with 36 (4.2%) node positive and T1b (1407 patients) with 327 (23.2%) node positive. Subgroup analysis of T1b lesions was available in 10 studies (405 patients). Node positivity for SM1, SM2, and SM3 was 16.3%, 16.2%, and 29.4%, respectively. T1 substage (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.45-13.38, P < 0.01), tumor differentiation (OR 2.82, 95% CI 2.06-3.87, P < 0.01), and lymphovascular invasion (OR 13.65, 95% CI 6.06-30.73, P < 0.01) were associated with LNM. T1a disease demonstrated a 4.2% nodal metastasis rate and T1b disease a rate of 23.2%. Endoscopic therapy should be reserved for T1a disease and perhaps select T1b disease, which has a moderately high rate of nodal metastasis. There were inadequate data to stratify T1b SM disease into 'low-risk' and 'high-risk' based on tumor differentiation and lymphovascular invasion.
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Affiliation(s)
- Chu Luan Nguyen
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - David Tovmassian
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Anna Isaacs
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Gregory L Falk
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Concord, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
- Sydney Heartburn Clinic, Lindfield, NSW, Australia
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Li Y, Wang JX, Yibi RH. Prediction of lymph node metastasis in early esophageal cancer. World J Gastrointest Surg 2023; 15:2294-2304. [PMID: 37969711 PMCID: PMC10642458 DOI: 10.4240/wjgs.v15.i10.2294] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 10/27/2023] Open
Abstract
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.
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Affiliation(s)
- Yan Li
- Department of Gastroenterology, Lhasa People’s Hospital, Lhasa 850000, Tibet Autonomous Region, China
| | - Jun-Xiong Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China
- National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing 100000, China
| | - Ran-Hen Yibi
- Department of Gastroenterology, Lhasa People’s Hospital, Lhasa 850000, Tibet Autonomous Region, China
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Ma C, Zhang Z, Li T, Tao Y, Zhu G, Xu L, Ju Y, Huang X, Zhai J, Wang X. Colonic expression of glutathione S-transferase alpha 4 and 4-hydroxynonenal adducts is correlated with the pathology of murine colitis-associated cancer. Heliyon 2023; 9:e19815. [PMID: 37810110 PMCID: PMC10559223 DOI: 10.1016/j.heliyon.2023.e19815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/30/2023] [Accepted: 09/01/2023] [Indexed: 10/10/2023] Open
Abstract
Chronic inflammation-induced oxidative stress is an important driving force for developing colitis-associated cancer (CAC). 4-hydroxynonenal (4-HNE) is a highly reactive aldehyde derived from lipid peroxidation of ω-6 polyunsaturated fatty acids that contributes to colorectal carcinogenesis. Glutathione S-transferase alpha 4 (Gsta4) specifically conjugates glutathione to 4-HNE and thereby detoxifies 4-HNE. The correlation of these oxidative biomarkers with the pathological changes in CAC is, however, unclear. In this study, we investigated the expression of Gsta4 and 4-HNE adducts in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced murine CAC, and analyzed the correlations of 4-HNE and Gsta4 with inflammatory cytokines and the pathological scores in the colon biopsies. Real-time quantitative PCR showed that expression of IL6, TNFα, and Gsta4 sequentially increased in colon tissues for mice treated with DSS for 1, 2, and 3 cycles, respectively. Moreover, immunohistochemical staining showed remarkably increased expression of 4-HNE adducts, Gsta4, TNFα, and IL6 in the colon biopsies after 3 cycles of DSS treatment. Correlation analysis demonstrated that 4-HNE adducts in the colon biopsies were positively correlated with Gsta4 expression. Additionally, the expression of Gsta4 and 4-HNE adducts were strongly correlated with the pathological changes of colon, as well as the expression of TNFα and IL6 in colon tissues. These results provide evidence for the association of oxidative biomarkers Gsta4 and 4-HNE with the pathological changes of CAC and may help developing novel histopathological biomarkers and prevention targets for CAC.
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Affiliation(s)
- Chunhua Ma
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Zhanhu Zhang
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Tianqi Li
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Yumei Tao
- Department of Pathology, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Guoxiang Zhu
- Department of Pathology, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Lili Xu
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Yuanyuan Ju
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Xu Huang
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
| | - Jinyun Zhai
- Department of Medical Experimental Technology, Nantong University Xinglin College, Nantong, China
| | - Xingmin Wang
- Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, China
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Zyla RE, Kalimuthu SN. Barrett’s Esophagus and Esophageal Adenocarcinoma: A Histopathological Perspective. Thorac Surg Clin 2022; 32:413-424. [DOI: 10.1016/j.thorsurg.2022.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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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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Duan X, Shang X, Yue J, Ma Z, Chen C, Tang P, Jiang H, Yu Z. A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma. BMC Cancer 2021; 21:431. [PMID: 33879102 PMCID: PMC8056635 DOI: 10.1186/s12885-021-08077-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 03/22/2021] [Indexed: 01/02/2023] Open
Abstract
Background A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC). Methods We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019. Results Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515–9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146–8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070–5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742–0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763–0.902) in the validation cohort (80 patients). Conclusions A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.
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Affiliation(s)
- Xiaofeng Duan
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Xiaobin Shang
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Jie Yue
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Zhao Ma
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Chuangui Chen
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Peng Tang
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Hongjing Jiang
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China.
| | - Zhentao Yu
- Department of Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, 300060, China.
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Li M, Xie H, Zhen F, Wang H, Peng Z, Xu L. Clinicopathologic factors associated with pathologic upstaging in patients clinically diagnosed stage T2N0M0 squamous cell esophageal carcinoma. J Cancer Res Ther 2020; 16:1106-1111. [PMID: 33004755 DOI: 10.4103/jcrt.jcrt_1171_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Even with the use of contrast-enhanced thin-layer chest computed tomography (CT) and endoscopic ultrasonography (EUS), the likelihood of cT2N0M0 squamous cell esophageal cancer correlating with the final pathologic outcome is exceedingly low. We therefore sought to investigate the associations between different risk factors and pathologic upstaging in stage T2N0M0 esophageal cancer patients who underwent esophagectomy. Materials and Methods We retrospectively reviewed the clinicopathological characteristics of 224 stage T2N0M0 squamous cell esophageal cancer patients who underwent complete resection over a 2-year period (October 2016-September 2018). The tumor volume (TV) was automatically measured from thin-layer chest CT scans using imaging software. Univariate and multivariate analyses were performed to identify the risk factors associated with upstaging. A receiver operating characteristic (ROC) curve was plotted, and its ability to identify pathological upstaging was assessed. Results A total of 224 patients with clinical stage T2N0M0 squamous cell esophageal carcinoma (SCEC) underwent esophagectomy; of these patients, 96 (42.86%) had a more advanced stage during the final pathologic review than during the initial diagnosis. The risk factors for pathologic upstaging included a large TV, high total cholesterol (TC), high triglycerides (TGs), high platelet-to-lymphocyte ratio (PLR), and high number of lymph nodes examined. The ROC analysis demonstrated an area under the curve of 0.845 (95% confidence interval 0.794-0.895). Conclusions In SECC diagnosed as stage T2N0M0 by CT and EUS, the incidence of postoperative pathologic upstaging increases with a large TV, high TC, high TGs, high PLR, and high number of lymph nodes examined.
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Affiliation(s)
- Meng Li
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
| | - Hounai Xie
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
| | - Feng Zhen
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
| | - Hui Wang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
| | - Zhongmin Peng
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
| | - Lin Xu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, P. R. China
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Harada K, Rogers JE, Iwatsuki M, Yamashita K, Baba H, Ajani JA. Recent advances in treating oesophageal cancer. F1000Res 2020; 9:F1000 Faculty Rev-1189. [PMID: 33042518 PMCID: PMC7531047 DOI: 10.12688/f1000research.22926.1] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy with an increasing incidence and a poor prognosis. EC is histologically divided into two major categories: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC and ESCC are molecularly different and therefore treatments should reflect the respective histological subtype. Combined modality therapy is needed for localized EC. When EC is advanced (stage 4), systemic therapy is the mainstay treatment for palliation. For localized EC, several strategies are considered standard, and more trials are necessary to determine a unified and more effective approach. The management for advanced EC is slowly evolving as immunotherapy is showing some promise for ESCC, but more data from ongoing studies are anticipated. Treatment advances will be based on high-definition genomic investigation of individual tumors. Herein, we review the contemporary trends in diagnosing and treating EAC and ESCC.
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Affiliation(s)
- Kazuto Harada
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Jane E. Rogers
- Department of Pharmacy Clinical Program, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Masaaki Iwatsuki
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kohei Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Jaffer A. Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
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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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Tian D, Jiang KY, Huang H, Jian SH, Zheng YB, Guo XG, Li HY, Zhang JQ, Guo KX, Wen HY. Clinical nomogram for lymph node metastasis in pathological T1 esophageal squamous cell carcinoma: a multicenter retrospective study. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:292. [PMID: 32355736 PMCID: PMC7186726 DOI: 10.21037/atm.2020.02.185] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Endoscopic resection is increasingly used to treat pathological T1 (pT1) esophageal cancer (EC) patients. However, the procedures are limited by lymph node metastasis (LNM) and remain controversial. We aimed to construct a nomogram to predict the risk of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). METHODS A total of 243 patients with pT1 ESCC who underwent esophagectomy and lymph node dissection at two different institutes between February 2013 and June 2019 were analyzed retrospectively. Patients were categorized into the negative group and the positive group according to whether there was LNM. Risk factors for LNM were evaluated by univariate and multivariate analyses. The nomogram was used to estimate the individual risk of LNM. RESULTS Forty-six (18.9%) of the 243 patients with pT1 ESCC exhibited LNM. The LNM rate in patients with stage T1a disease was 5.7% (5/88), and the rate in patients with stage T1b disease was 26.5% (41/155). Multivariable logistic regression analysis showed that tumor differentiation [odds ratio (OR) =1.942, 95% confidence interval (CI): 1.067-3.536, P=0.030], the T1 sub-stage (OR =4.750, 95% CI: 1.658-13.611, P=0.004), the preoperative alanine aminotransferase/aspartate aminotransferase ratio (LSR) (OR =5.371, 95% CI: 1.676-17.210, P=0.005), and the high-density lipoprotein cholesterol (HDL-C) level (OR =5.894, 95% CI: 1.917-18.124, P=0.002) were independent risk factors for LNM. The nomogram had relatively high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.803 (95% CI: 0.732-0.873). The calibration curve showed that the predicted probability of LNM was in good agreement with the actual probability. CONCLUSIONS Clinicopathological and hematological parameters of tumor differentiation, the T1 sub-stage, the preoperative LSR, and the HDL-C level may predict the risk of LNM in T1 ESCC. The risk of LNM can be predicted by the nomogram.
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Affiliation(s)
- Dong Tian
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kai-Yuan Jiang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
| | - Heng Huang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
| | - Shun-Hai Jian
- Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Yin-Bin Zheng
- Department of Thoracic Surgery, Nanchong Central Hospital, Nanchong 637000, China
| | - Xiao-Guang Guo
- Department of Pathology, Nanchong Central Hospital, Nanchong 637000, China
| | - Hong-Yun Li
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Jing-Qiu Zhang
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Ke-Xuan Guo
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Hong-Ying Wen
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
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Ye B, Zhang X, Su Y, Hao S, Teng H, Guo X, Yang Y, Sun Y, Mao T, Li Z. The possibility of endoscopic treatment of cN0 submucosal esophageal cancer: results from a surgical cohort. Surg Endosc 2020; 35:593-601. [PMID: 32072277 PMCID: PMC7819934 DOI: 10.1007/s00464-020-07420-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 02/10/2020] [Indexed: 12/16/2022]
Abstract
Background We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies. Methods We retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses. Results Postoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12–60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p < 0.01). Twenty-one patients with sm1 cancer, high tumor differentiation, and tumor length < 2 cm had no lymph node metastasis or lymphovascular invasion, and none of these patients experienced recurrence. Conclusions Endoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.
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Affiliation(s)
- Bo Ye
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Xiaobin Zhang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Yuchen Su
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Shuguang Hao
- Department of Thoracic Surgery, Xinxiang Central Hospital, Xinxiang, 453000, Henan Province, People's Republic of China
| | - Haohua Teng
- Department of Pathology, Shanghai Chest Hospital, Shanghai JiaoTong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Xufeng Guo
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Yu Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Yifeng Sun
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Teng Mao
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China
| | - Zhigang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Huaihaixi Road 241, Shanghai, 200030, People's Republic of China.
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Tanaka T, Ueno M, Iizuka T, Hoteya S, Haruta S, Udagawa H. Comparison of long-term outcomes between esophagectomy and chemoradiotherapy after endoscopic resection of submucosal esophageal squamous cell carcinoma. Dis Esophagus 2019; 32:5450336. [PMID: 30980070 DOI: 10.1093/dote/doz023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 02/26/2019] [Accepted: 03/02/2019] [Indexed: 12/11/2022]
Abstract
Esophagectomy represents the standard treatment strategy for superficial esophageal cancer diagnosed pathologically as submucosal disease (pT1b) following an endoscopic resection (ER). However, chemoradiotherapy (CRT) is expected to become an alternative treatment option. This study retrospectively compared the outcomes of patients who underwent ER of submucosal esophageal squamous cell carcinoma, and who received additional treatment in the form of surgery and CRT. Data were collected from 83 patients who underwent ER and were diagnosed as pT1b (sm) between January 2002 and December 2013. Of them, 52 patients underwent additional treatment (19 surgery, 33 CRT). The long-term outcomes, recurrent patterns, and recurrence risk factor were analyzed retrospectively. No significant differences were identified between the two groups regarding the following aspects: sex, Charlson comorbidity index, tumor size, macroscopic type, cut end positivity, and en bloc resection rate. On the contrary, significant differences were observed in age (P = 0.042) and lymphovascular invasion (P = 0.003) between the two groups. There were more patients with positive lymphovascular invasion, which was one of the strongest risk factors, in the surgery group. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were both 100% in the surgery group and 90.4% and 87.4%, respectively, in the CRT group. The 5-year OS and RFS rates both decreased to 89.5% in the surgery group and to 80.3% and 70.4%, respectively, in the CRT group. The surgery group achieved a superior OS and RFS compared to the CRT group, though not significant (P = 0.172, P = 0.127). Tumor recurrence was observed in 6 patients. All these patients were in the CRT group (P = 0.075). They included 3 patients with hematogenous metastases (of the lung, bone, and adrenal gland) and 3 patients with regional lymph node metastasis. The patient with hematogenous adrenal gland metastasis had simultaneous extended lymph node metastasis. Through a univariate analysis, it was observed that tumor size (≥ 40 mm) and positive lymphatic invasion represented the significant risk factors for recurrence in the CRT group (P = 0.048 and P = 0.035, respectively). To achieve a better long-term survival, surgery is recommended as the additional treatment for ER-pT1b esophageal cancer. While CRT represents an acceptable alternative, the indication should be carefully decided, especially in high-risk patients for recurrence with large tumor size (≥ 40 mm) or positive lymphatic invasion.
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Affiliation(s)
| | | | - Toshiro Iizuka
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
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Tian D, Huang H, Yang YS, Jiang KY, He X, Guo XG, Chen LQ. Depth of Invasion into the Circular and Longitudinal Muscle Layers in T2 Esophageal Squamous Cell Carcinoma Does Not Affect Prognosis or Lymph Node Metastasis: A Multicenter Retrospective Study. World J Surg 2019; 44:171-178. [PMID: 31552458 DOI: 10.1007/s00268-019-05194-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Although a greater depth of tumor invasion is correlated with a poorer prognosis in esophageal squamous cell carcinoma (ESCC), it remains controversial whether T2 ESCC should be subclassified by circular and longitudinal muscle invasion. We conducted a multicenter retrospective study to evaluate the relationship between the depth of invasion and long-term outcome and to identify the clinical significance of subclassifying T2 ESCC. METHODS Patients with T2 ESCC who underwent esophagectomy at two different institutes between January 2009 and December 2017 were analyzed retrospectively. ESCC with circular and longitudinal muscle invasion was defined as T2 circular and T2 longitudinal ESCC, respectively. Survival outcomes and risk factors for lymph node metastasis (LNM) were evaluated by univariate and multivariate analyses. In addition, data from stage T1b ESCC cases during the same period were retrieved for use as a comparison cohort to evaluate the prognostic significance of the T2 substage. RESULTS A total of 536 T2 ESCC patients were eligible, and 192 (36%) patients developed LNM. No significant difference was found in general characteristics between the T2 circular and T2 longitudinal ESCC groups (n = 219 and n = 317, P > 0.05), except for tumor location (P = 0.02). The T2 substage was not significantly correlated with survival on univariate or multivariate analysis (P = 0.30 and P = 0.34, respectively). Multivariate analysis also indicated that the T2 substage was not an independent risk factor for LNM (P = 0.15). When patients with stage T1b ESCC were considered, their survival time was significantly different from that of patients with T2 circular and T2 longitudinal disease (P = 0.01). CONCLUSIONS The depth of tumor invasion into the circular and longitudinal muscle layers in T2 ESCC does not affect the prognosis or risk of LNM.
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Affiliation(s)
- Dong Tian
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China
- Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Heng Huang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Yu-Shang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China
| | - Kai-Yuan Jiang
- College of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Xi He
- Institute of Imaging Medicine, North Sichuan Medical College, Nanchong, 637000, China
| | - Xiao-Guang Guo
- Department of Pathology, Nanchong Central Hospital, Nanchong, 637000, China
| | - Long-Qi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, China.
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17
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The prevalence of lymph node metastasis for pathological T1 esophageal cancer: a retrospective study of 143 cases. Surg Oncol 2017; 27:1-6. [PMID: 29549895 DOI: 10.1016/j.suronc.2017.11.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 05/27/2017] [Accepted: 11/02/2017] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate the prevalence, pattern and risk factors of lymph node metastasis (LNM) for pathological T1 (pT1) esophageal cancer (EC). METHODS The clinical data of 143 cases of pT1 patients who underwent esophagectomy and lymph node dissection during January 2011 and July 2016 were reviewed, including 120 male patients and 23 female patients with a median age of 60 years. The pattern of LNM was analyzed and the risk factors related to LNM were assessed by logistic regression analysis. The nomogram model was used to estimate the individual risk of lymph node metastasis. RESULTS Of 143 patients with T1 tumors, 25 patients had LNM, and the LNM rate was 17.5%. The LNM rate was 8.0% for T1a tumors, and 22.5% for T1b tumors. The logistic regression analysis showed that the depth of tumor infiltration (P < 0.05), tumor size (P < 0.01), tumor location (P < 0.05), and tumor differentiation (P < 0.01) were independent risk factors related to LNM for T1 EC. These four parameters allowed the compilation of a nomogram to estimate the individual risk of LNM. Tumor differentiation (P < 0.05) was an independent risk factor related to LNM for T1a tumors, and tumor size (P < 0.05) and tumor location (P < 0.05) were independent risk factors related to LNM for T1b tumors. Of 25 patients with LNM, one patient had cervical LNM, 15 patients with thoracic LNM, and 17 patients with abdominal LNM. The relatively highest LNM sites were laryngeal recurrent nerve (n = 8), the left gastric artery (n = 8), right and left cardiac (n = 6) and thoracic paraesophageal (n = 5). CONCLUSIONS T1 EC has a relatively high LNM rate, and the depth of tumor infiltration, tumor size, tumor location and tumor differentiation are correlated with LNM. The LNM risk and extent must be considered comprehensively in decision-making of a better surgical treatment and lymph node dissection strategy.
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Schwameis K, Green KM, Worrell SG, Samaan J, Cooper S, Tatishchev S, Oh DS, Hagen JA, DeMeester SR. Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma. Ann Surg Oncol 2017; 24:3921-3925. [PMID: 28975518 DOI: 10.1245/s10434-017-6091-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC). METHODS This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy. RESULTS There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4-8.0), and the median number of resected nodes was 48 (23-85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%. CONCLUSIONS Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.
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Affiliation(s)
- Katrin Schwameis
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Kyle M Green
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Stephanie G Worrell
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Jamil Samaan
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Shannon Cooper
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Sergei Tatishchev
- Department of Pathology, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Daniel S Oh
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Jeffrey A Hagen
- Department of Thoracic Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA
| | - Steven R DeMeester
- The Oregon Clinic, Gastrointestinal & Minimally Invasive Surgery, Portland, OR, USA.
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Role of EUS in patients with suspected Barrett's esophagus with high-grade dysplasia or early esophageal adenocarcinoma: impact on endoscopic therapy. Gastrointest Endosc 2017; 86:292-298. [PMID: 27889544 DOI: 10.1016/j.gie.2016.11.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 11/16/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Endoscopic therapy is the standard treatment for high-grade dysplasia and some cases of T1a esophageal adenocarcinoma (EAC), but it is not appropriate for deeply invasive disease. Data on the value of EUS for patient selection for endoscopic or surgical resection are conflicting. We investigated the outcome of esophageal EUS for the staging and treatment selection of patients with treatment-naive, premalignant Barrett's esophagus (BE) and suspected superficial EAC. METHODS We retrospectively reviewed consecutive patients who underwent EUS for staging of treatment-naive, suspected premalignant BE and superficial EAC from January 2006 to June 2014. All patients referred for endoscopic therapy routinely underwent EUS. Patients with esophageal masses, squamous cell cancers, previous neoadjuvant therapy, or unrelated pathologies were excluded. Each patient's final diagnosis was verified by EMR, esophagectomy, or forceps biopsy sampling. Test characteristics of EUS were calculated. RESULTS Three hundred thirty-five patients (mean age, 68 years; 86% male) with BE, a Prague C mean of 2.8 cm, and a Prague M mean of 4.5 cm were staged (pT0, 78% [6% nondysplastic, 24% low-grade dysplasia, 42% high-grade dysplasia]; pT1a, 14%; pT1b, 7%; and pT2, 1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for patient selection to endoscopic (T1aN0 or less) or surgical therapy with EUS TN staging were 50%, 93%, 40%, 95%, and 90%, respectively. Comparable rates were achieved for patients with nodular BE. Overstaging occurred in 7% of patients, and EUS selected 11% for incorrect treatment modalities compared with pathologic staging. CONCLUSIONS This study confirms the limited value of EUS suggested in the latest American College of Gastroenterology guidelines for BE management.
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Valero M, Robles-Medranda C. Endoscopic ultrasound in oncology: An update of clinical applications in the gastrointestinal tract. World J Gastrointest Endosc 2017; 9:243-254. [PMID: 28690767 PMCID: PMC5483416 DOI: 10.4253/wjge.v9.i6.243] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/10/2017] [Accepted: 05/05/2017] [Indexed: 02/06/2023] Open
Abstract
An accurate staging is necessary to select the best treatment and evaluate prognosis in oncology. Staging usually begins with noninvasive imaging such as computed tomography, magnetic resonance imaging or positron emission tomography. In the absence of distant metastases, endoscopic ultrasound plays an important role in the diagnosis and staging of gastrointestinal tumors, being the most accurate modality for local-regional staging. Its use for tumor and nodal involvement in pre-surgical evaluation has proven to reduce unnecessary surgeries. The aim of this article is to review the current role of endoscopic ultrasound in the diagnosis and staging of esophageal, gastric and colorectal cancer.
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Esophagectomy Following Endoscopic Resection of Submucosal Esophageal Cancer: a Highly Curative Procedure Even with Nodal Metastases. J Gastrointest Surg 2017; 21:62-67. [PMID: 27561633 DOI: 10.1007/s11605-016-3210-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 07/10/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND Despite the increased risk for nodal disease, definitive endoscopic resection is being increasingly offered for lesions invasive into the submucosa based on the success with intramucosal tumors. The aim of this study was to evaluate survival after esophagectomy alone for confirmed submucosal tumors after endoscopic resection. METHODS Patients from seven centers in the USA who underwent esophagectomy for submucosal tumors removed with endoscopic resection were analyzed. Nodal involvement was correlated with recurrence and survival. RESULTS We identified 23 patients with submucosal esophageal adenocarcinoma. Esophagectomy was performed at a median of 2 months (Interquartile range 1-3) after the endoscopic resection. There was no postoperative mortality. Positive nodal disease was seen in 26 % of patients on final pathology. At a median of 37 months (Interquartile range 25-55), 91 % of patients were alive and free of disease. The disease-specific 5-year survival was 88 %. Disease-specific 5-year survival was 67 % in patients with positive nodal metastases and 100 % in those without (p = 0.159). CONCLUSIONS Esophagectomy is curative in the majority of patients with submucosal tumors even in the presence of nodal metastases. These data serve as a benchmark for comparison when considering extending the indications for therapeutic endoscopic resection for submucosal tumors in the future.
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Zhou Y, Du J, Li H, Luo J, Chen L, Wang W. Clinicopathologic analysis of lymph node status in superficial esophageal squamous carcinoma. World J Surg Oncol 2016; 14:259. [PMID: 27729036 PMCID: PMC5059900 DOI: 10.1186/s12957-016-1016-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Accepted: 10/04/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Endoscopic approaches are gradually considered as a reliable treatment of intramucosal esophageal squamous carcinoma. However, endoscopic resection (ER) is limited by the potential lymph node metastasis (LNM) at various depths of mucosal and submucosal invasion. METHODS We conducted a retrospective review of 498 patients with pT1 superficial esophageal squamous carcinoma (SESC) who underwent surgical resection from January 2008 to August 2015. Pathological characteristics of tumors including location, size, appearance, differentiation, invasion depth, and nodal status were reviewed, and risk factors were analyzed. RESULTS LNM was found in 0.0, 2.7, 6.3, 18.2, 15.9, and 34.3 % of the m1, m2, m3, sm1, sm2, and sm3 lesions, respectively. Univariate logistic regression identified the presence of the tumor size > 2 cm (p < 0.05), the presence of the poor tumor differentiation (p < 0.05), and the depth of tumor invasion (p < 0.05) and angiolymphatic invasion (p < 0.05) to be the important risk factors associated with the prevalence of tumor-positive lymph nodes. These findings were confirmed in multivariate logistic regression as independent predictors for LNM. CONCLUSIONS ER is considered as a reliable treatment of m1 to m2 lesions. Radical surgical resection (SR) is the standard and irreplaceable therapy of sm1 to sm3 lesions. Patients with m3 lesions should undergo ER as the initial procedure for diagnosis. And this treatment is supported only by a successful description of the tumor's characteristics, including (1) only muscularis mucosa invasion and without invasion of the resection margins and (2) without any risk predictors for LNM. Otherwise, SR is recommended.
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Affiliation(s)
- Yue Zhou
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
| | - Junjie Du
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
| | - Hai Li
- Department of Pathology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
| | - Jinhua Luo
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
| | - Liang Chen
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
| | - Wei Wang
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 China
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Mohiuddin K, Dorer R, El Lakis MA, Hahn H, Speicher J, Hubka M, Low DE. Outcomes of Surgical Resection of T1bN0 Esophageal Cancer and Assessment of Endoscopic Mucosal Resection for Identifying Low-Risk Cancers Appropriate for Endoscopic Therapy. Ann Surg Oncol 2016; 23:2673-8. [PMID: 27020584 DOI: 10.1245/s10434-016-5138-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Invasive esophageal cancers have been managed historically with esophagectomy. Low-risk T1b patients are being proposed for nonsurgical management. The purpose of this study was to evaluate the ability of endoscopic mucosal resections (EMR) to identify low-risk T1b patients and to review surgical treatment outcomes for T1b cancer. METHODS All esophageal cancer patients, in an institutional review board-approved prospective database, between 2000 and 2013 with clinical stage (cT1bN0), pathological stage (pT1bN0), and no neoadjuvant therapy were retrospectively reviewed. RESULTS Fifty-one patients, 38 pT1b and 13 cT1b, were assessed. All cT1b had preoperative EMR and five were found to be understaged at esophagectomy. pT1bN0 patients had a mean age of 66 years, mean BMI of 30, and 95 % had adenocarcinoma. Thirty-eight pT1bN0 patients underwent esophagectomy with a median hospital length of stay (LOS) of 9 days. Complications occurred in 14 patients, but 71 % were minor (Accordion score 1-2). In-hospital 30- and 90-day mortality was zero. EMR specimens were re-reviewed to assess low-risk criteria. Degree of differentiation and the presence of lymphovascular invasion could be assessed in all EMR specimens; however, assessment of submucosal invasion limited to the superficial submucosal layer could not be determined in the majority of cases. Kaplan-Meier 5-year overall survival in pT1bN0 patients was 78.7 %. CONCLUSIONS Clinical staging of superficial esophageal cancer can be inaccurate especially in submucosal tumors. EMR should be routinely used for preoperative staging. Healthy patients with clinical tumor stage greater than cT1a should undergo multidisciplinary review and be considered for surgical resection.
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Affiliation(s)
- Kamran Mohiuddin
- Department of Thoracic Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Russell Dorer
- Department of Pathology, Virginia Mason Medical Center, Seattle, WA, USA
| | - Mustapha A El Lakis
- Department of Thoracic Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Hejin Hahn
- Department of Pathology, Virginia Mason Medical Center, Seattle, WA, USA
| | - James Speicher
- Department of Thoracic Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Michal Hubka
- Department of Thoracic Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Donald E Low
- Department of Thoracic Surgery, Virginia Mason Medical Center, Seattle, WA, USA.
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ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus. Am J Gastroenterol 2016; 111:30-50; quiz 51. [PMID: 26526079 DOI: 10.1038/ajg.2015.322] [Citation(s) in RCA: 1047] [Impact Index Per Article: 116.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 08/28/2015] [Indexed: 12/11/2022]
Abstract
Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with reflux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-definition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is also recommended for patients with BE and low-grade dysplasia, although endoscopic surveillance continues to be an acceptable alternative. Given the relatively common recurrence of BE after ablation, we suggest postablation endoscopic surveillance intervals. Although many of the recommendations provided are based on weak evidence or expert opinion, this document provides a pragmatic framework for the care of the patient with BE.
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25
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Litle VR. Staging Techniques for Carcinoma of the Esophagus. SABISTON AND SPENCER SURGERY OF THE CHEST 2016:645-656. [DOI: 10.1016/b978-0-323-24126-7.00037-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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26
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Aranda-Hernandez J, Cirocco M, Marcon N. Treatment of dysplasia in barrett esophagus. Clin Endosc 2014; 47:55-64. [PMID: 24570884 PMCID: PMC3928493 DOI: 10.5946/ce.2014.47.1.55] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 12/27/2013] [Accepted: 12/28/2013] [Indexed: 12/20/2022] Open
Abstract
Barrett esophagus is recognized as a risk factor for the development of dysplasia and adenocarcinoma of the esophagus. Cancer is usually diagnosed at an advanced stage with a 5-year survival rate of 15%. Most of these patients present de novo and are not part of a surveillance program. Endoscopic screening with improvement in recognition of early lesions may change this pattern. In the past, patients diagnosed with dysplasia and mucosal cancer were best managed by esophagectomy. Endoscopic techniques such as endoscopic mucosal resection and radiofrequency ablation have resulted in high curative rates and a shift away from esophagectomy. This pathway is supported by the literature review of esophagectomies performed for mucosal disease, as well as pathologists' interpretation of endoscopic mucosal specimens, which document the low risk of lymph node metastasis. The role of endoscopic therapy for superficial submucosal disease continues to be a challenge.
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Affiliation(s)
- Javier Aranda-Hernandez
- Division of Gastroenterology, Department of Medicine, The Center of Advanced Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Maria Cirocco
- Division of Gastroenterology, Department of Medicine, The Center of Advanced Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Norman Marcon
- Division of Gastroenterology, Department of Medicine, The Center of Advanced Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto Faculty of Medicine, Toronto, ON, Canada
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