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Huang S, Gu X, Zhou H, Feng Y, Shi R, Wang W, Zhou A, Lin J. Application of Esophageal Sponge Cytology in Screening Esophageal Squamous Cell Carcinoma in a High-Risk Region of China. Cancer Med 2025; 14:e70467. [PMID: 39856802 PMCID: PMC11761409 DOI: 10.1002/cam4.70467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 11/15/2024] [Accepted: 11/24/2024] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE To investigate the feasibility and accuracy of esophageal sponge cytology in screening esophageal squamous cell carcinoma (ESCC). METHODS From May 2021 to June 2022, an opportunistic screening was performed in people aged 40-75 from a high-risk region for ESCC. Using an esophageal cell collector that was independently developed in China for esophageal sponge cytology, a positive cytology was determined as detection of atypical squamous cells or more severe lesions. The safety, tolerability, and accuracy of esophageal sponge cytology were compared with those of pathological examination after endoscopy and biopsy. RESULTS A total of 1581 eligible participants were involved in the screening program, including 61 (3.86%) with high-grade lesions pathologically confirmed by endoscopic biopsy. No serious adverse events were reported during sampling. Major adverse events included vomiting during sampling (n = 2, 0.13%) and sore throat after sampling (n = 36, 2.27%). The majority of participants showed good tolerability and accessibility (n = 1568, 98.80%) accessed by the visual analogue scale (VAS). Esophageal sponge cytology offered a satisfactory diagnostic accuracy in screening advanced esophageal epithelial lesions, with a sensitivity of 98.36% (95%CI: 90.02%-99.91%) and a specificity of 91.15% (95%CI: 89.97%-92.84%), and a negative predictive value up to 99. 92% (95%CI: 99.53%-99.99%). CONCLUSION Esophageal sponge cytology is a highly feasible, safe, and accurate screening method for ESCC in a high-risk region of China. TRIAL REGISTRATION First Affiliated Hospital of Naval Medical University: NCT04609813.
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Affiliation(s)
- Shu Huang
- Department of GastroenterologyLianshui People's Hospital Affiliated to Kangda College of Nanjing Medical UniversityHuai'anChina
| | - Xuexiang Gu
- Cancer Institute of Jiangsu Province, Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingChina
| | - Hailang Zhou
- Department of GastroenterologyLianshui People's Hospital Affiliated to Kangda College of Nanjing Medical UniversityHuai'anChina
| | - Yadong Feng
- Department of Gastroenterology, Zhongda HospitalSoutheast UniversityNanjingChina
| | - Ruihua Shi
- Department of Gastroenterology, Zhongda HospitalSoutheast UniversityNanjingChina
| | - Wei Wang
- Department of GastroenterologyLianshui People's Hospital Affiliated to Kangda College of Nanjing Medical UniversityHuai'anChina
| | - Aijun Zhou
- Department of GastroenterologyLianshui People's Hospital Affiliated to Kangda College of Nanjing Medical UniversityHuai'anChina
| | - Jie Lin
- Cancer Institute of Jiangsu Province, Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingChina
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Zhang WY, Chang YJ, Shi RH. Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era. World J Gastroenterol 2024; 30:4267-4280. [PMID: 39492825 PMCID: PMC11525855 DOI: 10.3748/wjg.v30.i39.4267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/31/2024] [Accepted: 09/19/2024] [Indexed: 10/12/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.
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Affiliation(s)
- Wan-Yue Zhang
- School of Medicine, Southeast University, Nanjing 221000, Jiangsu Province, China
| | - Yong-Jian Chang
- School of Cyber Science and Engineering, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Rui-Hua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
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3
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Mou X, Peng Z, Yin T, Sun X. Non-endoscopic Screening for Esophageal Squamous Cell Carcinoma: Recent Advances. J Gastrointest Cancer 2024; 55:118-128. [PMID: 37924487 DOI: 10.1007/s12029-023-00980-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2023] [Indexed: 11/06/2023]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the gastrointestinal tract, and China has a high incidence area with a high burden on the disease. As early symptoms of ESCC are not obvious, the mortality rate is high, and it is often diagnosed in the intermediate and advanced stages. However, early screening and treatment may reduce morbidity and mortality. METHODS Screening methods are divided into endoscopic and non-endoscopic screening. RESULTS Endoscopic screening cannot be widely used because of its invasive nature and high cost. Currently, non-endoscopic screening consists primarily of tumor biomarkers and cytology, and tumor biomarkers including autoantibodies, circulating tumor cells, circulating tumor DNA, exosomes and serum metabolomics are more likely to be effective. But the efficiency of early diagnosis of esophageal cancer is low and the accuracy of screening needs to be improved. The aim of this study is to summarize advances in non-endoscopic esophageal cancer screening and strategies to provide a scientific basis and research idea for esophageal cancer prevention and control. CONCLUSIONS Non-endoscopic screening is better than endoscopic screening. And the application of tumor biomarkers is much better than other non-endoscopic screening methods.
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Affiliation(s)
- Xiao Mou
- School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.
| | - Zhenglin Peng
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Tao Yin
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
- Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xingwang Sun
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
- Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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4
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Gao Y, Li ZS, Wang LW. Concerns about pooled performances of cytology for esophageal squamous cell carcinoma screening. Gastrointest Endosc 2023; 97:1169. [PMID: 37208042 DOI: 10.1016/j.gie.2022.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 12/11/2022] [Indexed: 05/21/2023]
Affiliation(s)
- Ye Gao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, National Clinical Research Center for Digestive Diseases, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, National Clinical Research Center for Digestive Diseases, Shanghai, China
| | - Luo-Wei Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, National Clinical Research Center for Digestive Diseases, Shanghai, China
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5
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Dawsey SM, Duits LC. A substantial advance for screening of oesophageal cancer. Lancet Gastroenterol Hepatol 2023; 8:393-395. [PMID: 36931288 DOI: 10.1016/s2468-1253(23)00065-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 02/16/2023] [Indexed: 03/16/2023]
Affiliation(s)
- Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Lucas C Duits
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands.
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6
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Yao B, Feng Y, Zhao K, Liang Y, Huang P, Zang J, Song J, Li M, Wang X, Shu H, Shi R. Artificial intelligence assisted cytological detection for early esophageal squamous epithelial lesions by using low-grade squamous intraepithelial lesion as diagnostic threshold. Cancer Med 2023; 12:1228-1236. [PMID: 35766144 PMCID: PMC9883535 DOI: 10.1002/cam4.4984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/19/2022] [Accepted: 06/13/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Manual cytological diagnosis for early esophageal squamous cell carcinoma (early ESCC) and high-grade intraepithelial neoplasia (HGIN) is unsatisfactory. Herein, we have introduced an artificial intelligence (AI)-assisted cytological diagnosis for such lesions. METHODS Low-grade squamous intraepithelial lesion or worse was set as the diagnostic threshold for AI-assisted diagnosis. The performance of AI-assisted diagnosis was evaluated and compared to that of manual diagnosis. Feasibility in large-scale screening was also assessed. RESULTS AI-assisted diagnosis for abnormal cells was superior to manual reading by presenting a higher efficiency for each slide (50.9 ± 0.8 s vs 236.8 ± 3.9 s, p = 1.52 × 10-76 ) and a better interobserver agreement (93.27% [95% CI, 92.76%-93.74%] vs 65.29% [95% CI, 64.35%-66.22%], p = 1.03 × 10-84 ). AI-assisted detection showed a higher diagnostic accuracy (96.89% [92.38%-98.57%] vs 72.54% [65.85%-78.35%], p = 1.42 × 10-14 ), sensitivity (99.35% [95.92%-99.97%] vs 68.39% [60.36%-75.48%], p = 7.11 × 10-15 ), and negative predictive value (NPV) (97.06% [82.95%-99.85%] vs 40.96% [30.46%-52.31%], p = 1.42 × 10-14 ). Specificity and positive predictive value (PPV) were not significantly differed. AI-assisted diagnosis demonstrated a smaller proportion of participants of interest (3.73%, [79/2117] vs.12.84% [272/2117], p = 1.59 × 10-58 ), a higher consistence between cytology and endoscopy (40.51% [32/79] vs. 12.13% [33/272], p = 1.54 × 10- 8), specificity (97.74% [96.98%-98.32%] vs 88.52% [87.05%-89.84%], p = 3.19 × 10-58 ), and PPV (40.51% [29.79%-52.15%] vs 12.13% [8.61%-16.75%], p = 1.54 × 10-8 ) in community-based screening. Sensitivity and NPV were not significantly differed. AI-assisted diagnosis as primary screening significantly reduced average cost for detecting positive cases. CONCLUSION Our study provides a novel cytological method for detecting and screening early ESCC and HGIN.
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Affiliation(s)
- Bin Yao
- The Laboratory of Image Science and TechnologySoutheast UniversityNanjingChina
- Froeasy Technology Development CO., LTDRed Maple Park of Technological IndustryNanjingChina
| | - Yadong Feng
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
- Department of GastroenterologyJintan First People's Hospital Affiliated to Jiangsu UniversityChangzhouChina
| | - Kai Zhao
- Department of GastroenterologyJintan First People's Hospital Affiliated to Jiangsu UniversityChangzhouChina
| | - Yan Liang
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
| | - Peilin Huang
- School of MedicineZhongda Hospital Southeast UniversityNanjingChina
| | - Juncai Zang
- Froeasy Technology Development CO., LTDRed Maple Park of Technological IndustryNanjingChina
| | - Jie Song
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
| | - Mengjie Li
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
| | - Xiaofen Wang
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
| | - Huazhong Shu
- The Laboratory of Image Science and TechnologySoutheast UniversityNanjingChina
| | - Ruihua Shi
- Department of Gastroenterology, School of MedicineZhongda Hospital Southeast UniversityNanjingChina
- Department of GastroenterologyJintan First People's Hospital Affiliated to Jiangsu UniversityChangzhouChina
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7
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Yu Q, Xia N, Zhao Y, Jin H, Chen R, Ye F, Chen L, Xie Y, Wan K, Zhou J, Zhou D, Lv X. Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection. BMC Med Genomics 2022; 15:247. [PMID: 36447287 PMCID: PMC9706897 DOI: 10.1186/s12920-022-01401-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 11/22/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. METHODS The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. RESULTS We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. CONCLUSIONS We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.
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Affiliation(s)
- Qiuning Yu
- grid.412633.10000 0004 1799 0733Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Namei Xia
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Yanteng Zhao
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Huifang Jin
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Renyin Chen
- grid.412633.10000 0004 1799 0733Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Fanglei Ye
- grid.412633.10000 0004 1799 0733Otorhinolaryngology Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Liyinghui Chen
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Ying Xie
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Kangkang Wan
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Jun Zhou
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Dihan Zhou
- Wuhan Ammunition Life-tech Company, Ltd., Wuhan, Hubei China
| | - Xianping Lv
- grid.412633.10000 0004 1799 0733Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
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8
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Feng Y, Wang B, Pan L, Yao B, Deng B, Liang Y, Sun Y, Zang J, Xu X, Song J, Li M, Xu G, Zhao K, Cheng CE, Shi R. Study protocol for artificial intelligence-assisted sponge cytology as pre-endoscopy screening for early esophegeal squmaous epithelial lesions in China. BMC Cancer 2022; 22:1105. [PMID: 36307758 PMCID: PMC9617337 DOI: 10.1186/s12885-022-10220-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 10/24/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Endoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions. METHODS The study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524). DISCUSSION Our study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.
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Affiliation(s)
- Yadong Feng
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
- Department of Gastroenterology, Changshu No.2 People's Hospital, the Affiliated Changshu Hospital of Xuzhou Medical University, 18 Taishan Road, Suzhou, 215500, China.
- Department of Gastroenterology, Jintan Hospital Affiliated to Jiangsu University, 500 Jintan Avenue, Changzhou, 213200, China.
| | - Bin Wang
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
- Department of Gastroenterology, Changshu No.2 People's Hospital, the Affiliated Changshu Hospital of Xuzhou Medical University, 18 Taishan Road, Suzhou, 215500, China
| | - Liang Pan
- Department of Gastroenterology, Jintan Hospital Affiliated to Jiangsu University, 500 Jintan Avenue, Changzhou, 213200, China
| | - Bin Yao
- Southeast University, 2 Sipailou, Nanjing, 210096, China
| | - Bin Deng
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, 386 Hanjiang Middle Road, Yangzhou, 225001, China
| | - Yan Liang
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Yongzhen Sun
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Juncai Zang
- Froeasy Technology Development CO., LTD, Red Maple Park of Technological Industry, C1 Building, Nanjing, 210046, China
| | - Xinyi Xu
- Froeasy Technology Development CO., LTD, Red Maple Park of Technological Industry, C1 Building, Nanjing, 210046, China
| | - Jie Song
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Mengjie Li
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Guangpeng Xu
- Froeasy Technology Development CO., LTD, Red Maple Park of Technological Industry, C1 Building, Nanjing, 210046, China
| | - Kai Zhao
- Department of Gastroenterology, Jintan Hospital Affiliated to Jiangsu University, 500 Jintan Avenue, Changzhou, 213200, China
| | - Cui-E Cheng
- Department of Gastroenterology, Changshu No.2 People's Hospital, the Affiliated Changshu Hospital of Xuzhou Medical University, 18 Taishan Road, Suzhou, 215500, China
| | - Ruihua Shi
- Department of Gastroenterology, School of Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
- Department of Gastroenterology, Changshu No.2 People's Hospital, the Affiliated Changshu Hospital of Xuzhou Medical University, 18 Taishan Road, Suzhou, 215500, China
- Department of Gastroenterology, Jintan Hospital Affiliated to Jiangsu University, 500 Jintan Avenue, Changzhou, 213200, China
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Abstract
Esophageal squamous cell carcinoma (ESCC) is common in the developing world with decreasing incidence in developed countries and carries significant morbidity and mortality. Major risk factors for ESCC development include significant use of alcohol and tobacco. Screening for ESCC can be recommended in high-risk populations living in highly endemic regions. The treatment of ESCC ranges from endoscopic resection therapy or surgery in localized disease to chemoradiotherapy in metastatic disease, and prognosis is directly related to the stage at diagnosis. New immunotherapies and molecular targeted therapies may improve the dismal survival outcomes in patients with metastatic ESCC.
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Affiliation(s)
- D Chamil Codipilly
- Division of Gastroenterology and Hepatology, Mayo Clinic, SMH Campus, 6 Alfred GI Unit, 200 1st Street South West, Rochester MN 55905, USA
| | - Kenneth K Wang
- Division of Gastroenterology and Hepatology, Mayo Clinic, SMH Campus, 6 Alfred GI Unit, 200 1st Street South West, Rochester MN 55905, USA.
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Wong MCS, Deng Y, Huang J, Bai Y, Wang HHX, Yuan J, Zhang L, Yip HC, Chiu PWY. Performance of screening tests for esophageal squamous cell carcinoma: a systematic review and meta-analysis. Gastrointest Endosc 2022; 96:197-207.e34. [PMID: 35413332 DOI: 10.1016/j.gie.2022.04.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 04/04/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests. METHODS A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test. RESULTS We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy): .94 (95% confidence interval [CI], .87-.97), .92 (95% CI, .87-.95), and .97 (95% CI, .96-.99); endoscopy (transnasal endoscopy): .85 (95% CI, .70-.93), .96 (95% CI, .91-.98), and .97 (95% CI, .95-.98); microRNA: .77 (95% CI, .75-.80), .78 (95% CI, .75-.80), and .85 (95% CI, .81-.87); autoantibody: .45 (95% CI, .36-.53), .91 (95% CI, .89-.93), and .84 (95% CI, .81-.87); and cytology: .82 (95% CI, .60-.93), .97 (95% CI, .88-.99), and .97 (95% CI, .95-.98). There was high heterogeneity. CONCLUSIONS The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test.
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Affiliation(s)
- Martin C S Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China; School of Public Health, Peking Union Medical College and The Chinese Academy of Medical Sciences, Beijing, China; Department of Global Health, School of Public Health, Peking University, Beijing, China
| | - Yunyang Deng
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yijun Bai
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry H X Wang
- School of Public Health, Sun Yat-Sen University, Guangzhou, China; General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Scotland, UK
| | - Jinqiu Yuan
- Clinical Research Centre, Scientific Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Lin Zhang
- School of Public Health, Peking Union Medical College and The Chinese Academy of Medical Sciences, Beijing, China; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Hon Chi Yip
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Philip Wai Yan Chiu
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
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11
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Fan Z, Qin Y, Zhou J, Chen R, Gu J, Li M, Zhou J, Li X, Lin D, Wang J, Deng D, Wei W. Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study. Cancer Med 2022; 11:4033-4042. [PMID: 35352503 DOI: 10.1002/cam4.4718] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. METHODS Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115-bp MethyLight assay. Categorical data were compared by the Chi-square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high-grade ESCdys (high-grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000-bootstrap resample. RESULTS A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p = 0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p = 0.225). Bootstrap validation showed optimism-corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. CONCLUSION P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening.
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Affiliation(s)
- Zhiyuan Fan
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Qin
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Zhou
- Key Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Ru Chen
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianhua Gu
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Minjuan Li
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiachen Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Xinqing Li
- Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dongmei Lin
- Department of Pathology, Peking University Cancer Hospital, Beijing, China
| | - Jinwu Wang
- Department of Pathology, Linzhou Cancer Hospital, Linzhou, China
| | - Dajun Deng
- Key Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Wenqiang Wei
- Office of National Central Cancer Registry, 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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12
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Prevalence of esophageal squamous dysplasia in relatives of patients with esophageal cancer in Southwestern Kenya. Cancer Epidemiol 2022; 78:102141. [PMID: 35299153 DOI: 10.1016/j.canep.2022.102141] [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: 09/26/2021] [Revised: 02/19/2022] [Accepted: 03/09/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) and its asymptomatic precursor lesion, esophageal squamous dysplasia (ESD), are common in East Africa. It is unknown whether family history of esophageal cancer is a risk factor for both ESD and ESCC in Africa, and whether family members of affected persons should be screened. METHODS We recruited 296 asymptomatic adult first-degree relatives of ESCC patients residing in southwestern Kenya. Participants completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy to determine the prevalence of ESD. Prevalence comparisons were made with a prior population-based cohort from the same catchment area who also underwent Lugol's chromoendoscopy. RESULTS Mean age was 40.7 years, compared to 62.7 years in the prior population study. The overall prevalence of ESD/ESCC among first-degree relatives was 14.7%, comparable to the background population prevalence of 14.4%, and this comparability remained even after adjusting for the different age distributions of the studies. Post-primary education was the only measured variable that was associated with a decreased risk of ESD/ESCC (adjusted OR=0.31, 95% CI: 0.11, 0.83). There was heterogeneity in the ESD prevalence across families, even after adjustments for varying age and other measured factors. CONCLUSIONS The prevalence of esophageal squamous dysplasia among first-degree relatives of persons with ESCC was similar to that of the background population of southwestern Kenya; however, there was heterogeneity in ESD prevalence between families, suggesting other genetic or environmental factors may influence family prevalence. Further study of families with a high prevalence of ESD or ESCC is justified.
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13
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Feng Y, Liang Y, Yao B, Xu J, Zang J, Zhang Y, Zhang J, Xu G, Wei B, Yao X, Huang P, Shi R. A Rapid Cytological Screening as pre-Endoscopy Screening for Early Esophageal Squamous Cell Lesions: A Prospective Pilot Study from a Chinese Academic Center. Technol Cancer Res Treat 2022; 21:15330338211066200. [PMID: 35040718 PMCID: PMC8811134 DOI: 10.1177/15330338211066200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 10/24/2021] [Accepted: 11/24/2021] [Indexed: 01/22/2023] Open
Abstract
Background: Cytological detection of early esophageal squamous cell carcinoma (ESCC) remains challenging. Therefore, we introduced a rapid cytological screening method and evaluated its efficacy as a pre-endoscopy screening for early ESCC and precursor lesions. Methods: This method consisted of a sponge sample retrieval, automatic liquid-based cytological treatment and slides preparation, computer-assisted screening and manual diagnosis. Efficacy for detection of early ESCC and precursor lesions was evaluated. Also, diagnostic efficiency was compared with manual diagnosis. Results: Eighty-three patients with early ESCC and precursor lesions and 2,090 asymptomatic participants with high risks of ESCC were enrolled. Whole procedure was accomplished within two working days. Abnormal cells were detected in all 83 patients, and in 272 (13.01%) subjects among 2,090 asymptomatic participants. Early ESCC, high-grade intraepithelial neoplasia, low-grade intraepithelial neoplasia and reflux esophagitis and normal endoscopic findings were detected in 8, 13, 11, 187 and 53 participants with abnormal cells, respectively. The calculated sensitivity, specificity, positive predictive value and negative predictive value for detection of early ESCC and precursor lesions were 100%, 88.34%, 11.76%, and 100%, respectively. Compared with manual diagnosis, this method was accomplished in a shorter time duration (5.4 ± 0.45 min vs 320.2 ± 132.4 min, p < 0.001), a higher diagnostic accuracy (96.7% vs74.4%, p = 0.015) and a better inter-observer agreement (93.3% vs66.7%, K = 0.286, p < 0.001). Conclusions: Our study provides a promising methodology as pre-endoscopy screening for early ESCC and precursor lesions.
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Affiliation(s)
- Yadong Feng
- Department of Gastroenterology, Zhongda Hospital, School of
Medicine, Southeast University, 87 Dingjiaqiao Road, 210009, Nanjing, China
| | - Yan Liang
- Nanjing Medical University, 101 Longmian Road, 211166, Nanjing,
China
| | - Bin Yao
- Nanjing Froeasy Technology Development CO., LTD, C1 Building, Red
Maple Park of Technological Industry, 210046, Nanjing, China
| | - Jiajia Xu
- Department of Pathology, Zhongda Hospital, School of Medicine,
Southeast University, 87 Dingjiaqiao Road, 210009, Nanjing, China
| | - Juncai Zang
- Nanjing Froeasy Technology Development CO., LTD, C1 Building, Red
Maple Park of Technological Industry, 210046, Nanjing, China
| | - Youyu Zhang
- Department of Gastroenterology, Zhongda Hospital, School of
Medicine, Southeast University, 87 Dingjiaqiao Road, 210009, Nanjing, China
| | - Jiong Zhang
- Department of Gastroenterology, Zhongda Hospital, School of
Medicine, Southeast University, 87 Dingjiaqiao Road, 210009, Nanjing, China
| | - Guangpeng Xu
- Nanjing Froeasy Technology Development CO., LTD, C1 Building, Red
Maple Park of Technological Industry, 210046, Nanjing, China
| | - Bo Wei
- Nanjing Froeasy Technology Development CO., LTD, C1 Building, Red
Maple Park of Technological Industry, 210046, Nanjing, China
| | - Xiangyi Yao
- Faculty of Art Economic, University of Manitoba, 60 Shore Street,
Winnipeg, Canada, r3T 2C8
| | - Peilin Huang
- Research Institution of Southeast University, 87 Dingjiaqiao Road,
210009, Nanjing, China
| | - Ruihua Shi
- Department of Gastroenterology, Zhongda Hospital, School of
Medicine, Southeast University, 87 Dingjiaqiao Road, 210009, Nanjing, China
- Nanjing Medical University, 101 Longmian Road, 211166, Nanjing,
China
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14
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Gao Y, Xin L, Feng YD, Yao B, Lin H, Sun C, An W, Li ZS, Shi RH, Wang LW. Feasibility and Accuracy of Artificial Intelligence-Assisted Sponge Cytology for Community-Based Esophageal Squamous Cell Carcinoma Screening in China. Am J Gastroenterol 2021; 116:2207-2215. [PMID: 34546186 DOI: 10.14309/ajg.0000000000001499] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 07/15/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Screening is the pivotal strategy to relieve the burden of esophageal squamous cell carcinoma (ESCC) in high-risk areas. The cost, invasiveness, and accessibility of esophagogastroduodenoscopy (EGD) necessitate the development of preliminary screening methods. METHODS Residents aged 40-85 years were recruited in a high-risk area of ESCC. Esophageal cells were collected using an approved novel capsule sponge, and cytology slides were scanned by a trained artificial intelligence (AI) system before cytologists provided confirmation. Atypical squamous cell or more severe diagnosis was defined as positive cytology. AI-based abnormal cell counts were also reported. EGD was performed subsequently with biopsy as needed. Diagnostic accuracy, adverse events, and acceptability of cytology testing were assessed. Esophageal high-grade lesions (ESCC and high-grade intraepithelial neoplasia) were the primary target lesions. RESULTS In total, 1,844 participants were enrolled, and 20 (1.1%) high-grade lesions were confirmed by endoscopic biopsy. The AI-assisted cytologist-confirmed cytology showed good diagnostic accuracy, with a sensitivity of 90.0% (95% confidence interval [CI], 76.9%-100.0%), specificity of 93.7% (95% CI, 92.6%-94.8%), and positive predictive value of 13.5% (95% CI, 7.70%-19.3%) for detecting high-grade lesions. The area under the receiver operation characteristics curve was 0.926 (95% CI, 0.850-1.000) and 0.949 (95% CI, 0.890-1.000) for AI-assisted cytologist-confirmed cytology and AI-based abnormal cell count, respectively. The numbers of EGD could be reduced by 92.5% (from 99.2 to 7.4 to detect 1 high-grade lesion) if only cytology-positive participants were referred to endoscopy. No serious adverse events were documented during the cell collection process, and 96.1% participants reported this process as acceptable. DISCUSSION The AI-assisted sponge cytology is feasible, safe, and acceptable for ESCC screening in community, with high accuracy for detecting esophageal squamous high-grade lesions.
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Affiliation(s)
- Ye Gao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Lei Xin
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Ya-Dong Feng
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Bin Yao
- School of Computer Science and Engineering, Southeast University, Nanjing, Jiangsu Province, China
- Nanjing Froeasy Technology Development Co, Ltd, Nanjing, Jiangsu Province, China
| | - Han Lin
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Chang Sun
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Wei An
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Rui-Hua Shi
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Luo-Wei Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
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15
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Xie Y, Wang D, Gao C, Hu J, Zhang M, Gao W, Shu S, Chai X. Effect of perioperative flurbiprofen axetil on long-term survival of patients with esophageal carcinoma who underwent thoracoscopic esophagectomy: A retrospective study. J Surg Oncol 2021; 124:540-550. [PMID: 34143443 PMCID: PMC8453976 DOI: 10.1002/jso.26553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/07/2021] [Accepted: 05/12/2021] [Indexed: 12/24/2022]
Abstract
Background and Objectives Nonsteroidal anti‐inflammatory drugs (NSAIDs) have an anti‐inflammatory response, but it remains unclear whether the perioperative use of flurbiprofen axetil can influence postoperative tumor recurrence and survival in esophageal carcinoma. We aimed to explore the effect of perioperative intravenous flurbiprofen axetil on recurrence‐free survival (RFS) and overall survival (OS) in patients with esophageal carcinoma who underwent thoracoscopic esophagectomy. Methods This retrospective study included patients who underwent surgery for esophageal carcinoma between December 2009 and May 2015 at the Department of Thoracic Surgery, Anhui Provincial Hospital. Patients were categorized into a non‐NSAIDs group (did not receive flurbiprofen axetil), single‐dose NSAIDs group (received a single dose of flurbiprofen axetil intravenously), and multiple‐dose NSAIDs group (received multiple doses of flurbiprofen). Results A total of 847 eligible patients were enrolled. Univariable and multivariable analyses revealed that the intraoperative use of flurbiprofen was associated with long‐term RFS (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.42–0.76, p = .001) and prolonged OS (HR: 0.49, 95% CI: 0.38–0.63, p = .001). Conclusions Perioperative flurbiprofen axetil therapy may be associated with prolonged RFS and OS in patients with esophageal carcinoma undergoing thoracoscopic esophagectomy.
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Affiliation(s)
- Yanhu Xie
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Di Wang
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Chen Gao
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Jicheng Hu
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Min Zhang
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Wei Gao
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Shuhua Shu
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
| | - Xiaoqing Chai
- Department of Anesthesiology, Anhui Provincial Hospital, Hefei, Anhui, China.,Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei, Anhui, China
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16
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Hull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrotra R, Mkhize-Kwitshana Z, Hussain S, Kibiki G, Bates DO, Dlamini Z. A multinational review: Oesophageal cancer in low to middle-income countries. Oncol Lett 2020; 20:42. [PMID: 32802164 PMCID: PMC7412736 DOI: 10.3892/ol.2020.11902] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 10/08/2019] [Indexed: 12/12/2022] Open
Abstract
Oesophageal cancer (OC) is an aggressive neoplasm that manifests in the gastrointestinal tract and is the result of numerous factors that can contribute to the development of the disease. These may include old age, nutritional deficiencies, oesophageal obstruction and food ingestion difficulties. Environmental factors serve a large role in increasing the risk of developing OC. Two factors that serve an increasing risk of developing OC are the use of tobacco and the consumption of alcohol. Genetic factors also exhibit a large effect on the risk of developing OC, for example, the causative genes in Black Africans differ from other races. OC is 3-4 times more common among men than women. OC has been previously reported in >450 000 individuals worldwide, and its incidence is increasing. The current review compares OC in low to middle-income countries with developed countries. The incidence of OC, particularly squamous cell carcinoma (SCC) is high in low and middle-income countries. In developed countries, the incidence of SCC is low compared with adenocarcinoma. The majority of OC cases are diagnosed in the late stages of the disease, leading to high mortality rates. The current review aimed to discuss factors that contribute to the development of this disease in different geographical areas and genetic mechanisms governing these findings. The current review also aims to discuss the preventative treatment options for the disease, and also discusses the diagnosis and surveillance in five LMICs, including South Africa, China, Tanzania, India and Brazil.
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Affiliation(s)
- Rodney Hull
- South African-Medical Research Council/University of Pretoria Precision, Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Cancer Research Institute, University of Pretoria, Faculty of Health Sciences, Pretoria, Gauteng 0028, South Africa
| | - Mzwandile Mbele
- South African-Medical Research Council/University of Pretoria Precision, Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Cancer Research Institute, University of Pretoria, Faculty of Health Sciences, Pretoria, Gauteng 0028, South Africa
| | - Tshepiso Makhafola
- South African-Medical Research Council/University of Pretoria Precision, Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Cancer Research Institute, University of Pretoria, Faculty of Health Sciences, Pretoria, Gauteng 0028, South Africa
| | - Chindo Hicks
- Louisiana State University, School of Medicine, Department of Genetics, Bioinformatics and Genomics Centre, LA 70112, USA
| | - Shao Ming Wang
- National Cancer Centre, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China
| | - Rui Manuel Reis
- Molecular Oncology Research Centre, Barretos Cancer Hospital, CEP 14784 400, Sao Paulo, Brazil
| | - Ravi Mehrotra
- Indian Council of Medical Research, 110029 New Delhi, India
| | | | - Showket Hussain
- East African Health Research Commission, East African Community, Quartier Kigobe, 1096 Arusha, United Republic of Tanzania
| | - Gibson Kibiki
- East African Health Research Commission, East African Community, Quartier Kigobe, 1096 Arusha, United Republic of Tanzania
| | - David O. Bates
- University of Nottingham, Queens Medical Centre, Cancer Biology, NG7 2UH Nottingham, UK
| | - Zodwa Dlamini
- South African-Medical Research Council/University of Pretoria Precision, Prevention and Novel Drug Targets for HIV-Associated Cancers Extramural Unit, Cancer Research Institute, University of Pretoria, Faculty of Health Sciences, Pretoria, Gauteng 0028, South Africa
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17
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Qin Y, Taylor W, Bamlet WR, Ravindran A, Buglioni A, Cao X, Foote PH, Slettedahl SW, Mahoney DW, Albert PS, Kim S, Hu N, Taylor PR, Etemadi A, Sotoudeh M, Malekzadeh R, Abnet CC, Smyrk TC, Katzka D, Topazian MD, Dawsey SM, Ahlquist D, Kisiel JB, Iyer PG. Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study. Cancer Epidemiol Biomarkers Prev 2020; 29:2642-2650. [PMID: 32948633 DOI: 10.1158/1055-9965.epi-20-0616] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/22/2020] [Accepted: 09/11/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices. METHODS MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons. RESULTS Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004). CONCLUSIONS MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results. IMPACT MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
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Affiliation(s)
- Yi Qin
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - William Taylor
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - William R Bamlet
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Adharsh Ravindran
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alessia Buglioni
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Xiaoming Cao
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Patrick H Foote
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Seth W Slettedahl
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Douglas W Mahoney
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | | | - Sungduk Kim
- Biostatistics Branch, NCI, Rockville, Maryland
| | - Nan Hu
- Metabolic Epidemiology Branch, NCI, Rockville, Maryland
| | | | - Arash Etemadi
- Metabolic Epidemiology Branch, NCI, Rockville, Maryland.,Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Sotoudeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Thomas C Smyrk
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David Katzka
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Mark D Topazian
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - David Ahlquist
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John B Kisiel
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Prasad G Iyer
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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18
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Grillo F, Mastracci L, Saragoni L, Vanoli A, Limarzi F, Gullo I, Ferro J, Paudice M, Parente P, Fassan M. Neoplastic and pre-neoplastic lesions of the oesophagus and gastro-oesophageal junction. Pathologica 2020; 112:138-152. [PMID: 33179618 PMCID: PMC7931575 DOI: 10.32074/1591-951x-164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 06/29/2020] [Indexed: 12/12/2022] Open
Abstract
Oesophageal and gastro-oesophageal junction (GOJ) neoplasms, and their predisposing conditions, may be encountered by the practicing pathologist both as biopsy samples and as surgical specimens in daily practice. Changes in incidence of oesophageal squamous cell carcinomas (such as a decrease in western countries) and in oesophageal and GOJ adenocarcinomas (such as a sharp increase in western countries) are being reported globally. New modes of treatment have changed our histologic reports as specific aspects must be detailed such as in post endoscopic resections or with regards to post neo-adjuvant therapy tumour regression grades. The main aim of this overview is therefore to provide an up-to-date, easily available and clear diagnostic approach to neoplastic and pre-neoplastic conditions of the oesophagus and GOJ, based on the most recent available guidelines and literature.
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Affiliation(s)
- Federica Grillo
- Correspondence Federica Grillo Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova and Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, largo Rosanna Benzi 10, 16132 Genova, Italy Tel. +39 010 5555957 Fax: +39 010 5556392 E-mail:
| | | | - Luca Saragoni
- UO Anatomia Patologica, Ospedale G.B. Morgagni-L. Pierantoni, Forlì, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Francesco Limarzi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST/IRCCS), Meldola (FC), Italy
| | - Irene Gullo
- Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ) & Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal and Instituto de Investigação e Inovação em Saúde (i3S) & Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal
| | - Jacopo Ferro
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy
| | - Michele Paudice
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Italy
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Kamangar F, Nasrollahzadeh D, Safiri S, Sepanlou SG, Fitzmaurice C, Ikuta KS, Bisignano C, Islami F, Roshandel G, Lim SS, Abolhassani H, Abu-Gharbieh E, Adedoyin RA, Advani SM, Ahmed MB, Aichour MTE, Akinyemiju T, Akunna CJ, Alahdab F, Alipour V, Almasi-Hashiani A, Almulhim AM, Anber NH, Ansari-Moghaddam A, Arabloo J, Arab-Zozani M, Awedew AF, Badawi A, Berfield KSS, Berhe K, Bhattacharyya K, Biondi A, Bjørge T, Borzì AM, Bosetti C, Carreras G, Carvalho F, Castro C, Chu DT, Costa VM, Dagnew B, Darega Gela J, Daryani A, Demeke FM, Demoz GT, Dianatinasab M, Elbarazi I, Emamian MH, Etemadi A, Faris PS, Fernandes E, Filip I, Fischer F, Gad MM, Gallus S, Gebre AK, Gebrehiwot TT, Gebremeskel GG, Gebresillassie BM, Ghasemi-kebria F, Ghashghaee A, Ghith N, Golechha M, Gorini G, Gupta R, Hafezi-Nejad N, Haj-Mirzaian A, Harvey JD, Hashemian M, Hassen HY, Hay SI, Henok A, Hoang CL, Hosgood HD, Househ M, Ilesanmi OS, Ilic MD, Irvani SSN, Jain C, James SL, Jee SH, Jha RP, Joukar F, Kabir A, Kasaeian A, Kassaw MW, Kaur S, Kengne AP, Kerboua E, Khader YS, Khalilov R, Khan EA, Khoja AT, Kocarnik JM, Komaki H, Kumar V, La Vecchia C, Lasrado S, Li B, Lopez AD, et alKamangar F, Nasrollahzadeh D, Safiri S, Sepanlou SG, Fitzmaurice C, Ikuta KS, Bisignano C, Islami F, Roshandel G, Lim SS, Abolhassani H, Abu-Gharbieh E, Adedoyin RA, Advani SM, Ahmed MB, Aichour MTE, Akinyemiju T, Akunna CJ, Alahdab F, Alipour V, Almasi-Hashiani A, Almulhim AM, Anber NH, Ansari-Moghaddam A, Arabloo J, Arab-Zozani M, Awedew AF, Badawi A, Berfield KSS, Berhe K, Bhattacharyya K, Biondi A, Bjørge T, Borzì AM, Bosetti C, Carreras G, Carvalho F, Castro C, Chu DT, Costa VM, Dagnew B, Darega Gela J, Daryani A, Demeke FM, Demoz GT, Dianatinasab M, Elbarazi I, Emamian MH, Etemadi A, Faris PS, Fernandes E, Filip I, Fischer F, Gad MM, Gallus S, Gebre AK, Gebrehiwot TT, Gebremeskel GG, Gebresillassie BM, Ghasemi-kebria F, Ghashghaee A, Ghith N, Golechha M, Gorini G, Gupta R, Hafezi-Nejad N, Haj-Mirzaian A, Harvey JD, Hashemian M, Hassen HY, Hay SI, Henok A, Hoang CL, Hosgood HD, Househ M, Ilesanmi OS, Ilic MD, Irvani SSN, Jain C, James SL, Jee SH, Jha RP, Joukar F, Kabir A, Kasaeian A, Kassaw MW, Kaur S, Kengne AP, Kerboua E, Khader YS, Khalilov R, Khan EA, Khoja AT, Kocarnik JM, Komaki H, Kumar V, La Vecchia C, Lasrado S, Li B, Lopez AD, Majeed A, Manafi N, Manda AL, Mansour-Ghanaei F, Mathur MR, Mehta V, Mehta D, Mendoza W, Mithra P, Mohammad KA, Mohammadian-Hafshejani A, Mohammadpourhodki R, Mohammed JA, Mohebi F, Mokdad AH, Monasta L, Moosavi D, Moosazadeh M, Moradi G, Moradpour F, Moradzadeh R, Naik G, Negoi I, Nggada HA, Nguyen HLT, Nikbakhsh R, Nixon MR, Olagunju AT, Olagunju TO, Padubidri JR, Pakshir K, Patel S, Pathak M, Pham HQ, Pourshams A, Rabiee N, Rabiee M, Radfar A, Rafiei A, Ramezanzadeh K, Rath GK, Rathi P, Rawaf S, Rawaf DL, Rezaei N, Roro EM, Saad AM, Salimzadeh H, Samy AM, Sartorius B, Sarveazad A, Sekerija M, Sha F, Shamsizadeh M, Sheikhbahaei S, Shirkoohi R, Siddappa Malleshappa SK, Singh JA, Sinha DN, Smarandache CG, Soshnikov S, Suleria HAR, Tadesse DB, Tesfay BE, Thakur B, Traini E, Tran KB, Tran BX, Ullah I, Vacante M, Veisani Y, Vujcic IS, Weldesamuel GT, Xu R, Yazdi-Feyzabadi V, Yuce D, Zadnik V, Zaidi Z, Zhang ZJ, Malekzadeh R, Naghavi M. The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5:582-597. [PMID: 32246941 PMCID: PMC7232026 DOI: 10.1016/s2468-1253(20)30007-8] [Show More Authors] [Citation(s) in RCA: 282] [Impact Index Per Article: 56.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 01/09/2020] [Accepted: 01/10/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Oesophageal cancer is a common and often fatal cancer that has two main histological subtypes: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Updated statistics on the incidence and mortality of oesophageal cancer, and on the disability-adjusted life-years (DALYs) caused by the disease, can assist policy makers in allocating resources for prevention, treatment, and care of oesophageal cancer. We report the latest estimates of these statistics for 195 countries and territories between 1990 and 2017, by age, sex, and Socio-demographic Index (SDI), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD). METHODS We used data from vital registration systems, vital registration-samples, verbal autopsy records, and cancer registries, combined with relevant modelling, to estimate the mortality, incidence, and burden of oesophageal cancer from 1990 to 2017. Mortality-to-incidence ratios (MIRs) were estimated and fed into a Cause of Death Ensemble model (CODEm) including risk factors. MIRs were used for mortality and non-fatal modelling. Estimates of DALYs attributable to the main risk factors of oesophageal cancer available in GBD were also calculated. The proportion of oesophageal squamous cell carcinoma to all oesophageal cancers was extracted by use of publicly available data, and its variation was examined against SDI, the Healthcare Access and Quality (HAQ) Index, and available risk factors in GBD that are specific for oesophageal squamous cell carcinoma (eg, unimproved water source and indoor air pollution) and for oesophageal adenocarcinoma (gastro-oesophageal reflux disease). FINDINGS There were 473 000 (95% uncertainty interval [95% UI] 459 000-485 000) new cases of oesophageal cancer and 436 000 (425 000-448 000) deaths due to oesophageal cancer in 2017. Age-standardised incidence was 5·9 (5·7-6·1) per 100 000 population and age-standardised mortality was 5·5 (5·3-5·6) per 100 000. Oesophageal cancer caused 9·78 million (9·53-10·03) DALYs, with an age-standardised rate of 120 (117-123) per 100 000 population. Between 1990 and 2017, age-standardised incidence decreased by 22·0% (18·6-25·2), mortality decreased by 29·0% (25·8-32·0), and DALYs decreased by 33·4% (30·4-36·1) globally. However, as a result of population growth and ageing, the total number of new cases increased by 52·3% (45·9-58·9), from 310 000 (300 000-322 000) to 473 000 (459 000-485 000); the number of deaths increased by 40·0% (34·1-46·3), from 311 000 (301 000-323 000) to 436 000 (425 000-448 000); and total DALYs increased by 27·4% (22·1-33·1), from 7·68 million (7·42-7·97) to 9·78 million (9·53-10·03). At the national level, China had the highest number of incident cases (235 000 [223 000-246 000]), deaths (213 000 [203 000-223 000]), and DALYs (4·46 million [4·25-4·69]) in 2017. The highest national-level age-standardised incidence rates in 2017 were observed in Malawi (23·0 [19·4-26·5] per 100 000 population) and Mongolia (18·5 [16·4-20·8] per 100 000). In 2017, age-standardised incidence was 2·7 times higher, mortality 2·9 times higher, and DALYs 3·0 times higher in males than in females. In 2017, a substantial proportion of oesophageal cancer DALYs were attributable to known risk factors: tobacco smoking (39·0% [35·5-42·2]), alcohol consumption (33·8% [27·3-39·9]), high BMI (19·5% [6·3-36·0]), a diet low in fruits (19·1% [4·2-34·6]), and use of chewing tobacco (7·5% [5·2-9·6]). Countries with a low SDI and HAQ Index and high levels of indoor air pollution had a higher proportion of oesophageal squamous cell carcinoma to all oesophageal cancer cases than did countries with a high SDI and HAQ Index and with low levels of indoor air pollution. INTERPRETATION Despite reductions in age-standardised incidence and mortality rates, oesophageal cancer remains a major cause of cancer mortality and burden across the world. Oesophageal cancer is a highly fatal disease, requiring increased primary prevention efforts and, possibly, screening in some high-risk areas. Substantial variation exists in age-standardised incidence rates across regions and countries, for reasons that are unclear. FUNDING Bill & Melinda Gates Foundation.
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20
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Wang M, Hao C, Xie S, Ma S, Ma Q, Zheng R, Chen R, Li X, Wei W. Efficacy of endoscopic treatment on patients with severe dysplasia/carcinoma in situ of esophageal squamous cell carcinoma: A prospective cohort study. Chin J Cancer Res 2019; 31:357-365. [PMID: 31156306 PMCID: PMC6513741 DOI: 10.21147/j.issn.1000-9604.2019.02.10] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Objective To explore the natural history of severe dysplasia/carcinoma in situ (SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients.
Methods Between January 2005 and December 2009, a population-based prospective screening program on esophageal squamous cell carcinoma (ESCC) was performed in Linzhou, China, with endoscopic screening plus iodine staining. All the eligible histologically confirmed SD/CIS patients were followed up through the door-to-door follow-up and local cancer registry. The endpoint was diagnosed as ESCC or the December 31st, 2016. Kaplan-Meier survival analysis and Log-rank test were used to compare the survival rates among treated and untreated patients. Results A total of 175 SD/CIS patients were enrolled and grouped by whether they received endoscopic treatment. Eleven-year cumulative incidence rates for untreated and treated SD/CIS patients were 10.7% [95% confidence interval (95% CI): 6.9−16.1] and 3.2% (95% CI: 1.4−7.0), respectively. The ESCC incidence free survival rate, and all-cause incidence and mortality free survival rates were all significantly higher in the treated patientsvs. untreated patients (P=0.043, P=0.008 and P=0.015, respectively). The ESCC mortality free survival rate showed no significant differences between the two groups (P=0.847).
Conclusions The cumulative incidence rate of SD/CIS patients to ESCC was much lower than previously reported. The Kaplan-Meier survival analysis showed that endoscopic treatment could increase the ESCC and all-cause disease-free survival rates of SD/CIS patients significantly.
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Affiliation(s)
- Meng Wang
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Changqing Hao
- Department of Endoscopy, Linzhou Cancer Hospital, Anyang 456550, China
| | - Shuanghua Xie
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shanrui Ma
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qing Ma
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Rongshou Zheng
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ru Chen
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinqing Li
- Office of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- Office of Cancer Registry, 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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Mkarimi M, Mashimo H. Advanced Imaging for Barrett's Esophagus and Early Neoplasia: Surface and Subsurface Imaging for Diagnosis and Management. Curr Gastroenterol Rep 2018; 20:54. [PMID: 30302571 DOI: 10.1007/s11894-018-0661-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW Esophageal adenocarcinoma bears one of the fastest rising incidence of any cancers and generally arises in the setting of gastroesophageal reflux and Barrett's esophagus. However, early detection of neoplasia can be challenging since most patients are asymptomatic until they progress to more advanced and less curable stages, and early dysplastic lesions can be small, multifocal, and difficult to detect. Clearly, new imaging tools are needed in light of sampling error associated with random biopsies, the current standard of practice. RECENT FINDINGS Advances in endoscopic imaging including virtual chromoendoscopy, confocal laser endomicroscopy, and subsurface imaging with optical coherence tomography have ushered in a new era for detecting subtle neoplastic lesions. Moreover, in light of esophagus-sparing treatments for neoplastic lesions, such tools are likely to guide ablation and follow-up management. While there is no ideal single imaging modality to facilitate improved detection, staging, ablation, and follow-up of patients with dysplastic Barrett's esophagus, new advances in available technology, the potential for multimodal imaging, and the use of computer-aided diagnosis and biomarkers all hold great promise for improving detection and treatment.
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Affiliation(s)
- Mansoureh Mkarimi
- VA Boston Healthcare, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA, 02132, USA
| | - Hiroshi Mashimo
- VA Boston Healthcare, Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA, 02132, USA.
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Codipilly DC, Qin Y, Dawsey SM, Kisiel J, Topazian M, Ahlquist D, Iyer PG. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc 2018; 88:413-426. [PMID: 29709526 PMCID: PMC7493990 DOI: 10.1016/j.gie.2018.04.2352] [Citation(s) in RCA: 187] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 04/20/2018] [Indexed: 02/08/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer worldwide, with a high mortality due to advanced stage at diagnosis. Although most common in an area known as the Asian Esophageal Cancer Belt, which extends from the Caspian Sea to northern China, and in parts of Africa, high-risk populations also exist elsewhere in the world. Screening for ESCC has been practiced in a few geographic areas and high-risk populations, with varying levels of success. Esophageal squamous dysplasia is recognized as the precursor lesion for ESCC. Endoscopic screening for ESCC/esophageal squamous dysplasia is expensive and not sufficiently available in many high-risk regions. Recent advances in non-endoscopic screening enhanced by biomarker-based disease detection have raised the prospect of improved accuracy and availability of screening for esophageal squamous dysplasia and early stage ESCC. Development of a cost-effective, accurate, and well-tolerated screening test, if applied in endemic areas and high-risk populations, has the potential to reduce mortality from this deadly disease worldwide. In this review, we summarize recent developments in endoscopic and non-endoscopic screening modalities.
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Affiliation(s)
- DC Codipilly
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
| | - Y Qin
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
| | - Sanford M. Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
| | - John Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
| | - David Ahlquist
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
| | - PG Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester
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23
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Screening patients for Barrett esophagus: Why, who, and how. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2018. [DOI: 10.1016/j.tgie.2018.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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di Pietro M, Canto MI, Fitzgerald RC. Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy. Gastroenterology 2018; 154:421-436. [PMID: 28778650 PMCID: PMC6104810 DOI: 10.1053/j.gastro.2017.07.041] [Citation(s) in RCA: 160] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Revised: 07/24/2017] [Accepted: 07/26/2017] [Indexed: 12/16/2022]
Abstract
Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett's), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease.
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Affiliation(s)
| | - Marcia I Canto
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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25
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Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA, Dawsey SM, Etemadi A, Fitzgerald RC, Fleischer DE, Freedman ND, Goldstein AM, Gopal S, Hashemian M, Hu N, Hyland PL, Kaimila B, Kamangar F, Malekzadeh R, Mathew CG, Menya D, Mulima G, Mwachiro MM, Mwasamwaja A, Pritchett N, Qiao YL, Ribeiro-Pinto LF, Ricciardone M, Schüz J, Sitas F, Taylor PR, Van Loon K, Wang SM, Wei WQ, Wild CP, Wu C, Abnet CC, Chanock SJ, Brennan P. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann Oncol 2017; 28:2086-2093. [PMID: 28911061 PMCID: PMC5834011 DOI: 10.1093/annonc/mdx279] [Citation(s) in RCA: 142] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.
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Affiliation(s)
- G. Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | | | | | - M. Arnold
- Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - M. C. Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - N. A. Dar
- Department of Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir, India
| | - S. M. Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - A. Etemadi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - R. C. Fitzgerald
- MRC Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK
| | - D. E. Fleischer
- Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA
| | - N. D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - A. M. Goldstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - S. Gopal
- University of North Carolina Project-Malawi, Lilongwe, Malawi
| | - M. Hashemian
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - N. Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - P. L. Hyland
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - B. Kaimila
- University of North Carolina Project-Malawi, Lilongwe, Malawi
| | - F. Kamangar
- Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, USA
| | - R. Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - C. G. Mathew
- Department of Medical and Molecular Genetics, Kings College London
- Sydney Brenner Institute for Molecular Bioscience, University of Witwatersrand, Johannesburg, South Africa
| | - D. Menya
- School of Public Health, Moi University, Eldoret, Kenya
| | - G. Mulima
- University of North Carolina Project-Malawi, Lilongwe, Malawi
| | | | - A. Mwasamwaja
- Kilimanjaro Christian Medical Centre, Moshi, Tanzania
| | - N. Pritchett
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - Y.-L. Qiao
- Department of Etiology and Carcinogenesis & Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - L. F. Ribeiro-Pinto
- Molecular Carcinogenesis Program, Institute Nacional de Cancer, Sao Paulo, Brazil
| | - M. Ricciardone
- National Cancer Institute, Center for Global Health, National Institutes of Health, Bethesda, Maryland, USA
| | - J. Schüz
- Section of Environment and Radiation
| | - F. Sitas
- School of Public Health, University of Sydney, New South Wales, Australia
- School of Public Health & Community Medicine, University of New South Wales, Sydney, Australia
| | - P. R. Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - K. Van Loon
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - S.-M. Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
- Department of Etiology and Carcinogenesis & Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - W.-Q. Wei
- Department of Etiology and Carcinogenesis & Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - C. P. Wild
- Director's office, International Agency for Research on Cancer, Lyon, France
| | - C. Wu
- Department of Etiology and Carcinogenesis & Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - C. C. Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
| | - S. J. Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda Maryland, USA
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Abstract
PURPOSE OF REVIEW The costs to society and accuracy of screening for esophageal cancer and other esophageal diseases with standard endoscopy are formidable. As a result, the applicability of endoscopy as a general screening tool has been challenged. RECENT FINDINGS To maintain accuracy but reduce the price of endoscopy on society, multiple adjunct or replacement technologies are being developed that are less expensive and more easily applied. These devices include image-enhancing techniques that more reliably identify dysplasia and cancer reducing the need for extensive biopsy sampling during standard endoscopy. They also include ambulatory forms for procuring esophageal imaging including smaller endoscopes and capsule endoscopy. Finally, some of the newer methods either obtain samples of esophageal tissue through bedside maneuvers not requiring endoscopy or retrieve information about mucosal inflammation and function without the need to procure esophageal tissue. There is an exciting future for esophageal diagnosis with tools that will save cost and/or provide greater accuracy and safety for some of the most common esophageal disorders.
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Affiliation(s)
- David A Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Ave., S.W., Rochester, MN, 55905, USA.
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27
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Haisley KR, Dolan JP, Olson SB, Toledo-Valdovinos SA, Hart KD, Bakis G, Enestvedt BK, Hunter JG. Sponge Sampling with Fluorescent In Situ Hybridization as a Screening Tool for the Early Detection of Esophageal Cancer. J Gastrointest Surg 2017; 21:215-221. [PMID: 27561634 DOI: 10.1007/s11605-016-3239-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 08/03/2016] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Sponge cytology is a novel screening tool for esophageal cancer but has been unable to be validated for widespread use. Our aim was to apply fluorescent in situ hybridization to sponge cytology samples in order to evaluate the safety and efficacy of this modality in screening for esophageal cancer. MATERIALS AND METHODS At a single, multidisciplinary, NCI-designated cancer center, patients completed sponge cytology sampling prior to upper endoscopy. Samples were analyzed by p53 fluorescent in situ hybridization, and results were compared to the endoscopic diagnosis. RESULTS Fifty patients were enrolled (96 % Caucasian, 68 % male, median age of 67). All patients successfully swallowed the capsule. No complications (string breakage, bleeding, mucosal injury) occurred. Endoscopy revealed that 38 % had normal esophageal mucosa and 62 % had an esophageal mucosal abnormality. In total, six samples demonstrated p53 loss (94 % specificity for any abnormality). The sensitivity of the p53 fluorescent in situ hybridization probe was13.3 % for any abnormality, 10 % for intestinal metaplasia, and 0 % for dysplasia or esophageal cancer. DISCUSSION Esophageal sponge cytology is a promising, safe, and tolerable method for collecting esophageal cell samples. However, our data suggest that p53 fluorescent in situ hybridization does not improve the sensitivity for detecting cancer in these samples.
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Affiliation(s)
- Kelly R Haisley
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, L223A, Portland, OR, 97239, USA
| | - James P Dolan
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, L223A, Portland, OR, 97239, USA
| | - Susan B Olson
- Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA
| | - Sergio A Toledo-Valdovinos
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, L223A, Portland, OR, 97239, USA
| | - Kyle D Hart
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, L223A, Portland, OR, 97239, USA
| | - Gene Bakis
- Department of Gastroenterology, Oregon Health and Science University, Portland, OR, USA
| | - Brintha K Enestvedt
- Department of Gastroenterology, Oregon Health and Science University, Portland, OR, USA
| | - John G Hunter
- Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, L223A, Portland, OR, 97239, USA.
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Liang H, Fan JH, Qiao YL. Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China. Cancer Biol Med 2017; 14:33-41. [PMID: 28443201 PMCID: PMC5365188 DOI: 10.20892/j.issn.2095-3941.2016.0093] [Citation(s) in RCA: 246] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 12/23/2016] [Indexed: 12/22/2022] Open
Abstract
Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis. Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.
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Affiliation(s)
- He Liang
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jin-Hu Fan
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - You-Lin Qiao
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Chen W, Zeng H, Chen R, Xia R, Yang Z, Xia C, Zheng R, Wei W, Zhuang G, Yu X, He J. Evaluating efficacy of screening for upper gastrointestinal cancer in China: a study protocol for a randomized controlled trial. Chin J Cancer Res 2017; 29:294-302. [PMID: 28947861 PMCID: PMC5592817 DOI: 10.21147/j.issn.1000-9604.2017.04.02] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Objective To evaluate the efficacy and feasibility of screening procedure for upper gastrointestinal cancer in both high-risk and non-high-risk areas in China. Setting Seven cities/counties, representing three economical-geographical regions (Eastern, Central and Western) in China, were selected as screening centers: three in high-risk areas and four in non-high-risk areas. Participants Villages/communities in these seven centers regarded as clusters were randomly assigned to either intervention group (screening by endoscopic examination) or control group (with normal community care) in a 1:1 ratio stratified by each center. Eligible participants are local residents aged 40–69 years in the selected villages/communities with no history of cancer or endoscopic examination in the latest 3 years who are mentally and physically competent. Those who are not willing to take endoscopic examination or are unwilling to sign the consent form are excluded from the study. Totally 140,000 participants will be enrolled. Interventions In high-risk areas of upper gastrointestinal cancer, all subjects in screening group will be screened by endoscopy. In non-high-risk areas, 30% of the subjects in screening group, identified through a survey, will be screened by endoscopy. Primary and secondary outcome measures The primary outcome is the mortality caused by upper gastrointestinal cancer. The secondary outcomes include detection rate, incidence rate, survival rate, and clinical stage distribution. Additional data on quality of life and cost-effectiveness will also be collected to answer important questions regarding screening effects. Conclusions Screening strategy evaluated in those areas with positive findings may be promoted nationally and applied to the majority of Chinese people. On the other hand, negative findings will provide scientific evidence for abandoning a test and shifting resources elsewhere. Trial registration The study has been registered with the Protocol Registration System in Chinese Clinical Trial Registry (identifier: ChiCTR-EOR-16008577).
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Affiliation(s)
- Wanqing Chen
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hongmei Zeng
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ru Chen
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ruyi Xia
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhixun Yang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Changfa Xia
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Rongshou Zheng
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Guihua Zhuang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xueqin Yu
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jie He
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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30
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Zou X, Zhou W, Lu Y, Shen C, Hu Z, Wang H, Jiang H, Chu Y. Exhaled gases online measurements for esophageal cancer patients and healthy people by proton transfer reaction mass spectrometry. J Gastroenterol Hepatol 2016; 31:1837-1843. [PMID: 26996099 DOI: 10.1111/jgh.13380] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 02/06/2016] [Accepted: 03/14/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Esophageal cancer is a prevalent malignancy. There is a considerable demand for developing a fast and noninvasive method to screen out the suspect esophageal cancer patients who may undergo further clinical diagnosis. METHODS The exhaled breathes from 29 esophageal cancer patients and 57 healthy people were directly measured using our home-made proton transfer reaction mass spectrometer (PTR-MS). Mann-Whitney U test and stepwise discriminant analysis were applied to identify the ions in the breath mass spectral data which can distinguish cancer cohort from healthy group. Receiver operating characteristics (ROC) analysis was also performed. RESULTS Seven kinds of ions in the breath mass spectrum, viz., m/z 136, m/z 34, m/z 63, m/z 27, m/z 95, m/z 107 and m/z 45, have been found to distinguish between the esophageal cancer patients and healthy people with a sensitivity of 86.2% and a specificity of 89.5%, respectively. Compared with that from the healthy people, the breath mass spectra from esophageal cancer patients show that the mediant intensities of five kinds of ions were decrease and the rest two kinds of ions were increase. ROC analysis gave the area under the curve (AUC) of 0.943. CONCLUSIONS This pilot study shows that the ionic characteristics of exhaled VOCs detected by PTR-MS may be used to differentiate between the esophageal cancer patients and the healthy people. Although the breath tests for more patients are needed to confirm such results, the present work indicates that the PTR-MS may be a promising method in the esophageal cancer screening.
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Affiliation(s)
- Xue Zou
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Wenzhao Zhou
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Yan Lu
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Chengyin Shen
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Zongtao Hu
- Cancer Center, the 105 Hospital of Chinese People's Liberation Army, Hefei, China
| | - Hongzhi Wang
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.,Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Haihe Jiang
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
| | - Yannan Chu
- Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
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31
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Wang M, Hao C, Ma Q, Song G, Ma S, Zhao D, Zhao L, Li X, Wei W. DNA image cytometry test for primary screening of esophageal cancer: a population-based multi-center study in high-risk areas in China. Chin J Cancer Res 2016; 28:404-12. [PMID: 27647968 PMCID: PMC5018535 DOI: 10.21147/j.issn.1000-9604.2016.04.03] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 05/02/2016] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE To evaluate the feasibility of DNA image cytometry (DNA-ICM) as a primary screening method for esophageal squamous cell cancer (ESCC). METHODS A total of 5,382 local residents aged 40-69 years from three high-risk areas in China (Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province) from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol's iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity (SE), specificity (SP), negative predictive values (NPV) and positive predictive values (PPV) as well as their 95% confidence intervals (95% CI) for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic (ROC) curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. RESULTS DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions (χ(2)=18.016, P<0.001). The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test (cutoff point 5,803) combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance (ASCUS)] were separately 72.1% (95% CI: 70.3%-73.9%), 43.3% (95% CI: 41.3%-45.3%), 22.8% (95% CI: 21.1%-24.5%) and 87.0% (95% CI: 85.7%-88.3%) for LGIN, 85.7% (95% CI: 84.3%-87.1%), 41.3% (95% CI: 39.3%-43.3%), 4.6% (95% CI: 3.8%-5.4%) and 98.9% (95% CI: 98.5%-99.3%) for HGIN, and 96.0% (95% CI: 95.2%-96.8%), 40.8% (95% CI: 38.8%-42.8%), 1.7% (95% CI: 1.2%-2.2%) and 99.9% (95% CI: 99.8%-100.0%) for ESCC. CONCLUSIONS It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.
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Affiliation(s)
- Meng Wang
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Changqing Hao
- Department of Endoscopy, Linzhou Cancer Hospital, Henan 456550, China
| | - Qing Ma
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Guohui Song
- Department of Epidemiology, Cixian Cancer Hospital, Heibei 056500, China
| | - Shanrui Ma
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Deli Zhao
- Department of Cancer Center, Feicheng People Hospital, Shandong 271600, China; 5Medical Record Room, Xuanwu Hosital, Beijing 100053, China
| | - Lin Zhao
- Medical Record Room, Xuanwu Hosital, Beijing 100053, China
| | - Xinqing Li
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
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Couch G, Redman JE, Wernisch L, Newton R, Malhotra S, Dawsey SM, Lao-Sirieix P, Fitzgerald RC. The Discovery and Validation of Biomarkers for the Diagnosis of Esophageal Squamous Dysplasia and Squamous Cell Carcinoma. Cancer Prev Res (Phila) 2016; 9:558-66. [PMID: 27072986 DOI: 10.1158/1940-6207.capr-15-0379] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 03/11/2016] [Indexed: 02/07/2023]
Abstract
The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are esophageal squamous cell carcinomas (ESCC). Endoscopic screening is undertaken in high incidence areas. Biomarker analysis could reduce the subjectivity associated with histologic assessment of dysplasia and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publicly available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus. Each gene was ranked by a support vector machine separation score. Expression profiles were examined, before validation by qPCR and IHC. We found that 800 genes were overexpressed in ESCC compared with normal esophagus (P < 10(-5)). Of the top 50 genes, 33 were expressed in ESCC epithelium and not in normal esophagus epithelium or stroma using the Protein Atlas website. These were taken to qPCR validation, and 20 genes were significantly overexpressed in ESCC compared with normal esophagus (P < 0.05). TNFAIP3 and CHN1 showed differential expression with IHC. TNFAIP3 expression increased gradually through normal esophagus, mild, moderate and severe dysplasia, and SCC (P < 0.0001). CHN1 staining was rarely present in the top third of normal esophagus epithelium and extended progressively towards the surface in mild, moderate, and severe dysplasia, and SCC (P < 0.0001). Two novel promising biomarkers for ESCC were identified, TNFAIP3 and CHN1. CHN1 and TNFAIP3 may improve diagnostic accuracy of screening methods for ESCC. Cancer Prev Res; 9(7); 558-66. ©2016 AACR.
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Affiliation(s)
- George Couch
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom
| | - James E Redman
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom
| | - Lorenz Wernisch
- MRC Biostatistics Unit, Robinson Way, Cambridge, United Kingdom
| | - Richard Newton
- MRC Biostatistics Unit, Robinson Way, Cambridge, United Kingdom
| | - Shalini Malhotra
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Sanford M Dawsey
- Division of Cancer Epidemiology & Genetics, NCI, Bethesda, Maryland
| | - Pierre Lao-Sirieix
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom
| | - Rebecca C Fitzgerald
- MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.
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Mwachiro MM, Burgert SL, Lando J, Chepkwony R, Bett C, Bosire C, Abnet CC, Githanga J, Waweru W, Giffen CA, Murphy G, White RE, Topazian MD, Dawsey SM. Esophageal Squamous Dysplasia is Common in Asymptomatic Kenyans: A Prospective, Community-Based, Cross-Sectional Study. Am J Gastroenterol 2016; 111:500-7. [PMID: 26902228 PMCID: PMC5753423 DOI: 10.1038/ajg.2016.26] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 01/05/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Esophageal squamous cell carcinoma (ESCC) is endemic in east Africa and is a leading cause of cancer death among Kenyans. The asymptomatic precursor lesion of ESCC is esophageal squamous dysplasia (ESD). We aimed to determine the prevalence of ESD in asymptomatic adult residents of southwestern Kenya. METHODS In this prospective, community-based, cross-sectional study, 305 asymptomatic adult residents completed questionnaires and underwent video endoscopy with Lugol's iodine chromoendoscopy and mucosal biopsy for detection of ESD. RESULTS Study procedures were well tolerated, and there were no adverse events. The overall prevalence of ESD was 14.4% (95% confidence interval (CI): 10-19%), including 11.5% with low-grade dysplasia and 2.9% with high-grade dysplasia. The prevalence of ESD was >20% among men aged >50 years and women aged >60 years. Residence location was significantly associated with ESD (Zone A adjusted odds ratio (OR) 2.37, 95% CI: 1.06-5.30 and Zone B adjusted OR 2.72, 95% CI: 1.12-6.57, compared with Zone C). Iodine chromoendoscopy with biopsy of unstained lesions was more sensitive than white-light endoscopy or random mucosal biopsy for detection of ESD and had 67% sensitivity and 70% specificity. CONCLUSIONS ESD is common among asymptomatic residents of southwestern Kenya and is especially prevalent in persons aged >50 years and those living in particular local regions. Lugol's iodine chromoendoscopy is necessary for detection of most ESD but has only moderate sensitivity and specificity in this setting. Screening for ESD is warranted in this high-risk population, and endoscopic screening of Kenyans is feasible, safe, and acceptable, but more accurate and less invasive screening tests are needed.
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Affiliation(s)
| | | | | | | | | | | | | | - Jessie Githanga
- Department of Pathology, University of Nairobi, Nairobi, Kenya
| | - Wairimu Waweru
- Department of Pathology, University of Nairobi, Nairobi, Kenya
| | - Carol A Giffen
- Information Management Services, Inc, Calverton, MD, USA
| | - Gwen Murphy
- National Cancer Institute, Bethesda, MD, USA
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Diagnostic value of probe-based confocal laser endomicroscopy and high-definition virtual chromoendoscopy in early esophageal squamous neoplasia. Gastrointest Endosc 2016; 81:1346-54. [PMID: 25680899 DOI: 10.1016/j.gie.2014.10.041] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Accepted: 10/28/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Detection and differentiation of esophageal squamous neoplasia (ESN) are of value in improving patient outcomes. Probe-based confocal laser endomicroscopy (pCLE) can serve in targeted biopsies in the diagnosis of GI neoplasia. However, its performance in ESN has not yet been reported. OBJECTIVE To investigate the diagnostic value of pCLE for early ESN screened by high-definition virtual chromoendoscopy (I-Scan) and verified by Lugol chromoendoscopy and histopathology. DESIGN Prospective and noninferiority trial. SETTING Single center in China. PATIENTS Patients were enrolled who (1) previously had histologically verified early ESN or (2) were about to undergo screening endoscopy and were 50 to 80 years of age between February 2013 and February 2014. INTERVENTIONS The esophagus was investigated sequentially by white-light endoscopy, I-Scan, then pCLE and iodine chromoendoscopy. The results were interpreted and compared with histopathologic results. MAIN OUTCOME MEASUREMENTS Diagnostic characteristics of pCLE and I-Scan. RESULTS In total, 356 patients were enrolled. In all, 42 patients were histologically proven to have 47 neoplasias. The diagnostic value of pCLE for ESN during ongoing endoscopy has a sensitivity, specificity, and accuracy of 94.6%, 90.7%, and 92.3%, respectively. The interobserver and intraobserver agreement was good and excellent, with κ values of 0.699 and 0.895, respectively. The detection rate by using I-Scan and Lugol chromoendoscopy was 10.4% and 12.9%, respectively (P<.01 for noninferiority). LIMITATIONS Single center. CONCLUSIONS pCLE shows promise in diagnosing and differentiating ESN in vivo. The screening performance of I-Scan in the detection of ESN is noninferior to that of iodine chromoendoscopy.
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Chen L, Huang XJ, Sun Y. Endoscopic diagnosis of early esophageal carcinoma. Shijie Huaren Xiaohua Zazhi 2016; 24:51-58. [DOI: 10.11569/wcjd.v24.i1.51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Esophageal carcinoma is one of the common malignant tumors in the world and China has the highest incidence and mortality rates. With the development of endoscopic techniques, the diagnosis rate of early esophageal carcinoma is greatly improved in recent years, and endoscopic techniques have been accepted as the first choice for diagnosis of early esophageal carcinoma. This paper reviews endoscopic diagnosis methods, including chromoendoscopy, narrow-band imaging, endoscopic ultrasonography, magnification endoscopy, fluorescence endoscopy, confocal laser endomicroscopy, Fujinon intelligent chromoendoscopy, I-Scan, endocytoscopy, optical coherence tomography, three-dimensional endoscopic imaging, endoscopic capsule endoscopy, and elastic scattering spectroscopy.
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Wei WQ, Chen ZF, He YT, Feng H, Hou J, Lin DM, Li XQ, Guo CL, Li SS, Wang GQ, Dong ZW, Abnet CC, Qiao YL. Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening Study of Esophageal Cancer in China. J Clin Oncol 2015; 33:1951-7. [PMID: 25940715 DOI: 10.1200/jco.2014.58.0423] [Citation(s) in RCA: 249] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
PURPOSE There are no global screening recommendations for esophageal squamous cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of high incidence in China since the 1970s. This study aimed to evaluate whether an endoscopic screening and intervention program could reduce mortality caused by ESCC. METHODS Residents age 40 to 69 years were recruited from communities with high rates of ESCC. Fourteen villages were selected as the intervention communities. Ten villages not geographically adjacent to intervention villages were selected for comparison. Participants in the intervention group were screened once by endoscopy with Lugol's iodine staining, and those with dysplasia or occult cancer were treated. All intervention participants and a sample consisting of one tenth of the control group completed questionnaires. We compared cumulative ESCC incidence and mortality between the two groups. RESULTS Three thousand three hundred nineteen volunteers (48.62%) from an eligible population of 6,827 were screened in the intervention group. Seven hundred ninety-seven volunteers from an eligible population of 6,200 in the control group were interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified during the 10-year follow-up. A reduction in cumulative mortality in the intervention group versus the control group was apparent (3.35% v 5.05%, respectively; P < .001). Furthermore, the intervention group had a significantly lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%, respectively; P < .001). CONCLUSION We showed that endoscopic screening and intervention significantly reduced mortality caused by esophageal cancer. Detection and treatment of preneoplastic lesions also led to a reduction in the incidence of this highly fatal cancer.
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Affiliation(s)
- Wen-Qiang Wei
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Zhi-Feng Chen
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Yu-Tong He
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Hao Feng
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Jun Hou
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Dong-Mei Lin
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Xin-Qing Li
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Cui-Lan Guo
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Shao-Sen Li
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Guo-Qing Wang
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Zhi-Wei Dong
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - Christian C Abnet
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD
| | - You-Lin Qiao
- Wen-Qiang Wei, Hao Feng, Dong-Mei Lin, Xin-Qing Li, Guo-Qing Wang, Zhi-Wei Dong, and You-Lin Qiao, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing; Zhi-Feng Chen, Yu-Tong He, and Jun Hou, Cancer Institute of Hebei Province, Shijiazhuang; Cui-Lan Guo, Shao-Sen Li, Cancer Institute/Hospital of Ci County, Handan, China; and Christian C. Abnet, National Cancer Institute, Bethesda, MD.
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Lin SW, Freedman ND, Shi J, Gail MH, Vogtmann E, Yu G, Klepac-Ceraj V, Paster BJ, Dye BA, Wang GQ, Wei WQ, Fan JH, Qiao YL, Dawsey SM, Abnet CC. Beta-diversity metrics of the upper digestive tract microbiome are associated with body mass index. Obesity (Silver Spring) 2015; 23:862-9. [PMID: 25755147 PMCID: PMC4380747 DOI: 10.1002/oby.21020] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Accepted: 11/30/2014] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Studies of the fecal microbiome have implicated the gut microbiota in obesity, but few studies have examined the microbial diversity at other sites. The association between obesity and the upper gastrointestinal (UGI) microbial diversity was explored. METHODS The UGI microbiome of 659 healthy Chinese adults with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized using the 16S rRNA gene DNA microarray (HOMIM). RESULTS In multivariate-adjusted models, alpha diversity was not associated with BMI. However, beta diversity, assessed by principal coordinate vectors generated from an unweighted UniFrac distance matrix of pairwise comparisons, was associated with BMI (third and fourth vectors, P = 0.01 and P = 0.03, respectively). Moreover, beta diversity, assessed by cluster membership (three clusters), was also associated with BMI; individuals in the first cluster [median BMI 22.35, odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.05-4.34] and second cluster [median BMI 22.55, OR = 0.26, 95% CI = 0.09-0.75] were significantly less likely to be obese (BMI ≥ 27.5) than those in the third cluster (median BMI 23.59). CONCLUSIONS A beta-diversity metric of the UGI microbiome is associated with a four fold difference in obesity risk in this Asian population. Future studies should address whether the UGI microbiome plays a causal role in obesity.
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Affiliation(s)
- Shih-Wen Lin
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
- To whom correspondence should be addressed: 9609 Medical Center Drive, Rockville, MD 20850;
| | - Neal. D. Freedman
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Jianxin Shi
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Mitchell H. Gail
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Emily Vogtmann
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Guoqin Yu
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Vanja Klepac-Ceraj
- Department of Microbiology, Forsyth Institute, Boston, MA
- Department of Biological Sciences, Wellesley College, Wellesley, MA
| | | | - Bruce A. Dye
- Centers for Disease Control and Prevention, Hyattsville, MD
| | - Guo-Qing Wang
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Wen-Qiang Wei
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jin-Hu Fan
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - You-Lin Qiao
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Chinese correspondence should be addressed:
| | - Sanford M. Dawsey
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Christian C. Abnet
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
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Association between tobacco use and the upper gastrointestinal microbiome among Chinese men. Cancer Causes Control 2015; 26:581-8. [PMID: 25701246 DOI: 10.1007/s10552-015-0535-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 02/10/2015] [Indexed: 01/14/2023]
Abstract
PURPOSE Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. METHODS We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. RESULTS Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. CONCLUSIONS Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.
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Roshandel G, Khoshnia M, Sotoudeh M, Merat S, Etemadi A, Nickmanesh A, Norouzi A, Pourshams A, Poustchi H, Semnani S, Ghasemi-Kebria F, Noorbakhsh R, Abnet C, Dawsey SM, Malekzadeh R. Endoscopic screening for precancerous lesions of the esophagus in a high risk area in Northern Iran. ARCHIVES OF IRANIAN MEDICINE 2015; 17:246-52. [PMID: 24724600 DOI: 014174/aim.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in asymptomatic adults from Golestan Province, northern Iran, a high-risk area for ESCC, to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. METHODS This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects were consented and then asked to fill in a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with Lugol's iodine staining was performed, biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. RESULTS In total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). CONCLUSION We observed a low rate for participation in endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates.
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Affiliation(s)
- Gholamreza Roshandel
- 1)Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2)Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan,
| | - Masoud Khoshnia
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Masoud Sotoudeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Merat
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Etemadi
- 1)Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 3)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Arash Nickmanesh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Norouzi
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Akram Pourshams
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahryar Semnani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Ghasemi-Kebria
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Roya Noorbakhsh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Christian Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Muriithi RW, Muchiri LW, Lule GN. Esophageal cytology sponge diagnostic test results in kenyatta national referral hospital, kenya. Acta Cytol 2014; 58:483-8. [PMID: 25402761 DOI: 10.1159/000368793] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 09/30/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To describe the cytological findings of the esophagus using sponge cytology as a triage test in patients referred for esophageal endoscopy at Kenyatta National Hospital. STUDY DESIGN A cross-sectional descriptive study was undertaken to obtain specimens from the esophagus for cytological evaluation using a sponge. The cellular yield and pattern of esophageal cytological findings was described by cytopathologists using the Bethesda system. The cytological findings were compared with endoscopy findings and whenever possible with biopsy results. RESULTS All the participants (100%) swallowed the encapsulated sponge successfully and had smears with satisfactory material for evaluation. Negative smears for intraepithelial lesion or malignancy were the most common (86.6%), with intestinal metaplasia reported in 10% of all patients, high-grade squamous intraepithelial lesions in 1.7% and squamous cell carcinoma in 1.7%. There was good agreement between endoscopic and cytological findings. CONCLUSION Sponge cytology is a simple and inexpensive technique which seems to have promising results as a primary test as well as a triage test whenever there is any suspicion of an esophageal lesion, especially in clinical settings where endoscopic facilities and medical professionals are not available. Hence, further evaluation using a larger sample size is recommended.
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Affiliation(s)
- Ruth W Muriithi
- Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya
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Roshandel G, Merat S, Sotoudeh M, Khoshnia M, Poustchi H, Lao-Sirieix P, Malhotra S, O'Donovan M, Etemadi A, Nickmanesh A, Pourshams A, Norouzi A, Debiram I, Semnani S, Abnet CC, Dawsey SM, Fitzgerald RC, Malekzadeh R. Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran. Br J Cancer 2014; 111:2235-41. [PMID: 25247319 PMCID: PMC4264437 DOI: 10.1038/bjc.2014.506] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 07/31/2014] [Accepted: 08/18/2014] [Indexed: 11/09/2022] Open
Abstract
Background: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. Methods: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. Results: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99–100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. Conclusions: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.
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Affiliation(s)
- G Roshandel
- 1] Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran [2] Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4917774979, Iran
| | - S Merat
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - M Sotoudeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - M Khoshnia
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4917774979, Iran
| | - H Poustchi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - P Lao-Sirieix
- MRC Cancer Cell, Hutchison-MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK
| | - S Malhotra
- MRC Cancer Cell, Hutchison-MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK
| | - M O'Donovan
- MRC Cancer Cell, Hutchison-MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK
| | - A Etemadi
- 1] Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran [2] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20895, USA
| | - A Nickmanesh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - A Pourshams
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
| | - A Norouzi
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4917774979, Iran
| | - I Debiram
- MRC Cancer Cell, Hutchison-MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK
| | - S Semnani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4917774979, Iran
| | - C C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20895, USA
| | - S M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20895, USA
| | - R C Fitzgerald
- MRC Cancer Cell, Hutchison-MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK
| | - R Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 1411713135, Iran
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Yu G, Gail MH, Shi J, Klepac-Ceraj V, Paster BJ, Dye BA, Wang GQ, Wei WQ, Fan JH, Qiao YL, Dawsey SM, Freedman ND, Abnet CC. Association between upper digestive tract microbiota and cancer-predisposing states in the esophagus and stomach. Cancer Epidemiol Biomarkers Prev 2014; 23:735-41. [PMID: 24700175 DOI: 10.1158/1055-9965.epi-13-0855] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The human upper digestive tract microbial community (microbiota) is not well characterized and few studies have explored how it relates to human health. We examined the relationship between upper digestive tract microbiota and two cancer-predisposing states, serum pepsinogen I/pepsinogen II ratio (PGI/II; predictor of gastric cancer risk) and esophageal squamous dysplasia (ESD; the precursor lesion of esophageal squamous cell carcinoma; ESCC) in a cross-sectional design. METHODS The Human Oral Microbe Identification Microarray was used to test for the presence of 272 bacterial species in 333 upper digestive tract samples from a Chinese cancer screening cohort. Serum PGI and PGII were determined by ELISA. ESD was determined by chromoendoscopy with biopsy. RESULTS Lower microbial richness (number of bacterial genera per sample) was significantly associated with lower PGI/II ratio (P = 0.034) and the presence of ESD (P = 0.018). We conducted principal component (PC) analysis on a β-diversity matrix (pairwise difference in microbiota), and observed significant correlations between PC1, PC3, and PGI/II (P = 0.004 and 0.009, respectively), and between PC1 and ESD (P = 0.003). CONCLUSIONS Lower microbial richness in upper digestive tract was independently associated with both cancer-predisposing states in the esophagus and stomach (presence of ESD and lower PGI/II). IMPACT These novel findings suggest that the upper digestive tract microbiota may play a role in the etiology of chronic atrophic gastritis and ESD, and therefore in the development of gastric and esophageal cancers.
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Affiliation(s)
- Guoqin Yu
- Authors' Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville; National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland; Forsyth Institute, Cambridge; Wellesley College, Wellesley; Harvard School of Dental Medicine, Boston, Massachusetts; and Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
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Lin SW, Abnet CC, Freedman ND, Murphy G, Risques R, Prunkard D, Rabinovitch P, Pan QJ, Roth MJ, Wang GQ, Wei WQ, Lu N, Taylor PR, Qiao YL, Dawsey SM. Measuring telomere length for the early detection of precursor lesions of esophageal squamous cell carcinoma. BMC Cancer 2013; 13:578. [PMID: 24308314 PMCID: PMC3882883 DOI: 10.1186/1471-2407-13-578] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 11/27/2013] [Indexed: 01/13/2023] Open
Abstract
Background Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Esophageal balloon cytology successfully retrieves exfoliated and scraped superficial esophageal epithelial cells, but cytologic reading of these cells has poor sensitivity and specificity for detecting esophageal squamous dysplasia (ESD), the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring telomere length, a marker for chromosomal instability, may improve the utility of balloon cytology for detecting ESD and early ESCC. Methods We examined balloon cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high-grade) and 92 age- and sex-matched normal controls from an esophageal cancer early detection screening study. All subjects also underwent endoscopy and biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the balloon cytology cells, and telomere length was measured by quantitative PCR. A receiver operating characteristic (ROC) curve was plotted for telomere length as a diagnostic marker for high-grade dysplasia. Results Telomere lengths were comparable among the low- and high-grade dysplasia cases and controls, with means of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for telomere length as a diagnostic marker for high-grade dysplasia. Further adjustment for subject characteristics, including sex, age, smoking, drinking, hypertension, and body mass index did not improve the use of telomere length as a marker for ESD. Conclusions Telomere length of esophageal balloon cytology cells was not associated with ESCC precursor lesions. Therefore, telomere length shows little promise as an early detection marker for ESCC in esophageal balloon samples.
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Affiliation(s)
- Shih-Wen Lin
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20892, USA.
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The potential of molecular markers to improve interventions through the natural history of oesophageal squamous cell carcinoma. Biosci Rep 2013; 33:BSR20130063. [PMID: 23837802 PMCID: PMC3747595 DOI: 10.1042/bsr20130063] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
EC (oesophageal cancer) is one of the ten most frequent and fatal tumours worldwide and ESCC (oesophageal squamous cell carcinoma) accounts for about 80% of the cases. The first symptoms of ESCC arise late during the progression of the disease and, therefore, the diagnosis is usually done in advanced stages. This leads to an inefficient treatment and consequently to a poor prognosis. Thus, a comprehensive knowledge of ESCC biology is of major importance to identify risk factors, especially in high-incidence areas and biomarkers which could enable ESCC prevention and interventions throughout the natural history of the disease. In this review, we present the current knowledge regarding ESCC aetiology as well as the different genetic and epigenetic alterations already described in this tumour. We also discuss how these alterations could be used to anticipate ESCC diagnosis as well as how they can help improving treatment. A molecular natural history of the disease is proposed pointing out potential markers that may improve interventions at different points of ESCC development. Only when the different layers of complexity behind this tumour are elucidated, it will be possible to successfully perform prevention at different levels.
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Taylor PR, Abnet CC, Dawsey SM. Squamous dysplasia--the precursor lesion for esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2013; 22:540-52. [PMID: 23549398 PMCID: PMC3681095 DOI: 10.1158/1055-9965.epi-12-1347] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide, and esophageal squamous dysplasia (ESD) is the only histopathology that predicts the development of ESCC. The prevalence of ESD parallels rates of invasive ESCC and is typically found in 25% or more of adults above the age of 35 years in populations in north central China, where risk for ESCC is among the highest in the world. Results of chemoprevention and early detection studies to prevent progression of ESD suggest that these approaches, coupled with emerging endoscopic therapies, offer promise for the prevention of esophageal cancer mortality in high-risk populations. Future research on ESD and ESCC should focus on finding additional modifiable risk factors and on identifying biomarkers to incorporate into early detection strategies.
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Affiliation(s)
- Philip R Taylor
- National Cancer Institute, NIH, EPS, 6120 Executive Blvd, Rm 7006, Bethesda, MD 20892, USA.
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Yang S, Wu S, Huang Y, Shao Y, Chen XY, Xian L, Zheng J, Wen Y, Chen X, Li H, Yang C. Screening for oesophageal cancer. Cochrane Database Syst Rev 2012; 12:CD007883. [PMID: 23235651 PMCID: PMC11091427 DOI: 10.1002/14651858.cd007883.pub2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Oesophageal cancer is a global heath problem. The prognosis for advanced oesophageal cancer is generally unfavourable, but early-stage asymptomatic oesophageal cancer is basically curable and could achieve better survival rates. The two most commonly used tests are cytologic examination and endoscopy with mucosal iodine staining. The efficacy of the screening tests is controversial, and the true benefit and efficacy of screening remains uncertain because of the potential lead-time and length-time biases. This review was conducted to examine the evidence for the efficacy of screening for oesophageal cancer (squamous cell carcinoma and adenocarcinoma). OBJECTIVES To determine the efficacy of early screening, using endoscopy with iodine staining or cytologic examination, in reducing mortality from oesophageal cancer in asymptomatic individuals from high-risk and general populations. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 8), The Cochrane Library (2012, Issue 8), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012), Allied and Complementary Medicine (AMED) (1985 to August 2012), Chinese Biomedical Database (CBM) (January 1975 to August 2012), VIP Database (January 1989 to August 2012), China National Knowledge Infrastructure (CNKI) (January 1979 to August 2012), and the Internet. We also searched reference lists, conference proceedings, and databases of ongoing trials. There was no restriction on language or publication status in the search for trials. SELECTION CRITERIA We included only randomised controlled trials (RCT) of screening versus no screening for oesophageal cancer. Randomisation of groups or clusters of individuals was acceptable. DATA COLLECTION AND ANALYSIS Two review authors independently scanned the titles and abstracts from the initial search for potential trials for inclusion. We did not find any trials that met the inclusion criteria. MAIN RESULTS The electronic search identified 3482 studies. Two authors independently reviewed the references. The reports of 18 studies were retrieved for further investigation. None met the eligibility criteria for a RCT investigation of the effects of screening versus no screening for oesophageal cancer. AUTHORS' CONCLUSIONS There were no RCTs that determined the efficacy of screening for oesophageal cancer. Non-RCTs showed a high incidence and the reported better survival after screening could be caused by selection bias, lead-time and length-time biases. RCTs are needed to determine the efficacy of screening for oesophageal cancer.
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Affiliation(s)
- Shujuan Yang
- West China School of Public Health, Sichuan University, Chengdu, China.
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Abstract
Oesophageal cancer is a global health problem with high mortality due to the advanced nature of the disease at presentation; therefore, detection at an early stage significantly improves outcome. Oesophageal squamous-cell cancer is preceded by dysplasia and oesophageal adenocarcinoma is preceded by Barrett's oesophagus, which progresses to cancer via intermediate dysplastic stages. Screening to detect these preneoplastic lesions has the potential to substantially reduce mortality and morbidity. However, the risks and benefits of such programmes to individuals and to society need to be carefully weighed. Endoscopic screening is invasive, costly and error prone owing to sampling bias and the subjective diagnosis of dysplasia. Non-endoscopic cell-sampling methods are less invasive and more cost effective than endoscopy, but the sensitivity and specificity of cytological assessment of atypia has been disappointing. The use of biomarkers to analyse samples collected using pan-oesophageal cell-collection devices may improve diagnostic accuracy; however, further work is required to confirm this. The psychological and economic implications of screening as well as the feasibility of implementing such programmes must also be considered.
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Zhao L, Wei WQ, Zhao DL, Hao CQ, Lin DM, Pan QJ, Li XQ, Lei FH, Wang JW, Wang GQ, Shang Q, Qiao YL. Population-based study of DNA image cytometry as screening method for esophageal cancer. World J Gastroenterol 2012; 18:375-82. [PMID: 22294844 PMCID: PMC3261533 DOI: 10.3748/wjg.v18.i4.375] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Revised: 08/22/2011] [Accepted: 10/28/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions.
METHODS: This study was designed as a population-based screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse.
RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively.
CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions.
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Lopes AB, Fagundes RB. Esophageal squamous cell carcinoma - precursor lesions and early diagnosis. World J Gastrointest Endosc 2012; 4:9-16. [PMID: 22267978 PMCID: PMC3262175 DOI: 10.4253/wjge.v4.i1.9] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 12/03/2011] [Accepted: 01/12/2012] [Indexed: 02/05/2023] Open
Abstract
Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis. Early detection is highly desirable, since surgical and endoscopic resection offers the only possible cure for esophageal cancer. Population screening should be undertaken in high risk areas, and in low or moderate risk areas for people with risk factors (alcoholics, smokers, mate drinkers, history of head and neck cancer, achalasia and lye stricture of the esophagus). Esophageal balloon cytology is an easy and inexpensive sampling technique, but the current methods are insufficient for primary screening due to sampling errors. Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection. It may be enhanced by several techniques such as dye and optic chromoendoscopy, magnifying endoscopy, and optical-based spectroscopic and imaging modalities. Since more than 80% of SCCE deaths occur in developing countries, where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable, the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy, since it is easy, accurate, inexpensive and available worldwide. In ideal conditions, or in developed countries, is it reasonable to think that optimal detection will require a combination of techniques, such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique. The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.
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Affiliation(s)
- Antonio Barros Lopes
- Antonio Barros Lopes, Renato Borges Fagundes, Post-Graduate Program: Sciences in Gastroenterology and Hepatology - Universidade Federal do Rio Grande do Sul, Rio Grande do Sul 90035-003, Brazil
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Ishimura N, Amano Y, Appelman HD, Penagini R, Tenca A, Falk GW, Wong RK, Gerson LB, Ramirez FC, Horwhat JD, Lightdale CJ, DeVault KR, Freschi G, Taddei A, Bechi P, Ringressi MN, Castiglione F, Rossi Degl'Innocenti D, Wang HH, Huang Q, Bellizzi AM, Lisovsky M, Srivastava A, Riddell RH, Johnson LF, Saunders MD, Chuttani R. Barrett's esophagus: endoscopic diagnosis. Ann N Y Acad Sci 2011; 1232:53-75. [DOI: 10.1111/j.1749-6632.2011.06045.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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