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Sample records for esophageal cancer analysis

  1. Comparative genomic analysis of esophageal cancers.

    PubMed

    Caygill, Christine P J; Gatenby, Piers A C; Herceg, Zdenko; Lima, Sheila C S; Pinto, Luis F R; Watson, Anthony; Wu, Ming-Shiang

    2014-09-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.

  2. Esophageal cancer

    MedlinePlus

    Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...

  3. Esophageal Cancer

    MedlinePlus

    ... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...

  4. Esophageal Cancer

    MedlinePlus

    ... cancer is found, the better the chance of recovery; however, esophageal cancer is often found at an ... has decreased, the tubes will be removed. Recovery Recovery As with any surgery or operation, there are ...

  5. Esophageal Cancer

    MedlinePlus

    ... is the sixth most common cause of cancer deaths worldwide. Incidence rates vary within different geographic locations. In some regions, higher rates of esophageal cancer cases may be attributed to tobacco and alcohol use or particular nutritional habits and ...

  6. Esophageal cancer.

    PubMed

    Vakil, Nimish; Affi, Aboud

    2002-07-01

    Despite advances in our knowledge of esophageal cancer, 50% of patients present with incurable disease, and the overall survival after diagnosis is poor. The incidence of esophageal adenocarcinoma of the distal esophagus is rising at a rapid rate in developed countries. Recent advances in the epidemiology of esophageal cancer offer insights into preventive strategies in patients who are at risk. New developments in diagnosis may help detect the disease at an early stage. New diagnostic modalities permit more accurate staging procedures and allow appropriate selection of therapy. New studies provide more information on multimodality therapy for esophageal cancer, and new endoscopic techniques allow resection of small lesions without surgery. New stent designs provide better palliation by providing tumor ingrowth. These developments in the treatment of esophageal cancer are the focus of this review.

  7. [An epidemiological analysis on the geographic factors of esophageal cancer].

    PubMed

    Song, J

    1992-12-01

    The author collects the data of esophageal cancer mortality (1971-1973) of 78 counties in Hubei Province and the data of topography, climate, soil, rock formation and geochemical elements, including 40 suspected factors. The method of linear correlation and multiple stepwise regression are used for the comprehensive analysis of relation between the geographical factors and esophageal cancer. The result is that four factors metamorphic rock, zinc, copper, chromium are suspected factors. It suggests that the four factors will need future study.

  8. Stages of Esophageal Cancer

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  9. Esophageal Cancer

    MedlinePlus

    ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  10. Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

    2013-01-01

    The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

  11. Snapshot of Esophageal Cancer

    MedlinePlus

    ... consortium of three translational research centers studying the origins and pathogenesis of esophageal cancer, with the ultimate goal of improving patient outcomes and decreasing the burden of the disease. One center is studying the genetic basis of ...

  12. Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

    PubMed

    Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

    2016-06-08

    Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

  13. Cost-benefit analysis of screening for esophageal and gastric cardiac cancer.

    PubMed

    Wei, Wen-Qiang; Yang, Chun-Xia; Lu, Si-Han; Yang, Juan; Li, Bian-Yun; Lian, Shi-Yong; Qiao, You-Lin

    2011-03-01

    In 2005, a program named "Early Detection and Early Treatment of Esophageal and Cardiac Cancer" (EDETEC) was initiated in China. A total of 8279 residents aged 40-69 years old were recruited into the EDETEC program in Linzhou of Henan Province between 2005 and 2008. Howerer, the cost-benefit of the EDETEC program is not very clear yet. We conducted herein a cost-benefit analysis of screening for esophageal and cardiac cancer. The assessed costs of the EDETEC program included screening costs for each subject, as well as direct and indirect treatment costs for esophageal and cardiac severe dysplasia and cancer detected by screening. The assessed benefits of this program included the saved treatment costs, both direct and indirect, on esophageal and cardiac cancer, as well as the value of prolonged life due to screening, as determined by the human capital approach. The results showed the screening cost of finding esophageal and cardiac severe dysplasia or cancer ranged from RMB 2707 to RMB 4512, and the total cost on screening and treatment was RMB 13 115-14 920. The cost benefit was RMB 58 944-155 110 (the saved treatment cost, RMB 17 730, plus the value of prolonged life, RMB 41 214-137 380). The ratio of benefit-to-cost (BCR) was 3.95-11.83. Our results suggest that EDETEC has a high benefit-to-cost ratio in China and could be instituted into high risk areas of China.

  14. Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

    ClinicalTrials.gov

    2017-04-13

    Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer

  15. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

  16. Chemoradiotherapy for Esophageal Cancer

    PubMed Central

    Patel, Ashish; Suntharalingam, Mohan

    2009-01-01

    Radiotherapy and surgery have both played prominent roles in the treatment of esophageal cancer since the beginning of the 20th century. Although the use of radiotherapy alone to treat esophageal cancer has a long history, it has not demonstrated improved outcomes compared with surgery alone. The disappointing rates of survival and local control associated with single-modality therapy and the need for effective nonsurgical management led to the development of definitive chemoradiotherapy paradigms for esophageal cancer. Adding cytotoxic chemotherapy to radiotherapy for additive or synergistic effect was described as early as 1968, and over time, treatment has shifted from single-modality therapy toward combined-modality therapy using chemotherapy and radiotherapy. This approach eventually demonstrated superior outcomes in patients with esophageal cancer when compared to radiotherapy alone. Maximum benefit of this therapy depends on the appropriate addition of surgery and the optimization of radiosensitizing chemotherapy. A burgeoning area of research has focused on improving definitive chemoradiotherapy strategies through the incorporation of newer chemotherapeutic agents and targeted biologic agents. An overview of the history of chemoradiotherapy in the treatment of esophageal cancer is presented, as well as a discussion of ongoing studies and future areas of promising research. PMID:19461907

  17. Recursive Partitioning Analysis for New Classification of Patients With Esophageal Cancer Treated by Chemoradiotherapy

    SciTech Connect

    Nomura, Motoo; Shitara, Kohei; Kodaira, Takeshi; Kondoh, Chihiro; Takahari, Daisuke; Ura, Takashi; Kojima, Hiroyuki; Kamata, Minoru; Muro, Kei; Sawada, Satoshi

    2012-11-01

    Background: The 7th edition of the American Joint Committee on Cancer staging system does not include lymph node size in the guidelines for staging patients with esophageal cancer. The objectives of this study were to determine the prognostic impact of the maximum metastatic lymph node diameter (ND) on survival and to develop and validate a new staging system for patients with esophageal squamous cell cancer who were treated with definitive chemoradiotherapy (CRT). Methods: Information on 402 patients with esophageal cancer undergoing CRT at two institutions was reviewed. Univariate and multivariate analyses of data from one institution were used to assess the impact of clinical factors on survival, and recursive partitioning analysis was performed to develop the new staging classification. To assess its clinical utility, the new classification was validated using data from the second institution. Results: By multivariate analysis, gender, T, N, and ND stages were independently and significantly associated with survival (p < 0.05). The resulting new staging classification was based on the T and ND. The four new stages led to good separation of survival curves in both the developmental and validation datasets (p < 0.05). Conclusions: Our results showed that lymph node size is a strong independent prognostic factor and that the new staging system, which incorporated lymph node size, provided good prognostic power, and discriminated effectively for patients with esophageal cancer undergoing CRT.

  18. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    PubMed

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

  19. Drugs Approved for Esophageal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  20. Significant prognostic value of circulating tumor cells in esophageal cancer patients: A meta-analysis.

    PubMed

    Wang, Shuyu; Du, Hongyang; Li, Guixia

    2017-02-02

    Esophageal cancer is the sixth leading cause of cancer death worldwide. Detection of circulating tumor cells (CTCs) is emerging as a novel strategy for predicting cancer patient prognosis. Here we performed a comprehensive literature search to identify relevant articles in EMbase, PubMed, EBSCO, OVID, Cochrane Database, CNKI, WanFangdata and VIPdata. Meta-analysis was conducted using Stata12.0 software, according to the inclusion and exclusion criteria, extracted data and assessment methodology. Thirteen eligible literature studies were included with a total of 979 esophageal squamous cell carcinoma patients, including 424 CTC-positive and 684 CTC-negative cases. Meta-analysis showed that the presence of CTCs was associated with both worse progression-free/disease-free survival [hazard ration (HR) = 2.32, 95% confidence interval (CI) = 1.57 - 3.43, p < 0.001] and poorer overall survival [HR = 2.64, 95% CI = 1.69 - 4.14, p < 0.001]. Further subgroup analyses demonstrated that CTC-positive patients also showed worse progression-free/disease-free survival and poorer overall survival in different subsets. In summary, our meta-analysis provides strong evidence that detection of CTCs in the peripheral blood is an independent prognostic indicator of poor outcome for esophageal squamous cell carcinoma patients.

  1. Near-infrared confocal micro-Raman spectroscopy combined with PCA-LDA multivariate analysis for detection of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Chen, Long; Wang, Yue; Liu, Nenrong; Lin, Duo; Weng, Cuncheng; Zhang, Jixue; Zhu, Lihuan; Chen, Weisheng; Chen, Rong; Feng, Shangyuan

    2013-06-01

    The diagnostic capability of using tissue intrinsic micro-Raman signals to obtain biochemical information from human esophageal tissue is presented in this paper. Near-infrared micro-Raman spectroscopy combined with multivariate analysis was applied for discrimination of esophageal cancer tissue from normal tissue samples. Micro-Raman spectroscopy measurements were performed on 54 esophageal cancer tissues and 55 normal tissues in the 400-1750 cm-1 range. The mean Raman spectra showed significant differences between the two groups. Tentative assignments of the Raman bands in the measured tissue spectra suggested some changes in protein structure, a decrease in the relative amount of lactose, and increases in the percentages of tryptophan, collagen and phenylalanine content in esophageal cancer tissue as compared to those of a normal subject. The diagnostic algorithms based on principal component analysis (PCA) and linear discriminate analysis (LDA) achieved a diagnostic sensitivity of 87.0% and specificity of 70.9% for separating cancer from normal esophageal tissue samples. The result demonstrated that near-infrared micro-Raman spectroscopy combined with PCA-LDA analysis could be an effective and sensitive tool for identification of esophageal cancer.

  2. Folate intake, serum folate levels and esophageal cancer risk: an overall and dose-response meta-analysis.

    PubMed

    Zhao, Yan; Guo, Chenyang; Hu, Hongtao; Zheng, Lin; Ma, Junli; Jiang, Li; Zhao, Erjiang; Li, Hailiang

    2017-02-07

    Previously reported findings on the association between folate intake or serum folate levels and esophageal cancer risk have been inconsistent. This study aims to summarize the evidence regarding these relationships using a dose-response meta-analysis approach. We performed electronic searches of the Pubmed, Medline and Cochrane Library electronic databases to identify studies examining the effect of folate on the risk of esophageal cancer. Ultimately, 19 studies were included in the meta-analysis. Summary odds ratios (ORs) were estimated using a random effects model. A linear regression analysis of the natural logarithm of the OR was carried out to assess the possible dose-response relationship between folate intake and esophageal cancer risk. The pooled ORs for esophageal cancer in the highest vs. lowest levels of dietary folate intake and serum folate were 0.63 (95% CI: 0.56-0.71) and 0.71 (95% CI: 0.55-0.92), respectively. The dose-response meta-analysis indicated that a 100 μg/day increment in dietary folate intake reduced the estimate risk of esophageal cancer by 12%. These findings suggest that dietary and serum folate exert a protective effect against esophageal carcinogenesis.

  3. Treatment Option Overview (Esophageal Cancer)

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  4. General Information about Esophageal Cancer

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  5. Citrus Fruit Intake Substantially Reduces the Risk of Esophageal Cancer: A Meta-Analysis of Epidemiologic Studies.

    PubMed

    Wang, Anqiang; Zhu, Chengpei; Fu, Lilan; Wan, Xueshuai; Yang, Xiaobo; Zhang, Haohai; Miao, Ruoyu; He, Lian; Sang, Xinting; Zhao, Haitao

    2015-09-01

    Many epidemiologic studies indicate a potential association between fruit and vegetable intake and various cancers. The purpose of this meta-analysis is to investigate the association between citrus fruit intake and esophageal cancer risk. The authors conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Library from inception until July 2014. Studies presenting information about citrus intake and esophageal cancer were analyzed. The authors extracted the categories of citrus intake, study-specific odds ratio or relative risk, and the P value and associated 95% confidence intervals for the highest versus lowest dietary intake of citrus fruit level. The association was quantified using meta-analysis of standard errors with a random-effects model. Thirteen case-control studies and 6 cohort studies were eligible for inclusion. Citrus intake may significantly reduce risk of esophageal cancer (summary odds ratio = 0.63; 95% confidence interval = 0.52-0.75; P = 0), without notable publication bias (intercept = -0.79, P = 0.288) and with significant heterogeneity across studies (I = 52%). The results from epidemiologic studies suggest an inverse association between citrus fruit intake and esophageal cancer risk. The significant effect is consistent between case-control and cohort studies. Larger prospective studies with rigorous methodology should be considered to validate the association between citrus fruits and esophageal cancer.

  6. Analysis of Chemokine Receptor Gene Expression in Esophageal Cancer Cells Compared with Breast Cancer with Insights into Metastasis

    PubMed Central

    MISHAN, Mohammad Amir; HEIRANI-TABASI, Asieh; MOKHBERIAN, Neda; HASSANZADE, Malihe; KALALIAN MOGHADDAM, Hamid; BAHRAMI, Ahmad Reza; AHMADIANKIA, Naghmeh

    2015-01-01

    Background: Chemokine receptors have been shown to play an important role in the development and metastatic spread of various malignancies. In this study, the gene expression profile of some key chemokine receptors involved in metastasis has been investigated in esophageal and breast cancer cell lines. Methods: In a descriptive study, gene expression profile of CCR1, CCR6, CCR7, CCR9, CXCR1, and CXCR4 in human esophageal cancer cell line (KYSE-30) and human breast cancer cell line (MCF7) were analyzed using real-time PCR and their results were compared accordingly. Results: We demonstrated for the first time the expression of CCR1, CCR6, CCR7, CCR9, CXCR1, and CXCR4 at transcriptional level in human esophageal cancer cell line. The expression of CCR1, CCR7 and CXCR4 were lower in esophageal compared with breast cancer cells, although without significant difference. CCR9 was highly expressed in esophageal cancer cells as compared to the breast cancer cells (P < 0.05). Similarly, the expression of CCR6 and CXCR1 were higher, although without significant difference. Conclusion: Esophageal cancer cells like breast cancer express some key chemokine receptors involved in metastasis. Targeting of proposed receptors in esophageal cancer may be a novel strategy for prevention of cancer metastasis. PMID:26576348

  7. Detecting Esophageal Cancer Using Surface-Enhanced Raman Spectroscopy (SERS) of Serum Coupled with Hierarchical Cluster Analysis and Principal Component Analysis.

    PubMed

    Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Wang, Deli; Guan, Dagang

    2015-11-01

    Serum samples taken from healthy individuals and pre- and post-operative esophageal cancer patients were analyzed using surface-enhanced Raman spectroscopy (SERS) to explore the feasibility of diagnosing esophageal cancer using the technique. The serum spectrum data were collected using a He-Ne laser of wavelength 632.8 nm. Differences in peaks assigned to nucleic acids, lipids, and proteins were found to be statistically significant between groups, which implies that corresponding serum alterations occur with the development of esophageal diseases. For quantitative analysis, the chemometric methods of hierarchical clustering analysis and principal component analysis were utilized on the obtained SERS spectra for classification with good results.

  8. Convergent evidence from systematic analysis of GWAS revealed genetic basis of esophageal cancer

    PubMed Central

    Wang, Jiu-qiang; Qu, Su-su; Qu, Yue; Sun, Hong-lei; Liu, Si-dang; Shang, Ying-li

    2016-01-01

    Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with risk of esophageal cancer (EC). However, investigation of genetic basis from the perspective of systematic biology and integrative genomics remains scarce. In this study, we explored genetic basis of EC based on GWAS data and implemented a series of bioinformatics methods including functional annotation, expression quantitative trait loci (eQTL) analysis, pathway enrichment analysis and pathway grouped network analysis. Two hundred and thirteen risk SNPs were identified, in which 44 SNPs were found to have significantly differential gene expression in esophageal tissues by eQTL analysis. By pathway enrichment analysis, 170 risk genes mapped by risk SNPs were enriched into 38 significant GO terms and 17 significant KEGG pathways, which were significantly grouped into 9 sub-networks by pathway grouped network analysis. The 9 groups of interconnected pathways were mainly involved with muscle cell proliferation, cellular response to interleukin-6, cell adhesion molecules, and ethanol oxidation, which might participate in the development of EC. Our findings provide genetic evidence and new insight for exploring the molecular mechanisms of EC. PMID:27331408

  9. Consumption of red and processed meat and esophageal cancer risk: meta-analysis.

    PubMed

    Choi, Yuni; Song, Sujin; Song, Yoonju; Lee, Jung Eun

    2013-02-21

    To summarize the evidence about the association between red and processed meat intake and the risk of esophageal cancer, we systematically searched the PubMed and EMBASE databases up to May 2012, with a restriction to English publications, and the references of the retrieved articles. We combined the study-specific relative risks (RRs) and 95%CI, comparing the highest with the lowest categories of consumption by using a random-effects model. A total of 4 cohort studies and 23 case-control studies were included in the meta-analysis. The combined RRs (95%CI) of the cohort studies comparing the highest and lowest categories were 1.26 (1.00-1.59) for red meat and 1.25 (0.83-1.86) for processed meat. For the case-control studies, the combined RRs (95%CI) comparing the highest and lowest categories were 1.44 (1.16-1.80) for red meat and 1.36 (1.07-1.74) for processed meat. Findings from this meta-analysis suggest that a higher consumption of red meat was associated with a greater risk of esophageal cancer.

  10. Comparative proteome analysis of human esophageal cancer and adjacent normal tissues

    PubMed Central

    Yazdian–Robati, Rezvan; Ahmadi, Homa; Riahi, Maryam Matbou; Lari, Parisa; Aledavood, Seyed Amir; Rashedinia, Marzieh; Abnous, Khalil; Ramezani, Mohammad

    2017-01-01

    Objective(s): Ranking as the sixth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death worldwide. One of the main reasons for the low survival of patients with esophageal cancer is its late diagnosis. Materials and Methods: We used proteomics approach to analyze ESCC tissues with the aim of a better understanding of the malignant mechanism and searching candidate protein biomarkers for early diagnosis of esophageal cancer. The differential protein expression between cancerous and normal esophageal tissues was investigated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Then proteins were identified by matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and MASCOT web based search engine. Results: We reported 4 differentially expressed proteins involved in the pathological process of esophageal cancer, such as annexinA1 (ANXA1), peroxiredoxin-2 (PRDX2), transgelin (TAGLN) andactin-aortic smooth muscle (ACTA2). Conclusion: In this report we have introduced new potential biomarker (ACTA2). Moreover, our data confirmed some already known markers for EC in our region. PMID:28392898

  11. Esophageal Stenosis Associated With Tumor Regression in Radiotherapy for Esophageal Cancer: Frequency and Prediction

    SciTech Connect

    Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

    2012-04-01

    Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

  12. Trends of Esophageal Cancer Mortality in Rural China from 1989 to 2013: An Age-Period-Cohort Analysis.

    PubMed

    Gao, Xudong; Wang, Zhenkun; Kong, Chan; Yang, Fen; Wang, Ying; Tan, Xiaodong

    2017-02-23

    Background: Esophageal cancer is one of the most common cancers in rural China. The aim of this study was to describe the time trends of esophageal cancer mortality in rural China and to better elucidate the causes of these trends. Methods: The mortality data were obtained from the World Health Organization Mortality Database and the China Health Statistical Yearbook Database. The mortality data were analyzed with age-period-cohort (APC) analysis. Results: Our study indicates that the Age-Standardized Mortality Rates (ASMRs) in rural China generally decreased from 1989 to 2003, and thereafter increased until the year 2008 in both sexes. After 2008, the ASMRs decreased again. The results of APC analysis suggest that the general decrease in esophageal cancer mortality in rural China from 1989 to 2003 might be caused by the downtrend of the cohort effects and period effects, while the general increase in mortality from 2004 to 2008 might be caused by the uptrend of the period effects. The decrease in mortality after 2008 may be relevant to the Four Trillion RMB Investment Plan launched by the Chinese Government. Conclusions: The declining cohort effects were probably related to the improvement of socioeconomic status in childhood and the decreasing consumptions of alcohol drinking and smoking, while the trends of the period effects were relevant to the changes in the dietary pattern. Our findings may help predict future changes in esophageal cancer mortality.

  13. Trends of Esophageal Cancer Mortality in Rural China from 1989 to 2013: An Age-Period-Cohort Analysis

    PubMed Central

    Gao, Xudong; Wang, Zhenkun; Kong, Chan; Yang, Fen; Wang, Ying; Tan, Xiaodong

    2017-01-01

    Background: Esophageal cancer is one of the most common cancers in rural China. The aim of this study was to describe the time trends of esophageal cancer mortality in rural China and to better elucidate the causes of these trends. Methods: The mortality data were obtained from the World Health Organization Mortality Database and the China Health Statistical Yearbook Database. The mortality data were analyzed with age-period-cohort (APC) analysis. Results: Our study indicates that the Age-Standardized Mortality Rates (ASMRs) in rural China generally decreased from 1989 to 2003, and thereafter increased until the year 2008 in both sexes. After 2008, the ASMRs decreased again. The results of APC analysis suggest that the general decrease in esophageal cancer mortality in rural China from 1989 to 2003 might be caused by the downtrend of the cohort effects and period effects, while the general increase in mortality from 2004 to 2008 might be caused by the uptrend of the period effects. The decrease in mortality after 2008 may be relevant to the Four Trillion RMB Investment Plan launched by the Chinese Government. Conclusions: The declining cohort effects were probably related to the improvement of socioeconomic status in childhood and the decreasing consumptions of alcohol drinking and smoking, while the trends of the period effects were relevant to the changes in the dietary pattern. Our findings may help predict future changes in esophageal cancer mortality. PMID:28241504

  14. RANK overexpression as a novel esophageal cancer marker: validated immunohistochemical analysis of two different ethnicities

    PubMed Central

    Cui, Xiaobin; Peng, Hao; Jin, Jing; Li, Tingting; Zhang, Shumao; Jin, Tingting; Li, Su; Liu, Chunxia; Liang, Weihua; Li, Feng; Chen, Yunzhao

    2015-01-01

    This study aimed to evaluate the receptor activator of nuclear factor-κB (RANK) expression statuses of esophageal squamous cell carcinoma (ESCC) patients, high-grade intraepithelial neoplasia (HGIN), low-grade intraepithelial neoplasia (LGIN), and normal esophageal tissues (NETs) in Chinese Han and Kazakh ethnic, as well as the correlation of RANK expression with clinicopathological characteristics. RANK immunohistochemical analysis was conducted to investigate the expression of RANK in 113 ESCC, 36 HGIN, 63 LGIN, and 98 NETs from Han ethnic patients and in 196 ESCC and 76 NETs from Kazakh ethnic patients. The associations of RANK expression with ethnic and clinicopathological characteristics were examined using χ2-test. Upregulated RANK expression was detected in both Han and Kazakh ethnic ESCC tissues, compared with NETs (P = 1.11×10-5, 0.001, respectively). RANK expression was significantly increased during malignant transformation from normal epithelium into LGIN (P = 2.84×10-7) and HGIN (P = 7.83×10-6) tissues in Han ethnic patients. The increased expression of RANK also correlated with lymph node metastasis in Kazakh ethnic ESCC patients (P = 0.019). By contrast, no significant correlation existed between RANK expression and clinicopathological characteristics of Han ethnic ESCC patients. Furthermore, Kaplan-Meier survival analysis showed that ESCC patients with higher expression of RANK protein had significantly worse prognosis than ESCC patients with low or no expression (P = 0.001). In conclusion, this study is the first to identify RANK overexpression as a novel esophageal cancer marker in both Kazakh and Han ethnic ESCC patients. The results support the association of RANK with ESCC across ethnicities. In summary, RANK could be a therapeutic target in ESCC patients. PMID:25973136

  15. Esophageal Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  16. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    PubMed Central

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

  17. Gastric-tube versus whole-stomach esophagectomy for esophageal cancer: A systematic review and meta-analysis

    PubMed Central

    Zhang, Wenxiong; Yu, Dongliang; Peng, Jinhua; Xu, Jianjun; Wei, Yiping

    2017-01-01

    Objectives To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical technique of esophagectomy. Methods A comprehensive literature search was performed using PubMed, EMBASE, ScienceDirect, Ovid MEDLINE, Cochrane Library, Web of Science, Google Scholar, and Scopus. Clinical trials that compared the gastric-tube versus whole-stomach for esophageal cancer were selected. The clinical endpoints included anastomotic leakage, anastomotic stenosis, reflux esophagitis, pneumonia, delayed gastric emptying, and thoracic stomach syndrome. Results A total of 6 articles (1571 patients) were included. Compared to the whole-stomach approach, the gastric-tube approach was associated with a lower incidence of reflux esophagitis (95% confidence interval [CI]: 0.16 to 0.81, p = 0.01) and thoracic stomach syndrome (95% CI: 0.17 to 0.55, p < 0.0001). The rates of anastomotic leakage, anastomotic stenosis, pneumonia, and delayed gastric emptying did not significantly differ between the two groups. Conclusions The gastric-tube esophagectomy is superior to the whole-stomach approach, as it is associated with a lower incidence of postoperative reflux esophagitis and thoracic stomach syndrome. Our findings must be validated in large-scale randomized controlled trials. PMID:28267808

  18. Environmental Causes of Esophageal Cancer

    PubMed Central

    Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian; Dawsey, Sanford

    2009-01-01

    Synopsis This articles reviews the environmental risk factors and predisposing conditions for the two main histological types of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of ESCC. Results of investigations on several other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are also discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and probably absence of H. pylori in the stomach increase the risk of EA. Results of studies investigating other factors, including low intake of fresh fruits and vegetables, consumption of carbonated soft drink, use of H2 blockers, non-steroidal anti-inflammatory drugs, and drugs that relax the lower esophageal sphincter are also discussed. PMID:19327566

  19. Risks and Benefits of Multimodal Esophageal Cancer Treatments: A Meta-Analysis

    PubMed Central

    Sun, Lei; Zhao, Fen; Zeng, Yan; Yi, Cheng

    2017-01-01

    Background Esophageal cancer has traditionally been associated with very poor outcomes. A number of therapies are available for the treatment and palliation of esophageal cancer, but little systematic evidence compares the efficacy of different treatment strategies. This meta-analysis aimed to investigate whether treatments in addition to radiotherapy could provide better efficacy and safety. Material/Methods We identified a total of 12 eligible studies with 18 study arms by searching PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without time or language restrictions. The final search was conducted on 17 August 2016. We calculated mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) for continuous and dichotomous data, respectively. Heterogeneity was calculated and reported using Tau2, Chi2, and I2 analyses. Results Twelve studies with 18 study arms were included in the analysis. Addition of surgery to chemo-radiotherapy resulted in improved median survival time (p=0.009) compared with chemo-radiotherapy alone, but all other outcomes were unaffected. Strikingly, and in contrast with patients with squamous cell carcinomas, the subset of patients with adenocarcinoma who received therapies in addition to radiotherapy showed a significant improvement in median survival time (p<0.0001), disease-free survival (p=0.007), 2-year survival rates (p=0.002), and 3-year survival rates (p=0.01). The incidence of adverse effects increased substantially with additional therapies. Conclusions This meta-analysis reveals stark differences in outcomes in patients depending on the type of carcinoma. Patients with squamous cell carcinoma should be educated about the risks and benefits of undergoing multiple therapies. PMID:28214903

  20. Erlotinib Hydrochloride in Treating Patients With Advanced Esophageal Cancer or Stomach Cancer

    ClinicalTrials.gov

    2013-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Recurrent Esophageal Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IV Esophageal Cancer

  1. Human papillomavirus-related esophageal cancer survival

    PubMed Central

    Guo, Lanwei; Liu, Shuzheng; Zhang, Shaokai; Chen, Qiong; Zhang, Meng; Quan, Peiliang; Sun, Xi-Bin

    2016-01-01

    Abstract Background: Human papillomavirus (HPV) has been identified to be related to progression of esophageal cancer. However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: The electronic databases of MEDLINE and Excerpta Medica database were searched till April 30, 2016. Study-specific risk estimates were pooled using a random-effects model. Results: Ten studies involving a total of 1184 esophageal cancer cases were included in this meta-analysis. The pooled hazard ratio comparing HPV-positive to HPV-negative esophageal cancers was 1.03 (95% confidence interval 0.78–1.37), which was not significantly correlated with improved survival. However, HPV-16-positive patients might have a significantly favorable survival (hazard ratio 0.73, 95% confidence interval 0.44–1.21). Conclusion: The meta-analysis indicated that HPV infection may not be of prognostic utility in the evaluation of factors contributing to esophageal cancer. Further large prospective studies are encouraged to stratify survival analysis by HPV type. PMID:27861358

  2. Surgical treatments for esophageal cancers

    PubMed Central

    Allum, William H.; Bonavina, Luigi; Cassivi, Stephen D.; Cuesta, Miguel A.; Dong, Zhao Ming; Felix, Valter Nilton; Figueredo, Edgar; Gatenby, Piers A.C.; Haverkamp, Leonie; Ibraev, Maksat A.; Krasna, Mark J.; Lambert, René; Langer, Rupert; Lewis, Michael P.N.; Nason, Katie S.; Parry, Kevin; Preston, Shaun R.; Ruurda, Jelle P.; Schaheen, Lara W.; Tatum, Roger P.; Turkin, Igor N.; van der Horst, Sylvia; van der Peet, Donald L.; van der Sluis, Peter C.; van Hillegersberg, Richard; Wormald, Justin C.R.; Wu, Peter C.; Zonderhuis, Barbara M.

    2015-01-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy. PMID:25266029

  3. Radiation-induced esophagitis in lung cancer

    PubMed Central

    Baker, Sarah; Fairchild, Alysa

    2016-01-01

    Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. PMID:28210168

  4. Use of registration-based contour propagation in texture analysis for esophageal cancer pathologic response prediction

    NASA Astrophysics Data System (ADS)

    Yip, Stephen S. F.; Coroller, Thibaud P.; Sanford, Nina N.; Huynh, Elizabeth; Mamon, Harvey; Aerts, Hugo J. W. L.; Berbeco, Ross I.

    2016-01-01

    Change in PET-based textural features has shown promise in predicting cancer response to treatment. However, contouring tumour volumes on longitudinal scans is time-consuming. This study investigated the usefulness of contour propagation in texture analysis for the purpose of pathologic response prediction in esophageal cancer. Forty-five esophageal cancer patients underwent PET/CT scans before and after chemo-radiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumour ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. PET images were converted into 256 discrete values. Co-occurrence, run-length, and size zone matrix textures were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs from different algorithms were compared using Dice similarity index (DSI). Contours propagated by the fast-demons, fast-free-form and rigid algorithms did not fully capture the high FDG uptake regions of tumours. Fast-demons propagated ROIs had the least agreement with other contours (DSI  =  58%). Moderate to substantial overlap were found in the ROIs propagated by all other algorithms (DSI  =  69%-79%). Rigidly propagated ROIs with co-occurrence texture failed to significantly differentiate between responders and non-responders (AUC  =  0.58, q-value  =  0.33), while the differentiation was significant with other textures (AUC  =  0.71‒0.73, p  <  0.009). Among the deformable algorithms, fast-demons (AUC  =  0.68‒0.70, q-value  <  0.03) and fast-free-form (AUC  =  0.69‒0.74, q-value  <  0.04) were the least predictive. ROIs propagated by all other

  5. [Achalasia and esophageal cancer].

    PubMed

    Corti, R E; Monastra, L; Fernández Marty, P; Barco, J C; Ferro, F E; Galindo, F; Musi, A O; Kogan, Z

    1992-01-01

    During the period included between January 1970 and December 1990, we studied 242 patients with manometric and radiological diagnosis of esophageal achalasia. Eight of these patients (3.3%) developed during the evolution of their disease an esophageal carcinoma. Eight cases showed histologic type of epidermoid carcinoma: 3 differentiated, 3 semi-differentiated and 2 anaplastic. Therapy for achalasia was: one patient, Heller myotomy, 4 patients, dilatations with bougies in numerous opportunities, and the other two patients receive no treatment for achalasia. Two patients reported tracheobronchial fistulas as complication of carcinoma. Treatment received for carcinoma included: three patients, radiotherapy (4000 rads); one patient, chemotherapy; one patient, chemotherapy and radiotherapy, one resection surgery and two patients feeding gastrostomy. All of the eight patients died within the year of diagnosis of epidermoid carcinoma.

  6. Integrative analysis of copy number and transcriptional expression profiles in esophageal cancer to identify a novel driver gene for therapy

    PubMed Central

    Dong, Gaochao; Mao, Qixing; Yu, Decai; Zhang, Yi; Qiu, Mantang; Dong, Gaoyue; Chen, Qiang; Xia, Wenjie; Wang, Jie; Xu, Lin; Jiang, Feng

    2017-01-01

    An increasing amount of evidence has highlighted the critical roles that copy number variants play in cancer progression. Here, we systematically analyzed the copy number alterations and differentially transcribed genes. Integrative analysis of the association between copy number variants and differential gene expression suggested that copy number variants will lead to aberrant expression of the corresponding genes. We performed a KEGG pathway and GO analysis, which revealed that cell cycle may have an effective role in the progression of esophageal cancer. FAM60A was then screened out as a potential prognostic factor through survival analysis and correlation analysis with clinical-pathological parameters. We subsequently showed that silencing of FAM60A could inhibit esophageal carcinoma tumor cell growth, migration and invasion in vitro. Through the bioinformatic analysis, we predict that FAM60A may act as a transcriptional factor to regulate genes that are correlated with each cell cycle. In summary, we comprehensively analyzed copy number segments and transcriptional expression profiles, which provided a novel approach to identify clinical biomarkers and therapeutic targets of esophageal carcinoma. PMID:28169357

  7. Laboratory animal models for esophageal cancer

    PubMed Central

    Nair, Dhanya Venugopalan; Reddy, A. Gopala

    2016-01-01

    The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer. PMID:27956773

  8. Association of miR-21 with esophageal cancer prognosis: a meta-analysis.

    PubMed

    Wen, S-W; Zhang, Y-F; Li, Y; Liu, Z-X; Lv, H-L; Li, Z-H; Xu, Y-Z; Zhu, Y-G; Tian, Z-Q

    2015-06-12

    The present study aimed to explore the relationship between miRNA expression and survival in patients with esophageal cancer (EC) using meta-analysis. We searched PubMed, EMBASE, CNKI, Wanfang, and ISI Web of Science databases without time restrictions, and extracted relevant data, such as the name of first author, publication year, age, gender, number of case, etc. from the studies included. We calculated the pooled hazard ratios (HRs) using the RevMan 5.2 software. A total of five studies involving 504 subjects were included in the meta-analysis, with the purpose of analyzing the association of miRNA-21 expression with EC prognosis. The pooled HR of elevated versus decreased miR-21 expression in EC was 1.87 [95% confidence interval (CI): 1.37-2.55, P < 0.001], with elevated miR-21 expression being associated with poorer prognosis for patients with EC. Our results support a prognostic role for miR-21 in EC.

  9. Another Obesity Downside: Higher Esophageal Cancer Risk

    MedlinePlus

    ... In the United States, esophageal cancer is rare, accounting for only 1 percent of all new cancers ... advanced stage. Stomach cancer, likewise, is also rare, accounting for fewer than 2 percent of all new ...

  10. Meta-Analysis for the Therapeutic Effect of Neoadjuvant Therapy in Resectable Esophageal Cancer.

    PubMed

    Zhu, Yusen; Liu, Min; Yun, Xiaojing; Wang, Dongmei; Bai, Yuhuan; Zhang, Guizhi; Ji, Bei; Jing, Changchun

    2016-12-24

    We aimed to review the therapeutic effects of neoadjuvant chemoradiotherapy (NCRT), chemotherapy (NCT), and radiotherapy (NRT) on patients with resectable Esophageal cancer (EsC) by comparison with surgery alone (SA). PubMed, EMBASE and Cochrane were searched for eligible studies published up to March 2015. Cochrane reviews were used for quality assessment. Eight primary outcomes were analyzed. Risk ratios (RRs)/ hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the random- or fixed- effects model. Heterogeneity was assessed using the Chi-square-based Q statistic and the I (2) test. Publication bias was examined by the Begg's funnel plot. Totally 24 articles including 4718 EsC cases were eligible for this meta-analysis. The quality of the literatures was relatively high. Significant difference was found in five-year survival rate (RR = 1.45, 95% CI: 1.17-1.79, P < 0.01) between patients treated with NCT and SA, while the eight enrolled primary outcomes were all statistically different between NCRT and SA, and significant difference was identified in three-year survival between NCRT and NCT (RR = 1.35, 95% CI: 1.14-1.60, P < 0.01). No obvious publication bias was observed. NCRT and NCT provide an obvious benefit for EsC treatment over SA, and NCRT possesses a clear advantage compared with NCT.

  11. Esophageal Cancer Screening

    MedlinePlus

    ... medical care even if there are symptoms. False-positive test results can occur. Screening test results may ... even though no cancer is present. A false-positive test result (one that shows there is cancer ...

  12. Meat, fish, and esophageal cancer risk: a systematic review and dose-response meta-analysis.

    PubMed

    Salehi, Maryam; Moradi-Lakeh, Maziar; Salehi, Mohhamad Hossein; Nojomi, Marziyeh; Kolahdooz, Fariba

    2013-05-01

    Risk factors for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are well defined, while the role of diet in these conditions remains controversial. To help elucidate the role of particular dietary components, major bibliographic databases were searched for published studies (1990-2011) on associations between esophageal cancer risk (EC) and consumption of various types of meat and fish. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by histological subtype, study design, and nationality. Four cohorts and 31 case-control studies were identified. The overall pooled relative risk (RR) of EC and the confidence intervals (CIs) for the groups with the highest versus the lowest levels of intake were as follows: 0.99 (95% CI: 0.85-1.15) for total meat; 1.40 (95%CI: 1.09-1.81) for red meat; 1.41 (95%CI: 1.13-1.76) for processed meat; 0.87 (95%CI: 0.60-1.24) for poultry; and 0.80 (95%CI: 0.64-1.00) for fish. People with the highest levels of red meat intake had a significantly increased risk of ESCC. Processed meat intake was associated with increased risk of EAC. These results suggest that low levels of red and processed meat consumption and higher levels of fish intake might reduce EC risk.

  13. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer

    PubMed Central

    Xu, Wenjia; Liu, Zhongshun; Bao, Qunchao; Qian, Zhikang

    2015-01-01

    Background Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Summary Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Key Message Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Practical Implications Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC. PMID:26674173

  14. Changing incidence of esophageal cancer among white women: analysis of SEER data (1992–2010)

    PubMed Central

    Raman, Rachna; Deorah, Sundeep; McDowell, Bradley D.; Hejleh, Taher Abu; Lynch, Charles F.

    2015-01-01

    Aim of the study To analyse trends in the incidence rates of adenocarcinoma and squamous cell carcinoma of the oesophagus (ACE and SCC, respectively) in white women between 1992 and 2010. Material and methods We used data from the Surveillance, Epidemiology, and End Results (SEER program to identify cases of esophageal cancer). Age adjusted incidence rates (IR) were calculated for ACE and SCC for two different time periods (1992–1996 and 2006–2010) and stratified by age, stage, and histologic type. We used joinpoint analysis to detect changes in rates between 1992 and 2010. Results Between the time periods 1992–1996 and 2006–2010, the age-adjusted incidence rates for SCC in white women decreased from 1.2/100,000 to 0.8/100,000 personyears, and for ACE it increased from 0.5/100,000 to 0.7/100,000 personyears. Similar to white men, the increase in the incidence of ACE was consistent for all stages and all age groups in white women. However, it was most pronounced in women aged 45–59 years, where the incidence of ACE (0.9/100,000 person-years) in 2006–2010 exceeded the incidence of SCC (0.6/100,000 person-years). On joinpoint regression analysis, an inflection point was seen in 1999 for ACE, indicating a slower rate of increase for ACE after 1999 (annual percentage change of 8.00 before 1999 vs. 0.88 starting in 1999). Conclusions The incidence of ACE is increasing in white women, irrespective of age or stage. Indeed, ACE is now more common than SCC in white women between 45 and 59 years of age. PMID:26557784

  15. Treatment Options by Stage (Esophageal Cancer)

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  16. Esophageal Cancer Prevention

    MedlinePlus

    ... Overview History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers Advisory Boards & Groups Budget & Appropriations Current Year Budget Annual Plan & Budget ...

  17. Early enteral nutrition compared with parenteral nutrition for esophageal cancer patients after esophagectomy: a meta-analysis.

    PubMed

    Peng, J; Cai, J; Niu, Z-X; Chen, L-Q

    2016-05-01

    Early postoperative enteral nutrition (EN) after esophagectomy in esophageal cancer patient has been reported to be correlated with a better rehabilitation than parenteral nutrition (PN). However, a robust conclusion has not been achieved. Therefore, we performed a meta-analysis to compare the postoperative EN and PN in patients with esophageal cancer undergoing esophagectomy. Three electronic databases were searched for eligible studies to be included in the meta-analysis. The summary relative risk/weighted mean difference (RR/WMD) estimates and corresponding 95% confidence interval (CI) were calculated using fixed- and random-effects models. Ten studies met the inclusion criteria. The analysis demonstrated that the early postoperative EN could significantly decrease the pulmonary complications (RR = 0.37, 95% CI = 0.22-0.62, P = 0.00, test for heterogeneity: I(2) = 0.0%, P = 0.89) and anastomotic leakage (RR = 0.46, 95% CI = 0.22-0.96, P = 0.04, test for heterogeneity: I(2) = 0.0%, P = 0.66) compared with PN. On the eighth postoperative day, the EN group had a higher levels of albumin (WMD = 1.84, 95% CI = 0.47-3.21, P = 0.01, test for heterogeneity: I(2) = 84.5%, P = 0.00) and prealbumin (WMD = 12.96, 95% CI = 3.63-22.29, P = 0.01, test for heterogeneity: I(2) = 0.0%, P = 0.63) compared with the PN group. However, there was no difference in digestive complications between these two approaches (RR = 1.30, 95% CI = 0.79-2.13, P = 0.30, test for heterogeneity: I(2) = 0.0%, P = 0.97). For patients with esophageal cancer following esophagectomy, the early postoperative EN support could decrease the morbidity of severe complications, such as pulmonary complications and anastomotic leakage, and maintain patients at a better nutritional status than parenteral nutrion support.

  18. Detection of Esophageal Fiducial Marker Displacement During Radiation Therapy With a 2-dimensional On-board Imager: Analysis of Internal Margin for Esophageal Cancer

    SciTech Connect

    Fukada, Junichi; Hanada, Takashi; Kawaguchi, Osamu; Ohashi, Toshio; Takeuchi, Hiroya; Kitagawa, Yuko; Seki, Satoshi; Shiraishi, Yutaka; Ogata, Haruhiko; Shigematsu, Naoyuki

    2013-03-15

    Purpose: To quantify the interfraction displacement of esophageal fiducial markers for primary esophageal cancer radiation therapy. Methods and Materials: Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic clipping as fiducial metal markers. Displacement of the markers between the digitally reconstructed radiographs and on-board kilovoltage images during radiation therapy was analyzed according to direction and esophageal site. Results: Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29 distal), underwent 367 2D matching sessions during radiation therapy. The mean (SD) absolute marker displacement was 0.26 (0.30) cm in the right–left (RL), 0.50 (0.39) cm in the superior–inferior (SI), and 0.24 (0.21) cm in the anterior–posterior (AP) direction. Displacement was significantly larger in the SI than in the RL and AP directions (P<.0001). In the SI direction, mean absolute displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm, 0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement was significantly larger than those of the middle and proximal esophagus (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in the RL and AP directions. In the SI direction, the margin was 1.25 cm for the proximal and middle esophagus and 1.75 cm for the distal esophagus. Conclusions: The magnitude of interfraction displacement of esophageal clips was larger in the SI direction, particularly in the distal esophagus, but substantial displacement was observed in other directions and at other esophageal sites. It is practical to take estimated movements into account with internal margins, even if vertebrae-based 2D matching is performed.

  19. Esophageal Cancer Epigenomics and Integrome Analysis of Genome-Wide Methylation and Expression in High Risk Northeast Indian Population.

    PubMed

    Singh, Virendra; Singh, Laishram Chandreshwor; Vasudevan, Madavan; Chattopadhyay, Indranil; Borthakar, Bibhuti Bhusan; Rai, Avdhesh Kumar; Phukan, Rup Kumar; Sharma, Jagannath; Mahanta, Jagadish; Kataki, Amal Chandra; Kapur, Sujala; Saxena, Sunita

    2015-11-01

    Esophageal cancer is a major global health burden with a strong host-environment interaction component and epigenomics underpinnings that remain to be elucidated further. Certain populations such as the Northeast Indians suffer at a disproportionately higher rate from this devastating disease. Promoter methylation is correlated with transcriptional silencing of various genes in esophageal cancer. Very few studies on genome-wide methylation for esophageal cancer exist and yet, no one has carried out an integromics analysis of methylation and gene expression. In the present study, genome-wide methylation was measured in samples collected from the Northeast Indian population by Infinium 450k array, and integration of the methylation data was performed. To prepare a network of genes displaying enriched pathways, together with the list of genes exhibiting promoter hypermethylation or hypomethylation with inversely correlated expression, we performed an integrome analysis. We identified 23 Integrome network enriched genes with relevance to tumor progression and associated with the processes involved in metastasis such as cell adhesion, integrin signaling, cytoskeleton, and extracellular matrix organizations. These included four genes (PTK2, RND1, RND3, and UBL3) with promoter hypermethylation and downregulation, and 19 genes (SEMG2, CD97, CTNND2, CADM3, OMD, NEFM, FBN2, CTNNB1, DLX6, UGT2B4, CCDC80, PZP, SERPINA4, TNFSF13B, NPC1, COL1A1, TAC3, BMP8A, and IL22RA2) with promoter hypomethylation and upregulation. A Methylation Efficiency Index was further calculated for these genes; the top five gene with the highest index were COL1A1, TAC3, SERPINA4, TNFSF13B, and IL22RA2. In conclusion, we recommend that the circulatory proteins IL22RA2, TNFSF13B, SERPINA4, and TAC3 in serum of patients and disease-free healthy controls can be examined in the future as putative noninvasive biomarkers.

  20. Association between esophageal cancer risk and EPHX1 polymorphisms: A meta-analysis

    PubMed Central

    Li, Qin-Tao; Kang, Wei; Wang, Man; Yang, Jun; Zuo, Yang; Zhang, Wei; Su, Dan-Ke

    2014-01-01

    AIM: To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase (EPHX1) and risk for esophageal cancer (EC). METHODS: The MEDLINE/PubMed and EMBASE databases were searched for studies of the association between EPHX1 polymorphisms and EC risk that were published from the database inception date to April 2013. A total of seven case-control studies, including seven on p.Tyr113His (cases, n = 1118; controls, n = 1823) and six on p.His139Arg (cases, n = 861; controls, n = 1571), were included in the meta-analysis. After data extraction by two investigators working independently, the meta-analyses were carried out with STATA 11.0 software. Pooled odds ratios and 95%CI were calculated using a fixed-effects model or a random-effects model, as appropriate. RESULTS: The pooled EPHX1 p.Tyr113His polymorphism data showed no significant association with EC in any of the genetic models (OR = 1.00, 95%CI: 0.70-1.48 for Tyr/His vs Tyr/Tyr; OR = 1.10, 95%CI: 0.77-1.57 for His/His vs Tyr/Tyr; OR = 1.06, 95%CI: 0.75-1.49 for a dominant model; OR = 1.09, 95%CI: 0.89-1.34 for a recessive model). Similar results were obtained from the p.His139Arg polymorphism analysis (Arg/His vs His/His: OR = 1.02, 95%CI: 0.84-1.23; Arg/Arg vs His/His: OR = 0.96, 95%CI: 0.60-1.54; OR = 1.03, 95%CI: 0.78-1.37 for the dominant model; OR = 0.97, 95%CI: 0.61-1.56 for the recessive model). Subgroup analyses for ethnicity, subtype of EC, and source of controls (population-based or hospital-based) showed trends that were consistent with the pooled analysis (reported above), with no significant associations found. CONCLUSION: This meta-analysis suggests that the p.Tyr113His and p.His139Arg polymorphisms in EPHX1 may not be associated with EC development. PMID:24803829

  1. Interventional Therapy of Esophageal Cancer

    PubMed Central

    Mao, Aiwu

    2016-01-01

    Esophageal cancer (EC) is the fourth leading cause of cancer death in China. Despite a lot of advances in diagnosis and therapy, the survival rate of patients with EC is low. There is urgent need for a variety of methods and techniques to improve the survival time and alleviate the lesions of EC. Nowadays, alternative and less invasive approaches to the treatment of ECs are being identified. Here, we review several main interventional methods at different stages of EC, including endoscopic resection, stent placement, arterial infusion, photodynamic therapy, and radiofrequency ablation. This review will focus on the indications, methods, clinical outcomes, and complications of these methods, which may help guide the way forward. PMID:27904858

  2. Multidisciplinary management for esophageal and gastric cancer

    PubMed Central

    Boniface, Megan M; Wani, Sachin B; Schefter, Tracey E; Koo, Phillip J; Meguid, Cheryl; Leong, Stephen; Kaplan, Jeffrey B; Wingrove, Lisa J; McCarter, Martin D

    2016-01-01

    The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients. PMID:27217796

  3. Review of the Burden of Esophageal Cancer in Malaysia.

    PubMed

    Siti-Azrin, Ab Hamid; Wan-Nor-Asyikeen, Wan Adnan; Norsa'adah, Bachok

    2016-01-01

    Esophageal cancer is one of the top leading causes of cancer-related deaths in Malaysia. To date, neither the prevalence nor incidence of esophageal cancer nationally have been recorded. Esophageal cancer remains a major and lethal health problem even if it is not common in Malaysia. The late presentation of esophageal cancer makes it a difficult and challenging medical problem. Therefore, more governmental and non-governmental organizations of Malaysia should emphasize primary and secondary prevention strategies.

  4. Prognostic value of circulating tumor cells in esophageal cancer

    PubMed Central

    Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

    2017-01-01

    AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. METHODS PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted. PMID:28275311

  5. Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis.

    PubMed

    Yan, Y L; Chen, X; Liang, H J; Wang, J; Li, T J; Li, R L; Li, S; Qin, X

    2015-01-01

    The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis

  6. The Tumor Microenvironment in Esophageal Cancer

    PubMed Central

    Lin, Eric W.; Karakasheva, Tatiana A.; Hicks, Philip D.; Bass, Adam J.; Rustgi, Anil K.

    2016-01-01

    Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy. PMID:26923327

  7. Endoscopic submucosal dissection for early esophageal cancer associated with achalasia.

    PubMed

    Ohkura, Yu; Iizuka, Toshiro; Kikuchi, Daisuke; Yamashita, Satoshi; Nakamura, Masanori; Matsui, Akira; Mitani, Toshifumi; Hoteya, Shu; Kaise, Mitsuru; Yahagi, Naohisa

    2013-01-01

    Esophageal achalasia is often associated with esophageal cancer. However, in many cases, esophageal cancer tends to be found in an advanced stage, with a poor prognosis. However, early-stage cancer was detected recently due to the advances in endoscopic instruments. In those cases, it is important to facilitate successful treatment by endoscopic submucosal dissection. We analyzed a total of six cases of esophageal cancer with achalasia in four patients treated with endoscopic submucosal dissection. Three features common to all six cases had a bearing on how endoscopic submucosal dissection was performed. First, esophageal dilatation and diminished peristalsis facilitated the performance of successful endoscopic submucosal dissection. Second, the esophageal wall was thickened, primarily with muscular tissue. Third, the submucosal layer contained abundant blood vessels that made it difficult to minimize bleeding during dissection. Those findings suggest that endoscopic submucosal dissection for early esophageal cancer associated with achalasia is a safe and potentially curative procedure. It is important, therefore, to detect esophageal cancer early.

  8. Tumor necrosis factor-alpha promoter polymorphism 308 G/A is not significantly associated with esophageal cancer risk: a meta-analysis.

    PubMed

    Luo, Ming; Yang, Yuan; Luo, Dongmei; Liu, Liang; Zhang, Yuening; Xiao, Feifan; Yang, Jingcheng; Zhang, Chengdong; Fu, Shen; Luo, Zhiguo

    2016-11-29

    Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine.

  9. Tumor necrosis factor-alpha promoter polymorphism 308 G/A is not significantly associated with esophageal cancer risk: a meta-analysis

    PubMed Central

    Zhang, Yuening; Xiao, Feifan; Yang, Jingcheng; Zhang, Chengdong; Fu, Shen; Luo, Zhiguo

    2016-01-01

    Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine. PMID:27821804

  10. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  11. Sarcopenia and Visceral Obesity in Esophageal and Gastric Cancer

    ClinicalTrials.gov

    2017-02-17

    Esophageal Cancer; Gastric Cancer; Sarcopenia; Sarcopenic Obesity; Obesity; Visceral Obesity; Quality of Life; Surgery; Complication of Treatment; Chemotherapeutic Toxicity; Physical Activity; Oncology

  12. Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013

    PubMed Central

    Xue, Hengchuan; Yao, Jun

    2017-01-01

    Objective To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. Methods We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. Results The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. Conclusions The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades. PMID

  13. Endoscopic ultrasonography in the management of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Trowers, Eugene A.

    2000-05-01

    Precise tumor-staging is critical in the management of early esophageal caner. Endoscopic ultrasound (EUS) allows the endoscopist a view beyond the esophageal wall which opens the door to a variety of new gastroenterologic techniques. Endoscopic mucosal resection, laser photoablation and photodynamic therapy may be successfully employed in early esophageal cancer management. Combination radiation therapy and chemotherapy have shown better responses in advanced cancer. Expandable metallic stents may also provide palliation with inoperable esophageal cancer. The efficacy of EUS in the management of esophageal cancer is critically reviewed.

  14. Analysis of the relationships between esophageal cancer cases and climatic factors using a Geographic Information System (GIS): a case study of Ardabil province in Iran.

    PubMed

    Ahari, Saeid Sadeghieh; Agdam, Fridoon Babaei; Amani, Firouz; Yazdanbod, Abbas; Akhghari, Leyla

    2013-01-01

    Esophageal cancer is a mjaor health problems in many parts of the world. A geographical information system (GIS) allows investigation of the geographical distribution of diseases. The purpose of the present study was to explore the relationship between esophageal cancer and effective climatic factors using GIS. The dispersion distribution and the relationship between environmental factors effective on cancer were measured using Arc GIS. The highest degree of spread was in Germi town and the least was in Ardabil city. There was a significant relationship between effective environmental factors and esophageal cancer in Ardabil province. The results indicated that environmental factors probably are influential in determining the incidence of esophageal cancer. Also, these results can be considered as a window to future comprehensive research on esophageal cancer and related risk factors.

  15. Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

    ClinicalTrials.gov

    2017-01-24

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

  16. Metastatic lymph node ratio, 6th or 7th AJCC edition: witch is the best lymph node classification for esophageal cancer? Prognosis factor analysis in 487 patients

    PubMed Central

    CORAL, Roberto V.; BIGOLIN, André V.; CORAL, Roberto P.; HARTMANN, Antonio; DRANKA, Carolina; ROEHE, Adriana V.

    2015-01-01

    Background The esophageal cancer is one of the most common and aggressive worldwide. Recently, the AJCC changed the staging system, considering, among others, the important role of the lymph node metastasis on the prognosis. Aim To discuss the applicability of different forms of lymph node staging in a western surgical center. Methods Four hundred eighty seven patients with esophageal cancer were enrolled. Three staging systems were evaluated, the 6th and the 7th AJCC editions and the Lymph Node Metastatic Ratio. Results The majority of the cases were squamous cell carcinoma. The mean lymph node sample was eight. Considering the survival, there was no significant difference between the patients when they were classified by the 7th AJCC edition. Analysis of the Lymph Node Metastatic Ratio, just on the group of patients with 0 to 25%, has shown significant difference (p=0,01). The 6th AJCC edition shows the major significant difference between among the classifications evaluated. Conclusion In this specific population, the 7th AJCC edition for esophageal cancer was not able to find differences in survival when just the lymph node analysis was considered. PMID:26176242

  17. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients’ conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks. Abbreviations: SEPS = self expanding plastic stent, SREMS = self expanding metal stent, EBRT = Endoscopic brachy radiotherapy, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE

  18. Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

    SciTech Connect

    Palma, David A.; Senan, Suresh; Oberije, Cary; Belderbos, Jose; Dios, Núria Rodríguez de; Bradley, Jeffrey D.; Barriger, R. Bryan; Moreno-Jiménez, Marta; Kim, Tae Hyun; Ramella, Sara; Everitt, Sarah; Rengan, Ramesh; Marks, Lawrence B.; De Ruyck, Kim; and others

    2013-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors

  19. Current advances in esophageal cancer proteomics.

    PubMed

    Uemura, Norihisa; Kondo, Tadashi

    2015-06-01

    We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics.

  20. Study Points to Genetic Subtypes of Esophageal Cancer

    Cancer.gov

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

  1. Combined modality therapy for esophageal cancer.

    PubMed

    Minsky, Bruce D

    2003-08-01

    Treatment approaches for esophageal cancer include primary treatment (surgical or nonsurgical) or adjuvant treatment (preoperative or postoperative). Primary treatments include surgery alone, radiation therapy alone, and radiation therapy plus chemotherapy (combined modality therapy). Adjuvant therapies include preoperative or postoperative radiation therapy, preoperative chemotherapy, and preoperative combined modality therapy. There is considerable controversy as to the ideal therapeutic approach. This review will examine the results of these approaches as well as combined modality therapy using novel regimens.

  2. Medicolegal aspects of esophageal cancer surgery.

    PubMed

    De Giorgio, Fabio

    2005-01-01

    Forensic implications of esophageal cancer surgery are varied and complex depending on the field of specialization involved i.e. civil law, criminal law, insurance or social security and for the distinct probative requirements related to each field. The aim of this article is to reconstruct the logical procedure of a forensic doctor who actually examines a practical case to establish the profiles of professional responsibility in particular in civil or criminal law.

  3. Risks of Esophageal Cancer Screening

    MedlinePlus

    ... medical care even if there are symptoms. False-positive test results can occur. Screening test results may ... even though no cancer is present. A false-positive test result (one that shows there is cancer ...

  4. Thoracoscopic esophagectomy for intrathoracic esophageal cancer.

    PubMed

    Osugi, Harushi; Takemura, Masashi; Lee, Sigeru; Nishikawa, Takayuki; Fukuhara, Kennichirou; Iwasaki, Hiroshi; Higashino, Masayuki

    2005-08-01

    Thoracoscopic approaches for esophageal cancer are still disparate. Complete scopic technique is feasible for esophagectomy. Mini-thoracotomy is effective for excellent exposure of the mediastinum for lymph node dissection. The magnifying effect of a video, by keeping the camera in close proximity to the dissection is essential to perform the same quality of dissection as open surgery. The benefit, for respiratory morbidity, remains to be studied in a large number of patients. Minimizing the chest wall injury contributed, to the reduction of constrictive pulmonary damage. Survival after the thoracoscopic approach was favorably compared with open surgery, when extensive lymphadenectomy was performed. Because the efficacy improves with the surgeon's experience, satisfactory outcome will only be obtained in a center performing a sufficient volume of esophageal surgery to provide the surgeon with opportunities to refine his necessary skills. Improvements in technique and instrumentation should make the procedure more accessible and steepen the learning curve.

  5. Esophageal cancer management controversies: Radiation oncology point of view

    PubMed Central

    Tai, Patricia; Yu, Edward

    2014-01-01

    Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID:25132924

  6. Early esophageal cancer detection using RF classifiers

    NASA Astrophysics Data System (ADS)

    Janse, Markus H. A.; van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

    2016-03-01

    Esophageal cancer is one of the fastest rising forms of cancer in the Western world. Using High-Definition (HD) endoscopy, gastroenterology experts can identify esophageal cancer at an early stage. Recent research shows that early cancer can be found using a state-of-the-art computer-aided detection (CADe) system based on analyzing static HD endoscopic images. Our research aims at extending this system by applying Random Forest (RF) classification, which introduces a confidence measure for detected cancer regions. To visualize this data, we propose a novel automated annotation system, employing the unique characteristics of the previous confidence measure. This approach allows reliable modeling of multi-expert knowledge and provides essential data for real-time video processing, to enable future use of the system in a clinical setting. The performance of the CADe system is evaluated on a 39-patient dataset, containing 100 images annotated by 5 expert gastroenterologists. The proposed system reaches a precision of 75% and recall of 90%, thereby improving the state-of-the-art results by 11 and 6 percentage points, respectively.

  7. Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

    PubMed

    Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

    2015-05-01

    Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.

  8. Analysis of Preoperative Metabolic Risk Factors Affecting the Prognosis of Patients with Esophageal Squamous Cell Carcinoma: The Fujian Prospective Investigation of Cancer (FIESTA) Study.

    PubMed

    Peng, Feng; Hu, Dan; Lin, Xiandong; Chen, Gang; Liang, Binying; Zhang, Hejun; Dong, Xiaoqun; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2017-02-01

    Some metabolic factors have been shown to be associated with an increased risk of esophageal cancer; however the association with its prognosis is rarely reported. Here, we assessed the prediction of preoperative metabolic syndrome and its single components for esophageal cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Between 2000 and 2010, patients who underwent three-field lymphadenectomy were eligible for inclusion. Blood/tissue specimens, demographic and clinicopathologic data were collected at baseline. Metabolic syndrome is defined by the criteria proposed by Chinese Diabetes Society. In this study, analysis was restricted to esophageal squamous cell carcinoma (ESCC) due to the limited number of other histological types. The median follow-up in 2396 ESCC patients (males/females: 1822/574) was 38.2months (range, 0.5-180months). The multivariate-adjusted hazard ratio (HR) of metabolic syndrome for ESCC mortality was statistically significant in males (HR, 95% confidence interval, P: 1.45, 1.14-1.83, 0.002), but not in females (1.46, 0.92-2.31, 0.107). For single metabolic components, the multivariate-adjusted HRs were significant for hyperglycemia (1.98, 1.68-2.33, <0.001) and dyslipidemia (1.41, 1.20-1.65, <0.001) in males and for hyperglycemia (1.76, 1.23-2.51, <0.001) in females, independent of clinicopathologic characteristics and obesity. In tree-structured survival analysis, the top splitting factor in both genders was tumor-node-metastasis stage, followed by regional lymph node metastasis. Taken together, our findings demonstrate that preoperative metabolic syndrome was a significant independent predictor of ESCC mortality in males, and this effect was largely mediated by glyeolipid metabolism disorder.

  9. Characterization and effects of miR-21 expression in esophageal cancer.

    PubMed

    Wen, S-W; Zhang, Y-F; Li, Y; Liu, Z-X; Lv, H-L; Li, Z-H; Xu, Y-Z; Zhu, Y-G; Tian, Z-Q

    2015-08-03

    The aim of this study was to investigate the expression of miR-21 in esophageal cancer and the impact of miR-21 on apoptosis, invasion, and the expression of target genes in esophageal cancer cells. Fluorescence quantitative polymerase chain reaction analysis was used to detect the expression of miR-21 in human esophageal tissues, adjacent tissues, and an esophageal cancer cell line (TE-13). The antisense miR-21 oligonucleotide was generated commercially using the solid-phase chemical synthesis method. Transient transfection was used to transfect esophageal cancer cells (TE-13 antisense and TE-13 control cells). Flow cytometry and Transwell cell assays were used to detect the apoptosis and invasion of esophageal cancer cells, respectively. The western blot method was used to detect the expression of PTEN, PDCD4, and K-ras proteins. These analyses determined that mir-21 expression significantly increased in esophageal cancer tissues and in TE-13 cells, and that this phenomenon was not associated with staging or lymph node metastasis. The apoptosis rate of TE-13 control cells was lower than that of antisense TE-13 cells indicating an enhanced invasive ability. In tissues adjacent to esophageal cancer and in TE-13 antisense cells, the expression of PTEN and PDCD4 was found to be higher than that in the control group, whereas the expression of K-ras showed the opposite pattern. Together, these results suggest that miR- 21 might be involved in the development and metastasis of esophageal cancer, through interaction with its PDCD4 and K-ras target genes.

  10. Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database

    PubMed Central

    Gharzai, Laila; Verma, Vivek; Denniston, Kyle A.; Bhirud, Abhijeet R.; Bennion, Nathan R.; Lin, Chi

    2016-01-01

    Objective Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. Methods 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973–2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Results Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255–367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03–1.47, HR 1.961, 95% CI 1.466–2.624). Lower esophageal subsite (33–40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Conclusions Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death

  11. Esophageal Cancer: Role of Imaging in Primary Staging and Response Assessment Post Neoadjuvant Therapy.

    PubMed

    Griffin, Yvette

    2016-08-01

    Advances in the early detection and treatment of esophageal cancer have meant improved survival rates for patients with esophageal cancer. Accurate pretreatment and post-neoadjuvant treatment staging of esophageal cancer is essential for assessing operability and determining the optimum treatment plan. This article reviews the multimodality imaging approach in the diagnosis, staging, and assessment of treatment response in esophageal cancer.

  12. Advances in targeted therapies and new promising targets in esophageal cancer

    PubMed Central

    Belkhiri, Abbes; El-Rifai, Wael

    2015-01-01

    Esophageal cancer, comprising squamous carcinoma and adenocarcinoma, is a leading cause of cancer-related death in the world. Notably, the incidence of esophageal adenocarcinoma has increased at an alarming rate in the Western world. Unfortunately, the standard first-line chemo-radiotherapeutic approaches are toxic and of limited efficacy in the treatment of a significant number of cancer patients. The molecular analysis of cancer cells has uncovered key genetic and epigenetic alterations underlying the development and progression of tumors. These discoveries have paved the way for the emergence of targeted therapy approaches. This review will highlight recent progress in the development of targeted therapies in esophageal cancer. This will include a review of drugs targeting receptor tyrosine kinases and other kinases in esophageal cancer. Additional studies will be required to develop a rational integration of these targeted agents with respect to histologic types of esophageal cancer and the optimal selection of cancer patients who would most likely benefit from targeted therapy. Identification of AURKA and AXL as key molecular players in esophageal tumorigenesis and drug resistance strongly justifies the evaluation of the available drugs against these targets in clinical trials. PMID:25593196

  13. Etiology and Prevention of Esophageal Cancer

    PubMed Central

    Yang, Chung S.; Chen, Xiaoxin; Tu, Shuiping

    2016-01-01

    Background Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. Summary The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. Key Message The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. Practical Implications A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major

  14. Positive esophageal proximal resection margin: an important prognostic factor for esophageal cancer that warrants adjuvant therapy

    PubMed Central

    Wang, Yun-Cang; Deng, Han-Yu; Wang, Wen-Ping; He, Du; Ni, Peng-Zhi; Hu, Wei-Peng; Wang, Zhi-Qiang

    2016-01-01

    Background Positive esophageal proximal resection margin (ERM+) following esophagectomy was considered as incomplete or R1 resection. The clinicopathological data and long-term prognosis of esophageal cancer (EC) patients with ERM+ after esophagectomy were still unknown. Therefore, the aim of this study was to assess the clinical significance of ERM+ and its therapeutic option. Methods From November 2008 to December 2014, 3,594 patients with histologically confirmed EC underwent radical resection in our department. Among them there were 37 patients (1.03%) who had ERM+. ERM+ was defined as carcinoma or atypical hyperplasia (severe or moderate) at the residual esophageal margin in our study. For comparison, another 74 patients with negative esophageal proximal resection margin (ERM−) were propensity-matched at a ratio of 1:2 as control group according to sex, age, tumor location and TNM staging. The relevant prognostic factors were investigated by univariate and multivariate regression analysis. Results In this large cohort of patients, the rate of ERM+ was 1.03%. The median survival time was 35.000 months in patients with ERM+, significantly worse than 68.000 months in those with ERM− (Chi-square =4.064, P=0.044). Survival in patients with esophageal residual atypical hyperplasia (severe or moderate) was similar to those with esophageal residual carcinoma. Survival rate in stage I–II was higher than that in stage III–IV (Chi-square =27.598, P=0.000) in ERM−; But there was no difference between the two subgroups of patients in ERM+. Furthermore, in those patients with ERM+, survival was better in those who having adjuvant therapy, compared to those without adjuvant therapy (Chi-square =5.480, P=0.019). And the average survival time which was improved to a well situation for ERM+ patients who have adjuvant therapy was 68.556 months which is comparable to average survival time (65.815 months) of ERM− for those patients who are at earlier stages

  15. Radiation Therapy for Locally Advanced Esophageal Cancer.

    PubMed

    Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

    2017-04-01

    The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues.

  16. High-dose photoirradiation of esophageal cancer.

    PubMed Central

    Thomas, R J; Abbott, M; Bhathal, P S; St John, D J; Morstyn, G

    1987-01-01

    Fifteen patients with locally advanced esophageal cancer were treated with phototherapy. Each patient had dysphagia and weight loss before therapy and could not be operated on because of the extent of the tumor or poor performance status. Patients received a photosensitizer (hematoporphyrin derivative) 72 hours before phototherapy and were then treated by light delivered by an argon pumped dye laser or gold metal vapor laser at powers up to 2.2 W and doses of 337 J/cm2. Fourteen patients received 24 treatments. The results were all patients achieved a tumor response. The depth of response depended on the dose and dose rate of radiation. There were four of 24 local complications (mediastinitis 3, bronchoesophageal fistula 1). These occurred in patients treated with a power of greater than 1.5 W. There were two complete pathologic remissions in patients with locally advanced cancer. In conclusion, phototherapy is an effective alternative to other forms of palliation and potentially may be an alternative to surgery in selected cases of locally advanced esophageal cancer. Images Fig. 1. Fig. 2.,Fig. 3.,Fig. 4. Fig. 6. PMID:3606245

  17. C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

    ClinicalTrials.gov

    2015-01-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  18. A Meta-Analysis and Systematic Review on the Association between Human Papillomavirus (Types 16 and 18) Infection and Esophageal Cancer Worldwide

    PubMed Central

    Wang, Jing; Zhao, Lei; Yan, Han; Che, Juanjuan; Huihui, Li; Jun, Wu

    2016-01-01

    Background Esophageal cancer is a common and aggressive malignant tumor. This study aimed to investigate the association between human papillomavirus (HPV) Types 16 and 18 and esophageal carcinoma (EC) in the world population by conducting a meta-analysis. Materials and Methods Computerized bibliographic and manual searches were performed to identify all eligible literatures between 1982 and 2014. PUBMED (http://www.ncbi.nlm.nih.gov/pubmed/) and CNKI (http://www.cnki.net/) were the primary sources of case-control studies, and key words used include human papillomavirus, HPV, esophageal, esophagus, cancer, carcinoma, and tumor. All searches were performed by reviewing articles and abstracts cited in the published systematic reviews and case-control studies. Prospective studies that reported relative risk (RR) estimates with 95% CIs for the association between HPV and EC were included. Results Thirty-three randomized studies were identified, and the main features of these trials were included in this systematic review. HPV infection rate in the EC group was 46.5%, while HPV infection rate in the control group was 26.2% (OR = 1.62; 95% CI, 1.33–1.98). In China, the merger OR value was 1.62 (95% CI: 1.26–2.07); while in the Asian region, the merger OR value was 1.63 (95% CI: 1.29–2.04). There were statistical differences in HPV testing due to different detection methods such as PCR, IHC and ISH. In the PCR detection group, the merger OR value was 1.61 (95% CI: 1.33–1.95). Conclusions These results indicate that HPV infection and the incidence of EC are closely associated. PMID:27409078

  19. Surface-enhanced Raman spectra of hemoglobin for esophageal cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Zhou, Xue; Diao, Zhenqi; Fan, Chunzhen; Guo, Huiqiang; Xiong, Yang; Tang, Weiyue

    2014-03-01

    Surface-enhanced Raman scattering (SERS) spectra of hemoglobin from 30 esophageal cancer patients and 30 healthy persons have been detected and analyzed. The results indicate that, there are more iron ions in low spin state and less in high for the hemoglobin of esophageal cancer patients than normal persons, which is consistent with the fact that it is easier to hemolyze for the blood of cancer patients. By using principal component analysis (PCA) and discriminate analysis, we can get a three-dimensional scatter plot of PC scores from the SERS spectra of healthy persons and cancer patients, from which the two groups can be discriminated. The total accuracy of this method is 90%, while the diagnostic specificity is 93.3% and sensitivity is 86.7%. Thus SERS spectra of hemoglobin analysis combined with PCA may be a new technique for the early diagnose of esophageal cancer.

  20. From blood to breath: New horizons for esophageal cancer biomarkers

    PubMed Central

    Yazbeck, Roger; Jaenisch, Simone E; Watson, David I

    2016-01-01

    Esophageal cancer is a lethal cancer encompassing adenocarcinoma and squamous cell carcinoma sub-types. The global incidence of esophageal cancer is increasing world-wide, associated with the increased prevalence of associated risk factors. The asymptomatic nature of disease often leads to late diagnosis and five-year survival rates of less than 15%. Current diagnostic tools are restricted to invasive and costly endoscopy and biopsy for histopathology. Minimally and non-invasive biomarkers of esophageal cancer are needed to facilitate earlier detection and better clinical management of patients. This paper summarises recent insights into the development and clinical validation of esophageal cancer biomarkers, focussing on circulating markers in the blood, and the emerging area of breath and odorant biomarkers. PMID:28028355

  1. Androgens and esophageal cancer: What do we know?

    PubMed Central

    Sukocheva, Olga A; Li, Bin; Due, Steven L; Hussey, Damian J; Watson, David I

    2015-01-01

    Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer. PMID:26034350

  2. Radiation therapy of esophageal cancer

    SciTech Connect

    Hancock, S.L.; Glatstein, E.

    1984-06-01

    Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes. Esophagectomy is likely to cure a similar, small percentage of patients with the same presentation of minimal disease but has a substantial acute postoperative mortality rate and greater morbidity than irradiation. Combining surgery and either preoperative or postoperative irradiation may cure a small percentage of patients beyond the number cured with either modality alone. Radiation has demonstrated benefit as an adjuvant to surgery following the resection of minimal disease. However, radiation alone has never been compared directly with surgery for the highly select, minimal lesions managed by surgery. Radiation provides good palliation of dysphagia in the majority of patients, and roughly one third may have adequate swallowing for the duration of their illness when ''radical'' doses have been employed. Surgical bypass procedures have greater acute morbidity but appear to provide more reliable, prolonged palliation of dysphagia. Several approaches to improving the efficacy of irradiation are currently under investigation. These approahces include fractionation schedules, radiosensitizers, neutron-beam therapy, and helium-ion therapy.

  3. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  4. Adding Targeted Therapy to Treatment for Esophageal Cancer

    Cancer.gov

    In this phase III clinical trial, people with confirmed HER2-positive locally advanced esophageal cancer will be randomly assigned to receive preoperative radiation therapy and chemotherapy, with or without trastuzumab.

  5. Advances in Radiotherapy Management of Esophageal Cancer

    PubMed Central

    Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

    2016-01-01

    Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

  6. Magnetic stent hyperthermia for esophageal cancer: an in vitro investigation in the ECA-109 cell line.

    PubMed

    Liu, Jia-Yi; Zhao, Ling-Yun; Wang, Yu-Ying; Li, Dan-Ye; Tao, Dan; Li, Li-Ya; Tang, Jin-Tian

    2012-03-01

    Magnetic stent hyperthermia (MSH) is a novel approach for targeted thermotherapy for esophageal cancer, which is based on the mechanism that inductive heat can be generated by the esophageal stent upon exposure under an alternative magnetic field (AMF). A positive effect of MSH on esophageal cancer has been demonstrated, however, there is no study on the in vitro effects of heating treatment or of the effects of AMF exposure on human esophageal cancer cells. This study aimed to investigate the effect of MSH and of AMF exposure in esophageal cancer cells. Inductive heating characteristics of esophageal stents were assessed by exposing the stents under AMF. A rather rapid temperature rise of the Ni-Ti stent when subjected to AMF exposure was observed and the desired hyperthermic temperature could be controlled by adjusting the field parameter of the AMF. Human esophageal squamous carcinoma (ESCC) ECA-109 cells were divided into four groups: the control group, the water-bath heating group, the MSH group and the AMF exposure group. Hyperthermic temperatures were 43, 48 and 53˚C and the treatment time was in the range of 5-30 min. The MTT assay, apoptotic analysis and TUNEL staining were applied in the current investigation. Exposure of ECA-109 cells under AMF with a field intensity of 50 to 110 kA/m had negligible effect on cell viability, cell necrosis and apoptosis. Hyperthermia had a remarkable inhibitory effect on the cell viability and the effect was dependent on the thermal dose (temperature and time). The optimal thermal dose of MSH for ECA-109 cells was 48˚C for 20-30 min. The study also elucidated that there was a difference in the effects on cell necrosis and apoptosis between the heating mode of water bath and MSH. The data suggest that MSH may have clinical significance for esophageal cancer treatment.

  7. [Lugol's solution in endoscopic diagnosis of early esophageal cancer].

    PubMed

    Wang, G; Zhou, M; Cong, Q

    1995-07-01

    About 1500 high-risk subjects of esophageal cancer were found during screening by balloon cytology and all of them were examined endoscopically. Among them, 120 were considered as having early esophageal cancer and precancerous lesions. During the examination, Lugol's solution staining was used and guiding biopsy was taken. 98 subjects with unstained lesions were found, and biopsy showed early esophageal cancer in 60 (61.2%) and moderate and severe dysplasia in 38 (38.8%). It is usually extremely difficult to detect and localize the very early esophageal mucosal and submucosal carcinoma. But endoscopic examination and using Lugol's solution staining with multiple spots biopsy from unstained area are of great assistance. Minute malignant lesions may not be overlooked.

  8. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

    Lin, Steven H.; Komaki, Ritsuko; Liao Zhongxing; Wei, Caimiao; Myles, Bevan; Guo Xiaomao; Palmer, Matthew; Mohan, Radhe; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2012-07-01

    Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test. Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical

  9. Gene-environment interactions in esophageal cancer.

    PubMed

    Matejcic, Marco; Iqbal Parker, M

    2015-01-01

    Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which

  10. Impact of radiotherapy in the risk of esophageal cancer as subsequent primary cancer after breast cancer

    SciTech Connect

    Salminen, Eeva K. . E-mail: eevsal@utu.fi; Pukkala, Eero; Kiel, Krys D.; Hakulinen, Timo T.

    2006-07-01

    Purpose: To assess the risk of esophageal cancer as second cancer among breast-cancer patients treated with radiotherapy. Methods and Materials: The records of the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients were treated with surgery (n = 33,672), radiotherapy (n = 35,057), chemotherapy and radiotherapy (n = 4673), or chemotherapy (n = 2,447). The risk of a new primary cancer was expressed as standardized incidence ratio (SIR), defined as the ratio of observed to expected cases. Results: By the end of 2000, the number of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among patients followed for 15 years and treated with radiotherapy, the SIR for esophageal cancer was 2.3 (95% CI = 1.4 to 5.4). No increase in risk was seen for patients treated without radiotherapy. The risk of esophageal cancer was increased among patients diagnosed during 1953 to 1974, although age at the treatment did not have marked effect on the risk estimate. Conclusion: Increased risk of second cancer in the esophagus was observed for breast-cancer patients in Finland, especially among patients with over 15 years of follow-up and treated in the earliest period, which may relate to the type of radiotherapy.

  11. Fluorescence spectroscopy for diagnosis of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Overholt, Bergein F.; Vo-Dinh, Tuan; Farris, Christie; Schmidhammer, James L.; Sneed, Rick E.; Buckley, Paul F., III

    1994-07-01

    Laser-induced fluorescence spectroscopy was employed to measure fluorescence emission of normal and malignant tissue during endoscopy in patients with esophageal adenocarcinoma. A nitrogen/dye laser tuned at 410 nm was used for excitation source. The fluorescence lineshape of each spectrum was determined and sampled at 15 nm intervals from 430 nm to 716 nm. A calibration set from normal and malignant spectra were selected. Using stepwise discriminate analysis, significant wavelengths that separated normal and malignant spectra were selected. The intensities at these wavelengths were used to formulate a classification model using linear discriminate analysis. The model was used to classify additional tissue spectra from 26 malignant and 108 normal sites into either normal or malignant spectra with a sensitivity of 100 percent and specificity of 98 percent.

  12. Volumetric modulated arc radiotherapy for esophageal cancer

    SciTech Connect

    Vivekanandan, Nagarajan; Sriram, Padmanaban; Syam Kumar, S.A.; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

    2012-04-01

    A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V{sub 20Gy} and V{sub 30Gy} dose levels (range, 4.62-17.98%) compared with IMRT plans. The mean dose and D{sub 35%} of heart for the RA plans were better than the IMRT by 0.5-5.8%. Mean V{sub 10Gy} and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20-25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans.

  13. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  14. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  15. Time trends of esophageal cancer mortality in Linzhou city during the period 1988-2010 and a Bayesian approach projection for 2020.

    PubMed

    Liu, Shu-Zheng; Zhang, Fang; Quan, Pei-Liang; Lu, Jian-Bang; Liu, Zhi-Cai; Sun, Xi-Bin

    2012-01-01

    In recent decades, decreasing trends in esophageal cancer mortality have been observed across China. We here describe esophageal cancer mortality trends in Linzhou city, a high-incidence region of esophageal cancer in China, during 1988-2010 and make a esophageal cancer mortality projection in the period 2011-2020 using a Bayesian approach. Age standardized mortality rates were estimated by direct standardization to the World population structure in 1985. A Bayesian age-period-cohort (BAPC) analysis was carried out in order to investigate the effect of the age, period and birth cohort on esophageal cancer mortality in Linzhou during 1988-2010 and to estimate future trends for the period 2011-2020. Age-adjusted rates for men and women decreased from 1988 to 2005 and changed little thereafter. Risk increased from 30 years of age until the very elderly. Period effects showed little variation in risk throughout 1988-2010. In contrast, a cohort effect showed risk decreased greatly in later cohorts. Forecasting, based on BAPC modeling, resulted in a increasing burden of mortality and a decreasing age standardized mortality rate of esophageal cancer in Linzhou city. The decrease of esophageal cancer mortality risk since the 1930 cohort could be attributable to the improvements of social- economic environment and lifestyle. The standardized mortality rates of esophageal cancer should decrease continually. The effect of aging on the population could explain the increase in esophageal mortality projected for 2020.

  16. Cytoplasmic beta-catenin in esophageal cancers.

    PubMed

    Kimura, Y; Shiozaki, H; Doki, Y; Yamamoto, M; Utsunomiya, T; Kawanishi, K; Fukuchi, N; Inoue, M; Tsujinaka, T; Monden, M

    1999-04-20

    beta-Catenin has 2 distinct roles in E-cadherin-mediated cell adhesion and carcinogenesis through APC gene mutation. One occurs at cell-adhesion sites, where cadherins become linked to the actin-based cytoskeleton. The others occur in the cytoplasm and nuclei and are thought to regulate cell transformation. We studied these different beta-catenins and evaluated their significance in carcinogenesis. Fresh surgical specimens were obtained from 22 patients with squamous-cell carcinoma of the esophagus. beta-Catenin in the free soluble fraction and the insoluble fraction was immunoblotted separately. At the same time, its localization was observed by immuno-histochemical techniques. In the normal esophageal epithelium, 91% of beta-catenin was detected in the insoluble fraction and beta-catenin staining occurred at the cell membrane, in co-existence with E-cadherin. In cancerous tissues, the amount of soluble beta-catenin was significantly (about 4-fold) higher than in normal tissues. Also, in cancerous tissues with higher amounts of soluble beta-catenin, immuno-histochemical techniques revealed the presence of beta-catenin in the cytoplasm and nuclei, as well as in the cell membrane. However, in samples with lower amounts of beta-catenin, expression was found only at the cell boundaries. The amount of soluble beta-catenin was not associated with the clinico-pathological grading of the tumors. Our results show that the accumulation of free soluble beta-catenin in the cytoplasm and nuclei frequently occurs during carcinogenesis of the squamous epithelium of the esophagus.

  17. Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis.

    PubMed

    Salnikova, L E; Kolobkov, D S

    2016-06-01

    Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use.

  18. Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer

    SciTech Connect

    Wu, Abraham J.; Bosch, Walter R.; Chang, Daniel T.; Hong, Theodore S.; Jabbour, Salma K.; Kleinberg, Lawrence R.; Mamon, Harvey J.; Thomas, Charles R.; Goodman, Karyn A.

    2015-07-15

    Purpose/Objective(s): Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Methods and Materials: Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results: The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. Conclusions: This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.

  19. Endoscopic submucosal dissection for superficial Barrett’s esophageal cancer in the Japanese state and perspective

    PubMed Central

    Yamamoto, Sachiko; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Iishi, Hiroyasu

    2014-01-01

    The incidence of Barrett’s esophageal cancer is one of the most rapidly increasing among all cancers in the West, and it is also expected to increase in Japan. The optimal treatment for early Barrett’s esophageal cancer remains controversial. En bloc esophagectomy with regional lymph node dissection has been considered the standard therapy. Endoscopic therapies are currently being evaluated as alternatives to esophagectomy because they can provide the least postoperative morbidity and the best quality of life. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow for removal of visible lesions and histopathologic review of resected tissue, which help in diagnostic staging of the disease. EMR is limited with respect to resection size, and large lesions must be resected in several fragments. Piecemeal resection of lesions is associated with high local recurrence rates, probably because of minor remnants of neoplastic tissue being left in situ. ESD provides larger specimens than does EMR in patients with early Barrett’s neoplasia. This in turn allows for more precise histological analysis and higher en bloc and curative resection rates, potentially reducing the incidence of recurrence. Detailed endoscopic examination to determine the invasion depth and spread of Barrett’s esophageal cancer is essential before ESD. The initial inspection is usually conducted with white-light imaging followed by narrow-band imaging. The ESD procedure is similar to that for lesions in other parts of the gastrointestinal tract. However, the narrow space of the esophagogastric junction and contraction of the lower esophageal sphincter sometimes disturb the visual field and endoscopic control. Skilled endoscope handling, sometimes including retroflexion, is required during ESD for Barrett’s esophageal cancer. Previous reports have shown that ESD achieves en bloc resection in >80% of lesions. Although promising short-term results are reported, a long

  20. Correlation between NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and increased risk of esophageal cancer: evidence from a meta-analysis

    PubMed Central

    Diao, Jingfang; Bao, Jie; Peng, Jianxin; Mo, Jiaqiang; Ye, Qing; He, Junming

    2016-01-01

    NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1.15, 95% confidence interval [CI] 0.95–1.40, probability of rejection [POR] = 0.014; OR TT versus CC = 1.32, 95% CI 1.01–1.73, POR = 0.045; OR TC versus CC = 1.32, 95% CI 0.98–1.21, POR = 0.128; OR TT + TC versus CC = 1.10, 95% CI 1.00–1.20, POR = 0.05; OR TT versus CC + TC = 1.26, 95% CI 0.95–1.57, POR = 0.103). Sensitivity analysis confirmed the reliability of these findings. Our study shows that individuals carrying the NQO1 C609T variant allele and genotypes are more susceptible to EC. PMID:28203294

  1. [Endoscopic and histopathological studies of experimental esophageal cancer in beagles].

    PubMed

    Takeshita, K; Sunagawa, M; Nakajima, A; Ochi, K; Habu, H; Hoshi, K

    1985-02-01

    In order to obtain a reliable experimental model simulating human esophageal cancer, endoscopic and histopathological studies were undertaken in the esophageal cancer produced in the beagle dog. Thirty-seven dogs had been given a solution of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a concentration of 150 micrograms/ml for 3-9 months. Follow-up studies included serial endoscopy and biopsy, and almost all animals were eventually sacrificed for histological examination. The results were as follows: Squamous cell carcinoma was observed in 5 out of 22 female dogs, while none in male dogs at all. For the induction of squamous cell carcinoma in the esophagus, administration in the condition of 150 micrograms/ml (75mg/day) for 6-9 months was most suitable. Almost all of esophageal lesions were protruding and well-differentiated squamous cell carcinoma with invasion of the submucosa. The stages of hyperplasia, dysplasia and squamous cell carcinoma in the esophagus were chronologically followed. Carcinoma had been observed in the stomach about 4 months prior to the appearance of esophageal carcinoma. This experimental model was proved to be useful for studies on histogenesis of human esophageal cancer both light and electron microscopically.

  2. Analysis of esophageal cancer cell lines exposed to X-ray based on radiosensitivity influence by tumor necrosis factor-α.

    PubMed

    Wang, Buhai; Ge, Yizhi; Gu, Xiang

    2016-10-06

    Assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of esophageal cancer cell line in vitro. Three esophageal cancer cell line cells were exposed to X-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell growth curve, and flow cytometry was performed to assess the cell apoptosis. The radiosensitizing effects of TNF-α were detected by cell colony formation assay. Western blotting was applied to observe the expression of NF-κB and caspase-3 protein in the exposed cells. Our results indicated that cellular inhibition rate increased over time, the strongest is combined group (P < 0.05). Western blotting showed that the decline expression of NF-κB protein was stated between only rhTNF-α and only X-ray radiation group and the maximum degree was manifested in combined group. Caspase-3 protein content expression just works opposite. Three kinds of cells in the NF-κB protein were similar without rhTNF-α. Then SEG1 NF-κB protein content was reduced more than other two kinds. We concluded that the cells treated with TNF-α showed significantly suppressed cell proliferation, increasing the cell apoptosis, and caspase-3 protein expression after X-ray exposure. TNF-α can enhance the radiosensitivity of esophageal cancer to enhancing the effect of the former.

  3. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    PubMed

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  4. Green tea and prevention of esophageal and lung cancers.

    PubMed

    Yuan, Jian-Min

    2011-06-01

    Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enhance the detoxification pathway of environmental toxicants and carcinogens. Although epidemiological studies have provided inconclusive results on the effect of green tea consumption against the development of esophageal and lung cancers in humans overall, the inverse association between green tea intake and risk of esophageal cancer risk is more consistently observed in studies with adequate control for potential confounders. Epidemiological studies also have demonstrated an inverse, albeit moderate, association between green tea consumption and lung cancer, especially in non-smokers. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans.

  5. Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer.

    PubMed

    Liao, Juan; Liu, Ran; Shi, Ya-Juan; Yin, Li-Hong; Pu, Yue-Pu

    2016-06-01

    Recent evidence indicates that exosomes can mediate certain microRNAs (miRNAs) involved in a series of biological functions in tumor occurrence and development. Our previous studies showed that microRNA-21 (miR-21) was abundant in both esophageal cancer cells and their corresponding exosomes. The present study explored the function of exosome-shuttling miR-21 involved in esophageal cancer progression. We found that exosomes could be internalized from the extracellular space to the cytoplasm. The exosome-derived Cy3-labeled miR-21 mimics could be transported into recipient cells in a neutral sphingomyelinase 2 (nSMase2)-dependent manner. miR-21 overexpression from donor cells significantly promoted the migration and invasion of recipient cells by targeting programmed cell death 4 (PDCD4) and activating its downstream c-Jun N-terminal kinase (JNK) signaling pathway after co-cultivation. Our population plasma sample analysis indicated that miR-21 was upregulated significantly in plasma from esophageal cancer patients and showed a significant risk association for esophageal cancer. Our data demonstrated that a close correlation existed between exosome-shuttling miR-21 and esophageal cancer recurrence and distant metastasis. Thus, exosome-shuttling miR-21 may become a potential biomarker for prognosis among esophageal cancer patients.

  6. Overexpression of FOXO3, MYD88, and GAPDH Identified by Suppression Subtractive Hybridization in Esophageal Cancer Is Associated with Autophagy.

    PubMed

    Soltany-Rezaee-Rad, Mohammad; Mottaghi-Dastjerdi, Negar; Setayesh, Neda; Roshandel, Gholamreza; Ebrahimifard, Farzaneh; Sepehrizadeh, Zargham

    2014-01-01

    To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer.

  7. Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2015-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  8. Diaphragmatic Hernia after Transhiatal Esophagectomy for Esophageal Cancer

    PubMed Central

    Kim, Dohun; Kim, Si-Wook; Hong, Jong-Myeon

    2016-01-01

    Diaphragmatic hernia was found in a patient who had undergone transhiatal esophagectomy for early esophageal cancer. Chest X-ray was not helpful, but abdominal or chest computed tomography was useful for accurate diagnosis. Primary repair through thoracotomy was performed and was found to be feasible and effective. However, long-term follow-up is required because hernia recurrence is common. PMID:27525243

  9. The Role of Induction Therapy for Esophageal Cancer.

    PubMed

    Berry, Mark F

    2016-08-01

    Survival of esophageal cancer generally is poor but has been improving. Induction chemoradiation is recommended before esophagectomy for locally advanced squamous cell carcinoma. Both induction chemotherapy and induction chemoradiation are found to be beneficial for locally advanced adenocarcinoma. Although a clear advantage of either strategy has not yet been demonstrated, consensus-based guidelines recommend induction chemoradiation for locally advanced adenocarcinoma.

  10. In vivo diagnosis of esophageal cancer using image-guided Raman endoscopy and biomolecular modeling.

    PubMed

    Bergholt, M S; Zheng, W; Lin, K; Ho, K Y; Teh, M; Yeoh, K G; So, J B; Huang, Z

    2011-04-01

    The aim of this work was to evaluate the biochemical foundation and clinical merit of multimodal image-guided Raman endoscopy technique for real-time in vivo diagnosis of cancer in the esophagus during clinical endoscopic examinations. A novel fiber-optic Raman endoscopy system was utilized for in vivo esophageal Raman measurements at 785 nm laser excitation within 0.5 second under the multimodal wide-field endoscopic imaging (white light reflectance (WLR) imaging, narrow-band imaging (NBI) and autofluorescence imaging (AFI) guidance. A total of 75 esophageal tissue sites from 27 patients were measured, in which 42 in vivo Raman spectra were from normal tissues and 33 in vivo Raman spectra were from malignant tumors as confirmed by histopathology. The biomolecular modeling (non-negativity-constrained least-squares minimization (NNCLSM) utilizing six basis reference spectra from the representative biochemicals (i.e., actin, collagen, DNA, histones, triolein and glycogen) were employed to estimate the biochemical compositions of esophageal tissue. The resulting diagnostically significant fit coefficients were further utilized through linear discriminant analysis (LDA) and leave-one tissue site-out, cross validation method to develop diagnostic algorithms for esophageal cancer diagnosis. High-quality in vivo Raman spectra in the range of 800-1800 cm-1 can be acquired from normal and cancerous esophageal mucosa in real-time under multimodal endoscopic imaging guidance. Esophageal cancer tissue showed distinct Raman signals mainly associated with cell proliferation, lipid reduction, abnormal nuclear activity and neovasculation. The fit coefficients for actin, DNA, histones, triolein, and glycogen were found to be most significant for construction of the LDA diagnostic model, giving rise to an accuracy of 96.0% (i.e., sensitivity of 97.0% and specificity of 95.2%) for in vivo diagnosis of esophageal cancer. This study demonstrates that multimodal image-guided Raman

  11. Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

    PubMed

    Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

    2014-01-01

    The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.

  12. Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer

    PubMed Central

    PENG, QIAO; CHEN, HUI; HUO, JI-RONG

    2016-01-01

    Esophageal cancer is the eighth most common type of cancer in the world, and the sixth most common cause of mortality from cancer. Alcohol consumption is the major risk factor for esophageal cancer, due to the worldwide prevalence and high carcinogenicity of the ethanol metabolite. In epidemiological studies, the efficiency of alcohol intake to enhance the risk of esophageal cancer is altered by daily ethanol consumption, type of alcoholic beverages ingested, time since quitting drinking, age of drinking initiation, differences in population and subtypes of esophageal cancer. Corresponding factors, including gene polymorphisms, tobacco smoking, oral microorganisms and folate deficiency, reveal a synergistic effect in concurrent alcohol users that may lead to an increased risk of developing esophageal cancer. Consequently, esophageal cancer prevention involves multiple aspects, including quitting drinking and smoking, maintaining an adequate oral health and ingesting adequate quantities of folate, particularly in genetically high-risk populations. PMID:27123096

  13. Risk Factors for Complications After Esophageal Cancer Resection

    PubMed Central

    Viklund, Pernilla; Lindblad, Mats; Lu, Ming; Ye, Weimin; Johansson, Jan; Lagergren, Jesper

    2006-01-01

    Objective: To identify risk factors for complications after resection for esophageal or cardia cancer. Summary Background Data: Knowledge of risk factors for complications after esophageal resection for cancer is sparse, and prospective population-based studies are lacking. Methods: A prospective, nationwide, population-based study was conducted in Sweden in April 2, 2001 through December 31, 2003. Details about tumor characteristics and stage, surgical procedures, and complications were collected prospectively from the Swedish Esophageal and Cardia Cancer register. Medical records and specific charts from surgical procedures, histopathology reports, and intensive care units were continuously scrutinized. Multivariable logistic regression analyses were used to estimate relative risks and their 95% confidence intervals. Results: Among 275 patients undergoing surgical resection for esophageal or cardia cancer, 122 (44%) had at least one predefined complication. Operation by low-volume surgeons (<5 operations annually) were followed by more anastomotic leakages than those by surgeons with higher volume (odds ratio, 7.86; 95% confidence interval, 2.13–29.00). Hand-sewn and stapled anastomoses did not differ regarding risk of anastomotic leakage. Among cardia cancer patients, transthoracic approach resulted in more respiratory complications compared with transhiatal (abdominal only) approach (odds ratio, 4.78; 95% confidence interval, 1.66–13.76). Older age, adjuvant oncologic therapy, and higher preoperative bleeding volume nonsignificantly increased the risks of complications, while no influence of sex or tumor stage was found. Conclusions: High-volume esophageal surgeons seem to lower the risk of anastomotic leakage. More large-scale studies are warranted to establish the roles of the other potentially important risk factors suggested in our study. PMID:16432353

  14. Prognostic significance of differentially expressed miRNAs in esophageal cancer

    PubMed Central

    Hu, Yuxin; Correa, Arlene M.; Hoque, Ashraful; Guan, Baoxiang; Ye, Fei; Huang, Jie; Swisher, Stephen G.; Wu, Tsung Teh; Ajani, Jaffer A.; Xu, Xiao-chun

    2010-01-01

    Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21, and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126, and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-β2 expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell de-differentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e, and miR-200a expression were associated with shorter overall and disease-free survival in esophageal adenocarcinoma patients; however, miR-16-2, miR-30e, and miR-200a expression was not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study. PMID:20309880

  15. Esophagitis

    MedlinePlus

    ... irritates the tissue. This problem is called gastroesophageal reflux (GERD). An autoimmune disorder called eosinophilic esophagitis also ... include: Cough Difficulty swallowing Painful swallowing Heartburn (acid reflux) Hoarseness Sore throat Exams and Tests The doctor ...

  16. Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer in China: a meta-analysis

    PubMed Central

    Liu, Yan; Mu, Ying; Zhang, Anqi; Ren, Shaoda; Wang, Weihua; Xie, Jiaping; Zhang, Yingxin; Zhou, Changhui

    2017-01-01

    Background Immunotherapy based on cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells (CIK/DC-CIK) showed promising clinical outcomes for treating esophageal cancer (EC). However, the clinical benefit varies among previous studies. Therefore, it is necessary to systematically evaluate the curative efficacy and safety of CIK/DC-CIK immunotherapy as an adjuvant therapy for conventional therapeutic strategies in the treatment of EC. Materials and methods Clinical trials published before October 2016 and reporting CIK/DC-CIK immunotherapy treatment responses or safety for EC were searched in Cochrane Library, EMBASE, PubMed, Wanfang and China National Knowledge Internet databases. Research quality and heterogeneity were evaluated before analysis, and pooled analyses were performed using random- or fixed-effect models. Results This research covered 11 trials including 994 EC patients. Results of this meta-analysis indicated that compared with conventional therapy, the combination of conventional therapy with CIK/DC-CIK immunotherapy significantly prolonged the 1-year overall survival (OS) rate, overall response rate (ORR) and disease control rate (DCR) (1-year OS: P=0.0005; ORR and DCR: P<0.00001). Patients with combination therapy also showed significantly improved quality of life (QoL) (P=0.02). After CIK/DC-CIK immunotherapy, lymphocyte percentages of CD3+ and CD3−CD56+ subsets (P<0.01) and cytokines levels of IFN-γ, -2, TNF-α and IL-12 (P<0.00001) were significantly increased, and the percentage of cluster of differentiation (CD)4+CD25+CD127− subset was significantly decreased, whereas analysis of CD4+, CD8+, CD4+/CD8+ and CD3+CD56+ did not show significant difference (P>0.05). Conclusion The combination of CIK/DC-CIK immunotherapy and conventional therapy is safe and markedly prolongs survival time, enhances immune function and improves the treatment efficacy for EC.

  17. Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

    PubMed

    Chiba, Itaru; Ogawa, Kazuhiko; Morioka, Takamitsu; Shimoji, Hideaki; Sunagawa, Nao; Iraha, Shiro; Nishimaki, Tadashi; Yoshimi, Naomi; Murayama, Sadayuki

    2011-01-01

    This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.

  18. Molecular cloning and characterization of a novel esophageal cancer related gene.

    PubMed

    Cui, Yongping; Bi, Meixia; Su, Tao; Liu, Hailing; Lu, Shih-Hsin

    2010-12-01

    We previously identified four novel cDNA fragments related to human esophageal cancer. One of the fragments was named esophageal cancer related gene 2 (ECRG2). We report here the molecular cloning, sequencing, and expression of the ECRG2 gene. The ECRG2 cDNA comprises a 258 bp nucleotide sequence which encodes for 85 amino acids with a predicted molecular weight of 9.2 kDa. Analysis of the protein sequence reveals the presence at the N terminus of a signal peptide followed by 56 amino acids with a significant degree of sequence similarity with the conserved Kazal domain which characterizes the serine protease inhibitor family. Pulse-chase experiments showed that ECRG2 protein was detected in both cell lysates and culture medium, indicating that the ECRG2 protein was extracellularly secreted after the post-translational cleavage. In vitro uPA/plasmin activity analysis showed the secreted ECRG2 protein inhibited the uPA/plasmin activity, indicating that ECRG2 may be a novel serine protease inhibitor. Northern blot analysis revealed the presence of the major band corresponding to a size of 569 kb throughout the fetal skin, thymus, esophagus, brain, lung, heart, stomach, liver, spleen, colon, kidney, testis, muscle, cholecyst tissues and adult esophageal mucosa, brain, thyroid tissue and mouth epithelia. However, ECRG2 gene was significantly down-regulated in primary esophageal cancer tissues. Taken together, these results indicate that ECRG2 is a novel member of the Kazal-type serine protease inhibitor family and may function as a tumor suppressor gene regulating the protease cascades during carcinogenesis and migration/invasion of esophageal cancer.

  19. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    PubMed

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

  20. Definitive, Preoperative, and Palliative Radiation Therapy of Esophageal Cancer

    PubMed Central

    Fokas, Emmanouil; Rödel, Claus

    2015-01-01

    Summary Background Long-term survival in patients with esophageal cancer remains dismal despite the recent improvements in surgery, the advances in radiotherapy (RT) technology, and the refinement of systemic treatments, including the advent of targeted therapies. Although surgery constitutes the treatment of choice for early-stage disease (stage I), a multimodal approach, including preoperative or definitive chemoradiotherapy (CRT) and perioperative chemotherapy, is commonly pursued in patients with locally advanced disease. Methods A review of the literature was performed to assess the role of RT, alone or in combination with chemotherapy, in the management of esophageal cancer. Results Evidence from large, randomized phase III trials and meta-analyses supports the application of perioperative chemotherapy alone or preoperative concurrent CRT in patients with lower esophageal and esophagogastric junction adenocarcinomas. Preoperative CRT but not preoperative chemotherapy alone is now routinely used in patients with locally advanced squamous cell carcinoma (SCC). Additionally, definitive CRT without surgery has also emerged as a valuable approach in the management of resectable esophageal SCC to avoid surgery-related morbidity and mortality, whereas salvage surgery is reserved for those with persistent disease. Furthermore, brachytherapy offers a valuable option in the palliative treatment of patients with locally advanced, unresponsive disease. Fluorodeoxyglucose-positron emission tomography (FDG-PET) can facilitate a more accurate treatment response assessment and patient selection. Finally, the development of modern RT techniques, such as intensity-modulated and image-guided RT as well as FDG-PET-based RT planning, could further increase the therapeutic ratio of CRT. Conclusion Altogether, CRT constitutes an important tool in the treatment armamentarium for esophageal cancer. Further optimization of CRT using modern technology and imaging, targeted therapies

  1. Water contamination and esophageal cancer at Gassim Region, Saudi Arabia

    SciTech Connect

    Amer, M.H.; El-Yazigi, A.; Hannan, M.A.; Mohamed, M.E. )

    1990-05-01

    Between January 1980 and December 1982, 183 patients with histologically confirmed carcinoma of the esophagus who were referred to a tertiary referral hospital were studied. Thirty-two (17%) patients were referred from Gassim Region at the north central part of Saudi Arabia. In contrast, only 5% of total cancer patient referrals were from this area. A case-control study showed a significant regional difference within Saudi Arabia and the most referrals from Gassim area. A prospective case-control study showed persistently high numbers of referrals from that region during 1983-1987. When patients from Gassim Region were compared with those referred from other locations, no statistical differences were noted between the two groups except for the source of drinking water. Water analysis from Gassim area showed a high solid content with elevated levels of calcium, magnesium, and to a lesser extent, chromium iron, cadmium, and cobalt. Traces of petroleum oil were found in five of six water samples from Gassim during 1983, compared with 3 of 49 samples from other areas. Mutagenicity tests on water specimens form Gassim Region indicated the presence of possible carcinogens. It is being suggested that the high prevalence of esophageal cancer in this region may be related to contamination of water by impurities such as petroleum oils. Malnutrition, particularly vitamin A deficiency, as well as other factors may have promoted such malignancies.

  2. Morphofunctional analysis of experimental model of esophageal achalasia in rats.

    PubMed

    Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

    2010-10-01

    We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

  3. Genetic diagnosis of patients with esophageal cancer using FISH.

    PubMed

    Awut, Idiris; Niyaz, Madiniyet; Huizhong, Xie; Biekemitoufu, Hadeti; Yan, Zhang Hong; Zhu, Zhang; Sheyhedin, Ilyar; Changmin, Zhang; Wei, Zhangli; Hao, Wen

    2010-09-01

    This study aimed to the clarify the diagnostic efficacy of fluorescence in situ hybridization (FISH) in Kazakh patients with esophageal cancer (EC). FISH was compared with the pathological examination of biopsy specimens with DNA probes. We enrolled 20 patients, of which 15 were males and 5 females, with an average age of 58.3 years, who had abnormal esophaguses on barium radiological digital imaging. Touch preparations were performed on biopsy specimens from all of the patients and were examined using FISH for chromosomal abnormalities. We compared the FISH results with the pathology slides stained with hematoxylin and eosin. Classification, according to pathology, identified 2 cases of class II, 3 cases of IIIa, 1 case of IIIb, 2 cases of IV, 12 cases of class V and no cases of class I. The cases classified as class IIIb or higher were considered to be positive for cancer. Using histopathology, 10 cases were diagnosed with squamous cell carcinoma and 5 were diagnosed as adenocarcinoma, with one case being false-negative. Thus, the sensitivity of the pathological examination was 93% and the specificity was 100%. Using FISH, 16 cases showed aberrant copy numbers in either chromosome 3 or 17. By comparison, pathology did not reveal any false-positive or false-negative cases with a sensitivity and specificity of 100%. The centromeres of chromosome 3 copy numbers was significantly higher (p=0.035) than the centromeres of chromosome 17. Our study compared FISH to diagnose aneusomic esophageal cancer cells with the pathology of biopsied tissue. Our findings suggest that FISH is a useful and objective assay for the detection of malignant cells of esophageal cancer. In our study, the centromeres of chromosome 3 was the more sensitive probe for the diagnosis of esophageal cancer in Kazakh patients.

  4. Cytochrome P450 2E1 RsaI/PstI polymorphism and risk of esophageal cancer: A meta-analysis of 17 case-control studies

    PubMed Central

    LENG, WEI-DONG; ZENG, XIAN-TAO; CHEN, YONG-JI; DUAN, XIAO-LI; NIU, YU-MING; LONG, RONG-PEI; LUO, ZHI-XIAO

    2012-01-01

    The aim of this study was to explore the cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and risk of esophageal cancer (EC) in mainland Chinese populations. A systematic search of PubMed, EMBASE, Web of Science, CBM, CNKI and VIP databases for publications on the CYP2E1 RsaI/PstI polymorphism and risk of EC was performed. and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity and assessment of publication bias were performed. The search yielded 17 studies including 18 trails involving 1,663 cases and 2,603 controls. The meta-analyses showed a significant association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population (c2 vs. c1: OR=0.64; 95% CI, 0.50–0.81; P<0.001; c2/c2 vs. c1/c1: OR=0.73; 95% CI, 0.57–0.93; c2/c2 vs. c1/c1+c1/c2: OR=0.76; 95% CI, 0.60–0.96; P=0.02; c1/c2 vs. c1/c1: OR=0.54; 95% CI, 0.38–0.75; P<0.001; c1/c2+c2/c2 vs. c1/c1: OR=0.48; 95% CI, 0.34–0.70; P<0.001). An increased cancer risk in all genetic models was identified following stratification by ethnicity, source of controls and tumor type. In conclusion, in all genetic models, the association between the CYP2E1 RsaI/PstI polymorphism and risk of EC in the mainland Chinese population was significant. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism is a risk factor for EC, and the c2 allele is a factor that lowers the possibility of EC in the mainland Chinese population and this association did not change due to ethnic differences in genetic backgrounds and the environment. PMID:23226753

  5. MKK6 is upregulated in human esophageal, stomach, and colon cancers.

    PubMed

    Parray, Arif Ali; Baba, Rafia Anjum; Bhat, Hina Fayaz; Wani, Lateef; Mokhdomi, Taseem Ahmad; Mushtaq, Umar; Bhat, Sehar Saleem; Kirmani, Deeba; Kuchay, Sanaullah; Wani, Mudassir Maqbool; Khanday, Firdous Ahmad

    2014-10-01

    Expression analysis of MKK6 protein in solid tumors has never been investigated. Here, we report systematic analysis of MKK6 protein in different types of human tumor samples using western blotting and immunofluorescence techniques. We observed significant increase in the expression of MKK6 in Esophageal, Stomach, and Colon cancers as compared to controls. Results were alternately confirmed by Immunofluorescence studies. Upregulation of MKK6 protein is indicative of its role in human cancers and could possibly be used as a novel diagnostic or prognostic marker in these cancers.

  6. Diagnosis of early-stage esophageal cancer by Raman spectroscopy and chemometric techniques.

    PubMed

    Ishigaki, Mika; Maeda, Yasuhiro; Taketani, Akinori; Andriana, Bibin B; Ishihara, Ryu; Wongravee, Kanet; Ozaki, Yukihiro; Sato, Hidetoshi

    2016-02-07

    Esophageal cancer is a disease with high mortality. In order to improve the 5 year survival rate after cancer treatment, it is important to develop a method for early detection of the cancer and for therapy support. There is increasing evidence that Raman spectroscopy, in combination with chemometric analysis, is a powerful technique for discriminating pre-cancerous and cancerous biochemical changes. In the present study, we used Raman spectroscopy to examine early-stage (stages 0 and I) esophageal cancer samples ex vivo. Comparison between the Raman spectra of cancerous and normal samples using a t-test showed decreased concentrations of glycogen, collagen, and tryptophan in cancerous tissue. Partial least squares regression (PLSR) analysis and self-organization maps (SOMs) discriminated the datasets of cancerous and normal samples into two groups, but there was a relatively large overlap between them. Linear discriminant analysis (LDA) based on Raman bands found in the t-test was able to predict the tissue types with 81.0% sensitivity and 94.0% specificity.

  7. Esophageal Cancers: A Clinicopathologic and Immunohistochemical Study of 223 Cases

    PubMed Central

    Terada, Tadashi

    2009-01-01

    The author reviewed 950 cases of consecutive esophageal biopsies in the last 15 years in out pathology laboratory of our hospital. There were 223 malignant lesions (23.5%). The number and frequency (percentages) were as follows: 54 mild dysplasia (5.7%), 30 moderate dyplasia (3.2%), 32 severe dysplasia (3.4%), 13 carcinoma in situ (1.4%), 71 squamous cell carcinoma (7.5%), 7 primary adenocarcinoma (0.7%), 1 primary signet ring cell carcinoma (0.1%), 4 primary small cell carcinoma (0.4%), 2 primary amelanotic malignant melanoma (0.2%), 1 primary undifferentiated sarcoma (0.1%), 7 gastric cancer invasion (0.7%), and 1 primary adenoid cystic carcinoma (0.1%). In this article, the clinical, histopathologic and immunohistochemical features of these esophageal cancers were described. PMID:27933124

  8. Role of periostin in esophageal, gastric and colon cancer

    PubMed Central

    Moniuszko, Tadeusz; Wincewicz, Andrzej; Koda, Mariusz; Domysławska, Izabela; Sulkowski, Stanisław

    2016-01-01

    Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer. PMID:27446351

  9. Metastatic Invasive Lobular Breast Cancer Presenting Clinically with Esophageal Dysphagia

    PubMed Central

    Cuison, Reuben

    2017-01-01

    Background. Intra-abdominal metastases of invasive lobular breast cancer (ILBC) may be insidious. We report a case of metastatic ILBC that presented with dysphagia within weeks of a negative mammogram and before the development of intra-abdominal symptoms. Case. A 70-year-old female developed esophageal dysphagia. She underwent EGD which showed a short segment of stricture of the distal esophagus without significant mucosal changes. Biopsy was unremarkable and patient underwent lower esophageal sphincter (LES) dilation. Severe progressive dysphagia led to esophageal impaction and three LES dilatations. CT scan showed bilateral pleural effusions, more prominent on right side, and ascites. The pleural effusions were transudative. Repeat EGD with biopsy showed lymphocytic esophagitis, and she was started on swallowed fluticasone. Abdominal ultrasound with Doppler showed that the main portal vein had atypical turbulent flow that was felt to possibly be due to retroperitoneal process. The patient underwent diagnostic laparoscopy which revealed diffuse punctate lesions on the peritoneum. Pathology was consistent with metastatic ILBC. Conclusion. Dysphagia in the setting of peritoneal carcinomatosis from metastatic ILBC is a rare finding. The case highlights the importance of metastatic ILBC as a differential diagnosis for female patients with progressive dysphagia and associated ascites or pleural effusions. PMID:28191357

  10. Current Status and Future Prospects for Esophageal Cancer Treatment

    PubMed Central

    Kuwano, Hiroyuki

    2016-01-01

    The local control effect of esophagectomy with three-field lymph node dissection (3FLD) is reaching its limit pending technical advancement. Minimally invasive esophagectomy (MIE) by thoracotomy is slowly gaining acceptance due to advantages in short-term outcomes. Although the evidence is slowly increasing, MIE is still controversial. Also, the results of treatment by surgery alone are limiting, and multimodality therapy, which includes surgical and non-surgical treatment options including chemotherapy, radiotherapy, and endoscopic treatment, has become the mainstream therapy. Esophagectomy after neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stages II/III (except for T4) esophageal cancer, whereas chemoradiotherapy (CRT) is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. CRT is also usually selected for clinical stage IV esophageal cancer. On the other hand, with the spread of CRT, salvage esophagectomy has traditionally been recognized as a feasible option; however, many clinicians oppose the use of surgery due to the associated unfavorable morbidity and mortality profile. In the future, the improvement of each treatment result and the establishment of individual strategies are important although esophageal cancer has many treatment options. PMID:28003586

  11. A health-risk appraisal model and endoscopic mass screening for esophageal cancer in Japanese men.

    PubMed

    Yokoyama, A; Oda, J; Iriguchi, Y; Kumagai, Y; Okamura, Y; Matsuoka, M; Mizukami, T; Yokoyama, T

    2013-01-01

    A strong association between inactive aldehyde dehydrogenase-2 (ALDH2) and risk of esophageal cancer has been demonstrated in East Asian drinkers. An alcohol flushing questionnaire asking about past and current tendency for facial flushing to occur after drinking a glass (≈180 mL) of beer predicts the presence of inactive ALDH2 among Japanese aged 40 years or older with a sensitivity and specificity of approximately 90%. We invented a health-risk appraisal (HRA) model that makes it possible to identify Japanese men who are at high risk for esophageal cancer based on their past and current alcohol flushing tendency, drinking, smoking, and intake of vegetables and fruits. Between 2008 and 2009, 2221 Japanese men aged 50 years or older filled out the HRA questionnaire before undergoing a screening examination by upper gastrointestinal endoscopy at five medical facilities. The endoscopic examination resulted in a diagnosis of esophageal cancer in 19 subjects, and 117 (5.27%) subjects had an HRA score ≥ 11. The proportion of subjects with an HRA score ≥ 11 was higher in the 50-69 age group (6.11-6.88%) than in 70-89 age group (2.84-2.86%). The esophageal cancer detection rate was 4.27% among the subjects with an HRA score ≥ 11 and only 0.67% among the other subjects. Based on a receiver operating characteristic curve analysis, when an HRA score of ≥ 9 was used for subjects aged 50-69 years and of ≥ 8 for those aged 70-89 years as the cutoff value to select individuals with a high risk for esophageal cancer, its sensitivity and false-positive rate was 52.6% and 15.2%, respectively, and the cancer detection rate was 2.91% in the high-risk group, as opposed to 0.48% in the other group. In conclusion, the high detection rates for esophageal cancer in the high-risk groups encouraged screening based on our HRA model in larger Japanese populations.

  12. The spatial distribution of esophageal and gastric cancer in Caspian region of Iran: An ecological analysis of diet and socio-economic influences

    PubMed Central

    2011-01-01

    Recent studies have suggested a systematic geographic pattern of esophageal cancer (EC) and gastric cancer (GC) incidence in the Caspian region of Iran. The aims of this study were to investigate the association between these cancers and the region's dietary and socioeconomic risk factors and to map EC and GC after adjustment for the risk factors and the removal of random and geographic variations from area specific age standardised incidence ratios (SIRs). We obtained cancer data from the Babol cancer registry from 2001 to 2005, socioeconomic indices from the Statistical Centre of Iran, and dietary patterns from the control group in a case control study conducted in the study region. Regression models were fitted to identify significant covariates, and clusters of elevated rates were identified. We found evidence of systematic clustering for EC and GC in men and women and both sexes combined. EC and GC SIRs were lower in urban areas, and were also lower in areas of high income. EC SIRs were lower in areas with higher proportions of people having unrestricted food choice and higher in areas with higher proportions of people with restricted food choice. EC and GC were associated with aggregated risk factors, including income, urbanisation, and dietary patterns. These variables represent the influence of improved lifestyle which has coincided with a decrease in upper gastrointestinal cancer frequency over recent decades but which has not necessarily been uniform throughout the region. PMID:21324144

  13. Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeuchi, Hiroya; Ohashi, Toshio; Saikawa, Yoshiro; Takaishi, Hiromasa; Hanada, Takashi; Shiraishi, Yutaka; Kitagawa, Yuko; Fukuda, Keiichi

    2013-11-01

    Purpose: We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials: We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results: The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the

  14. Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

    PubMed Central

    Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

    2014-01-01

    Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward. PMID:25386186

  15. Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

    PubMed Central

    DaVee, Tomas; Ajani, Jaffer A; Lee, Jeffrey H

    2017-01-01

    Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer (EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound (EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection (ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography (PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis (over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, cross-sectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented. PMID:28223720

  16. Activation of PPARγ suppresses proliferation and induces apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway.

    PubMed

    Wu, Kai; Yang, Yang; Liu, Donglei; Qi, Yu; Zhang, Chunyang; Zhao, Jia; Zhao, Song

    2016-07-12

    Although substantial studies on peroxisome proliferator-activated receptor g (PPARg) have focused on the mechanisms by which PPARg regulates glucose and lipid metabolism, recent reports have suggested that PPARg shows tumorigenic or antitumorigenic effects. The roles and mechanisms of PPARg activation in esophageal cancer remain unclarified. EC109 and TE10 esophageal cancer cells were treated with 0, 10, 20 and 40 mM of PPARg agonist rosiglitazone (RGZ) for 24, 48, and 72 h, and the cell viability and apoptosis were detected using methyl thiazolyl tetrazolium (MTT) assay and Flow cytometric (FCM) analysis, respectively. Moreover, the effects of inhibition of PPARg by antagonist or specific RNA interference on cell viability, apoptosis, the Toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) pathways were evaluated. Additionally, the effect of TLR4 signaling on the MAPK pathway, cell viability and apoptosis was assessed. The results showed that RGZ suppressed proliferation and induced apoptosis of esophageal cancer cells, which could be partly restored by inactivation of PPARg. RGZ suppressed the MAPK and TLR4 pathways, and the inhibitory effect could be counteracted by PPARg antagonist or specific RNA interference. We also suggested that MAPK activation was regulated by the TLR4 pathway and that blocking the TLR4 and MAPK pathways significantly suppressed proliferation and induced apoptosis of esophageal cancer cells. In conclusion, our data suggested that activation of PPARg suppressed proliferation and induced apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway.

  17. Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations.

    PubMed

    Sherman, Scott K; Maxwell, Jessica E; Qian, Qining; Bellizzi, Andrew M; Braun, Terry A; Iannettoni, Mark D; Darbro, Benjamin W; Howe, James R

    2015-01-01

    Germline mutations in the PTEN tumor-suppressor gene cause autosomal-dominant conditions such as Cowden and Bannayan-Riley-Ruvalcaba syndromes with variable presentations, including hamartomatous gastrointestinal tumors, dermatologic abnormalities, neurologic symptoms, and elevated cancer risk. We describe a father and son with extensive hamartomatous gastrointestinal polyposis who both developed early-onset esophageal cancer. Exome sequencing identified a novel germline PTEN frameshift mutation (c.568_569insC, p.V191Sfs*11). In addition, a missense mutation of SMAD7 (c.115G>A, p.G39R) with an allele frequency of 0.3% in the Exome Variant Server was detected in both affected individuals. Fluorescence in situ hybridization for PTEN in the resected esophageal cancer specimen demonstrated no PTEN copy loss in malignant cells; however, results of an immunohistochemical analysis demonstrated a loss of PTEN protein expression. While the risks of many cancers are elevated in the PTEN hamartoma tumor syndromes, association between esophageal adenocarcinoma and these syndromes has not been previously reported. Esophageal adenocarcinoma and extensive polyposis/ganglioneuromatosis could represent less common features of these syndromes, potentially correlating with this novel PTEN frameshift and early protein termination genotype. Alternatively, because simultaneous disruption of both the PTEN and TGF-β/SMAD4 pathways is associated with development of esophageal cancer in a mouse model and because SMAD4 mutations cause gastrointestinal hamartomas in juvenile polyposis syndrome, the SMAD7 mutation may represent an additional modifier of these individuals' PTEN-mutant phenotype.

  18. Nicotine activates YAP1 through nAChRs mediated signaling in esophageal squamous cell cancer (ESCC).

    PubMed

    Zhao, Yue; Zhou, Wei; Xue, Liyan; Zhang, Weimin; Zhan, Qimin

    2014-01-01

    Cigarette smoking is an established risk factor for esophageal cancers. Yes-associated protein 1 (YAP1), the key transcription factor of the mammalian Hippo pathway, has been reported to be an oncogenic factor for many cancers. In this study, we find nicotine administration can induce nuclear translocation and activation of YAP1 in ESCC. Consistently, we observed nuclear translocation and activation of YAP1 by knockdown of CHRNA3, which is a negative regulator of nicotine signaling in bronchial and esophageal cancer cells. Nicotine administration or CHRNA3 depletion substantially increased proliferation and migration in esophageal cancer cells. Interestingly, we find that YAP1 physically interacts with nAChRs, and nAChRs-signaling dissociates YAP1 from its negative regulatory complex composed with α-catenin, β-catenin and 14-3-3 in the cytoplasm, leading to upregulation and nuclear translocation of YAP1. This process likely requires PKC activation, as PKC specific inhibitor Enzastaurin can block nicotine induced YAP1 activation. In addition, we find nicotine signaling also inhibits the interaction of YAP1 with P63, which contributes to the inhibitory effect of nicotine on apoptosis. Using immunohistochemistry analysis we observed upregulation of YAP1 in a significant portion of esophageal cancer samples. Consistently, we have found a significant association between YAP1 upregulation and cigarette smoking in the clinical esophageal cancer samples. Together, these findings suggest that the nicotine activated nAChRs signaling pathway which further activates YAP1 plays an important role in the development of esophageal cancer, and this mechanism may be of a general significance for the carcinogenesis of smoking related cancers.

  19. Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment.

    PubMed

    Dodbiba, Lorin; Teichman, Jennifer; Fleet, Andrew; Thai, Henry; Sun, Bin; Panchal, Devang; Patel, Devalben; Tse, Alvina; Chen, Zhuo; Faluyi, Olusola O; Renouf, Daniel J; Girgis, Hala; Bandarchi, Bizhan; Schwock, Joerg; Xu, Wei; Bristow, Robert G; Tsao, Ming-Sound; Darling, Gail E; Ailles, Laurie E; El-Zimaity, Hala; Liu, Geoffrey

    2013-04-01

    There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (P<0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P=0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances.

  20. Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review.

    PubMed

    Ghidini, Michele; Petrelli, Fausto; Hahne, Jens Claus; De Giorgi, Annamaria; Toppo, Laura; Pizzo, Claudio; Ratti, Margherita; Barni, Sandro; Passalacqua, Rodolfo; Tomasello, Gianluca

    2017-04-01

    The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.

  1. MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer

    SciTech Connect

    Lee, Kuen-Haur; Goan, Yih-Gang; Hsiao, Michael; Lee, Chien-Hsing; Jian, Shu-Huei; Lin, Jen-Tai; Chen, Yuh-Ling; Lu, Pei-Jung

    2009-09-10

    LATS2 is a member of the LATS tumor suppressor family. It has been implicated in regulation of the cell cycle and apoptosis. Frequent loss of heterozygosity (LOH) of LATS2 has been reported in human esophageal cancer. But, the LATS2 gene expression and its regulatory mechanism in esophageal cancer remain unclear. The present study has shown that LATS2 protein expression was mediated by miR-373 at the post-transcriptional level and inversely correlated with miR-373 amounts in esophageal cancer cell lines. Furthermore, we demonstrated that the direct inhibition of LATS2 protein was mediated by miR-373 and manipulated the expression of miR-373 to affect esophageal cancer cells growth. Moreover, this correlation was supported by data collected ex vivo, in which esophageal cancer tissues from esophageal squamous cell carcinoma (ESCC) patients were analyzed. Finally, by miRNA microarray analysis, four miRNAs including miR-373 were over-expressed in ESCC samples. Our findings reveal that miR-373 would be a potential oncogene and it participates in the carcinogenesis of human esophageal cancer by suppressing LATS2 expression.

  2. [Nutritional screening before surgery for esophageal cancer - current status and evaluation results].

    PubMed

    Shimakawa, Takeshi; Asaka, Shinich; Sagawa, Masano; Shimazaki, Asako; Yamaguchi, Kentaro; Usui, Takebumi; Yokomizo, Hajime; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Katsube, Takao; Naritaka, Yoshihiko

    2014-10-01

    The incidence of postoperative complications and mortality are usually higher in patients with preoperative malnutrition. Malnutrition often preexists, particularly in patients undergoing surgery for esophageal cancer, which is substantially invasive. It is therefore important to understand the nutritional condition of patients and actively control perioperative nutrition.Our hospital has been providing nutritional status screening for patients before resection of esophageal cancer, and we report the current status and evaluation results in this article.This screening included 158 patients requiring radical resection of esophageal cancer.Age, comorbidity with diabetes, body mass index(BMI), serum albumin(Alb), Onodera's prognostic nutritional index(PNI), and Glasgow prognostic score(GPS)were used as nutritional indicators to stratify patients for analysis.Evaluation parameters included the incidence of postoperative complications(any complication, pulmonary complications, psychiatric disorder, and anastomotic leakage)and rates of long-term postoperative hospitalization.The analysis indicated that age, BMI, serum Alb, PNI, and GPS are useful for predicting the onset of postoperative complications and prolonged postoperative hospitalization.For such patients, more active nutritional control should be provided.

  3. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    PubMed

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  4. Esophageal Cancer, the Topmost Cancer at MTRH in the Rift Valley, Kenya, and Its Potential Risk Factors

    PubMed Central

    Patel, Kirtika; Wakhisi, Johnston; Mining, Simeon; Mwangi, Ann; Patel, Radheka

    2013-01-01

    Esophageal cancer at Moi Teaching and Referral Hospital (MTRH) is the leading cancer in men with a poor prognosis. A case control study (n = 159) aimed at the histology type, gender, and risk indicators was carried out at MTRH. Mantel Haenszel chi-square and logistic regression were employed for analysis. Squamous-cell carcinoma was the common histological type occurring in the middle third portion of the oesophagus. The occurrence of the cancer in males was 1.4 times that of females. The mean age was 56.1 yrs. Low socioeconomic, smoking, snuff use, alcohol, tooth loss, cooking with charcoal and firewood, hot beverage, and use of mursik were independently associated with esophageal cancer (P < 0.05). Using logistic regression adjusted for various factors, alcohol consumption was associated with the increased risk of esophageal cancer. AHR was 0.45 and 95% CI: 0.205–0.985, P = 0.046. A societal component of low socioeconomic conditions, a lifestyle component with specific practices such as the consumption of mursik, chang'aa, busaa, snuff, smoking, hot tea, poor oral hygiene, and an environmental component with potential exposure to high levels of nitrosamines, passive smoking, and cooking with coal, could be involved. The increase in experts at MTRH capable of diagnosing could be responsible for the increase in reporting this neoplasm. PMID:24490085

  5. Expression of immune checkpoints in T cells of esophageal cancer patients

    PubMed Central

    Xie, Jinhua; Wang, Ji; Cheng, Shouliang; Zheng, Liangfeng; Ji, Feiyue; Yang, Lin; Zhang, Yan; Ji, Haoming

    2016-01-01

    Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients. Further, the expressions of PD-1, TIM-3 and TIGIT were upregulated in tumor infiltrating lymphocytes (TILs), which might be associated with TILs exhaustion. Meanwhile, the expressions of PD-1 and TIM-3 on CD4+ T cells were closely associated with clinic pathological features of esophageal cancer patients. These results indicate that co-inhibitory receptors PD-1, TIM-3 and TIGIT may be potential therapeutic oncotargets for esophageal cancer. PMID:27577071

  6. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  7. Computer analysis of radionuclide esophageal transit studies

    SciTech Connect

    Klein, H.A.; Wald, A.

    1984-09-01

    For detailed examination of the esophageal transit of a swallowed radioactive liquid bolus, three computer-based techniques have been developed: analysis of time-activity curves with decomposition into rapid and residual components, yielding the mean transit time for the former and the residual fraction for the latter; reduction of dynamic image sequences to single condensed images, facilitating subjective assessment; and tracking of the centroid of radioactivity, permitting quantification of retrograde motion. Studies were performed on 12 normal subjects and on six patients with motility disorders. Elevated residual fractions were observed in all the patients, and an abnormal degree of retrograde motion in two. Two normal and two abnormal studies exemplify the variety of patterns observed in condensed images.

  8. Endoscopic mucosectomy: an alternative treatment for superficial esophageal cancer.

    PubMed

    Lambert, R

    2000-01-01

    Recent trends in the management of superficial esophageal cancer consist of improved detection, pretherapeutic staging and reliable criteria for curative endoscopic therapy. The endoscopic treatment is legitimate when the cancer is at an early stage, intra-epithelial or microinvasive (m1 or m2) and N0. Submucosal cancer should not be treated with a curative intent by endotherapy. Concerning squamous cell cancer, the oriental and occidental pathologists include high-grade dysplasia in the same group as intramucosal cancer. The distinction is however maintained for adenocarcinoma in the Barrett's esophagus. Indications of endoscopic rather than surgical treatment rely on: (1) the small size of the tumor (not more than 2 cm in diameter); (2) the endoscopic morphology in the type 0 of the Japanese classification with the flat subtypes IIa and IIb rather than type IIc--there is high risk of submucosal invasion for the polypoid (type I) or ulcerated superficial cancer (type III); and (3) the endoscopic ultrasound staging, with confirmed integrity of the hyperechoic submucosal layer. The high-frequency (20 MHz) miniprobe is preferred to the standard (7.5 MHz) instrument. The elective procedure for tumor eradication is endoscopic mucosectomy. The technique is associated with a 6.8% risk of severe complications (hemorrhage or perforation) and a recurrence rate of 3%-7%. The 5-year survival rate is similar to that of surgery (over 80%). In the small group of patients with superficial esophageal cancer (less than 10% of the disease) endoscopic treatment may now be proposed in about 30% of cases, surgery is preferred for submucosal cancer and for neoplasia with a large surface. Areas of high-grade dysplasia in the Barrett's esophagus offer a new and increasing sector of indications. The concurrent endoscopic procedure of destruction--photodynamic therapy--is preferred for the destruction of lesions with poorly delineated limits.

  9. Esophageal Cancer Dose Escalation Using a Simultaneous Integrated Boost Technique

    SciTech Connect

    Welsh, James; Palmer, Matthew B.; Ajani, Jaffer A.; Liao Zhongxing; Swisher, Steven G.; Hofstetter, Wayne L.; Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko

    2012-01-01

    Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

  10. Genetic variants in the ZNF208 gene are associated with esophageal cancer in a Chinese Han population

    PubMed Central

    Wang, Huijie; Yu, Jianzhong; Guo, Yanling; Zhang, Zhengxing; Liu, Guoqi; Li, Jingjie; Zhang, Xiyang; Jin, Tianbo; Wang, Zhaoxia

    2016-01-01

    Previous studies showed an association between the ZNF208 gene and gastric cancer. In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in ZNF208 and the risk of esophageal cancer in a Chinese Han population. We conducted a case-control study that included 386 cases and 495 controls. Five SNPs were selected from previous genome-wide association studies and genotyped using the Sequenom MassARRAY platform. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals after adjustment for age and gender. Logistic regressionl analysis showed that two SNPs (rs8103163 and rs7248488) were associated with an increased risk of esophageal cancer under different inheritance models after Bonferroni correction. Haplotype analysis suggested that the four variants comprised one block, and that the Grs2188972Crs2188971Crs8103163Crs7248488 haplotype was significantly correlated with an increased risk of esophageal cancer. Our data indicate that variants in ZNF208 are contribute to the susceptibility to esophageal cancer in a Chinese Han population. PMID:27907911

  11. Implication of lncRNAs in pathogenesis of esophageal cancer

    PubMed Central

    Tang, Wei-Wei; Wu, Qingquan; Li, Su-Qing; Tong, Yu-Suo; Liu, Zi-Hao; Yang, Tong-Xin; Xu, Yong; Cao, Xiu-Feng

    2015-01-01

    Long non-coding RNAs (lncRNAs), transcripts as longer than 200 nt in length with a great number of varieties in human genomics, play important roles in the regulation of genetics and epigenetics including gene transcription and post-transcription. Increasing evidence have demonstrated the upregulation of lncRNAs in tumorigenesis and metastasis of esophageal cancer (EC), a type of malignant tumors particularly in Asia. In this review, we briefly discuss the profiles and functions of lncRNAs involved in the progression of EC, which may provide a new approach to improve EC diagnosis and treatment. PMID:26609239

  12. Esophageal cancer screening in achalasia: is there a consensus?

    PubMed

    Ravi, K; Geno, D M; Katzka, D A

    2015-04-01

    Achalasia is an important but relatively uncommon disorder. While highly effective therapeutic options exist, esophageal cancer remains a long-term potential complication. The risk of esophageal cancer in achalasia remains unclear, with current guidelines recommending against routine endoscopic screening. However, given limited data and conflicting opinion, it is unknown whether consensus regarding screening practices in achalasia among experts exists. A 10-question survey to assess screening practices in achalasia was created and distributed to 28 experts in the area of achalasia. Experts were identified based on publications and meeting presentations in the field. Survey responses were received from 17 of 28 (61%) experts. Wide geographic distribution was seen among respondents, with eight (47%) from Europe or Australia, seven (41%) from the United States, and two (12%) from Asia. Screening for esophageal cancer was inconsistent, with nine (53%) experts endorsing the practice and eight (47%) not. Screening practices did not differ among geographic regions. No consensus regarding the risk for esophageal cancer in achalasia was seen, with three experts reporting no increased risk compared with the general population, eight experts a lifetime risk of 0.1-0.5%, three experts a 0.5-1% risk, two experts a 1-2% risk, and one expert a 3-5% risk. However, these differences in perception of risk did not influence screening practices. Upper endoscopy was utilized among all experts who endorsed screening. However, practices still varied with screening commencing at or within 1 year of diagnosis in two practices compared with 5 and 10 years in three respective practices each. Surveillance intervals also varied, performed every 2 years in four practices, every 3 years in four practices, and every 5 years in one practice. Practice variation in the management of achalasia itself was also seen, with initial treatment with Heller myotomy endorsed by eight experts, pneumatic

  13. Impacts of physically active and under-active on clinical outcomes of esophageal cancer patients undergoing esophagectomy

    PubMed Central

    Wang, Lu; Wang, Cong; Guan, Shanghui; Cheng, Yufeng

    2016-01-01

    Physical activity has been reported to positively influence quality of life and survival in certain cancers. However, the associations between them in esophageal cancer are previously undefined. The aims of this study are to investigate whether physically active esophageal cancer patients have improved quality of life and lower risk of recurrence as well as death compared with physically inactive patients. We evaluated the relationships between postoperative leisure time physical activity and quality of life and recurrence and death among patients diagnosed with esophageal cancer. We respectively used generalized estimating equations and Cox proportional regression to analysis quality of life and survival, adjusting for known potential confounding factors. Comparing esophageal cancer patients reporting more than 9 MET hours per week of postoperative leisure time physical activity with those reporting less, we found improved quality of life. Additionally, we also found that postoperative leisure time physical activity ≥9 MET hours per week, compared with less, was associated with a 23% lower risk of all-cause mortality (HR, 0.666; 95% CI, 0.481-0.921; P=0.014) and a 53% lower risk of recurrence (HR, 0.306; 95% CI 0.218-0.429; P<0.001). Leisure time physical activity was significantly associated with quality of life and risk of recurrence and death of esophageal cancer patients. Clinicians should consider increasing physical activity, regardless of previous behaviors, as a part of primary cancer treatment. The ultimate goal is to improve quality of life and prolong survival of cancer survivors. PMID:27508099

  14. Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

    SciTech Connect

    Wang, Jingya; Wei, Caimiao; Tucker, Susan L.; Myles, Bevan; Palmer, Matthew; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing; Lin, Steven H.

    2013-08-01

    Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ{sup 2} or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.

  15. Concurrent Chemoradiotherapy for Esophageal Cancer With Malignant Fistula

    SciTech Connect

    Koike, Ryuta; Nishimura, Yasumasa Nakamatsu, Kiyoshi; Kanamori, Shuichi; Shibata, Toru

    2008-04-01

    Background: We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. Methods and Materials: The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m{sup 2} x 14 days) and cisplatin (7 mg/m{sup 2} x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. Results: The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. Conclusion: Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

  16. PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts

    PubMed Central

    Oi, Naomi; Chen, Hanyong; Reddy, Kanamata; Jiang, Yanan; Yao, Ke; Li, Haitao; Li, Wei; Zhang, Yi; Saleem, Mohammad; Ma, Wei-Ya; Bode, Ann M.; Dong, Ziming; Dong, Zigang

    2016-01-01

    Esophageal cancer is one of the least studied and deadliest cancers worldwide with a poor prognosis due to limited options for treatment. Chemotherapy agents such as the microtubule-targeting compounds are the mainstay of palliation for advanced esophageal cancer treatment. However, the toxicity and side effects of tubulin-binding agents (TBAs) have promoted the development of novel, more potent but less toxic TBAs. Herein, we identified 2-[4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-5-[(2-methylprop-2-en-1-yl)oxy] phenol (PPMP) as a novel TBA for esophageal cancer treatment. PPMP markedly inhibited tubulin polymerization, and decreased viability and anchorage-independent growth of esophageal cancer cell lines, effects that were accompanied by G2/M arrest and apoptosis. Importantly, we produced patient-derived esophageal cancer xenografts to evaluate the therapeutic effect of PPMP in a setting that best mimics the clinical context in patients with esophageal cancer. Overall, we identified PPMP as a novel microtubule-destabilizing compound and as a new therapeutic agent against esophageal carcinoma. PMID:27129160

  17. Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract.

    PubMed

    Diakowska, Dorota; Krzystek-Korpacka, Malgorzata; Markocka-Maczka, Krystyna; Diakowski, Witold; Matusiewicz, Malgorzata; Grabowski, Krzysztof

    2010-08-01

    We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract.

  18. Esophageal Cancer in Kashmir (India): An Enigma for Researchers

    PubMed Central

    Mir, M. Muzaffar; Dar, Nazir Ahmad

    2009-01-01

    About 90% of esophageal cancers worldwide are Squamous Cell Carcinomas (SCC), mostly occurring in defined high-incidence areas of low and middle-resource countries. Historically, the highest incidences are reported in regions of Central Asia. One such region is Kashmir Valley in Northern India. In this review, we summarize a large body of epidemiological, toxicological and observational information on occurrence, dietary patterns and lifestyles to discuss factors that may be involved in the etiology of SCC in Kashmir Valley. To date, no single factor can be identified as the main cause of the excess incidence of SCC as compared to other regions of India. Three main components emerge as important factors: a societal component with poor, rural lifestyle and general deprivation, status in particular in vitamins and oligoelements; a lifestyle component with the use of copper utensil in cooking, the consumption of spicy, deep fried foodstuffs, and the drinking of hot salty tea; and an environmental component with exposure to high levels of dietary nitrosamines from diverse sources. Overall, these three components are similar to the general pattern of factors that have been involved in causing SCC in other high-incidence area in the so-called “esophageal cancer belt”, namely in central China (Cixian, Lixian) and in Northern Iran (Golestan). Further comparative studies between these regions are needed to identify the contributions of these various components. PMID:21475514

  19. A submucosal tumor-like recurrence of early esophageal cancer after endoscopic submucosal dissection.

    PubMed

    Choi, Jeong Cheon; Kim, Gwang Ha; Park, Do Youn; Seoung, Hyeog Gyu; Lee, Yong Jae; Kim, Ji Hye; Kim, Tae Kyun; I, Hoseok

    2013-03-01

    Early esophageal cancer is defined as a tumor invading the mucosa with or without lymph node or distant organ metastasis. In the current guidelines for early esophageal cancer, absolute indication for endoscopic resection include lesions limited to the epithelium or lamina propria mucosa not exceeding two-thirds of the circumference, and relative indications include lesions limited to the muscularis mucosa or the upper third of the submucosal layer and not accompanied by clinical evidence of lymph node metastasis. After endoscopic submucosal dissection for early esophageal cancer, locally recurrent cancer can occur, especially in the case of incomplete resection. Here, we report a rare case of a submucosal tumor-like recurrence after endoscopic resection of early esophageal cancer.

  20. Identification of a RNA-Seq Based 8-Long Non-Coding RNA Signature Predicting Survival in Esophageal Cancer

    PubMed Central

    Fan, Qiaowei; Liu, Bingrong

    2016-01-01

    Background Accumulating evidence suggests the involvement of long non-coding RNAs (lncRNAs) as oncogenic or tumor suppressive regulators in the development of various cancers. In the present study, we aimed to identify a lncRNA signature based on RNA sequencing (RNA-seq) data to predict survival in esophageal cancer. Material/Methods The RNA-seq lncRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs were screened out between esophageal cancer and normal tissues. Univariate and multivariate Cox regression analysis were performed to establish a lncRNA-related prognostic model. Receiver operating characteristic (ROC) analysis was conducted to test the sensitivity and specificity of the model. GO (gene ontology) functional and KEGG pathway enrichment analyses were performed for mRNAs co-expressed with the lncRNAs to explore the potential functions of the prognostic lncRNAs. Results A total of 265 differentially expressed lncRNAs were identified between esophageal cancer and normal tissues. After univariate and multivariate Cox regression analysis, eight lncRNAs (GS1-600G8.5, LINC00365, CTD-2357A8.3, RP11-705O24.1, LINC01554, RP1-90J4.1, RP11-327J17.1, and LINC00176) were finally screened out to establish a predictive model by which patients could be classified into high-risk and low-risk groups with significantly different overall survival. Further analysis indicated independent prognostic capability of the 8-lncRNA signature from other clinicopathological factors. ROC curve analysis demonstrated good performance of the 8-lncRNA signature. Functional enrichment analysis showed that the prognostic lncRNAs were mainly associated with esophageal cancer related biological processes such as regulation of glucose metabolic process and amino acid and lipids metabolism. Conclusions Our study developed a novel candidate model providing additional and more powerful prognostic information

  1. PROGNOSTIC FACTORS AND SURVIVAL ANALYSIS IN ESOPHAGEAL CARCINOMA

    PubMed Central

    TUSTUMI, Francisco; KIMURA, Cintia Mayumi Sakurai; TAKEDA, Flavio Roberto; UEMA, Rodrigo Hideki; SALUM, Rubens Antônio Aissar; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan

    2016-01-01

    ABSTRACT Background: Despite recent advances in diagnosis and treatment, esophageal cancer still has high mortality. Prognostic factors associated with patient and with disease itself are multiple and poorly explored. Aim: Assess prognostic variables in esophageal cancer patients. Methods: Retrospective review of all patients with esophageal cancer in an oncology referral center. They were divided according to histological diagnosis (444 squamous cell carcinoma patients and 105 adenocarcinoma), and their demographic, pathological and clinical characteristics were analyzed and compared to clinical stage and overall survival. Results: No difference was noted between squamous cell carcinoma and esophageal adenocarcinoma overall survival curves. Squamous cell carcinoma presented 22.8% survival after five years against 20.2% for adenocarcinoma. When considering only patients treated with curative intent resection, after five years squamous cell carcinoma survival rate was 56.6 and adenocarcinoma, 58%. In patients with squamous cell carcinoma, poor differentiation histology and tumor size were associated with worse oncology stage, but this was not evidenced in adenocarcinoma. Conclusion: Weight loss (kg), BMI variation (kg/m²) and percentage of weight loss are factors that predict worse stage at diagnosis in the squamous cell carcinoma. In adenocarcinoma, these findings were not statistically significant. PMID:27759773

  2. [Current Status and Effectiveness of Perioperative Oral Health Care Management for Lung Cancer and Esophageal Cancer Patients].

    PubMed

    Nishino, Takeshi; Takizawa, Hiromitsu; Yoshida, Takahiro; Inui, Tomohiro; Takasugi, Haruka; Matsumoto, Daisuke; Kawakita, Naoya; Inoue, Seiya; Sakiyama, Shoji; Tangoku, Akira; Azuma, Masayuki; Yamamura, Yoshiko

    2016-01-01

    The effectiveness of perioperative oral health care management to decrease the risk of postoperative pneumonia have been reported lately. Since 2014, we introduced perioperative oral health care management for lung cancer and esophageal cancer patients. We report current status and effectiveness of perioperative oral health care management for lung cancer and esophageal cancer patients. Every 100 cases of lung cancer and esophageal cancer patients treated by surgery were classified 2 group with or without perioperative oral health care management and compared about postoperative complications retrospectively. In the lung cancer patients, the group with oral health care management could prevent postoperative pneumonia significantly and had shorter length of hospital stay than the group without oral health care management. In the esophageal cancer patients, there was little occurrence of postoperative pneumonia without significant difference between both group with or without oral health care management. A large number of esophageal cancer patients received neo-adjuvant chemotherapy and some patients developed oral mucositis and received oral care treatment before surgery. Treatment for oral mucositis probably improved oral environment and affected prevention of postoperative pneumonia. Perioperative oral health care management can prevent postoperative pneumonia of lung cancer and esophageal cancer patients by improvement of oral hygiene.

  3. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    SciTech Connect

    Alexander, Brian M.; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-05-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  4. [Present and future state of cancer screening for esophageal cancer and gastric cancer].

    PubMed

    Nakashima, Hirotaka; Nagahama, Ryuji; Yoshida, Misao

    2012-01-01

    Recently, endoscopic examinations have played a major role in the diagnosis and treatment in the field of gastroenterology. It is considered that endoscopy would be an important examination for cancer screening of the esophagus and the stomach. However, endoscopic services for cancer screening are in short supply. Furthermore, we have to take the complications and poor economic benefits of endoscopy in to consideration when we apply it as a practical cancer screening system. Thus, an effective primary screening system must be provided for the endoscopic screening of cancer of the esophagus and the stomach. People with a defect in aldehyde dehydrogenase-2(ALDH2)should be distinguished by their facial flushing in drinking and for their high risks of esophageal cancer. In cases with gastric cancer screening by endoscopy, an x-ray study is expected to be a primary screening because of its efficacy. It already has been recommended for population-based screening in Japanese guidelines for gastric cancer screening. In cases with opportunistic screening of gastric cancer, patients should be allowed to choose from several studies such as the x-ray study, direct endoscopy, and the so-called high risk screening of gastric cancer for estimating risks and planning of screening for gastric cancer.

  5. Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature

    PubMed Central

    Taccioli, C; Chen, H; Jiang, Y; Liu, XP; Huang, K; Smalley, KJ; Farber, JL; Croce, CM; Fong, LY

    2011-01-01

    Chronic inflammation is implicated in the pathogenesis of esophageal squamous cell cancer (ESCC). The causes of inflammation in ESCC, however, are undefined. Dietary zinc-deficiency (ZD) increases the risk of ESCC. We have previously shown that short-term ZD (6 weeks) in rats induces overexpression of the proinflammatory mediators S100a8 and S100a9 in the esophageal mucosa with accompanying esophageal epithelial hyperplasia. Here we report that prolonged ZD (21 weeks) in rats amplified this inflammation that when combined with non-carcinogenic low doses of the environmental carcinogen N-nitrosomethylbenzylamine (NMBA) elicited a 66.7% (16/24) incidence of ESCC. With zinc-sufficiency NMBA produced no cancers (0/21) (P<0.001). At tumor endpoint, the neoplastic ZD esophagus as compared with zinc-sufficient esophagus had an inflammatory gene signature with upregulation of numerous cancer-related inflammation genes (CXC and CC chemokines, chemokine receptors, cytokines, and Cox-2) in addition to S100a8 and S100a9. This signature was already activated in the earlier dysplastic stage. Additionally, time-course bioinformatics analysis of expression profiles at tumor endpoint and prior to NMBA exposure revealed that this sustained inflammation was due to ZD rather than carcinogen exposure. Importantly, zinc replenishment reversed this inflammatory signature at both the dysplastic and neoplastic stages of ESCC development, and prevented cancer formation. Thus, the molecular definition of ZD-induced inflammation as a critical factor in ESCC development has important clinical implications with regard to development and prevention of this deadly disease. PMID:22179833

  6. Sociodemographic Parameters of Esophageal Cancer in Northwest India: A Regional Cancer Center Experience of 10 Years

    PubMed Central

    Kapoor, Akhil; Kumar, Vanita; Singhal, Mukesh Kumar; Nirban, Raj Kumar; Beniwal, Surender Kumar; Kumar, Harvindra Singh

    2015-01-01

    Background: Despite various advances in the treatment of Esophageal Cancer (EC), being one of the least responsive tumors to cancer therapy, the overall prognosis remains poor. Therefore, it is significant to understand various sociodemographic factors associated with EC to find out various schemes for primary prevention of the disease. Materials and Methods: This is a retrospective analysis of medical records of the EC patients registered in the regional cancer center of northwest India from January 2003 to December 2012. The site of the disease and the histology were also recorded in addition to the various sociodemographic parameters. Results: Out of 55,742 patients registered in our hospital; 3,667 were diagnosed to have EC. Male:female ratio was 1.15:1. The mean age was 54.6 ± 11.74 years; 66.15% of the patients were illiterate and 48.6% belonged to the low socioeconomic status. Smoking and alcohol consumption were identified as risk factors in 48 and 25.6% of the patients, respectively. Conclusions: The etiology in majority of the patients is linked to tobacco and alcohol, thus, modification of life style with limiting the use of addictions may be an effective strategy in the prevention of this dreaded and mostly incurable disease. PMID:26435600

  7. Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

    PubMed Central

    CHEN, YONGSHUN; LI, XIAOHONG; GUO, LEIMING; WU, XIAOYUAN; HE, CHUNYU; ZHANG, SONG; XIAO, YANJING; YANG, YUANYUAN; HAO, DAXUAN

    2015-01-01

    Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3-methyladenine (3-MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3-MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3-MA effectively inhibited radiation-induced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3-MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiation-induced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma. PMID:25891159

  8. Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers

    PubMed Central

    Xing, Xiaofang; Du, Hong; Zhou, Chunlian; Zhang, Qingyun; Hao, Chunyi; Wen, Xianzi; Ji, Jiafu

    2016-01-01

    Background Lysosome-associated transmembrane-4 beta (LAPTM4B) is an oncogene that participates tumorgenesis in a variety of human solid tumors, and it has two alleles named as LAPTM4B*1 and *2. The present study aimed to identify the association of LAPTM4B genotype with clinicopathological features and prognosis in colorectal and esophageal cancer patients. Method Genotypes of LAPTM4B were determined by PCR in 167 colon cancer cases (72 patients in a discovery cohort and 95 patients in a testing cohort), 160 rectal cancer cases and 164 esophageal cancer cases. Association between the LAPTM4B gene polymorphism and clinicopathological variables was calculated by Chi-square test or Fisher’s exact test. Patient survival differences were calculated by the Kaplan-Meier method. Prognostic factors were determined with Log-rank test and Cox regression model. Results LAPTM4B *1/1 was more frequently detected in colon cancer patients with lymph node metastasis and TNM III+IV stages in total colon cancer (discovery + testing cohorts). LAPTM4B *2/2 decreased in recurrent patients in total colon cancer patients (P = 0.045). Kaplan-Meier survival curves and Log-rank test showed that LAPTM4B*1 was correlated with shorter overall survival (OS) in discovery and testing cohorts of colon cancer (P = 0.0254 and 0.0292, respectively), but not in rectal and esophageal cancer cases (P = 0.7669 and 0.9356, respectively). Multivariate analysis showed that LAPTM4B genotype was an independent prognostic factor for OS in total colon cancer [P = 0.004, hazard ratio (HR) = 0.432; 95% confidence interval (CI) = 0.243–0.768], but not in rectal and esophageal cancers (P = 0.791, HR = 1.073, 95% CI = 0.638–1.804 and 0.998, HR = 1.000, 95% CI = 0.663–1.530, respectively). Conclusion These findings suggested that LAPTM4B allele *1 was a risk factor associated with poor prognosis in patients with colon cancer, but not in patients with rectal or esophageal cancers. LAPTM4B genotype status might

  9. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  10. Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay

    PubMed Central

    Ling, Zhi-qiang; Qi, Chun-jian; Lu, Xiao-xiao; Qian, Li-juan; Gu, Lin-hui; Zheng, Zhi-guo; Zhao, Qiang; Wang, Shi; Fang, Xian-hua; Yang, Zhi-xing; Yin, Jian; Mao, Wei-min

    2012-01-01

    Aim: Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers. Methods: A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). Results: Thirty eight specimens produced evaluable results (90.5%). The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity: cisplatin+paclitaxel was sensitive in 16 of 38 (42.1%) of samples, while nedaplatin+paclitaxel was more effective, which was sensitive in 20 of 38 cases (52.6%). Conclusion: There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients. PMID:22286916

  11. Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes

    PubMed Central

    Bradbury, Penelope A.; Kulke, Matthew H.; Heist, Rebecca S.; Zhou, Wei; Ma, Clement; Xu, Wei; Marshall, Ariela L.; Zhai, Rihong; Hooshmand, Susanne M.; Asomaning, Kofi; Su, Li; Shepherd, Frances A.; Lynch, Thomas J.; Wain, John C.; Christiani, David C.; Liu, Geoffrey

    2011-01-01

    Objectives Genetic variations or polymorphisms within genes of the nucleotide excision repair (NER) pathway alter DNA repair capacity. Reduced DNA repair (NER) capacity may result in tumors that are more susceptible to cisplatin chemotherapy, which functions by causing DNA damage. We investigated the potential predictive significance of functional NER single nucleotide polymorphisms in esophageal cancer patients treated with (n = 262) or without (n = 108) cisplatin. Methods Four NER polymorphisms XPD Asp312Asn; XPD Lys751Gln, ERCC1 8092C/A, and ERCC1 codon 118C/T were each assessed in polymorphism–cisplatin treatment interactions for overall survival (OS), with progression-free survival (PFS) as a secondary endpoint. Results No associations with ERCC1 118 were found. Polymorphism–cisplatin interactions were highly significant in both OS (P = 0.002, P = 0.0001, and P < 0.0001) and PFS (P = 0.006, P = 0.008, and P = 0.0007) for XPD 312, XPD 751, and ERCC1 8092, respectively. In cisplatin-treated patients, variant alleles of XPD 312, XPD 751, and ERCC1 8092 were each associated with significantly improved OS (and PFS): adjusted hazard ratios of homozygous variants versus wild-type ranged from 0.22 [95% confidence interval (CI): 0.1–0.5] to 0.31 (95% CI: 0.1–0.7). In contrast, in patients who did not receive cisplatin, variant alleles of XPD 751 and ERCC1 8092 had significantly worse survival, with adjusted hazard ratios of homozygous variants ranging from 2.47 (95% CI: 1.1–5.5) to 3.73 (95% CI: 1.6–8.7). Haplotype analyses affirmed these results. Conclusion DNA repair polymorphisms are associated with OS and PFS, and if validated may predict for benefit from cisplatin therapy in patients with esophageal cancer. PMID:19620936

  12. Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening

    PubMed Central

    Konda, Vani JA; Cherkezyan, Lusik; Subramanian, Hariharan; Wroblewski, Kirsten; Damania, Dhwanil; Becker, Valentin; Gonzalez, Mariano Haba Ruiz; Koons, Ann; Goldberg, Michael; Ferguson, Mark K; Waxman, Irving; Roy, Hermant K; Backman, Vadim

    2014-01-01

    Background and study aims Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett’s esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett’s esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett’s esophagus. Methods During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. Results A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett’s esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). Conclusion Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological

  13. Occupational asbestos exposure and risk of esophageal, gastric and colorectal cancer in the prospective Netherlands Cohort Study.

    PubMed

    Offermans, Nadine S M; Vermeulen, Roel; Burdorf, Alex; Goldbohm, R Alexandra; Keszei, András P; Peters, Susan; Kauppinen, Timo; Kromhout, Hans; van den Brandt, Piet A

    2014-10-15

    The evidence for an association between occupational asbestos exposure and esophageal, gastric and colorectal cancer is limited. We studied this association specifically addressing risk differences between relatively low and high exposure, risk associated with cancer subtypes, the influence of potential confounders and the interaction between asbestos and smoking in relation to cancer risk. Using the Netherlands Cohort Study (n = 58,279 men, aged 55-69 years at baseline), asbestos exposure was estimated by linkage to a job-exposure matrix. After 17.3 years of follow-up, 187 esophageal, 486 gastric and 1,724 colorectal cancer cases were available for analysis. The models adjusted for age and family history of cancer showed that mainly (prolonged) exposure to high levels of asbestos was statistically significantly associated with risk of esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer. For overall gastric cancer and gastric non-cardia adenocarcinoma (GNCA), also exposure to lower levels of asbestos was associated. Additional adjustment for lifestyle confounders, especially smoking status, yielded non-significant associations with overall gastric cancer and GNCA in the multivariable-adjusted model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR 2.67, 95% CI: 1.11-6.44 and HR 3.35, 95% CI: 1.33-8.44, respectively). No statistically significant additive or multiplicative interaction between asbestos and smoking was observed for any of the studied cancers. This prospective population-based study showed that (prolonged) high asbestos exposure was associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer and rectal cancer.

  14. Label-free detection of blood plasma using silver nanoparticle based surface-enhanced Raman spectroscopy for esophageal cancer screening.

    PubMed

    Li, Duo; Feng, Shangyuan; Huang, Hao; Chen, Weisheng; Shi, Hong; Liu, Nenrong; Chen, Long; Chen, Weiwei; Yu, Yun; Chen, Rong

    2014-03-01

    A surface-enhanced Raman spectroscopy (SERS) based on silver nanoparticle technology was applied to analyze and classify human blood plasma with the aim to develop a simple and label-free blood test for esophageal cancer detection. High quality SERS spectra in the range of 400-1800 cm(-1) can be acquired from 36 esophageal cancer patients and 50 healthy volunteers' blood plasma samples. Tentative assignments of the SERS bands indicated specific biomolecular changes associated with cancer transformation, including an increase in the relative amounts of nucleic acid and phenylalanine, a decrease in the percentage of saccharide and proteins contents in the cancer blood plasma compared to that of healthy subjects. Furthermore, both SVM and PCA-LDA diagnostic algorithm were employed to analyze and classify the obtained blood plasma SERS spectra between normal and cancer plasma with a high diagnostic accuracy (around 90%). This exploratory work demonstrates that the label-free plasma SERS analysis technique in conjunction with SVM and PCA-LDA diagnostic algorithms has great potential for improving esophageal cancer detection and screening.

  15. The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: A population-registered study in Feicheng, China

    PubMed Central

    Sun, Xiubin; Zhao, Deli; Liu, Yi; Liu, Yunxia; Yuan, Zhongshang; Wang, Jialin; Xue, Fuzhong

    2017-01-01

    Background Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005. Methods The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY) and changing trends in esophageal cancer according to age and sex were calculated and described. Results The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden. Conclusion Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures. PMID:28267769

  16. Efficacy of Intensity Modulated Radiation Therapy After Surgery in Early Stage of Esophageal Carcinoma;

    ClinicalTrials.gov

    2016-07-30

    Esophageal Neoplasm; Esophageal Cancer TNM Staging Primary Tumor (T) T2; Esophageal Cancer TNM Staging Primary Tumor (T) T3; Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0; Esophageal Cancer TNM Staging Distal Metastasis (M) M0

  17. Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged ≥ 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute

    PubMed Central

    Guo, Hongbo; Zhang, Yan; Shi, Fang; Han, Anqin; Li, Minghuan; Kong, Li; Yu, Jinming

    2015-01-01

    Purpose We conducted a retrospective analysis to assess the feasibility of involved field irradiation (IFI) in elderly patients with esophageal squamous cell cancer (ESCC). Materials and Methods We performed a retrospective review of the records of elderly patients (≥ 70 years) with unresectable ESCC and no distant metastases who received treatment with radiotherapy between January 2009 and March 2013. According to the irradiation volume, patients were allocated into either the elective nodal irradiation (ENI) group or the IFI group. Overall survival (OS), progression-free survival (PFS) and treatment-related toxicities were compared between the two groups. Results A total of 137 patients were enrolled. Fifty-four patients (39.4%) were allocated to the ENI group and 83 patients (60.6%) to the IFI group, the median doses in the two groups were 60 Gy and 59.4 Gy, respectively. For the entire group, the median survival time (MST) and PFS were 16 months and 12 months, respectively. The median PFS and 3-year PFS rate in the ENI group were 13 months and 20.6%, compared to 11 months and 21.0% in the IFI groups (p = 0.61). The MST and 3-year OS rate in the ENI and IFI groups were 17 months and 26.4% and 15.5 months and 21.7%, respectively (p = 0.25). The rate of grade ≥ 3 acute irradiation esophagitis in the ENI group was significantly higher than that in the IFI group (18.5% vs. 6.0%; p = 0.027). Other grade ≥ 3 treatment-related toxicities did not significantly differ between the two groups. Conclusions IFI resulted in decreased irradiation toxicities without sacrificing OS in elderly patients with ESCC. PMID:26636574

  18. Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins.

    PubMed

    Gao, Yu-Fei; Yuan, Fei; Liu, Junbao; Li, Li-Peng; He, Yi-Chun; Gao, Ru-Jian; Cai, Yu-Dong; Jiang, Yang

    2015-01-01

    Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method--the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.

  19. Radiation dose to the lymph drainage area in esophageal cancer with involved-field irradiation.

    PubMed

    Shen, Wenbin; Gao, Hongmei; Zhu, Shuchai; Li, Youmei; Li, Juan; Liu, Zhikun; Su, Jinwei

    2016-01-01

    The aim of this study was to quantify the radiation dose to the corresponding lymph drainage area in esophageal cancer using three-dimensional conformal radiation therapy (3D-CRT) with involvED-field IRradiation (IFI) and to analyze associated factors. A retrospective analysis oF 81 patients with esophageal cancer was conducted. According to the location of the lesions, the lymph drainage area was delineated and the dosimetric parameters were calculated. The 1-, 3-, 5- and 8-year survival rates of the patients were 67.90, 33.33, 20.99 and 11.11%, respectively. Based on the dose-volume histogram in the treatment plan, we calculated the volume percentage of the planning target volume including clinically positive lymph nodes (PTV-N) receiving radiation doses of 30, 35, 40, 45 and 50 Gy (VPTV-N30-50). The median values of VPTV-N30-50 were 73, 70, 67, 64 and 58%, respectively. The prescribed dose size exhibited no correlation with VPTV-N30-35, but did exhibit a significant correlation with VPTV-N40-50; the radiation field was not correlated with VPTV-N30-45, but exhibited a significant correlation with VPTV-N50; The length of the lesion on esophageal barium meal X-ray and the PTV were significantly correlated with VPTV-N30-50. The analysis of variance revealed that the VPTV-NX value in the upper thoracic segment was higher compared with that in the middle and lower thoracic segments; VPTV-N30-35 values differed significantly according to the different locations of the lesions, whereas VPTV-N40-50 values exhibited no significant differences. The value of VPTV-NX exerted no significant effect on long-term patient survival. Therefore, the corresponding lymph drainage area of esophageal cancer IS subjected to a certain Radiation dose when patients undergo 3D-CRT with IFI, which may play a role in the prevention of regional nodal metastasis. However, this hypothesis requires confirmation by further clinical studies.

  20. Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening

    PubMed Central

    Yamasaki, Yasushi; Takenaka, Ryuta; Hori, Keisuke; Takemoto, Koji; Kawano, Seiji; Kawahara, Yoshiro; Okada, Hiroyuki; Fujiki, Shigeatsu; Yamamoto, Kazuhide

    2015-01-01

    AIM: To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy. METHODS: We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer. All patients were divided into two groups: a magnifying narrow band imaging group, and a lugol chromoendoscopy group, for comparison of adverse symptoms. Esophageal cancer screening was performed on withdrawal of the endoscope. The primary endpoint was a score on a visual analogue scale for heartburn after the examination. The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations, change in vital signs, total procedure time, and esophageal observation time. RESULTS: The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group (P = 0.004, 0.024, respectively, ANOVA for repeated measures). The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group. There was no significant difference between the two groups with respect to other vital sign. The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group (450 ± 116 vs 565 ± 174, P = 0.004, 44 ± 26 vs 151 ± 72, P < 0.001, respectively). CONCLUSION: Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy. Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically. PMID:25759551

  1. Cronkhite-Canada syndrome associated with esophageal and gastric cancers: report of a case.

    PubMed

    Ito, Masahiro; Matsumoto, Sohei; Takayama, Tomoyoshi; Wakatsuki, Kohei; Tanaka, Tetsuya; Migita, Kazuhiro; Nakajima, Yoshiyuki

    2015-06-01

    Cronkhite-Canada Syndrome (CCS) is a rare non-inherited gastrointestinal polyposis syndrome with characteristic ectodermal changes. We report an extremely unusual case of CCS associated with primary esophageal and gastric cancers. A 74-year-old Japanese man with symptoms of anorexia and diarrhea was found to have primary esophageal and gastric cancers, as well as multiple gastric and colonic polyps. Based on the physical findings of onychodystrophy and alopecia, we diagnosed CCS. Because of his age and nutritional status, we decided to perform total gastrectomy for gastric cancer and chemoradiotherapy for esophageal cancer, upon completion of which the patient was started on steroid therapy for the CCS. After 1 week of steroid therapy, the patient's watery diarrhea improved. We recommend that for patients with CCS, the therapeutic strategy be carefully considered based on the patient's nutritional status, the severity of the CCS, and the extent of gastrointestinal cancer.

  2. Clinical application of iodine-eluting stent in patients with advanced esophageal cancer

    PubMed Central

    DAI, ZHENBO; ZHOU, DEJUN; HU, JIANZHANG; ZHANG, LEI; LIN, YUNSHOU; ZHANG, JING; LI, FENGLING; LIU, PENG; LI, HUA; CAO, FULIANG

    2013-01-01

    The aim of the present study was to compare the clinical effectiveness of an iodine-eluting stent with a conventional stent in patients with advanced esophageal cancer. Patients with malignant esophageal cancer were randomly assigned to receive a conventional stent (group A) or an iodine-eluting stent (group B). Following implantation, the relief from dysphagia, survival time, routine blood tests, thyroid function examination and complications were compared in the two groups. Groups A and B consisted of 36 and 31 patients, respectively. The mean value that the dysphagia score decreased by was significantly lower in group A (0.83) compared with group B (1.65). The median survival time was longer in group B compared with group A (P=0.0022). No significant differences were observed in the severe complications between the two groups (P=0.084). The iodine-eluting esophageal stent is a relatively safe, feasible and effective treatment for malignant esophageal strictures. PMID:24137396

  3. Accumulated promoter methylation as a potential biomarker for esophageal cancer

    PubMed Central

    Shi, Peiyi; Wang, Jianping; Wang, Jianming

    2017-01-01

    We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965–1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928–1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC. PMID:27893424

  4. Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers.

    PubMed

    Yokoyama, Akira; Watanabe, Hiroshi; Fukuda, Haruhiko; Haneda, Tatsumasa; Kato, Hoichi; Yokoyama, Tetsuji; Muramatsu, Taro; Igaki, Hiroyasu; Tachimori, Yuji

    2002-09-01

    Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme for the elimination of acetaldehyde, an established animal carcinogen generated by alcohol metabolism. In the presence of ALDH2*2, a mutant allele that is prevalent in East Asians, this enzyme is inactive, leading to excessive accumulation of acetaldehyde. Only among Japanese alcoholic patients has the positive association between this inactive form of ALDH2 and multiple-field cancerization in the upper aerodigestive tract been demonstrated. Whether this finding could be extended to multiple-cancer patients in general is of great interest, because the prevalence of esophageal cancer with other organ cancers has increased dramatically during recent decades in Japan. This study compared the ALDH2 genotypes of groups of male Japanese drinkers who had either esophageal squamous cell carcinomas (SCCs) with (n = 26) or without (n = 48) multiplicity or oropharyngolaryngeal SCCs with (n = 17) or without (n = 29) multiplicity. After adjustments for age and drinking and smoking habits, logistic regression analysis showed significantly increased risk for each multiplicity associated with either esophageal or oropharyngolaryngeal SCCs in the presence of the ALDH2*2 allele (odds ratio, 5.26; 95% confidence interval, 1.08-51.06 and odds ratio, 7.36; 95% confidence interval, 1.29-80.70, respectively). This study is the first to strongly link inactive ALDH2 with the multiple cancer susceptibility of male Japanese drinkers with either esophageal or oropharyngolaryngeal cancers. A simple questionnaire about both current and past facial flushing after drinking a glass of beer was highly sensitive (95.6%) in detecting inactive ALDH2 in these patients and may be useful for identifying high-risk patients.

  5. Malignant progression in O6-methylguanine-DNA methyltransferase-deficient esophageal cancer cells is associated with Ezrin protein.

    PubMed

    Su, Yaoyao; Liu, Ran; Sheng, JingYi; Liu, Hui; Wang, Yi; Pan, Enchun; Guo, Wei; Pu, Yuepu; Zhang, Juan; Liang, Geyu; Tang, Derong; Yin, Lihong

    2012-05-01

    The abnormal function of O(6)-methylguanine-DNA methyltransferase (MGMT) is reported to be associated with the occurrence of various tumors and malignant tumor progression. However, little evidence is available to describe its role in esophageal carcinogenesis. To address this issue, we constructed a stable MGMT-silenced esophageal cancer cell line by RNA interference, and exposed the cells to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) to investigate the role that MGMT plays in toxicity. During this time, we also observed the malignant behavior of cells in vitro and in vivo. In addition, two-dimensional electrophoresis and mass spectrometry were used to detect and confirm the proteins that were differentially expressed in the MGMT-deficient and MGMT-proficient cells, which might be responsible for the malignant alteration of cells. Results showed that the IC(50) of MGMT-deficient and MGMT-proficient cells exposed to MNNG was 30 μM and 65 μM, respectively, and MGMT-deficient cells had more aggressive motility and invasive abilities compared with MGMT-proficient cells. Nineteen differentially expressed proteins were detected between the MGMT-deficient and MGMT-proficient cells, 14 of which were identified, including the membrane-cytoskeleton linker protein, Ezrin, which was confirmed by both mass spectrometry and western blot analysis. The correlation between MGMT, Ezrin expression, and the malignant behavior of one normal epithelial esophageal cell line and seven esophageal cancer lines is discussed. In conclusion, loss of MGMT expression leads EC109 esophageal cancer cells to have increased malignant behavior, which may correlate with its high Ezrin protein expression.

  6. Predictors of Acute Esophagitis in Lung Cancer Patients Treated With Concurrent Three-Dimensional Conformal Radiotherapy and Chemotherapy

    SciTech Connect

    Rodriguez, Nuria Algara, Manuel; Foro, Palmira; Lacruz, Marti; Reig, Anna; Membrive, Ismael; Lozano, Joan; Lopez, Jose Luis; Quera, Jaime; Fernandez-Velilla, Enric; Sanz, Xavier

    2009-03-01

    Purpose: To evaluate the risk factors for acute esophagitis (AET) in lung cancer patients treated with concurrent 3D-CRT and chemotherapy. Methods and Materials: Data from 100 patients treated with concurrent chemoradiotherapy with a mean dose of 62.05 {+-} 4.64 Gy were prospectively evaluated. Esophageal toxicity was graded according to criteria of the Radiation Therapy Oncology Group. The following dosimetric parameters were analyzed: length and volume of esophagus in treatment field, percentage of esophagus volume treated to {>=}10, {>=}20, {>=}30, {>=}35, {>=}40, {>=}45, {>=}50, {>=}55, and {>=}60 Gy, and the maximum (D{sub max}) and mean doses (D{sub mean}) delivered to the esophagus. Also, we developed an esophagitis index (EI) to account the esophagitis grades over treatment time. Results: A total of 59 patients developed AET (Grade 1, 26 patients; Grade 2, 29 patients; and Grade 3, 4 patients). V50 was associated with AET duration (p = 0.017), AET Grade 1 duration (p = 0.016), maximum analgesia (p = 0.019), esophagitis index score (p = 0.024), and AET Grade {>=}1 (p = 0.058). If V50 is <30% there is a 47.3% risk of AET Grade {>=}1, which increases to 73.3% if V50 is {>=}30% (p = 0.008). The predictive abilities of models (sensitivity and specificity) were calculated by receiver operating characteristic curves. Conclusions: According to the receiver operating characteristic curve analysis, the 30% of esophageal volume receiving {>=}50 Gy was the most statistically significant factor associated with AET Grade {>=}1 and maximum analgesia (A{sub max}). There was an association with AET Grade {>=}2 but it did not achieve statistical significance (p = 0.076)

  7. Aortic Pseudoaneurysm Formation Following Concurrent Chemoradiotherapy And Metallic Stent Insertion in a Patient With Esophageal Cancer

    PubMed Central

    Hou, Pei-Yu; Teng, Chung-Jen; Chung, Chen-Shuan; Liu, Chao-Yu; Huang, Chun-Chieh; Chang, Miu-Hsiang; Shueng, Pei-Wei; Hsieh, Chen-Hsi

    2015-01-01

    Abstract Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition. A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m2) and 5-Fluorouracil (500 mg/m2) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 103 /μL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection. Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation. PMID:25997064

  8. Feeding Challenges in Patients with Esophageal and Gastroesophageal Cancers

    PubMed Central

    Reim, Daniel; Friess, Helmut

    2016-01-01

    Background Patients undergoing treatment for esophagogastric or esophageal cancer are exposed to a considerably high risk of malnutrition due to early obstruction of the gastrointestinal passage. Presently most of the patients undergo modern multimodal therapies which require chemoradiation or chemotherapy ahead of surgery. Therefore reconstruction of the obstructed gastrointestinal passage is considerably delayed. Surgery as the only curative option after neoadjuvant treatment is the mainstay of therapy in this setting. However, many patients are at risk for the development of postoperative complications associated with the complexity of the surgical procedure. Therefore enteral feeding as a prerequisite to avoid malnutrition represents a special therapeutic challenge. Summary This review describes the recent literature on the incidence and influence of perioperative malnutrition on oncologic outcome, measures to determine patients at risk, possible strategies to reduce or avoid malnutrition by supportive enteral/parenteral nutrition, implementation of the enhanced recovery after surgery programs and feeding routes, but also surgical and adjuvant procedures in the curative and palliative setting for patients undergoing treatment for gastroesophageal cancers Key Messages Appropriate identification of patients at risk is crucial to avoid malnutrition. Early nutritional interventions during multimodal/neoadjuvant treatment may be beneficial for weight loss reduction although the evidence is not conclusive. Pouch reconstructions during surgery should be applied in order to increase quality of life and eating capacity. Reduction of postoperative complications could provide potential benefits. In palliative patients, insertion of self-expanding metal stents can reduce dysphagia and improve quality of life, but does not prolong overall survival. Further evidence is required to determine the value of the procedures and measures described in this review Practical

  9. [Magnesium premedication prevents Cisplatin-induced nephrotoxicity in patients with esophageal and hypopharyngeal cancer].

    PubMed

    Hirai, Shiho; Kaida, Sachiko; Ito, Tadaaki; Hasebe, Shinobu; Ueno, Masaki; Udagawa, Harushi; Hayashi, Masahiro

    2013-06-01

    Hypomagnesemia is one of the well-known side effects in patients receiving cisplatin-containing chemotherapy. However, the relevance between hypomagnesemia and cisplatin-induced nephrotoxicity remain to be completely elucidated. Although patients with esophageal and hypopharyngeal cancer are susceptible to dehydration, there is no evidence yet that magnesium supplementation for these patients will prevent nephrotoxicity during cisplatin-containing chemotherapy. The aim of this study was to examine the effect of magnesium supplementation on the prevention of cisplatin-induced nephrotoxicity for patients with esophageal and hypopharyngeal cancer. Twenty-three patients with esophageal or hypopharyngeal cancer were studied over 2 weeks. Ten of them received magnesium supplementation and 13 did not. Magnesium sulphate(20 mEq) was administered before 5-fluorouracil(800mg/m2/24 h/day 1-5)and cisplatin(80mg/m2/day 1)(FP)treatment. The maximum serum creatinine concentration of magnesium-supplemented group demonstrated a significantly lower concentration compared to the non-magnesium-supplemented group(p=0. 018). As a result, magnesium supplementation successfully reduced the incidence rate of nephrotoxicity(p=0. 038). These results showed that magnesium supplementation before FP treatment may be quite beneficial for preventing nephrotoxicity in patients with esophageal and hypopharyngeal cancer, and it is therefore recommended that magnesium be routinely supplemented during FP treatment for esophageal or hypopharyngeal cancer.

  10. [Sensitivity of esophageal cancer to anticancer agents and supplementary chemotherapy combined with surgical treatment].

    PubMed

    Masaki, Y; Ishigami, K; Oka, M; Matsumoto, N; Honma, K; Uchiyama, T

    1986-04-01

    The authors examined the sensitivities of esophageal cancer to Bleomycin (BLM), Peplomycin (PEP), Cisplatin (CDDP) and 5-FU by the INAS method using 3H-thymidine or 14C-formate as labeled precursors, and determined the concentrations of anticancer agents in cancer lesions by the Band Culture method. On the other hand, the authors investigated the superiority or inferiority of various methods of BLM administration by observing the prevention effect of BLM on the development of experimental esophageal cancer in rats. Forty-three cases out of 76, 57%, showed a sensitivity to BLM, 60% to PEP, 38% to CDDP and 56% to 5-FU. As to the types of roentgenological findings, the superficial and tumorous types showed a high sensitivity rate. As to the types of macroscopical findings, the protruded and superficial types showed a high sensitivity rate. As to the types of histological findings, well differentiated squamous cell carcinoma showed a high sensitivity rate. Sensitivity was higher in metastatic lymph nodes than in main cancer lesions. Tumor tissues which had undergone previous hyperthermic management (at 42 degrees C) showed a higher sensitivity than those which had not. PEP at a half dose brought about the same grade of anticancer effect as BLM. The sensitivities of esophageal cancer to various anticancer agents showed individual differences among clinical cases. Therefore, combination chemotherapy for esophageal cancer was thought to be an effective administration method. The divided administration of small doses of BLM was thought to be more superior than the one-shot administration of a large dose for esophageal cancer. The results of the INAS sensitivity test were perfectly coincident with the effects of chemotherapy in clinical cases of esophageal cancer.

  11. Association of tumor necrosis factor-α polymorphism with chemotherapy-induced oral mucositis in patients with esophageal cancer

    PubMed Central

    Sakamoto, Kazuhiko; Takeda, Shigeru; Kanekiyo, Shinsuke; Nishiyama, Mitsuo; Kitahara, Masahiro; Ueno, Tomio; Yamamoto, Shigeru; Yoshino, Shigefumi; Hazama, Shoichi; Okayama, Naoko; Nagano, Hiroaki

    2017-01-01

    The purpose of this study was to evaluate the association between tumor necrosis factor (TNF)-α polymorphisms and oral mucositis (OM) from 5-fluorouracil (5-FU) plus cisplatin (CDDP) chemotherapy for esophageal cancer. The rs1799964 polymorphism of TNF-α was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction. The experimental group comprised 64 patients who received chemotherapy for esophageal cancer between 1997 and 2004; a total of 106 patients between 2005 and 2013 were investigated as the validation group. Univariate analysis of the experimental group revealed that the TT genotype of TNF-α rs1799964 was significantly higher in patients with grade 1–4 OM compared with the TC/CC genotypes [univariate odds ratio (OR)=4.0; P=0.029]. Similarly, univariate analysis of the validation group revealed that the percentage of the TT genotype was significantly higher in patients with grade 1–4 OM compared with the TC/CC genotypes (OR=2.8; P=0.043). This difference in risk was replicated in the validation cohort. Thus, the TT genotype of TNF-α rs1799964 may be a predictor of chemotherapy-induced OM in patients with esophageal cancer. PMID:28123745

  12. IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells

    SciTech Connect

    Yoshino, Kei; Motoyama, Satoru; Koyota, Souichi; Shibuya, Kaori; Usami, Shuetsu; Maruyama, Kiyotomi; Saito, Hajime; Minamiya, Yoshihiro; Sugiyama, Toshihiro; Ogawa, Jun-ichi

    2011-01-28

    Research highlights: {yields} TE-12 cell had greater radiosensitivity and higher levels of caspase 3/7 activity for radiotherapy than TE-5 or TE-9 cells. {yields} The expression of IGFBP3 and BAG1 was five or more times higher in TE-12 cell in DNA microarrays analysis. {yields} Knocking down IGFBP3 and/or BAG1 expression using targeted siRNA diminished their susceptibility to radiation. -- Abstract: Identification of reliable markers of radiosensitivity and the key molecules that enhance the susceptibility of esophageal cancer cells to anticancer treatments would be highly desirable. To identify molecules that confer radiosensitivity to esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE-5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly greater susceptibility to radiotherapy at 5 and 10 Gy than either TE-5 or TE-9 cells. Consistent with that finding, 24 h after irradiation (5 Gy), TE-12 cloneA1 cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12 cloneA1 cells, we found that the mRNA and protein expression of insulin-like growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1) was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely, knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using small interfering RNA (siRNA) significantly reduced radiosensitivity. These data suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.

  13. Heat treatment of human esophageal tissues: Effect on esophageal cancer detection using oxygenated hemoglobin diffuse reflectance ratio

    NASA Astrophysics Data System (ADS)

    Zhao, Q. L.; Guo, Z. Y.; Si, J. L.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Guo, X.; Zhong, H. Q.; Li, L. Q.; Li, X. Y.

    2011-03-01

    The main objective of the present work is to study the influence of heat treatment on the esophageal cancer detection using the diffuse reflectance (DR) spectral intensity ratio R540/R575 of oxygenated hemoglobin (HbO2) absorption bands to distinguish the epithelial tissues of normal human esophagus and moderately differentiated esophageal squamous cell carcinoma (ESCC) at different heat treatment temperature of 20, 37, 42, 50, and 60°C, respectively. The DR spectra for the epithelial tissues of the normal esophagus and ESCC in vitro at different heat-treatment temperature in the wavelength range 400-650 nm were measured with a commercial optical fiber spectrometer. The results indicate that the average DR spectral intensity overall enhancement with concomitant increase of heat-treatment temperature for the epithelial tissues of normal esophagus and ESCC, but the average DR spectral intensity for the normal esophageal epithelial tissues is relatively higher than that for ESCC epithelial tissues at the same heat-treatment temperature. The mean R540/R575 ratios of ESCC epithelial tissues were always lower than that of normal esophageal epithelial tissues at the same temperature, and the mean R540/R575 ratios of the epithelial tissues of the normal esophagus and ESCC were decreasing with the increase of different heat-treatment temperatures. The differences in the mean R540/R575 ratios between the epithelial tissues of normal esophagus and ESCC were 13.33, 13.59, 11.76, and 11.11% at different heat-treatment temperature of 20, 37, 42, and 50°C, respectively. These results also indicate that the DR intensity ratio R540/R575 of the hemoglobin bands is a useful tool for discrimination between the epithelial tissues of normal esophagus and ESCC in the temperature range from room temperature to 50°C, but it was non-effective at 60°C or over 60°C.

  14. Salivary MicroRNAs as Promising Biomarkers for Detection of Esophageal Cancer

    PubMed Central

    Zhang, Xuchao; Li, Dongfeng; Huang, Jian; Yang, Cuiqin; Zhang, Pingyong; Qin, Yuxuan; Duan, Yifan; Gong, Bo; Li, Zijun

    2013-01-01

    Background and Purpose Tissue microRNAs (miRNAs) can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the discriminatory power of salivary miRNAs (including whole saliva and saliva supernatant) for detection of esophageal cancer. Materials and Methods By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls. Results Six miRNAs (miR-10b*, miR-144, miR-21, miR-451, miR-486-5p, and miR-634) were identified as targets by Agilent microarray. After validation by RT-qPCR, miR-10b*, miR-144, and miR-451 in whole saliva and miR-10b*, miR-144, miR-21, and miR-451 in saliva supernatant were significantly upregulated in patients, with sensitivities of 89.7, 92.3, 84.6, 79.5, 43.6, 89.7, and 51.3% and specificities of 57.9, 47.4, 57.9%, 57.9, 89.5, 47.4, and 84.2%, respectively. Conclusions We found distinctive miRNAs for esophageal cancer in both whole saliva and saliva supernatant. These miRNAs possess discriminatory power for detection of esophageal cancer. Because saliva collection is noninvasive and convenient, salivary miRNAs show great promise as biomarkers for detection of esophageal cancer in areas at high risk. PMID:23560033

  15. Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients

    PubMed Central

    Araujo, James L.; Altorki, Nasser K.; Sonett, Joshua R.; Rodriguez, Adriana; Sungur-Stasik, Kivilcim; Spinelli, Cathy F.; Neugut, Alfred I.; Abrams, Julian A.

    2016-01-01

    Background: Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer. Methods: We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases. Results: We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96). Conclusions: In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications. PMID:27803735

  16. Trichosporon inkin Esophagitis: An Uncommon Disease in a Patient with Pulmonary Cancer.

    PubMed

    Macêdo, Danielle Patrícia Cerqueira; de Oliveira, Neiva Tinti; da Silva, Vanessa Karina Alves; de Almeida Farias, Aline Mary; de Lima Neto, Reginaldo Gonçalves; Wilheim, Ana Botler; de Oliveira, Patrícia Cariolano; Pedi, Nadyr; de Andrade, Suanni Lemos; Neves, Rejane Pereira

    2011-04-01

    Trichosporon species are usually opportunistic pathogens. Here, we present a case of esophagitis caused by T. inkin in a 54-year-old woman with pulmonary cancer and severe neutropenia in whom the susceptibility profile of the isolate against azoles and polyenes was verified. The patient was diagnosed with esophagitis grade I of Wilcox, presenting scattered whitish plaques and exudates in upper two-thirds of the esophageal mucosa. Antifungal therapy involving oral fluconazole (150 mg/day for 14 days) was ineffective. In vitro, the isolate showed no resistance to this azole and sensitivity to amphotericin B. Since T. inkin is of growing importance as an agent of invasive infections in immunocompromised patients, we stress that the diagnosis of esophagitis by this species should be followed by an assessment of the therapeutic sensitivity of the strain involved.

  17. Paclitaxel or 5-fluorouracil/esophageal stent combinations as a novel approach for the treatment of esophageal cancer.

    PubMed

    Liu, Jieying; Wang, Zhongmin; Wu, Keqin; Li, Jing; Chen, Weiluan; Shen, Yuanyuan; Guo, Shengrong

    2015-01-01

    Currently, esophageal cancer is rarely curable, and herein, a paclitaxel or 5-fluorouracil/esophageal stent combination (PTX or 5-FU/stent) was used to provide a new approach to treat this cancer. The PTX or 5-FU/stent was prepared by covering a nitinol stent with a bilayered polymer film that consisted of a layer of 50% PTX or 5-FU and a layer of drug-free backing. These treatment modalities were evaluated in vivo after implantation into the porcine esophagus. The percentages of the drugs that permeated from the backing layer over a period of 95 days were very small (0.61% for 5-FU), and an overwhelming majority of the PTX and the 5-FU was released from the other side of the film. During the follow-up period (120 days), the drug/stent was always maintained in the porcine esophagus, and did not show any obvious systemic or local toxicities. In contrast, this treatment had an effect on the inhibition of tissue proliferation and ulceration. In addition, the drug concentrations were highest in the esophagus compared with in the heart, liver, spleen, lung, kidney and blood (81500.0 ± 9475.2 ng/g vs. 3.9 ± 0.3 ng/mL of PTX in the plasma at 13 days). The PTX/stent and the 5-FU/stent have a dual function as both a stent and a local drug delivery device, which provides a potential treatment modality with high efficacy and non systematic toxicity for esophageal cancer.

  18. Salvage endoscopic resection as a treatment for locoregional failure or recurrence following chemoradiotherapy or radiotherapy for esophageal cancer

    PubMed Central

    NAKAMURA, RIEKO; OMORI, TAI; TAKEUCHI, HIROYA; KAWAKUBO, HIROFUMI; TAKAHASHI, TSUNEHIRO; WADA, NORIHITO; SAIKAWA, YOSHIRO; KITAGAWA, YUKO

    2016-01-01

    Radiotherapy (RT) or chemoradiotherapy (CRT) is a potentially curative, non-surgical treatment option for esophageal cancer, although the rate of local failure within the esophagus remains relatively high. Salvage esophagectomy is not regarded as a common treatment for esophageal cancer, since it is a high-risk surgery with a relatively high surgical mortality rate. Salvage endoscopic resection (ER) for local failure is used for treatment when esophageal cancer is localized and superficial. To evaluate to usefulness of salvage ER, the present study reviewed the clinicopathological records and follow-up data of 37 patients that underwent salvage ER for esophageal cancer, following initial treatment with RT or CRT. Salvage ER was conducted on a total of 78 lesions observed in the 37 patients. Since a thick epithelium and lack of normal vessels on the surface of the mucosa are characteristics of esophageal mucosa following RT or CRT, almost all the lesions were detected using iodine dyeing, and not by narrow band imaging. The growth rate of the detected lesions was relatively high, and early treatment was required. No particular complications occurred during the endoscopic treatment. A total of 11 patients survived for >5 years subsequent to initial endoscopic treatment. Only 4 patients succumbed to esophageal cancer. In conclusion, the present study demonstrated that salvage ER following CRT or RT for esophageal cancer is a minimally invasive, safe, adaptive and curative method for superficial lesions without distant metastases in patients with esophageal cancer with local failure following CRT or RT. PMID:27284365

  19. Postoperative change of the psoas muscle area as a predictor of survival in surgically treated esophageal cancer patients

    PubMed Central

    Park, Seong Yong; Lee, Su Jin; Haam, Seokjin; Jung, Joonho

    2017-01-01

    Background Although a decrease in the psoas muscle area (PMA) has been reported as a risk factor for survival after esophagectomy in esophageal cancer, no previous studies have focused on the change in the PMA after surgery. We investigated the prognostic role of PMA changes in patients with surgically treated esophageal cancer. Methods Fifty-eight patients with esophageal cancer who underwent surgical resection and complete lymph node dissection were reviewed retrospectively. The PMA was measured at the level of the L3 vertebrae on preoperative and one-year postoperative follow-up computed tomography images. The percentage change of the PMA was calculated as follows: delta (%) = (postoperative PMA − preoperative PMA) / (preoperative PMA × 100). Results The study patients included 54 (93.1%) males and 4 females (mean age, 60.59±9.16 years), of whom 17 (29.3%) were pathological Stage I, 18 (31.0%) were Stage II, and 23 (39.7%) were Stage III. The mean change of the PMA was −10.17% and the postoperative PMA was decreased significantly compared with the preoperative PMA (P<0.001). The PMA was increased in 13 (22.4%) patients, whereas it was decreased in 45 (77.6%). Multivariate analysis revealed that the change of the PMA (hazard ratio, HR =0.688; P=0.001) and the pathologic stage (Stage III vs. Stage I, HR =3.388; P=0.016) were risk factors for overall survival (OS). The 3-year OS in patients with a PMA decrease of more than 10%, and those with a PMA decrease of less than 10% or an increase, were 18.9% and 59.5%, respectively (P=0.049). Conclusions The decrease in the PMA had a negative prognostic effect on OS in patients with surgically treated esophageal cancer. PMID:28275484

  20. Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous cell carcinoma susceptibility: A meta-analysis of case-control studies

    PubMed Central

    Shujuan, Yang; Jianxing, Zhang; Xin-yue, Chen

    2013-01-01

    Objectives: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methodology: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: Nineteen studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T. PMID:24353609

  1. Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

    ClinicalTrials.gov

    2015-12-18

    Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

  2. SU-E-J-103: Setup Errors Analysis by Cone-Beam CT (CBCT)-Based Imaged-Guided Intensity Modulated Radiotherapy for Esophageal Cancer

    SciTech Connect

    Yang, H; Wang, W; Hu, W; Chen, X; Wang, X; Yu, C

    2014-06-01

    Purpose: To quantify setup errors by pretreatment kilovolt cone-beam computed tomography(KV-CBCT) scans for middle or distal esophageal carcinoma patients. Methods: Fifty-two consecutive middle or distal esophageal carcinoma patients who underwent IMRT were included this study. A planning CT scan using a big-bore CT simulator was performed in the treatment position and was used as the reference scan for image registration with CBCT. CBCT scans(On-Board Imaging v1. 5 system, Varian Medical Systems) were acquired daily during the first treatment week. A total of 260 CBCT scans was assessed with a registration clip box defined around the PTV-thorax in the reference scan based on(nine CBCTs per patient) bony anatomy using Offline Review software v10.0(Varian Medical Systems). The anterior-posterior(AP), left-right(LR), superiorinferior( SI) corrections were recorded. The systematic and random errors were calculated. The CTV-to-PTV margins in each CBCT frequency was based on the Van Herk formula (2.5Σ+0.7σ). Results: The SD of systematic error (Σ) was 2.0mm, 2.3mm, 3.8mm in the AP, LR and SI directions, respectively. The average random error (σ) was 1.6mm, 2.4mm, 4.1mm in the AP, LR and SI directions, respectively. The CTV-to-PTV safety margin was 6.1mm, 7.5mm, 12.3mm in the AP, LR and SI directions based on van Herk formula. Conclusion: Our data recommend the use of 6 mm, 8mm, and 12 mm for esophageal carcinoma patient setup in AP, LR, SI directions, respectively.

  3. Gene-environment interactions on the risk of esophageal cancer among Asian populations with the G48A polymorphism in the alcohol dehydrogenase-2 gene: a meta-analysis.

    PubMed

    Zhang, Long; Jiang, Yingjiu; Wu, Qingcheng; Li, Qiang; Chen, Dan; Xu, Ling; Zhang, Cheng; Zhang, Min; Ye, Ling

    2014-05-01

    The aim of this study is to investigate the gene-environment interactions between the G48A polymorphism in the alcohol dehydrogenase-2 (ADH2) gene and environmental factors in determining the risk of esophageal cancer (EC). A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before November 1, 2013. We performed a meta-analysis of 18 case-control studies with a total of 8,906 EC patients and 13,712 controls. The overall analysis suggested that individuals with the GG genotype were associated with a 2.77-fold increased risk of EC, compared with carriers of the GA and AA genotypes. In a stratified analysis by ethnic group, Japanese, Mainland Chinese, and Taiwan Chinese with the GG genotype had a significantly higher risk of EC, compared with Thai and Iranian populations, indicating ethnic variance in EC susceptibility. An analysis of combined effect indicated that GG genotype of ADH2 G48A was associated with the highest risk of EC in heavy drinkers and smokers. A striking difference was found to exist between males and females, showing gender variance for the association between ADH2 G48A and EC risk. This meta-analysis shows that the GG genotype of ADH2 G48A may be associated with an increased risk of EC in Asian populations. In addition, significant gene-environment interactions were found. Heavy drinkers, smokers, and males with the GG genotype may have a higher EC risk. Thus, our results shed new light on the complex gene-environment interactions that exist between environmental factors and ADH2 G48A polymorphism in EC risk.

  4. Pneumo-CT assessing response to neoadjuvant therapy in esophageal cancer: Imaging-pathological correlation.

    PubMed

    Ulla, Marina; Gentile, Ernestina; Yeyati, Ezequiel Levy; Diez, Maria L; Cavadas, Demetrio; Garcia-Monaco, Ricardo D; Ros, Pablo R

    2013-12-15

    Pneumo-computed tomography (PnCT) is a technique primarily developed and used to study stenotic lesions of the esophagus, gastroesophageal junction and stomach for pre-surgical planning. It helps to define both upper and lower borders of neoplasms located in the aforementioned areas. It achieves maximum lumen distension with CO2 highlighting thickened areas of the esophageal wall, thus allowing an accurate quantification of their extents. Although there are other alternatives for distension (oral contrast agents, water and effervescent granules), they may be suboptimal. Patients with locally advanced esophageal cancer have a dismal prognosis despite surgical resection. Therefore, neoadjuvant treatment strategies using radiation therapy and chemotherapy were developed to improve survival. Neoadjuvant therapy improves esophageal tumor prognosis in a substantial proportion of patients, and the use of imaging techniques is mandatory to detect their response. PnCT combined with virtual endoscopy and multiplanar reconstruction enhances morphologic details in esophageal cancer, and thus would allow an improved assessment of response to neoadjuvant treatment. Therefore, more information could be provided to assess the efficacy of pre-surgical treatment. We describe the potential use of PnCT to assess the response to neoadjuvant therapy in esophageal cancer with an imaging pathologic correlation.

  5. Pneumo-CT assessing response to neoadjuvant therapy in esophageal cancer: Imaging-pathological correlation

    PubMed Central

    Ulla, Marina; Gentile, Ernestina; Yeyati, Ezequiel Levy; Diez, Maria L; Cavadas, Demetrio; Garcia-Monaco, Ricardo D; Ros, Pablo R

    2013-01-01

    Pneumo-computed tomography (PnCT) is a technique primarily developed and used to study stenotic lesions of the esophagus, gastroesophageal junction and stomach for pre-surgical planning. It helps to define both upper and lower borders of neoplasms located in the aforementioned areas. It achieves maximum lumen distension with CO2 highlighting thickened areas of the esophageal wall, thus allowing an accurate quantification of their extents. Although there are other alternatives for distension (oral contrast agents, water and effervescent granules), they may be suboptimal. Patients with locally advanced esophageal cancer have a dismal prognosis despite surgical resection. Therefore, neoadjuvant treatment strategies using radiation therapy and chemotherapy were developed to improve survival. Neoadjuvant therapy improves esophageal tumor prognosis in a substantial proportion of patients, and the use of imaging techniques is mandatory to detect their response. PnCT combined with virtual endoscopy and multiplanar reconstruction enhances morphologic details in esophageal cancer, and thus would allow an improved assessment of response to neoadjuvant treatment. Therefore, more information could be provided to assess the efficacy of pre-surgical treatment. We describe the potential use of PnCT to assess the response to neoadjuvant therapy in esophageal cancer with an imaging pathologic correlation. PMID:24363830

  6. Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D.; Dawsey, Sanford M.; Pierce, Mark C.; Kim, Michelle Kang; Schwarz, Richard A.; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S.; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2014-01-01

    Background & Aims High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can readily be interpreted by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods We performed image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and 1 in the United States from May 2010 to October 2012. Biopsies were collected from imaged sites (n=375); a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. PMID:25066838

  7. Prognosis of Esophageal Cancer Patients With Pathologic Complete Response After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    Park, Jae Won; Kim, Jong Hoon; Choi, Eun Kyung; Lee, Sang-wook; Yoon, Sang Min; Song, Si Yeol; Lee, Yu Sun; Kim, Sung Bae; Park, Seung il; Ahn, Seung Do

    2011-11-01

    Purpose: To define failure patterns and predictive factors in esophageal cancer patients who had a pathologic complete response (pCR) after preoperative concurrent chemoradiotherapy (PCRT). Methods and Materials: We performed a retrospective analysis of 61 esophageal cancer patients who were enrolled in prospective studies and showed pCR after PCRT. All of the patients had squamous cell carcinoma. Of the patients, 40 were treated with hyperfractionated radiotherapy (4,560 cGy in 28 fractions) with 5-fluorouracil (5-FU) and cisplatin (FP), and 21 patients received conventional fractionation radiotherapy with capecitabine and cisplatin (XP). Results: The median follow-up time was 45.2 months (range, 6.5-162.3 months). The 5-year overall survival (OS) and disease-free survival rates (DFS) were 60.2% and 80.4%, respectively. In univariate analysis, age and lymph node (LN) metastasis were poor prognostic factors for OS, and pretreatment weight loss (>2 kg) was a poor prognostic factor for DFS. In multivariate analysis, lymph node metastasis and pretreatment weight loss were independent prognostic factors for OS and DFS. Nine patients (15%) had disease recurrence. Of the nine patients, 5 patients had locoregional failure, 1 patients had distant metastasis, and 3 patients had distant and locoregional failure. In-field failure occurred in 5 patients; out-of-field failure occurred in 1 patient; both in-field and out-of-field failure occurred in 2 patients; and both marginal and out-of-field failure occurred in 1 patient. Conclusions: Even in pCR patients, the most common failure site was within the radiation field, which suggests that more efficient local treatment is needed. Tumor recurrence was more common in patients with older age and with pretreatment weight loss.

  8. High resolution microendoscopy for early detection of esophageal cancer in low-resource settings (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Richards-Kortum, Rebecca

    2016-03-01

    Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol's chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.

  9. Relationships between esophageal cancer and spatial environment factors by using Geographic Information System.

    PubMed

    Wu, Ku-Sheng; Huo, Xia; Zhu, Guang-Hui

    2008-04-15

    To explore the relationships between esophageal cancer (EC) and climatic, geographic factors in China by using Geographic Information System, database of EC mortality of 237 sampling areas surveyed in 1990-1992 was established in Excel and linked with the digital polygon maps of study areas. Geographic and climate data of sampling areas were extracted from the raster dataset and finished in Arc/Info 9.0 and ENVI4.2 software by using spatial analysis. Spearman correlation analysis and multiple regression analysis after principal component analysis (PCA) were performed to analyze the relationship between EC and these factors. The counties that have the highest EC morality show significant aggregation. Spearman correlation analysis shows weak negative correlation between precipitation, water-heat index (WHI), highest/lowest temperature and EC mortality, and weak positive correlation between drought index (DI), wind speed, population density and EC mortality. Multiple linear regression analysis indicated that the variables associated with EC mortality were precipitation, temperature, wind speed, elevation, DI, WHI and normalized difference vegetation index (NDVI) of July. Our study suggested that the high-risk areas of EC in China are mostly drought and low altitude areas relatively. There were relatively lower NDVI in summer and higher wind speed in these areas. GIS can be applied to cancer epidemiology study and will exert active effect, which should be further explored.

  10. Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation.

    PubMed

    Chang, Xiaobin; Zhao, Jimin; Tian, Fang; Jiang, Yanan; Lu, Jing; Ma, Junfen; Zhang, Xiaoyan; Jin, Guoguo; Huang, Youtian; Dong, Zigang; Liu, Kangdong; Dong, Ziming

    2016-09-01

    Aberrant AKT and extracellular signal-regulated kinase (ERK) activation is often observed in various human cancers. Both AKT and ERK are important in the phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase kinase/ERK signaling pathways, which play vital roles in cell proliferation, differentiation and survival. Compounds that are able to block these pathways have therefore a promising use in cancer treatment and prevention. The present study revealed that AKT and ERK are activated in esophageal cancer TE1 cells. Aloe-emodin, an anthraquinone present in aloe latex, can suppress TE1 cell proliferation and anchor-independent cell growth. Aloe-emodin can also reduce the number of TE1 cells in S phase. Protein analysis indicated that aloe-emodin inhibits the phosphorylation of AKT and ERK in a dose-dependent manner. Overall, the present data indicate that aloe-emodin can suppress TE1 cell growth by inhibiting AKT and ERK phosphorylation, and suggest its clinical use for cancer therapy.

  11. Esophagectomy as a Treatment Consideration for Early-Stage Esophageal Cancer and High-Grade Dysplasia.

    PubMed

    McLaren, Patrick J; Dolan, James P

    2016-10-01

    In recent years, a number of endoluminal procedures such as endoscopic resection and thermal ablation have emerged as less invasive treatment options for early esophageal cancer. These therapies have demonstrated excellent oncologic outcomes for dysplasia as well as intramucosal cancers. However, few studies have directly compared long-term outcomes of endoscopic therapy versus traditional esophagectomy. Current esophagectomy techniques now deliver consistently good outcomes in the hands of experienced surgeons at high volume centers, and this option should be considered an important treatment consideration for early esophageal cancer. Under current recommendations, esophagectomy should be considered for tumors invading the submucosa, tumors with high-risk pathologic features, bulky tumors, multinodular tumors, tumors within a long segment of Barrett's esophagus, and tumors adjacent to a hiatal hernia. Likewise, individual patient factors and comorbidities must also be considered when determining the best treatment for a patient with early esophageal cancer. The risk of missing metastatic disease or recurrence that is associated with endoscopic treatment must be weighed against the surgical risks of esophagectomy. With these considerations in mind, the aim of this article is to review the current guidelines and literature that explore the role of esophagectomy for early esophageal malignancy in the era of endoscopic therapies.

  12. Leptomeningeal carcinomatosis in esophageal cancer: a case series and systematic review of the literature.

    PubMed

    Lukas, R V; Mata-Machado, N A; Nicholas, M K; Salgia, R; Antic, T; Villaflor, V M

    2015-01-01

    The aim of this study was to more clearly define the clinical course of leptomeningeal carcinomatosis due to esophageal cancer. A single institution retrospective case series was conducted. Additionally, a systematic review of the literature was performed. We present a large case series (n = 7) of leptomeningeal carcinomatosis due to esophageal cancer. Our case series and systematic review of the literature report similar findings. In our series, we report a predominance of male patients (86%) with adenocarcinoma histology (77%). Variable onset of leptomeningeal involvement of esophageal cancer in relation to the original diagnosis of the primary disease (5 months to 3 years and 11 weeks) was noted. Disease progresses quickly and overall survival is poor, measured in weeks (2.5-16 weeks) from the diagnosis of leptomeningeal involvement. Four of our patients initiated whole-brain radiation therapy with only two completing the course prior to clinical deterioration. Our patient with the longest survival (16 weeks) received intrathecal topotecan and oral temozolomide. Leptomeningeal carcinomatosis secondary to esophageal cancer has a poor prognosis. A clearly beneficial treatment modality is lacking.

  13. Molecular profiling to identify molecular mechanism in esophageal cancer with familial clustering.

    PubMed

    Chattopadhyay, Indranil; Phukan, Rupkumar; Singh, Avninder; Vasudevan, Madavan; Purkayastha, Joydeep; Hewitt, Stephen; Kataki, Amal; Mahanta, Jagadish; Kapur, Sujala; Saxena, Sunita

    2009-05-01

    To identify the genes and molecular functional pathways involved in esophageal cancer, we analyzed the gene expression profile of esophageal tumor tissue from patients having family history of esophageal cancer by cDNA microarray. Three hundred and fifty differentially expressed genes (26 up-regulated and 324 down-regulated) were identified. Genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-beta signaling (SMAD1) and calcium signaling pathways (VDAC1) were down-regulated and genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A) were up-regulated. Validation of differential expression of subset of genes by QRT-PCR and tissue microarray in familial and non-familial cases showed no significant difference in expression of these genes in two groups suggesting familial clustering occurs as result of sharing of common environmental factors. Gene expression profiling of clinical specimens from well characterized populations that have familial clustering of cancer identified molecular mechanism associated with progression of esophageal cancer.

  14. Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Woodward, Timothy A.; Wolfsen, Herbert C.

    2000-05-01

    In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.

  15. Influence of mate drinking, hot beverages and diet on esophageal cancer risk in South America.

    PubMed

    Castellsagué, X; Muñoz, N; De Stefani, E; Victora, C G; Castelletto, R; Rolón, P A

    2000-11-15

    To estimate the effects of consuming hot beverages, including mate (an infusion of the herb Ilex paraguayensis), tea, coffee and coffee with milk, and other food items on esophageal cancer risk, we analyzed data from 830 cases and 1,779 controls participating in a series of 5 hospital-based case-control studies of squamous-cell carcinoma of the esophagus conducted in high-risk areas of South America. After adjusting for the strong effects of tobacco and alcohol consumption, both heavy mate drinking (>1 l/day) and self-reported very hot mate drinking were significantly associated with esophageal cancer risk in men and women. The magnitude and strength of the association for mate amount and, to a lesser extent, mate temperature were higher for women than men. The joint effects of mate amount and mate temperature were more than multiplicative, following a statistically significant synergistic interaction (p = 0.02) which was particularly evident among heavy drinkers (>1.50 l/day) of very hot mate (odds ratio = 4.14, 95% confidence interval: 2.24-7.67) compared to light drinkers (<0.50 l/day) of cold/warm/hot mate. Consumption of other very hot beverages, such as tea and coffee with milk but not coffee alone, was also significantly associated with an increased risk, in the 2- to 4-fold range. Statistically significant protective associations were identified for high consumption of vegetables, fruits, cereals and tea. In contrast, frequent consumption of meat, animal fats and salt was associated with a moderately increased risk. This pooled analysis adds evidence for a carcinogenic effect of chronic thermal injury in the esophagus induced by the consumption of very hot drinks, including mate. Our study further confirms the protective effect of a dietary pattern characterized by daily consumption of fruits and vegetables and low consumption of meat and animal fats.

  16. The Hippo coactivator YAP1 mediates EGFR overexpression and confers chemo-resistance in esophageal cancer

    PubMed Central

    Song, Shumei; Honjo, Soichiro; Jin, Jiankang; Chang, Shih-Shin; Scott, Ailing W; Chen, Qiongrong; Kalhor, Neda; Correa, Arlene M.; Hofstetter, Wayne L.; Albarracin, Constance T.; Wu, Tsung-Teh; Johnson, Randy L.; Hung, Mien-Chie; Ajani, Jaffer A.

    2015-01-01

    Purpose Esophageal cancer (EC) is an aggressive malignancy and often resistant to therapy. Overexpression of EGFR has been associated with poor prognosis of EC patients. However, clinical trials using EGFR inhibitors have not provided benefit for EC patients. Failure of EGFR inhibition may be due to crosstalk with other oncogenic pathways. Experimental Design In this study, expression of YAP1 and EGFR were examined in EAC resistant tumor tissues vs sensitive tissues by immunohistochemistry. Western blot, immunofluorescence, real-time PCR, promoter analysis, site-directed mutagenesis and in vitro and in vivo functional assays were performed to elucidate the YAP1 mediate EGFR expression and transcription and the relationship with chemoresistance in esophageal cancer. Results We demonstrate that Hippo pathway coactivator YAP1 can induce EGFR expression and transcription in multiple cell systems. Both YAP1 and EGFR are overexpressed in resistant EC tissues compared to sensitive EC tissues. Further, we found that YAP1 increases EGFR expression at the level of transcription requiring an intact TEAD binding site in the EGFR promoter. Most importantly, exogenous induction of YAP1 induces resistance to 5-FU and docetaxcel, while knockdown of YAP sensitizes EC cells to these cytotoxics. Verteporfin, a YAP1 inhibitor, effectively inhibits both YAP1 and EGFR expression and sensitizes cells to cytotoxics. Conclusions Our data provide evidence that YAP1 up-regulation of EGFR plays an important role in conferring therapy resistance in EC cells. Targeting YAP1-EGFR axis may be more efficacious than targeting EGFR alone in EC. PMID:25739674

  17. Combined brachytherapy and external beam radiation: an effective approach for palliation in esophageal cancer

    PubMed Central

    Lewis, Shirley; Agarwal, Jai Prakash; Mishra, Shagun; Mehta, Shaesta; Patil, Prachi

    2015-01-01

    Purpose Palliation of dysphagia is a challenge in advanced esophageal cancer. The addition of external beam radiotherapy (EBRT) to intraluminal brachytherapy (ILBT) has shown significant improvement in dysphagia relief and symptom scores. The aim of the present study was to evaluate the efficacy of combined use of ILBT and EBRT. Material and methods The medical records of 148 patients with advanced/metastatic esophageal cancer were screened from January 2008 to April 2014, and 74 patients were found eligible for the analysis. All patients received two fractions of 8 Gy each of ILBT, followed by EBRT. Patients were assessed for the symptom scores of dysphagia, odynophagia, regurgitation, and chest pain and weight was recorded periodically. Results For a median follow-up of 6 months, the median OS was 9.5 months (95% CI: 7.5-10.5). The median dysphagia free survival was 6 months (95% CI: 4.8-7.1). The scores for dysphagia significantly improved after completion of 1st ILBT (p = 0.000), 2nd ILBT (p = 0.000), and at 3 months after EBRT compared to ILBT (p = 0.02). Overall 47% had improvement in dysphagia scores and 35% maintained the improvement of scores till last follow up. There was significant improvement in weight after completion of ILBT (p = 0.001) and at 3 months after completion of EBRT (p = 0.00). Twenty nine (39%) patients required nasogastric (NGT) insertions and 12 (16%) needed hospitalization for supportive care. 36.4% had complications in the form of stricture (27%), fistula (5.4%), and bleeding (4%). Conclusions Palliative radiotherapy is an effective alternative for palliation of dysphagia with improvement in symptom scores being evident and sustained. The results of this clinical audit were comparable with those from the trial setting. PMID:26816502

  18. MO-F-CAMPUS-I-05: Quantitative ADC Measurement of Esophageal Cancer Before and After Chemoradiation

    SciTech Connect

    Yang, L; Son, JB; Ma, J; Hazle, J; Carter, BW; Lin, S; Cheng, S

    2015-06-15

    Purpose: We investigated whether quantitative diffusion imaging can be used as an imaging biomarker for early prediction of treatment response of esophageal cancer. Methods: Eight patients with esophageal cancer underwent a baseline and an interim MRI studies during chemoradiation on a 3T whole body MRI scanner with an 8-channel torso phased array coil. Each MRI study contained two axial diffusion-weighted imaging (DWI) series with a conventional DWI sequence and a reduced field-of-view DWI sequence (FOCUS) of varying b-values. ADC maps with two b-values were computed from conventional DWI images using a mono-exponential model. For each of DWI sequences, separate ADCall was computed by fitting the signal intensity of images with all the b-values to a single exponential model. For the FOCUS sequence, a bi-exponential model was used to extract perfusion and diffusion coefficients (ADCperf and ADCdiff) and their contributions to the signal decay. A board-certified radiologist contoured the tumor region and mean ADC values and standard deviations of tumor and muscle ROIs were recorded from different ADC maps. Results: Our results showed that (1) the magnitude of ADCs from the same ROIs by the different analysis methods can be substantially different. (2) For a given method, the change between the baseline and interim muscle ADCs was relatively small (≤10%). In contrast, the change between the baseline and interim tumor ADCs was substantially larger, with the change in ADCdiff by FOCUS DWI showing the largest percentage change of 73.2%. (3) The range of the relative change of a specific parameter for different patients was also different. Conclusion: Presently, we do not have the final pathological confirmation of the treatment response for all the patients. However, for a few patients whose surgical specimen is available, the quantitative ADC changes have been found to be useful as a potential predictor for treatment response.

  19. Prognostic Indicators of Surgery for Esophageal Cancer: A 5 Year Experience

    PubMed Central

    Khan, Nadim; Bangash, Adil; Sadiq, Muzaffaruddin

    2010-01-01

    Background/Aim: To assess the prognostic indicators preoperatively presenting and influencing the mortality rate following esophagectomy for esophageal cancer. Materials and Methods: This study was a retrospective cohort study, conducted at the Department of Surgery, Lady Reading Hospital, Peshawar, from 1 January 2003 till 31 December 2008. Group 1 included patients who had undergone sub-total esophagectomy and were alive at completion of 12 months; whereas Group 2 included those patients who died by the completion of 12 months. Data were recollected from the Data Bank. A list of variables common to all patients from both groups was categorized and subsequently all data related to each individual patient were placed and analyzed on the version 13.0 of SPSSR for Windows. Results: Significant findings of a lower mean level of serum albumin from Group 2 were observed, whereas serum transferrin levels, also found lower in Group 2, were not statistically significant. Findings of serum pre-albumin, with a mean value of 16.12 mg/dl (P<0.05) and Geansler’s index for the evaluation of the presence of obstructive pulmonary disease prior to surgery showed a lower reading of mean ratio in Group 2. Anastamotic leak was not a common finding in the entire study. In most cases, the choice of conduit was the remodeled stomach. Nine patients from Group 2 were observed with evident leak on the fifth to seventh post-operative day following contrast swallow studies. This was statistically insignificant (P = 0.051) on multivariate analysis. Conclusion: Pre-operative variables including weight loss, low serum albumin and pre-albumin, Geansler’s index, postoperative chylothorax, pleural effusion, and hospital stay, are predictive of mortality in patients who undergo esophagectomy for esophageal cancer. PMID:20871187

  20. Esophageal cancer mortality trends in rural and urban China between 1987 and 2009.

    PubMed

    Guo, Bill; Huang, Zheng-Liang

    2011-01-01

    Esophageal cancer is one of the most commonly diagnosed malignant tumors in China. This study aimed to examine the temporal trend of esophageal cancer mortality rates during the period 1987-2009 in both rural and urban settings and to detect the effects of year of death and year of birth on the trends using joinpoint regression analysis and an age-period-cohort model. Age-standardized mortality rates were calculated by the direct method using the world population of 1960, and joinpoint regression was performed to obtain the annual percentage change (APC) in mortality rate. Poisson regression models were fitted to evaluate the period and cohort effects after adjusting for age. During the period 1987-2009, age-standardized mortality rates showed an overall significant decrease for rural females (APC=-2.3, 95% confidence interval [CI]: -3.3%, -1.2%), urban males (APC=-1.8, 95% CI: -2.6%, -1.0%) and urban females (APC=-3.7, 95% CI: -4.9%, -2.4%), but the decrease was not statistically significant for rural males (APC=-0.9, 95% CI: -2.0%, 0.3%). After adjusting for age and with the birth cohort of 1900-1904 or period 1987-1991 as reference, the relative risk of successive cohorts decreased steadily and that of more recent periods kept relatively stable. The decreasing birth cohort effect in the recent generations could correspond to increased adoption of healthy dietary habits and life-styles in the population.

  1. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

    SciTech Connect

    Peng, Yi; Zhou, Yajuan; Cheng, Long; Hu, Desheng; Zhou, Xiaoyi; Wang, Zhaohua; Xie, Conghua; Zhou, Fuxiang

    2015-09-11

    Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.

  2. [A Case of Advanced Esophageal Cancer and Tongue Cancer Treated with Induction DCF Chemotherapy Followed by Radical Surgery].

    PubMed

    Tanaka, Motomu; Koyanagi, Kazuo; Sugiura, Hitoshi; Kakefuda, Toshihiro

    2015-11-01

    A man in his 60s was admitted for the treatment of advanced cervical esophageal cancer with metastasis to the lymph nodes and advanced tongue cancer with metastasis to the lymph nodes. Esophageal cancer was suspected to have invaded the trachea. The tongue cancer was located on the left side and had invaded beyond the median line of the tongue. Both cancers were pathologically diagnosed as squamous cell carcinomas. Therefore, it was determined that pharyngo-laryngo- esophagectomy and total glossectomy were required prior to the treatment. However, after 2 courses of docetaxel/cisplatin/ 5-FU combined induction chemotherapy, both cancers remarkably decreased; consequently, an esophagectomy to preserve laryngeal function and partial glossectomy could be performed simultaneously. The patient is well without recurrence 1 year post-surgery.

  3. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer

    PubMed Central

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    Introduction We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. Presentation of case After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. Discussion In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Conclusion Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. PMID:26851395

  4. Esophageal cancer: The latest on chemoprevention and state of the art therapies.

    PubMed

    Le Bras, Gregoire F; Farooq, Muhammad H; Falk, Gary W; Andl, Claudia D

    2016-11-01

    Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low. As we will discuss in this review, multiple characteristics specific to the disease stage and patient must be considered when choosing a treatment plan. This article will summarize current standard therapies, potential application of chemoprevention drugs and the promise and partial failure of personalized medicine, as well as novel treatments addressing this disease.

  5. Induction of esophageal cancer associated with gastric cancer in a dog by N-ethyl-N'-nitro-N-nitrosoguandine.

    PubMed

    Sekizuka, H; Doi, H; Sunagawa, M; Nagai, S; Kojima, S

    1975-12-01

    The experimental induction of gastric cancer was studied in four dogs given oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in solution. Esophageal cancer with the regional lymph node metastasis was found in one dog at autopsy, with concomitantly existing gastric cancer. This dog, which ingested a total amount of about 38 g of ENNG, died of weakness on the 513th experimental day. Three remaining dogs are still living and under observation.

  6. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

    PubMed Central

    Wang, Jian-Lin; Yu, Jing-Ping; Sun, Zhi-Qiang; Sun, Su-Ping

    2014-01-01

    AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. METHODS: A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44+CD271+ expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. RESULTS: The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44+CD271+ cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44+CD271+ cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44+CD271+ cell percentage for KYSE-150 stem

  7. miRNA-mRNA crosstalk in esophageal cancer: From diagnosis to therapy.

    PubMed

    Sharma, Priyanka; Sharma, Rinu

    2015-12-01

    The asymptomatic nature of esophageal cancer (EC) at early stages results in late clinical presentation leading to poor prognosis and limited success of therapeutic modalities. Efforts to identify diagnostic/prognostic markers have proven to be unsuccessful for translation into clinics. Hence, there is a pressing need for establishment of novel non-invasive biomarker for early diagnosis/better prognosis of EC. Recently, alteration in microRNA (miRNA) expression has emerged as an important hallmark of cancer. This review summarizes the differential expression of miRNAs in EC and addresses how their aberrant expression influences crucial biological processes such as apoptosis, cell proliferation, invasion and metastasis. Additionally, this review highlights the current status of circulating miRNA based diagnostic/prognostic markers. An effort has been made to find a connection between different miRNAs involved in EC and a detailed analysis has been done to screen out micoRNAs involved in prognosis and multidrug resistance. Further, investigation of these miRNAs would not only provide a gene therapy based strategy to prevent/treat cancer but also to reverse multidrug resistance leading to decreased requirement of harmful chemotherapeutic drugs.

  8. RHBDF2 Mutations Are Associated with Tylosis, a Familial Esophageal Cancer Syndrome

    PubMed Central

    Blaydon, Diana C.; Etheridge, Sarah L.; Risk, Janet M.; Hennies, Hans-Christian; Gay, Laura J.; Carroll, Rebecca; Plagnol, Vincent; McRonald, Fiona E.; Stevens, Howard P.; Spurr, Nigel K.; Bishop, D. Timothy; Ellis, Anthony; Jankowski, Janusz; Field, John K.; Leigh, Irene M.; South, Andrew P.; Kelsell, David P.

    2012-01-01

    Tylosis esophageal cancer (TOC) is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. We have previously localized the TOC locus to a small genomic interval within chromosomal region 17q25. Using a targeted capture array and next-generation sequencing, we have now identified missense mutations (c.557T>C [p.Ile186Thr] and c.566C>T [p.Pro189Leu] in RHBDF2, which encodes the inactive rhomboid protease RHBDF2 (also known as iRhom2), as the underlying cause of TOC. We show that the distribution of RHBDF2 in tylotic skin is altered in comparison with that in normal skin, and immortalized tylotic keratinocytes have decreased levels of total epidermal growth factor receptor (EGFR) and display an increased proliferative and migratory potential relative to normal cells, even when normal cells are stimulated with exogenous epidermal growth factor. It would thus appear that EGFR signaling is dysregulated in tylotic cells. Furthermore, we also show an altered localization of RHBDF2 in both tylotic and sporadic squamous esophageal tumors. The elucidation of a role of RHBDF2 in growth-factor signaling in esophageal cancer will help to determine whether targeting this pathway in chemotherapy for this and other squamous cell carcinomas will be effective. PMID:22265016

  9. Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy

    SciTech Connect

    De Ruyck, Kim; Sabbe, Nick; Oberije, Cary; Vandecasteele, Katrien; Thas, Olivier; De Ruysscher, Dirk; Lambin, Phillipe; Van Meerbeeck, Jan; De Neve, Wilfried; Thierens, Hubert

    2011-10-01

    Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

  10. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries.

    PubMed

    Domper Arnal, María José; Ferrández Arenas, Ángel; Lanas Arbeloa, Ángel

    2015-07-14

    Esophageal cancer is one of the most unknown and deadliest cancers worldwide, mainly because of its extremely aggressive nature and poor survival rate. Esophageal cancer is the 6(th) leading cause of death from cancer and the 8(th) most common cancer in the world. The 5-year survival is around 15%-25%. There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide. There are areas of high incidence of squamous cell carcinoma (some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas. In Europe and United States the predominant histologic subtype is adenocarcinoma. The role of early diagnosis of adenocarcinoma in Barrett's esophagus remains controversial. The differences in the therapeutic management of early esophageal carcinoma (high-grade dysplasia, T1a, T1b, N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage. In areas where the incidence is high (China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus.

  11. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  12. Risk of Esophageal Cancer Following Percutaneous Endoscopic Gastrostomy in Head and Neck Cancer Patients: A Nationwide Population-Based Cohort Study in Taiwan.

    PubMed

    Lin, Kuen-Tze; Lin, Chun-Shu; Lee, Shih-Yu; Huang, Wen-Yen; Chang, Wei-Kuo

    2016-03-01

    Esophageal cancers account for majority of synchronous or metachronous head and neck cancers. This study examined the risk of esophageal cancer following percutaneous endoscopic gastrostomy (PEG) in head and neck cancer patients using the Taiwan National Health Insurance Research Database. From 1997 to 2010, we identified and analyzed 1851 PEG patients and 3702 sex-, age-, and index date-matched controls. After adjusting for esophagitis, esophagus stricture, esophageal reflux, and primary sites, the PEG cohort had a higher adjusted hazard ratio (2.31, 95% confidence interval [CI] = 1.09-4.09) of developing esophageal cancer than the controls. Primary tumors in the oropharynx, hypopharynx, and larynx were associated with higher incidence of esophageal cancer. The adjusted hazard ratios were 1.49 (95% CI = 1.01-1.88), 3.99 (95% CI = 2.76-4.98), and 1.98 (95% CI = 1.11-2.76), respectively. Head and neck cancer patients treated with PEG were associated with a higher risk of developing esophageal cancer, which could be fixed by surgically placed tubes.

  13. Dose-Volume Histogram Parameters and Clinical Factors Associated With Pleural Effusion After Chemoradiotherapy in Esophageal Cancer Patients

    SciTech Connect

    Shirai, Katsuyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi; Murata, Kazutoshi; Satoh, Yumi; Higuchi, Keiko; Nonaka, Tetsuo; Ishikawa, Hitoshi; Katoh, Hiroyuki; Takahashi, Takeo; Nakano, Takashi

    2011-07-15

    Purpose: To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose {>=}50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving {>=}10-60 Gy (Heart-V{sub 10} to V{sub 60} and Lung-V{sub 10} to V{sub 60}, respectively) were analyzed in relation to pleural effusion. Results: The median follow-up time was 26.9 months (range, 6.7-70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V{sub 10} to V{sub 60}, and Lung-V{sub 50} to V{sub 60} were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age {>=}65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V{sub 50} as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V{sub 50} <20%, 20%{<=} Heart-V{sub 50} <40%, and Heart-V{sub 50} {>=}40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01). Conclusion: Heart-V{sub 50} is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion.

  14. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    SciTech Connect

    Swisher, Stephen G.; Winter, Kathryn A.; Komaki, Ritsuko U.; Ajani, Jaffer A.; Wu, Tsung T.; Hofstetter, Wayne L.; Konski, Andre A.; Willett, Christopher G.

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  15. Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients

    PubMed Central

    Forghanifard, Mohammad Mahdi; Vahid, Elham Emami; Dadkhah, Ezzat; Gholamin, Mehran; Noghabi, Samaneh Broumand; Ghahraman, Martha; Farzadnia, Mehdi; Abbaszadegan, Mohammad Reza

    2016-01-01

    Objective(s): Variation in microsatellite sequences that are dispersed in the genome has been linked to a deficiency in cellular mismatch repair system and defects in several genes of this system are involved in carcinogenesis. Our aim in this study was to illustrate microsatellite DNA alteration in esophageal cancer. Materials and Methods: DNA was extracted from formalin fixed paraffin embedded (FFPE) tissues from surgical and matched margin-normal samples. Microsatellite instability (MSI) and loss of heterozygosity (LOH) were studied in 50 cases of esophageal squamous cell carcinoma (ESCC) by amplifying six microsatellite markers: D13S260 (13q12.3), D13S267 (13q12.3), D9S171 (9p21), D2S123 (2p), D5S2501 (5q21) and TP53 (17p13.1) analyzed on 6% denaturing polyacrylamide gel electrophoresis. Results: Statistical analysis indicated a near significant reverse correlation between grade and LOH (P= 0.068, correlation coefficient= -0.272). Specifically, increased LOH in tumor DNA has a significant correlation with increased differentiation from poorly differentiated to well differentiated tumors (P= 0.002 and P= 0.016 respectively). In addition, higher number of chromosomal loci with LOH showed a reverse correlation with lymph node metastasis (P= 0.026, correlation coefficient= -0.485). Furthermore, there was a positive correlation between addiction and MSI (P= 0.026, correlation coefficient= 0.465). Conclusion: Microsatellite DNA alterations may be a prognostic tool for detection and the evolution of prognosis in patients with SCC of esophagus. It can be concluded that regional lymph node metastasis would be less likely with increased heterozygote loci and addiction with any of opium, cigarette, water pipe or alcohol can be a susceptibility factor(s) for MSI. PMID:27635196

  16. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    SciTech Connect

    Fujiwara, Daisuke; Kato, Kazunori; Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki

    2013-05-17

    Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present in esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9 expression

  17. Esophageal cancer diagnosed by high-resolution manometry of the esophagus: A case report

    PubMed Central

    LIU, RONGBEI; CHU, HUA; XU, FEI; CHEN, SHUJIE

    2016-01-01

    A 48-year-old female who presented with a history of dysphagia for 5 months and regurgitation for 1 week was referred to the Sir Run Run Shaw Hospital (Hangzhou, China) for further evaluation, since the gastroscopy and endoscopic ultrasound performed in local hospitals did not reveal the presence of cancer. High-resolution manometry (HRM) of the esophagus was performed to determine the patient's condition, and revealed an abnormal high-pressure zone that was located 33 cm from the incisor and did not relax upon swallowing. Synchronous waves were observed, and the pressure of the esophageal lumen was found to increase with secondary synchronous peristaltic waves. The lower esophageal sphincter was 39 cm from the incisor and relaxed upon swallowing. The abnormal high-pressure zone could have been caused by an obstruction, and therefore an upper gastrointestinal series (barium swallow) test and gastroscopy were recommended to further pinpoint the cause. Following the two examinations, mid-esophageal cancer was considered as a possible diagnosis. A biopsy was performed and the final diagnosis was that of basaloid squamous cell carcinoma. The findings of the present study suggest that, for patients with evident symptoms of esophageal motor dysfunction without significant gastroscopy findings, HRM is recommended. PMID:27123076

  18. Impact of the number of resected lymph nodes on survival after preoperative radiotherapy for esophageal cancer

    PubMed Central

    He, Zhen-Yu; Li, Feng-Yan; Lin, Huan-Xin; Sun, Jia-Yuan; Lin, Hui; Li, Qun

    2016-01-01

    To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer-directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan–Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy (P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11–71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603–0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636–0.824, P < 0.001) than patients with 1–10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1–10 RLNs and 11–71 RLNs, respectively (P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery. PMID:26992210

  19. Drinking water: a risk factor for high incidence of esophageal cancer in Anyang, China.

    PubMed

    Cao, Wenbo; Han, Jianying; Yuan, Yi; Xu, Zhixiang; Yang, Shengli; He, Weixin

    2016-06-01

    Anyang is known to be a high-incidence area of esophageal cancer (EC) in China. Among a long list of risk factors, the quality of drinking water was evaluated. We have selected 3806 individuals and collected 550 drinking water samples correspondent with this not-matched case-control survey. There are 531 EC patients included based on Population Cancer Registry from 92 townships, of which 3275 controls with long-lived aged over 90 years and free from EC are used as controls in the same regions. Our result suggests that the quality of drinking water is a highly associated risk factor for EC. The residential ecological environment and the quality of water resource positively link with each other. The analysis of water samples also demonstrated that the concentrations of methyl ethylamine, morpholine, N-methylbenzylamine, nitrate and chloride in water from springs and rivers are higher than those in well and tap water (P = 0.001). Micronuclei formation tests show that well water and tap water in these regions have no mutagenicity.

  20. Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer

    NASA Astrophysics Data System (ADS)

    Overholt, Bergein F.; Panjehpour, Masoud

    1995-03-01

    Fifteen patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy. Four patients also had early, superficial esophageal cancers and 5 had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Eight patients maintained on omeprazole and followed for 6 - 54 months are the subject of this report. Photodynamic therapy ablated dysplastic or malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barrett's mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in two. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5 - 7 days. In three patients with extensive circumferential mucosal ablation in the proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.

  1. Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method

    PubMed Central

    Ito, Hitoshi; Itasaka, Satoshi; Sakanaka, Katsuyuki; Araki, Norio; Mizowaki, Takashi; Hiraoka, Masahiro

    2017-01-01

    Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior–posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful. PMID:27475126

  2. Value of screening endoscopy in evaluation of esophageal, gastric and colon cancers.

    PubMed

    Ro, Tae H; Mathew, Michelle A; Misra, Subhasis

    2015-09-07

    Esophageal, gastric, and colorectal cancers are deadly diseases that continue to plague our world today. The value of screening endoscopy in evaluating these types of cancers is a critical area of discussion due to a potential reduction in morbidity and mortality. This article describes how to identify a good screening test and explains what are important criteria in the field of screening endoscopy. Furthermore, the current status and progress of screening endoscopy for esophageal, gastric, and colorectal cancer will be evaluated and discussed. Mass screening programs have not been implemented for esophageal and gastric carcinomas in those with average or low risk populations. However, studies of high-risk populations have found value and a cost-benefit in conducting screening endoscopy. Colorectal cancer, on the other hand, has had mass screening programs in place for many years due to the clear evidence of improved outcomes. As the role of endoscopy as a screening tool has continued to develop, newer technology and techniques have emerged to improve its utility. Many new image enhancement techniques and computer processing programs have shown promise and may have a significant role in the future of endoscopic screening. These developments are paving the way for improving the diagnostic and therapeutic capability of endoscopy in the field of gastroenterology.

  3. Nimotuzumab Combined with Chemotherapy is a Promising Treatment for Locally Advanced and Metastatic Esophageal Cancer

    PubMed Central

    Han, Xinghua; Lu, Nannan; Pan, Yueyin; Xu, Jianming

    2017-01-01

    Background Nimotuzumab is an anti-EGFR monoclonal antibody which has been widely used in cancer treatment. However, the safety and efficacy of nimotuzumab combined with chemotherapy in locally advanced or metastatic esophageal cancer patients remain unclear. Material/Methods To address this open question, we collected a total data of 21 patients diagnosed with locally advanced or metastatic esophageal cancer between 2012 and 2016 in a, retrospective study. The patient characteristics, efficacy safety, and toxicity were evaluated in our study. Results We observed 1 (4.8%) patient with complete response, 7 (33.3%) patients with partial response, 9 (42.9%) patients with stable response and 4 (19%) patients with progression response. The objective response rate was 38.1% and disease control rate was 81%. The mean progression-free-survival was 7 months and the 18-month overall survival (OS) was 10%. The incidence rate of anemia and leukopenia was 71.4% and 81%, respectively. Two patients showed the serious adverse event of myelosuppression, with nausea, fatigue, and anorexia. No long-term drug-related toxicity was observed during the follow-up. Conclusions Nimotuzumab combined with chemotherapy can achieve promising clinical outcomes in locally advanced or metastatic esophageal cancer, without accumulation of toxicity and was well-tolerated. PMID:28115730

  4. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

    PubMed

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L; Han, Jessica H; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H; Bussey, Kimberly J; Meldrum, Deirdre R

    2016-08-09

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

  5. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells

    PubMed Central

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L.; Han, Jessica H.; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H.; Bussey, Kimberly J.; Meldrum, Deirdre R.

    2016-01-01

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an ‘epigenetic’ drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat’s differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action. PMID:27503568

  6. Metastatic Esophageal Cancer Presenting as an Orbital Mass

    PubMed Central

    Kabbach, Ghassan; Richter, Seth J.; Chiu, Laura

    2016-01-01

    We report a case of adenocarcinoma of the esophagus presenting as an orbital metastasis prior to the primary diagnosis. A 66-year-old white male presented to his ophthalmologist with right orbital swelling for several months. Magnetic resonance imaging revealed a supraorbital infiltrative mass. Pathology from the mass revealed findings consistent with adenocarcinoma of gastrointestinal origin. Upper endoscopy revealed distal esophageal stricture and irregularities. Pathology from the esophagus showed the same malignancy found in the orbit. An orbital swelling can manifest as the initial presentation of metastatic disease and should be taken seriously to avoid delay in diagnosis and treatment. PMID:27921053

  7. [Usefulness of endoscopic salvage treatment in a patient with local failure esophageal cancer after CRT].

    PubMed

    Higashino, Koji; Hanafusa, Masao; Ishihara, Ryu

    2011-11-01

    Chemoradiotherapy (CRT) is widely used as non-surgical treatment for esophageal cancer in recent years. CRT is very useful, but it allows about 40% relapse. Salvage surgery after CRT, long-term survival can be expected, but perioperative mortality is high. In contrast, EMR for local failure after definitive CRT has been reported showing a 5-year survival rate of 49. 1%. If it can safely control of local failure, then we thought it's useful for long-term survival. If the depth of invasion was to the submucosal layer of the local failure lesion, we performed an endoscopic resection. If vertical margins are positive pathologically, we have added a photodynamic therapy. In cases of difficult endoscopic resection, PDT alone was performed. We experienced a case of recurrent esophageal cancer after CRT was useful for local treatment with PDT and EMR.

  8. [Definition of accurate planning target volume margins for esophageal cancer radiotherapy].

    PubMed

    Lesueur, P; Servagi-Vernat, S

    2016-10-01

    More than 4000 cases of esophagus neoplasms are diagnosed every year in France. Radiotherapy, which can be delivered in preoperative or exclusive with a concomitant chemotherapy, plays a central role in treatment of esophagus cancer. Even if efficacy of radiotherapy no longer has to be proved, the prognosis of esophagus cancer remains unfortunately poor with a high recurrence rate. Toxicity of esophageal radiotherapy is correlated with the irradiation volume, and limits dose escalation and local control. Esophagus is a deep thoracic organ, which undergoes cardiac and respiratory motion, making the radiotherapy delivery more difficult and increasing the planning target volume margins. Definition of accurate planning target volume margins, taking into account the esophagus' intrafraction motion and set up margins is very important to be sure to cover the clinical target volume and restrains acute and late radiotoxicity. In this article, based on a review of the literature, we propose planning target volume margins adapted to esophageal radiotherapy.

  9. What's New in Esophageal Cancer Research and Treatment?

    MedlinePlus

    ... and Treatment? Esophagus Cancer About Esophagus Cancer What’s New in Cancer of the Esophagus Research and Treatment? ... people with Barrett’s esophagus. This may lead to new tests for finding the people who are likely ...

  10. Histone demethylase JMJD1C regulates esophageal cancer proliferation Via YAP1 signaling

    PubMed Central

    Cai, Yixin; Fu, Xiangning; Deng, Yu

    2017-01-01

    Esophageal cancer (EC) is the most lethal cancer, and it is of significant concern worldwide, particularly in China. However, there are no effective treatments to cure it, such as chemotherapy, surgery, or radiotherapy. This is attributed to the lack of understanding of the molecular mechanisms of EC. Recently, the superfamily of Jmj-containing KDMs has been shown to play an important role in tumorigenesis in various cancers, including EC. In this study, we demonstrated that JMJD1C was upregulated in patient EC tissues and different EC cell lines. Furthermore, JMJD1C levels were positively correlated with the TNM stage. Moreover, the colony formation assay, CCK8, and cell number count assay showed that the knockdown of JMJD1C inhibited EC cell proliferation. Western blot analysis and the quantitative real-time polymerase chain reaction assay showed that the knockdown of JMJD1C repressed the protein and mRNA levels of YAP1 via regulating the H3K9me2 activity, but not the H3K9me1 activity. The colony formation assay, CCK8 analysis, and cell number count assay revealed that inhibition of EC cell proliferation by the knockdown of JMJD1C was rescued by overexpression of YAP1. Taken together, our results demonstrated that JMJD1C controls the proliferation of EC via modulation of H3K9me2 activity, targeting the YAP1 gene expression and functions as a tumor suppressor in EC. This novel pathway may serve as a therapeutic target for EC patients. PMID:28123852

  11. The effect of individual and neighborhood socioeconomic status on esophageal cancer survival in working-age patients in Taiwan

    PubMed Central

    Wu, Chin-Chia; Chang, Chun-Ming; Hsu, Ta-Wen; Lee, Cheng-Hung; Chen, Jian-Han; Huang, Chih-Yuan; Lee, Ching-Chih

    2016-01-01

    Abstract Esophageal cancer is the sixth leading cause of cancer mortality. More than 90% of patients with esophageal cancer in Taiwan have squamous cell carcinoma. Survival of such patients is related to socioeconomic status (SES). We studied the association between SES (individual and neighborhood) and the survival of working-age patients with esophageal cancer in Taiwan. A population-based study was conducted of 4097 patients diagnosed with esophageal cancer between 2002 and 2006. Each was traced for 5 years or until death. Individual SES was defined by enrollee job category. Neighborhood SES was based on household income and dichotomized into advantaged or disadvantaged. Multilevel logistic regression was used to compare the survival rates by SES group after adjustment for possible confounding and risk factors. Hospital and neighborhood SES were used as random effects in multilevel logistic regression. In patients younger than 65 years, 5-year overall survival rates were worst for those with low individual SES living in disadvantaged neighborhoods. After adjustment for patient characteristics, esophageal cancer patients with high individual SES had a 39% lower risk of mortality than those with low individual SES (odds ratio 0.61, 95% confidence interval 0.48–0.77). Patients living in disadvantaged areas with high individual SES were more likely to receive surgery than those with low SES (odds ratio 1.45, 95% confidence interval 1.11–1.89). Esophageal cancer patients with low individual SES have the worst 5-year survival, even with a universal healthcare system. Public health, education, and social welfare programs should address the inequality of esophageal cancer survival. PMID:27399129

  12. The effect of individual and neighborhood socioeconomic status on esophageal cancer survival in working-age patients in Taiwan.

    PubMed

    Wu, Chin-Chia; Chang, Chun-Ming; Hsu, Ta-Wen; Lee, Cheng-Hung; Chen, Jian-Han; Huang, Chih-Yuan; Lee, Ching-Chih

    2016-07-01

    Esophageal cancer is the sixth leading cause of cancer mortality. More than 90% of patients with esophageal cancer in Taiwan have squamous cell carcinoma. Survival of such patients is related to socioeconomic status (SES). We studied the association between SES (individual and neighborhood) and the survival of working-age patients with esophageal cancer in Taiwan. A population-based study was conducted of 4097 patients diagnosed with esophageal cancer between 2002 and 2006. Each was traced for 5 years or until death. Individual SES was defined by enrollee job category. Neighborhood SES was based on household income and dichotomized into advantaged or disadvantaged. Multilevel logistic regression was used to compare the survival rates by SES group after adjustment for possible confounding and risk factors. Hospital and neighborhood SES were used as random effects in multilevel logistic regression. In patients younger than 65 years, 5-year overall survival rates were worst for those with low individual SES living in disadvantaged neighborhoods. After adjustment for patient characteristics, esophageal cancer patients with high individual SES had a 39% lower risk of mortality than those with low individual SES (odds ratio 0.61, 95% confidence interval 0.48-0.77). Patients living in disadvantaged areas with high individual SES were more likely to receive surgery than those with low SES (odds ratio 1.45, 95% confidence interval 1.11-1.89). Esophageal cancer patients with low individual SES have the worst 5-year survival, even with a universal healthcare system. Public health, education, and social welfare programs should address the inequality of esophageal cancer survival.

  13. Esophageal Cancer in Golestan Province, Iran: A Review of Genetic Susceptibility and Environmental Risk Factors

    PubMed Central

    Gholipour, Mahin; Islami, Farhad; Roshandel, Gholamreza; Khoshnia, Masoud; Badakhshan, Abbas; Moradi, Abdolvahab; Malekzadeh, Reza

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor (19%), even with improved surgical techniques and adjuvant chemoradiation therapy. Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC. Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors (including substance abuse, environmental contaminants, dietary factors, and human papillomavirus [HPV]), and molecular factors (including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers). Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons (PAHs), cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan. HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens. There are few studies at molecular level on ESCC in Golestan. Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed. PMID:27957288

  14. Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.

    PubMed

    Piselli, Pierluca; Burra, Patrizia; Lauro, Augusto; Baccarani, Umberto; Ettorre, Giuseppe M; Vizzini, Giovanni B; Rendina, Maria; Rossi, Massimo; Tisone, Giuseppe; Zamboni, Fausto; Bortoluzzi, Ilaria; Pinna, Antonio D; Risaliti, Andrea; Galatioto, Laura; Vennarecci, Giovanni; Di Leo, Alfredo; Nudo, Francesco; Sforza, Daniele; Fantola, Giovanni; Cimaglia, Claudia; Verdirosi, Diana; Virdone, Saverio; Serraino, Diego

    2015-07-01

    This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant cancers were diagnosed-including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2-6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1-17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high-risk recipients like those with ALD.

  15. Intramural esophageal tumors

    PubMed Central

    Kozak, Katarzyna; Rębowski, Marek; Kozak, Józef

    2016-01-01

    Introduction Intramural esophageal tumors (IET) are located between unchanged mucous membrane and muscularis mucosae. They can be both benign and malignant. Aim To evaluate diagnostic and therapeutic difficulties of IET. Material and methods During the years 2010–2015, 11 patients with IET were treated in our clinic. Diagnostics included gastroscopy, computed tomography of the chest, endoscopic ultrasound (EUS) guided fine needle biopsy, and positron emission tomography (PET) of the esophagus in cases with no histopathological confirmation. Results Based on the conducted analysis we diagnosed 1 case of gastrointestinal stromal tumor (GIST), 1 case of adenocarcinoma, and 2 cases of esophageal cysts. In another 7 cases radiological images resembled leiomyoma but with no histopathological confirmation. Esophagectomy was performed in 2 cases of malignant tumors and 1 case of a large benign tumor. In other cases surgical enucleation of tumors was performed. Postoperatively we diagnosed 6 cases of leiomyoma, 1 case of schwannoma, 2 esophageal cysts, 1 case of GIST and 1 of esophageal cancer. Conclusions Intramural esophageal tumors is a very diverse group of tumors, both malignant and benign. In every case of IET we should seek histopathological conformation. Treatment of IET depends on localization, size and histopathological type of lesion. PMID:28096828

  16. SU-C-BRA-04: Use of Esophageal Wall Thickness in Evaluation of the Response to Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Wang, J; Kligerman, S; Lu, W; Kang, M

    2015-06-15

    Purpose: To quantitatively evaluate the esophageal cancer response to chemoradiation therapy (CRT) by measuring the esophageal wall thickness in CT. Method: Two datasets were used in this study. The first dataset is composed of CT scans of 15 esophageal cancer patients and 15 normal controls. The second dataset is composed of 20 esophageal cancer patients who underwent PET/CT scans before (Pre-CRT) and after CRT (Post-CRT). We first segmented the esophagus using a multi-atlas-based algorithm. The esophageal wall thickness was then computed, on each slice, as the equivalent circle radius of the segmented esophagus excluding the lumen. To evaluate the changes of wall thickness, we computed the standard deviation (SD), coefficient of variation (COV, SD/Mean), and flatness [(Max–Min)/Mean] of wall thickness along the entire esophagus. Results: For the first dataset, the mean wall thickness of cancer patients and normal controls were 6.35 mm and 6.03 mm, respectively. The mean SD, COV, and flatness of the wall thickness were 2.59, 0.21, and 1.27 for the cancer patients and 1.99, 0.16, and 1.13 for normal controls. Statistically significant differences (p < 0.05) were identified in SD and flatness. For the second dataset, the mean wall thickness of pre-CRT and post-CRT patients was 7.13 mm and 6.84 mm, respectively. The mean SD, COV, and flatness were 1.81, 0.26, and 1.06 for pre-CRT and 1.69, 0.26, and 1.06 for post-CRT. Statistically significant difference was not identified for these measurements. Current results are based on the entire esophagus. We believe significant differences between pre- and post-CRT scans could be obtained, if we conduct the measurements at tumor sites. Conclusion: Results show thicker wall thickness in pre-CRT scans and differences in wall thickness changes between normal and abnormal esophagus. This demonstrated the potential of esophageal wall thickness as a marker in the tumor CRT response evaluation. This work was supported in part by

  17. Stents in patients with esophageal cancer before chemoradiotherapy: high risk of complications and no impact on the nutritional status.

    PubMed

    Mão-de-Ferro, S; Serrano, M; Ferreira, S; Rosa, I; Lage, P; Alexandre, D P; Freire, J; Mirones, L; Casaca, R; Bettencourt, A; Pereira, A D

    2016-03-01

    Preoperative chemoradiotherapy is the standard of care for locally advanced esophageal cancer, causing persistent deterioration in the nutritional status. We performed a prospective study to evaluate the safety and efficacy of esophageal double-covered self-expandable metal stents in patients with esophageal cancer before chemoradiotherapy. The nutritional status and dysphagia were prospectively recorded. Eleven patients were included: eight were moderate and three were severely malnourished. After stent placement, dysphagia improved in all patients. With regard to complications, one patient developed an esophageal perforation that required urgent esophagectomy. Four patients presented stent migration. Three of these patients required enteral nutrition and none was submitted to surgery because of poor nutritional status. Of the other six patients, only four were operated upon. Stent placement presented a high complication rate and did not prevent weight loss or malnutrition. Other alternatives, including naso-gastric tube placement or endoscopic percutaneous gastrostomy or jejunostomy, should be considered.

  18. Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

    PubMed Central

    Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The co-stimulatory ligands of B7-family have been confirmed to play an important role in negatively regulating the T-cell mediated anti-tumor immunity. In addition, these inhibitory molecules are also aberrantly expressed on various human cancers tissues, and significantly associated with cancer progression and patients' poor prognoses. We have previously reported that B7-H3 and B7-H4 ligands are highly expressed in human esophageal cancer tissues. Herein, we tried to further analyze the value of their combined expression on prognostic prediction for esophageal cancer patients. We found that the combined expression of both B7-H3 and B7-H4 could be used as a valuable risk factor for predicting the prognosis of esophageal cancer patients (P=0.003). Moreover the status of these patients with high expression of both B7-H3 and B7-H4, was positively and significantly associated with the tumor invasion depth (P=0.0414) and TNM stage (P=0.0414). The Cox multivariate proportional hazards regression analysis revealed that the tumor size (P=0.007), the TNM stage (P=0.024) and the status of both B7-H3 and B7-H4 high expression (P=0.011), could be used as an independent risk factor for predicting patients' postoperative prognosis, respectively. In conclusion, our data indicated that the combined application of B7-H3 and B7-H4 expression can be effectively used as a prognostic marker in esophageal cancer patients. PMID:27764786

  19. Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

    SciTech Connect

    Amini, Arya; Xiao Lianchun; Allen, Pamela K.; Suzuki, Akihiro; Hayashi, Yuki; Liao, Zhongxing; Hofstetter, Wayne; Crane, Christopher; Komaki, Ritsuko; Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A.; Welsh, James

    2012-06-01

    Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment

  20. Esophageal cancer risk by type of alcohol drinking and smoking: a case-control study in Spain

    PubMed Central

    Vioque, Jesus; Barber, Xavier; Bolumar, Francisco; Porta, Miquel; Santibáñez, Miguel; de la Hera, Manuela García; Moreno-Osset, Eduardo

    2008-01-01

    Background The effect of tobacco smoking and alcohol drinking on esophageal cancer (EC) has never been explored in Spain where black tobacco and wine consumptions are quite prevalent. We estimated the independent effect of different alcoholic beverages and type of tobacco smoking on the risk of EC and its main histological cell type (squamous cell carcinoma) in a hospital-based case-control study in a Mediterranean area of Spain. Methods We only included incident cases with histologically confirmed EC (n = 202). Controls were frequency-matched to cases by age, sex and province (n = 455). Information on risk factors was elicited by trained interviewers using structured questionnaires. Multiple logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (CI). Results Alcohol drinking and tobacco smoking were strong and independent risk factors for esophageal cancer. Alcohol was a potent risk factor with a clear dose-response relationship, particularly for esophageal squamous-cell cancer. Compared to never-drinkers, the risk for heaviest drinkers (≥ 75 g/day of pure ethanol) was 7.65 (95%CI, 3.16–18.49); and compared with never-smokers, the risk for heaviest smokers (≥ 30 cigarettes/day) was 5.07 (95%CI, 2.06–12.47). A low consumption of only wine and/or beer (1–24 g/d) did not increase the risk whereas a strong positive trend was observed for all types of alcoholic beverages that included any combination of hard liquors with beer and/or wine (p-trend<0.00001). A significant increase in EC risk was only observed for black-tobacco smoking (2.5-fold increase), not for blond tobacco. The effects for alcohol drinking were much stronger when the analysis was limited to the esophageal squamous cell carcinoma (n = 160), whereas a lack of effect for adenocarcinoma was evidenced. Smoking cessation showed a beneficial effect within ten years whereas drinking cessation did not. Conclusion Our study shows that the risk of EC, and

  1. Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia.

    PubMed

    Liu, Jiayi; Li, Ning; Li, Li; Li, Danye; Liu, Kai; Zhao, Lingyun; Tang, Jintian; Li, Liya

    2013-12-01

    Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.

  2. Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer

    ClinicalTrials.gov

    2015-12-10

    Stage I Esophageal Adenocarcinoma; Stage II Esophageal Adenocarcinoma; Stage III Esophageal Adenocarcinoma; Stage I Esophageal Squamous Cell Carcinoma; Stage II Esophageal Squamous Cell Carcinoma; Stage III Esophageal Squamous Cell Carcinoma

  3. Quality of drinking water and high incidence rate of esophageal cancer in Golestan province of Iran: a probable link.

    PubMed

    Keshavarzi, Behnam; Moore, Farid; Najmeddin, Ali; Rahmani, Farah; Malekzadeh, Ahad

    2012-02-01

    Golestan province in north Iran is known to be a high-risk area for esophageal cancer (EC). Of a long list of multiple risk factors, this study focuses on a possible link between the epidemiologic patterns of EC and the anomalous concentration of some ions and elements in the drinking water sources. A total of 183 samples from 45 villages covering a wide range of EC mortality rates are collected and analyzed. The results demonstrate that NO(3)(-), SO(4)(2-), Sb, and Sr exceed the recommended maximum concentration level (MCL) in drinking water. This is more prominent in the villages with high esophageal cancer mortality rate, suggesting a possible link between EC incidence and water quality. Se concentration in drinking water increases from low to the high EC areas, a finding contrary to the expected trend. It is concluded that Se deficiency does not play a major role in the etiology of EC in the Golestan province. The statistical results obtained from Mann-Whitney and Kruskal-Wallis tests along with cluster analysis are consistent with the observed trend of EC mortality rate in Golestan province.

  4. Neoadjuvant Chemoradiation Therapy Is Beneficial for Clinical Stage T2 N0 Esophageal Cancer Patients Due to Inaccurate Preoperative Staging

    PubMed Central

    Zhang, Jennifer Q.; Hooker, Craig M.; Brock, Malcolm V.; Shin, James; Lee, Sue; How, Remealle; Franco, Noreli; Prevas, Helen; Hulbert, Alicia; Yang, Stephen C.

    2014-01-01

    Background It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. Methods This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. Results A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. Conclusions For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation. PMID:22269708

  5. Primary combined-modality therapy for esophageal cancer.

    PubMed

    Minsky, Bruce D

    2006-04-01

    Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

  6. Dietary Patterns and Risk of Esophageal Cancer Mortality: The Japan Collaborative Cohort Study.

    PubMed

    Okada, Emiko; Nakamura, Koshi; Ukawa, Shigekazu; Sakata, Kiyomi; Date, Chigusa; Iso, Hiroyasu; Tamakoshi, Akiko

    2016-01-01

    Several case-control studies have associated dietary patterns with esophageal cancer (EC) risk, but prospective studies are scarce. We investigated dietary pattern and EC mortality risk associations by smoking status. Participants were 26,562 40- to 79-yr-old Japanese men, who enrolled in the Japan Collaborative Cohort Study between 1988 and 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for EC mortality in nonsmokers and smokers were estimated using Cox proportional models. During follow-up (1988-2009), 132 participants died of EC. Using a baseline food frequency questionnaire and factor analysis, vegetable, animal, and dairy product food patterns were identified. EC risk decreased significantly with a higher factor score for the dairy product pattern (Ptrend = 0.042) and was more pronounced in smokers [multivariable HR (4th vs. 1st quartiles) = 0.57, 95% CI: 0.30, 1.09; Ptrend = 0.021]. Neither vegetable nor animal food patterns were significant overall; however, EC risk increased with a higher factor score for the animal food pattern in nonsmokers [multivariable HR (4th vs. 1st quartiles) = 6.01, 95% CI: 1.17, 30.88; Ptrend = 0.021], although the small number of events was a limitation. Our findings suggest a dairy product pattern may reduce EC risk in Japanese men, especially smokers.

  7. Epidemiological studies of esophageal cancer in the era of genome-wide association studies

    PubMed Central

    Wang, An-Hui; Liu, Yuan; Wang, Bo; He, Yi-Xuan; Fang, Ye-Xian; Yan, Yong-Ping

    2014-01-01

    Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90%-95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved in the process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies (GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC. PMID:25133033

  8. Long-term results of definitive radiotherapy for stage I esophageal cancer

    SciTech Connect

    Sai, Heitetsu . E-mail: hsai@kuhp.kyoto-u.ac.jp; Mitsumori, Michihide; Araki, Norio; Mizowaki, Takashi; Nagata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    2005-08-01

    Purpose: To analyze retrospectively the long-term results of external beam radiotherapy (RT) with or without intraluminal brachytherapy (ILBT) for patients with Stage I esophageal cancer. Methods and Materials: A total of 34 patients with esophageal squamous cell carcinoma, clinically diagnosed as having Stage I disease, were treated with definitive RT, with or without ILBT. The median age was 69 years. Seven patients were treated with external beam RT alone (median, 64 Gy), and 27 were treated with external beam RT (median, 52 Gy) plus ILBT (8-12 Gy in two to three fractions). Results: The 5-year overall survival, local relapse-free survival, and cause-specific survival rate was 58.9%, 68.4%, and 80.0%, respectively, with a median follow-up of 61 months. Of 9 patients with local recurrence after initial therapy, 7 were successfully treated, and the 5-year cumulative rate of esophagectomy was 19.6%. The 2-year local relapse-free rate for patients with and without ILBT was 79.1% and 53.6%, respectively. Conclusion: Although local recurrence was frequent within 2 years, the disease-specific survival rate was high owing to effective salvage therapy. Definitive RT is a reasonable treatment option for highly comorbid and elderly patients with Stage I esophageal cancer. The role of ILBT needs to be clarified.

  9. Exposure to an atomic bomb explosion is a risk factor for in-hospital death after esophagectomy to treat esophageal cancer.

    PubMed

    Nakashima, Y; Takeishi, K; Guntani, A; Tsujita, E; Yoshinaga, K; Matsuyama, A; Hamatake, M; Maeda, T; Tsutsui, S; Matsuda, H; Ishida, T

    2015-01-01

    Esophagectomy, one of the most invasive of all gastrointestinal operations, is associated with a high frequency of postoperative complications and in-hospital mortality. The purpose of the present study was to determine whether exposure to the atomic bomb explosion at Hiroshima in 1945 might be a preoperative risk factor for in-hospital mortality after esophagectomy in esophageal cancer patients. We thus reviewed the outcomes of esophagectomy in 31 atomic bomb survivors with esophageal cancer and 96 controls (also with cancer but without atomic bomb exposure). We compared the incidences of postoperative complications and in-hospital mortality. Of the clinicopathological features studied, mean patient age was significantly higher in atomic bomb survivors than in controls. Of the postoperative complications noted, atomic bomb survivors experienced a longer mean period of endotracheal intubation and higher incidences of severe pulmonary complications, severe anastomotic leakage, and surgical site infection. The factors associated with in-hospital mortality were exposure to the atomic bomb explosion, pulmonary comorbidities, and electrocardiographic abnormalities. Multivariate analysis revealed that exposure to the atomic bomb explosion was an independent significant preoperative risk factor for in-hospital mortality. Exposure to the atomic bomb explosion is thus a preoperative risk factor for in-hospital death after esophagectomy to treat esophageal cancer.

  10. Amonafide treatment of refractory esophageal cancer. A Southwest Oncology Group study.

    PubMed

    Poplin, E; Fleming, T; MacDonald, J S; Eisenberg, P; Fisher, R I; Conrad, M E

    1993-02-01

    Amonafide, a synthetic benzisoquinolinedione, was evaluated for treatment of squamous esophageal cancer. Eleven men and 5 women were eligible with a median performance status of 1 and median age of 63 years. Six had no prior treatment. All patients had measurable disease. Therapy consisted of amonafide 300 mg/m2d days 1-5 every 21 days. Thirty-five courses of therapy were delivered. The median number of courses received was two. Sixteen patients are evaluable for toxicity. Thirteen are evaluable for response. Toxicity was severe. Seven patients were hospitalized for toxicity. Six patients had grade IV granulocytopenia; two, grade IV thrombocytopenia. Angioedema developed in one patient; severe exfoliative dermatitis in another. A single partial response, with the decrease in size a supraclavicular node, was noted in a previously untreated patient. Amonafide, in this dose and schedule, is associated with occasionally severe toxicity precluding its likely use in squamous cell esophageal carcinoma.

  11. Radiation Therapy for Esophageal Cancer in Japan: Results of the Patterns of Care Study 1999-2001

    SciTech Connect

    Kenjo, Masahiro Uno, Takashi; Murakami, Yuji; Nagata, Yasushi; Oguchi, Masahiko; Saito, Susumu; Numasaki, Hodaka; Teshima, Teruki; Mitsumori, Michihide

    2009-10-01

    Purpose: To describe patient characteristics and the process of radiotherapy (RT) for patients with esophageal cancer treated between 1999 and 2001 in Japan. Methods and Materials: The Japanese Patterns of Care Study (PCS) Working Group conducted a third nationwide survey of 76 institutions. Detailed information was accumulated on 621 patients with thoracic esophageal cancer who received RT. Results: The median age of patients was 68 years. Eighty-eight percent were male, and 12% were female. Ninety-nine percent had squamous cell carcinoma histology. Fifty-five percent had the main lesion in the middle thoracic esophagus. Fourteen percent had clinical Stage 0-I disease, 32% had Stage IIA-IIB, 43% had Stage III, and 10% had Stage IV disease. Chemotherapy was given to 63% of patients; 39% received definitive chemoradiotherapy (CRT) without surgery and 24% pre- or postoperative CRT. Sixty-two percent of the patients aged {>=}75 years were treated with RT only. Median total dose of external RT was 60 Gy for definitive CRT patients, 60 Gy for RT alone, and 40 Gy for preoperative CRT. Conclusions: This PCS describes general aspects of RT for esophageal cancer in Japan. Squamous cell carcinoma accounted for the majority of patients. The standard total external RT dose for esophageal cancer was higher in Japan than in the United States. Chemoradiotherapy had become common for esophageal cancer treatment, but patients aged {>=}75 years were more likely to be treated by RT only.

  12. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    PubMed

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N

  13. Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in Farm Soils

    PubMed Central

    Lee, Chien-Pang; Lee, Yen-Hsin; Lian, Ie-Bin; Su, Che-Chun

    2016-01-01

    Background: Heavy metal pollution in farm soils is a grave concern in Taiwan. Previously, we found the incidence of oral cancer (OC) correlated positively with levels of nickel and arsenic in farm soils. Many OC patients have a second malignancy, among which esophageal cancer (EC) is the most common one in Taiwan. Objectives: We aimed to investigate whether these two cancers share some common risk factors. Methods: Taiwan began a compulsory national health insurance program in 1995. We used a database from this program to calculate the prevalence of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel nut chewers in adults and the information of heavy metal in farm soils to look for any association. Results: The prevalence of OC and prevalence of EC were strongly correlated. The prevalence of betel nut chewing correlated with OC prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC was found where the farm soils contained high levels of nickel. Meanwhile, among the eight heavy metals studied, only the levels of nickel in the farm soils correlated statistically with the prevalence of EC. Conclusion: Nickel is probably a common environmental risk factor for esophageal cancer and oral cancer. PMID:27698910

  14. Sweet-spot training for early esophageal cancer detection

    NASA Astrophysics Data System (ADS)

    van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

    2016-03-01

    Over the past decade, the imaging tools for endoscopists have improved drastically. This has enabled physicians to visually inspect the intestinal tissue for early signs of malignant lesions. Besides this, recent studies show the feasibility of supportive image analysis for endoscopists, but the analysis problem is typically approached as a segmentation task where binary ground truth is employed. In this study, we show that the detection of early cancerous tissue in the gastrointestinal tract cannot be approached as a binary segmentation problem and it is crucial and clinically relevant to involve multiple experts for annotating early lesions. By employing the so-called sweet spot for training purposes as a metric, a much better detection performance can be achieved. Furthermore, a multi-expert-based ground truth, i.e. a golden standard, enables an improved validation of the resulting delineations. For this purpose, besides the sweet spot we also propose another novel metric, the Jaccard Golden Standard (JIGS) that can handle multiple ground-truth annotations. Our experiments involving these new metrics and based on the golden standard show that the performance of a detection algorithm of early neoplastic lesions in Barrett's esophagus can be increased significantly, demonstrating a 10 percent point increase in the resulting F1 detection score.

  15. Trihalomethanes in drinking water and the risk of death from esophageal cancer: does hardness in drinking water matter?

    PubMed

    Tsai, Shang-Shyue; Chiu, Hui-Fen; Yang, Chun-Yuh

    2013-01-01

    The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of esophageal cancer occurrence and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop esophageal cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to esophageal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All esophageal cancer deaths in the 53 municipalities from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level <4.9 ppb, the adjusted odds ratio (OR) with 95% confidence interval (CI) for esophageal cancer was 1.02 (0.84-1.23) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. There was evidence of an interaction between drinking-water TTHM levels and low Ca and Mg intake. Our findings showed that the correlation between TTHM exposure and risk of esophageal cancer development was influenced by Ca and Mg levels in drinking water. This is the first study to report effect modification by Ca and Mg intake from drinking water on the correlation between TTHM exposure and risk of esophageal cancer occurrence

  16. Paclitaxel-Based Chemoradiotherapy in the Treatment of Patients With Operable Esophageal Cancer

    SciTech Connect

    Kelsey, Chris R. Chino, Junzo P.; Willett, Christopher G.; Clough, Robert W.; Hurwitz, Herbert I.; Morse, Michael A.; Bendell, Johanna C.; D'Amico, Thomas A.; Czito, Brian G.

    2007-11-01

    Purpose: To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer. Methods and Materials: All patients receiving neoadjuvant chemotherapy (CT) and RT for EC/GEJ cancer at Duke University between January 1995 and December 2004 were included. Clinical end points were compared for patients receiving paclitaxel-based regimens (TAX) vs. alternative regimens (non-TAX). Local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Chi-square analysis was performed to test the effect of TAX on pathologic complete response (pCR) rates and toxicity. Results: A total of 109 patients received CT-RT followed by esophagectomy (95 M; 14 F). Median RT dose was 45 Gy (range, 36-66 Gy). The TAX and non-TAX groups comprised 47% and 53% of patients, respectively. Most (83%) TAX patients received three drug regimens including platinum and a fluoropyrimidine. In the non-TAX group, 89% of the patients received cisplatin and 5-FU. The remainder received 5-FU or capecitabine alone. Grade 3-4 toxicity occurred in 41% of patients receiving TAX vs. 24% of those receiving non-TAX (p = 0.19). Overall pCR rate was 39% (39% with TAX vs. 40% with non-TAX, p = 0.9). Overall LC, DFS, and OS at 3 years were 80%, 34%, and 37%, respectively. At 3 years, there were no differences in LC (75% vs. 85%, p = 0.33) or OS (37% vs. 37%, p = 0.32) between TAX and non-TAX groups. Conclusions: In this large experience, paclitaxel-containing regimens did not improve pCR rates or clinical end points compared to non-paclitaxel-containing regimens.

  17. Video-assisted thoracoscopic esophagectomy in the left lateral decubitus position in an esophageal cancer patient with pectus excavatum.

    PubMed

    Sato, Shinsuke; Nagai, Erina; Hazama, Hiroyuki; Taki, Yusuke; Takahashi, Michiro; Kyoden, Yusuke; Watanabe, Masaya; Ohata, Ko; Kanemoto, Hideyuki; Oba, Noriyuki; Takagi, Masakazu

    2015-08-01

    During thoracic cavity operations, it is difficult to obtain sufficient working space and good operative field visibility in patients with pectus excavatum because the space between the vertebral bodies and sternum is very narrow. Here, we report the successful treatment of esophageal cancer in a patient with pectus excavatum. A 77-year-old man with esophageal cancer was referred to our hospital for further treatment. He was diagnosed with multiple early esophageal squamous cell carcinomas. The patient had pectus excavatum, but because it was asymptomatic, a video-assisted thoracoscopic radical esophagectomy in the left lateral decubitus position without pectus excavatum repair was selected. Despite the patient's unusual anatomy, video-assisted thoracoscopic esophagectomy in the left decubitus position allowed for good operative field visibility, as the videoscope was inserted from the side of the diaphragm. This operative procedure is useful in patients with esophageal cancer who also have pectus excavatum. To the best of our knowledge, this is the second report of video-assisted thoracoscopic esophagectomy in an esophageal cancer patient with pectus excavatum.

  18. Diet and esophageal disease

    PubMed Central

    Dawsey, Sanford M.; Fagundes, Renato B.; Jacobson, Brian C.; Kresty, Laura A.; Mallery, Susan R.; Paski, Shirley; van den Brandt, Piet A.

    2014-01-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett’s esophagus; micronutrients, trace elements, and risk of Barrett’s esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient. PMID:25266021

  19. In vivo multiplexed molecular imaging of esophageal cancer via spectral endoscopy of topically applied SERS nanoparticles

    PubMed Central

    Wang, Yu Winston; Kang, Soyoung; Khan, Altaz; Bao, Philip Q.; Liu, Jonathan T.C.

    2015-01-01

    The biological investigation and detection of esophageal cancers could be facilitated with an endoscopic technology to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and investigation through the sensitive and multiplexed detection of cell-surface biomarkers. Here, we demonstrate that the topical application and endoscopic imaging of a multiplexed cocktail of receptor-targeted SERS NPs enables the rapid detection of tumors in an orthotopic rat model of esophageal cancer. Antibody-conjugated SERS NPs were topically applied on the lumenal surface of the rat esophagus to target EGFR and HER2, and a miniature spectral endoscope featuring rotational scanning and axial pull-back was employed to comprehensively image the NPs bound on the lumen of the esophagus. Ratiometric analyses of specific vs. nonspecific binding enabled the visualization of tumor locations and the quantification of biomarker expression in agreement with immunohistochemistry and flow cytometry validation data. PMID:26504623

  20. Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity

    PubMed Central

    Song, Min; He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2016-01-01

    Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivirus system. Our data showed the gene expression of HDAC1 could be efficiently knockdown by RNAi mediated by lentivirus in esophageal carcinoma EC109 cells. Knockdown of HDAC1 led to significant decrease of cell growth and altered cell cycle distribution. The result of transwell assay showed that the numbers of cells travelled through the micropore membrane was significantly decreased as HDAC1 expression was knockdown. Moreover, HDAC1 knockdown inhibited the migration of EC109 cells as determining by scratch test. Additionally, enhancement of cisplatin-stimulated apoptosis was detected by HDAC1 knockdown. Our data suggested inhibition of HDAC1 expression by lentivirus mediated shRNA might be further applied for esophageal cancer chemotherapy. PMID:27698906

  1. Magnesium in drinking water modifies the association between nitrate ingestion and risk of death from esophageal cancer.

    PubMed

    Liao, Yen-Hsiung; Chen, Pei-Shih; Chiu, Hui-Fen; Yang, Chun-Yuh

    2013-01-01

    The objective of this study was to explore whether magnesium (Mg) levels in drinking water modified the effects of nitrate on esophageal cancer risk occurrence. A matched cancer case-control study was used to investigate the relationship between the risk of death from esophageal cancer and exposure to nitrate in drinking water in Taiwan. All esophageal cancer deaths of Taiwan residents from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N and Mg exposure via drinking water. Evidence of an interaction was noted between drinking water NO(3)-N and Mg intake. This is the first study to report effect modification by Mg intake originating from drinking water on an association between NO(3)-N exposure and increased risk mortality attributed to esophageal cancer.

  2. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy.

    PubMed

    Suda, Takako; Tsunoda, Takuya; Daigo, Yataro; Nakamura, Yusuke; Tahara, Hideaki

    2007-11-01

    For the development of cancer vaccine therapies, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to the TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K) and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), which were previously identified to be transactivated in the majority of lung and esophageal cancers. We screened 31, 17 and 17 candidate human leukocyte antigen (HLA)-A*2402-binding peptides to parts of TTK, LY6K and IMP-3, respectively. As a result, we successfully established strong CTL clones stimulated by TTK-567 (SYRNEIAYL), LY6K-177 (RYCNLEGPPI) and IMP-3-508 (KTVNELQNL) that have specific cytotoxic activities against the HLA-A24-positive target cells pulsed with the candidate peptides. Subsequent analysis of the CTL clones also revealed their cytotoxic activities against lung and esophageal tumor cells that endogenously express TTK, LY6K or IMP-3. A cold target inhibition assay further confirmed that the CTL cell clones specifically recognized the MHC class I–peptide complex. Our results strongly imply that TTK, LY6K and IMP-3 are novel tumor-associated antigens recognized by CTL, and TTK-567 (SYRNEIAYL), LY6K-177 (RYCNLEGPPI) and IMP-3-508 (KTVNELQNL) are HLA-A24-restricted epitope peptides that can induce potent and specific immune responses against lung and esophageal cancer cells expressing TTK, LY6K and IMP-3.

  3. Frequent mutation of the p53 gene in human esophageal cancer

    SciTech Connect

    Hollstein, M.C.; Montesano, R. ); Metcalf, R.A.; Welsh, J.A.; Harris, C.C. )

    1990-12-01

    Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. The authors examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5,6,7,8, and 9. Two cell lines and five of the tumor speicmens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G{center dot}C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 genes alleles in one-third of the tumors they tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus.

  4. Effects of metallothionein-3 and metallothionein-1E gene transfection on proliferation, cell cycle, and apoptosis of esophageal cancer cells.

    PubMed

    Tian, Z Q; Xu, Y Z; Zhang, Y F; Ma, G F; He, M; Wang, G-Y

    2013-10-17

    Metallothionein (MT)-3 has cell growth inhibitory activity, and is the only currently known MT subtype with unique physiological functions. The expression levels of MT-1E, a subtype of MT-1, were positively correlated with the degree of esophageal cancer malignancy. The present study aimed to investigate the effects of MT-3 and MT-1E gene transfection on the proliferation, cell cycle, and apoptosis of esophageal cancer cells. The cationic liposome method was used to transfect the esophageal cancer strains Eca-109 and TE13. Reverse transcription-polymerase chain reaction was used to detect target gene expression, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction was applied to detect cell proliferation, and flow cytometry was used for cell cycle and apoptosis detection. Esophageal cancer cells with MT-3 and MT-1E gene transfection showed high expression of the foreign target gene and mRNA. Cells with MT-3 gene transfection showed markedly inhibited proliferation (P < 0.05), a significantly higher proportion of cells in the G0/G1 phase (P < 0.05), a significantly lower proportion of cells in the S phase (P < 0.05), and a significantly increased apoptosis rate (P < 0.05). Cells with MT-1E gene transfection did not show significant changes in proliferation, cell cycle, or apoptosis rate (P > 0.05). Therefore, the upregulation of MT-3 gene expression can inhibit esophageal cancer cell proliferation and induce apoptosis, which may be achieved by blocking the tumor cell growth cycle, whereas effects of the MT-1E gene on the proliferation of esophageal cancer cells were not evident.

  5. mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

    PubMed Central

    Luo, Judong; Wang, Wenjie; Tang, Yiting; Zhou, Dandan; Gao, Yi; Zhang, Qi; Zhou, Xifa; Zhu, Hui; Xing, Ligang; Yu, Jinming

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy. PMID:28367244

  6. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

    SciTech Connect

    Chen, Pei-Chun; Chen, Yen-Ching; Lai, Liang-Chuan; Tsai, Mong-Hsun; Chen, Shin-Kuang; Yang, Pei-Wen; Lee, Yung-Chie; Hsiao, Chuhsing K.; Lee, Jang-Ming; Chuang, Eric Y.

    2012-04-01

    Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

  7. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    PubMed Central

    2012-01-01

    Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders. PMID:22873795

  8. Transcriptional regulation of miR-146b by C/EBPβ LAP2 in esophageal cancer cells

    SciTech Connect

    Li, Junxia; Shan, Fabo; Xiong, Gang; Wang, Ju-Ming; Wang, Wen-Lin; Xu, Xueqing; Bai, Yun

    2014-03-28

    Highlights: • MiR-146b promotes esophageal cancer cell proliferation. • MiR-146b inhibits esophageal cancer cell apoptosis. • C/EBPβ directly binds to miR-146b promoter conserved region. • MiR-146b is up-regulated by C/EBPβ LAP2 transcriptional activation. - Abstract: Recent clinical study indicated that up-regulation of miR-146b was associated with poor overall survival of patients in esophageal squamous cell carcinoma. However, the underlying mechanism of miR-146b dysregulation remains to be explored. Here we report that miR-146b promotes cell proliferation and inhibits cell apoptosis in esophageal cancer cell lines. Mechanismly, two C/EBPβ binding motifs are located in the miR-146b promoter conserved region. Among the three isoforms of C/EBPβ, C/EBPβ LAP2 positively regulated miR-146b expression and increases miR-146b levels in a dose-dependent manner through transcription activation of miR-146b gene. Together, these results suggest a miR-146b regulatory mechanism involving C/EBPβ, which may contribute to the up-regulation of miR-146b in esophageal squamous cell carcinoma.

  9. Radiation treatment for newly diagnosed esophageal cancer with prior radiation to the thoracic cavity

    SciTech Connect

    Sponseller, Patricia; Lenards, Nishele; Kusano, Aaron; Patel, Shilpen

    2014-10-01

    The purpose of this report is to communicate the use of single-positron emission computed tomography scan in planning radiation treatments for patients with a history of radiation to the thoracic cavity. A patient presented with obstructive esophageal cancer, having previously received chemotherapy and radiation therapy to the mediastinum for non-Hodgkin lymphoma 11 years earlier. Owing to a number of comorbidities, the patient was not a surgical candidate and was referred to the University of Washington Medical Center for radiation therapy. Prior dose to the spinal cord and lung were taken into account before designing the radiation treatment plan.

  10. Role of Berberine on molecular markers involved in migration of esophageal cancer cells.

    PubMed

    Mishan, M A; Ahmadiankia, N; Matin, M M; Heirani-Tabasi, A; Shahriyari, M; Bidkhori, H R; Naderi-Meshkin, H; Bahrami, A R

    2015-12-14

    Berberine is an isoquinoline alkaloid found in several plant species like famous chinese herb, Rhizoma coptidis which has been used locally as a strong gastrointestinal remedy for thousands of years. The inhibitory effects of berberine on tumor progression properties have been reported before. In this study, we investigated the effect of berberine on an esophageal cancer cell line, KYSE-30 with emphasis on its effects on the expression of certain chemokine receptors. The cytotoxic effect of berberine on KYSE-30 cells was analyzed by MTT assay. In vitro cell migration assay was also applied to the treated cells and the expression levels of the selected chemokine receptors (CXCR4 and CCR7) was measured at mRNA level. A retarded growth, associated with increasing concentrations of berberine, was obvious. On the other hand, the migration rate of the cells was decreased when they were treated with different concentrations of berberine and the expression levels of the two chemokine receptors, involved in the migration and metastasis of esophageal cancer cells, were decreased following the same treatments. With these results, we tend to conclude that berberine might be a proper candidate for further investigations, by targeting the chemokine receptors, and possible applications as anti-metastatic agent in cancer studies.

  11. Risk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization

    PubMed Central

    Thrift, Aaron P.; Risch, Harvey A.; Onstad, Lynn; Shaheen, Nicholas J.; Casson, Alan G.; Bernstein, Leslie; Corley, Douglas A.; Levine, David M.; Chow, Wong–Ho; Reid, Brian J.; Romero, Yvonne; Hardie, Laura J.; Liu, Geoffrey; Wu, Anna H.; Bird, Nigel C.; Gammon, Marilie D.; Ye, Weimin; Whiteman, David C.; Vaughan, Thomas L.

    2014-01-01

    BACKGROUND & AIMS Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). METHODS We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett’s and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. RESULTS Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62–0.79 for men and OR, 0.57; 95% CI 0.40–0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62–0.77 for men and OR, 0.61; 95% CI, 0.48–0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. CONCLUSIONS Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification. PMID:24530603

  12. Overexpression of miR-214-3p in Esophageal Squamous Cancer Cells Enhances Sensitivity to Cisplatin by Targeting Survivin Directly and Indirectly Through CUG-BP1

    PubMed Central

    Phatak, Pornima; Byrnes, Kimberly A.; Mansour, Daniel; Liu, Lan; Cao, Shan; Li, Ruiyun; Rao, Jaladanki N.; Turner, Douglas J.; Wang, Jian-Ying; Donahue, James M.

    2015-01-01

    Based on its marked overexpression in multiple malignancies and its roles in promoting cell survival and proliferation, survivin is an attractive candidate for targeted therapy. Towards this end, a detailed understanding of the mechanisms regulating survivin expression in different cancer cells will be critical. We have previously shown that the RNA-binding protein (RBP) CUG-BP1 is overexpressed in esophageal cancer cells and post-transcriptionally regulates survivin in these cells. The objective of this study was to investigate the role of microRNAs (miRs) in regulating survivin expression in esophageal cancer cells. Using miR expression profiling analysis, we found that miR-214-3p is one of the most markedly downregulated miRs in two esophageal squamous cancer cell lines compared to esophageal epithelial cells. Interestingly, using miR target prediction programs, both survivin and CUG-BP1 mRNA were found to contain potential binding sites for miR-214-3p. Forced expression of miR-214-3p in esophageal cancer cells leads to a decrease in the mRNA and protein levels of both survivin and CUG-BP1. This effect is due to decreased mRNA stability of both targets. By contrast, silencing miR-214-3p in esophageal epithelial cells leads to an increase in both survivin and CUG-BP1 mRNA and protein. To determine whether the observed effect of miR-214-3p on survivin expression was direct, mediated through CUG-BP1, or both, binding studies utilizing biotin pull-down assays and heterologous luciferase reporter constructs were performed. These demonstrated that the mRNA of survivin and CUG-BP1 each contain two functional miR-214-3p binding sites as confirmed by mutational analysis. Finally, forced expression of miR-214-3p enhances the sensitivity of esophageal cancer cells to Cisplatin-induced apoptosis. This effect is abrogated with rescue expression of survivin or CUG-BP1. These findings suggest that miR-214-3p acts as a tumor suppressor and that its downregulation contributes to

  13. Breast cancer resistance protein (BCRP) and excision repair cross complement-1 (ERCC1) expression in esophageal cancers and response to cisplatin and irinotecan based chemotherapy

    PubMed Central

    Bharthuar, Anubha; Black, Jennifer D.; Levea, Charles; Malhotra, Usha; Mashtare, Terry L.; Iyer, Renuka

    2014-01-01

    Background Esophageal cancer patients face a dismal outcome despite tri-modality management and median survival remains 15-18 months. Breast cancer resistance protein (BCRP) is an ATP-dependent efflux protein associated with chemotherapy resistance. The role of BCRP expression in esophageal cancer and normal esophageal cells is not known. Excision repair cross complement-1 (ERCC1) overexpression has been correlated with poorer response to cisplatin based chemotherapy. We examined the expression of BCRP and ERCC1 in patients with esophageal cancer and correlated it with survival in patients receiving irinotecan and cisplatin based chemotherapy. Methods With IRB approval, 40 cases of esophageal cancer diagnosed from 2004-2008, were stained for BCRP and ERCC1 expression by immunohistochemistry and scored by a pathologist blinded to clinical data. Baseline demographics, therapy given and survival data were collected and correlated with BCRP and ERCC1 expression. Fisher’s exact test was used to determine association between BCRP and ERCC1 expression and demographics. Cox proportional hazards model was used for association of BCRP and ERCC1 with survival. Results On immunohistochemistry, 30/40 cancers (75%) expressed BCRP. Interestingly, down-regulation of BCRP expression in tumor compared with normal cells was seen in 40% of patients. ERCC1 positivity was seen in 15/30 cases (50%). Median overall survival (OS) was 19 months with no difference in survival between BCRP positive and negative patients (P=0.13) or ERCC1 positive and negative patients (P=0.85). Estimated hazard ratio (HR) of death for BRCP positive patients was 2.29 (95% CI: 0.79-6.64) and for ERCC1 positive patients was 1.09 (95% CI: 0.46-2.56). There was no association of BCRP and ERCC1 expression with disease stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line chemotherapy, there was no difference in survival based on BCRP or ERCC1 status. Conclusions BCRP

  14. Association between Postoperatively Developed Atrial Fibrillation and Long-Term Mortality after Esophagectomy in Esophageal Cancer Patients: An Observational Study

    PubMed Central

    Chin, Ji-Hyun; Moon, Young-Jin; Jo, Jun-Young; Han, Yun A.; Kim, Hyeong Ryul; Choi, In-Cheol

    2016-01-01

    Background Newly developed atrial fibrillation (AF) in patients who have undergone an esophagectomy increases the incidence of postoperative complications. However, the clinical implications of AF have not been fully elucidated in these patients. This retrospective observational study investigated the predictors for AF and the effect of AF on the mortality in esophageal cancer patients undergoing esophagectomy. Methods This study evaluated 583 patients undergoing esophagectomy, from January 2005 to April 2012. AF was defined as newly developed postoperative AF requiring treatment. The risk factors for AF and the association between AF and mortality were evaluated. The long-term mortality was the all-cause mortality, for which the cutoff date was May 31, 2014. Results AF developed in 63 patients (10.8%). Advanced age (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.056–1.144, P < 0.001), preoperative calcium channel blocker (CCB) (OR 2.339, 95% CI 1.143–4.786, P = 0.020), and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) (OR 0.206, 95% CI 0.067–0.635, P = 0.006) were associated with the incidence of AF. The Kaplan-Meier curve showed a significantly lower survival rate in the AF group compared to the non-AF group (P = 0.045), during a median follow-up of 50.7 months. The multivariable analysis revealed associations between AF and the 1-year mortality (hazard ratio [HR] 2.556, 95% CI 1.430–4.570, P = 0.002) and between AF and the long-term mortality (HR 1.507, 95% CI 1.003–2.266, P = 0.049). Conclusions In esophageal cancer patients, the advanced age and the preoperative medications (CCB, ACEI or ARB) were associated with the incidence of AF. Furthermore, postoperatively developed AF was associated with mortality in esophageal cancer patients after esophagectomy, suggesting that a close surveillance might be required in patients who showed AF during postoperative period. PMID:27148877

  15. Patient feature based dosimetric Pareto front prediction in esophageal cancer radiotherapy

    SciTech Connect

    Wang, Jiazhou; Zhao, Kuaike; Peng, Jiayuan; Xie, Jiang; Chen, Junchao; Zhang, Zhen; Hu, Weigang; Jin, Xiance; Studenski, Matthew

    2015-02-15

    Purpose: To investigate the feasibility of the dosimetric Pareto front (PF) prediction based on patient’s anatomic and dosimetric parameters for esophageal cancer patients. Methods: Eighty esophagus patients in the authors’ institution were enrolled in this study. A total of 2928 intensity-modulated radiotherapy plans were obtained and used to generate PF for each patient. On average, each patient had 36.6 plans. The anatomic and dosimetric features were extracted from these plans. The mean lung dose (MLD), mean heart dose (MHD), spinal cord max dose, and PTV homogeneity index were recorded for each plan. Principal component analysis was used to extract overlap volume histogram (OVH) features between PTV and other organs at risk. The full dataset was separated into two parts; a training dataset and a validation dataset. The prediction outcomes were the MHD and MLD. The spearman’s rank correlation coefficient was used to evaluate the correlation between the anatomical features and dosimetric features. The stepwise multiple regression method was used to fit the PF. The cross validation method was used to evaluate the model. Results: With 1000 repetitions, the mean prediction error of the MHD was 469 cGy. The most correlated factor was the first principal components of the OVH between heart and PTV and the overlap between heart and PTV in Z-axis. The mean prediction error of the MLD was 284 cGy. The most correlated factors were the first principal components of the OVH between heart and PTV and the overlap between lung and PTV in Z-axis. Conclusions: It is feasible to use patients’ anatomic and dosimetric features to generate a predicted Pareto front. Additional samples and further studies are required improve the prediction model.

  16. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    PubMed

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

  17. Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway.

    PubMed

    Yan, Shu; Tian, Shuxia; Kang, Qingwei; Xia, Yafei; Li, Caixia; Chen, Qing; Zhang, Shukun; Li, Zhigang

    2015-01-01

    Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1 mg/kg) for 10 weeks. RPS (350 mg/kg or 100 mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.

  18. Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway

    PubMed Central

    Yan, Shu; Tian, Shuxia; Kang, Qingwei; Xia, Yafei; Li, Caixia; Chen, Qing; Zhang, Shukun; Li, Zhigang

    2015-01-01

    Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1mg/kg) for 10 weeks. RPS (350 mg/kg or 100mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer. PMID:26147856

  19. Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

    SciTech Connect

    Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S.

    2011-07-15

    Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

  20. Endoscopic surveillance of head and neck cancer in patients with esophageal squamous cell carcinoma

    PubMed Central

    Kato, Minoru; Ishihara, Ryu; Hamada, Kenta; Tonai, Yusuke; Yamasaki, Yasushi; Matsuura, Noriko; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Multiple squamous cell carcinomas (SCCs) frequently arise in the upper aerodigestive tract, referred to as the field cancerization phenomenon. The aim of this study was to elucidate the detailed clinical features of second primary head and neck (H&N) SCCs arising in patients with esophageal SCC. Patients and methods: A total of 818 patients underwent endoscopic resection for superficial esophageal cancer between January 2006 and December 2013. Of these, 439 patients met our inclusion criteria, and we retrospectively investigated the incidence, primary sites, and stages of second primary H&N SCCs in these patients. Results: A total of 53 metachronous H&N SCCs developed in 40 patients after a median follow-up period of 46 months (range 9 – 109). The cumulative incidence rates of metachronous H&N SCCs at 3, 5, and 7 years were 5.3 %, 9.7 %, and 17.2 %, respectively. These lesions were frequently located at pyriform sinus or in the posterior wall of the pharynx (70 %, 37/53 lesions). Most of the lesions were detected at an early stage, though 4 lesions were associated with lymph node metastasis when their primary sites were detected (1 postcricoid area, 2 posterior wall of hypopharynx, and 1 lateral wall of oropharynx). Conclusions: Patients with esophageal SCC should undergo careful inspection of the pyriform sinus and posterior wall of the pharynx for detection of H&N SCCs. Methods to open the hypopharyngeal space, such as the Valsalva maneuver, should be included in the surveillance program. PMID:27556090

  1. Differences in esophageal cancer characteristics and survival between Chinese and Caucasian patients in the SEER database

    PubMed Central

    Lin, Min-Qiang; Li, Yue-Ping; Wu, San-Gang; Sun, Jia-Yuan; Lin, Huan-Xin; Zhang, Shi-Yang; He, Zhen-Yu

    2016-01-01

    Background To compare the clinicopathologic characteristics and survival of Chinese and Caucasian esophageal cancer (EC) patients residing in the US, using a population-based national registry (Surveillance Epidemiology and End Results [SEER]) database. Methods Patients with EC were identified from the SEER program from 1988 to 2012. Kaplan–Meier survival methods and Cox proportional hazards regression were performed. Results A total of 479 Chinese and 35,748 Caucasian EC patients were identified. Compared with Caucasian patients, the Chinese patients had a later year of diagnosis, remained married after EC was diagnosed, had esophageal squamous cell carcinomas (ESCCs) more frequently, had tumors located in the upper-third and middle-third of the esophagus more frequently, and fewer patients presented with poorly/undifferentiated EC and underwent cancer-directed surgery. In Chinese patients, the incidence of esophageal adenocarcinomas (EACs) increased from 1988 to 2012 (P=0.054), and the majority of EAC patients had tumors located in the lower thoracic esophagus. The overall survival (OS) was not significantly different between Chinese and Caucasian patients (P=0.767). However, Chinese patients with ESCC had a significantly better OS when compared to their Caucasian counterparts, whereas there was no significant difference in the OS between Chinese and Caucasian patients with EAC. Conclusion The presenting demographic features, tumor characteristics, and outcomes of EC patients differed between Chinese and Caucasian patients residing in the US. Chinese patients diagnosed with EAC tended to share similar clinical features with their Caucasian counterparts, and the Chinese patients with ESCC had better OS than their Caucasian counterparts. PMID:27799791

  2. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms.

    PubMed

    Stoner, Gary D; Chen, Tong; Kresty, Laura A; Aziz, Robeena M; Reinemann, Tiffany; Nines, Ronald

    2006-01-01

    For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry preparations for study, each berry type is of the same cultivar, picked at about the same degree of ripeness, washed and frozen within 2-4 h of the time of picking, and freeze-dried under conditions that preserve the components in the berries. Some of the known chemopreventive agents in berries include vitamins A, C, and E and folic acid; calcium and selenium; beta-carotene, alpha-carotene, and lutein; polyphenols such as ellagic acid, ferulic acid, p-coumaric acid, quercetin, and several anthocyanins; and phytosterols such as beta-sitosterol, stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10% and fed to Fischer 344 rats before, during, and after treatment with the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). At 25 wk of the bioassay, all three berry types were found to inhibit the number of esophageal tumors (papillomas) in NMBA-treated animals by 24-56% relative to NMBA controls. This inhibition correlated with reductions in the formation of the NMBA-induced O6-methylguanine adduct in esophageal DNA, suggesting that the berries influenced the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to determine the mechanisms by which berries influence NMBA metabolism and DNA adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and were found to inhibit NMBA-induced esophageal tumorigenesis by 31-64% when administered in the diet following treatment of the animals with NMBA. Berries, therefore, inhibit tumor promotion and progression events as well as tumor initiation. In vivo mechanistic studies

  3. Esophageal cancer: anatomic particularities, staging, and imaging techniques.

    PubMed

    Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

    2016-01-01

    Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.

  4. A comparison of postoperative early enteral nutrition with delayed enteral nutrition in patients with esophageal cancer.

    PubMed

    Wang, Gongchao; Chen, Hongbo; Liu, Jun; Ma, Yongchen; Jia, Haiyong

    2015-06-02

    We examined esophageal cancer patients who received enteral nutrition (EN) to evaluate the validity of early EN compared to delayed EN, and to determine the appropriate time to start EN. A total of 208 esophagectomy patients who received EN postoperatively were divided into three groups (Group 1, 2 and 3) based on whether they received EN within 48 h, 48 h-72 h or more than 72 h, respectively. The postoperative complications, length of hospital stay (LOH), days for first fecal passage, cost of hospitalization, and the difference in serum albumin values between pre-operation and post-operation were all recorded. The statistical analyses were performed using the t-test, the Mann-Whitney U test and the chi square test. Statistical significance was defined as p < 0.05. Group 1 had the lowest thoracic drainage volume, the earliest first fecal passage, and the lowest LOH and hospitalization expenses of the three groups. The incidence of pneumonia was by far the highest in Group 3 (p = 0.019). Finally, all the postoperative outcomes of nutritional conditions were the worst by a significant margin in Group 3. It is therefore safe and valid to start early enteral nutrition within 48 h for postoperative esophageal cancer patients.

  5. Establishment of an international database for genetic variants in esophageal cancer.

    PubMed

    Vihinen, Mauno

    2016-10-01

    The establishment of a database has been suggested in order to collect, organize, and distribute genetic information about esophageal cancer. The World Organization for Specialized Studies on Diseases of the Esophagus and the Human Variome Project will be in charge of a central database of information about esophageal cancer-related variations from publications, databases, and laboratories; in addition to genetic details, clinical parameters will also be included. The aim will be to get all the central players in research, clinical, and commercial laboratories to contribute. The database will follow established recommendations and guidelines. The database will require a team of dedicated curators with different backgrounds. Numerous layers of systematics will be applied to facilitate computational analyses. The data items will be extensively integrated with other information sources. The database will be distributed as open access to ensure exchange of the data with other databases. Variations will be reported in relation to reference sequences on three levels--DNA, RNA, and protein-whenever applicable. In the first phase, the database will concentrate on genetic variations including both somatic and germline variations for susceptibility genes. Additional types of information can be integrated at a later stage.

  6. A human esophageal epithelial cell model for study of radiation induced cancer and DNA repair

    NASA Astrophysics Data System (ADS)

    Huff, Janice; Patel, Zarana; Hada, Megumi; Cucinotta, Francis A.

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma. Development of squamous cell carcinoma of the esophagus is associated with radiation exposure, as revealed by the significant enhanced in incidence rates for this type of cancer in the survivors of the atomic bomb detonations in Japan. It is also associated with poor nutritional status and micronutrient deficiencies, which are also important issues for long duration spaceflight. The possible synergies between nutritional issues and radiation exposure are unknown. Here we present the results of preliminary characterization of both normal and hTERT-immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of gamma-H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron.

  7. Esophageal cancer epidemiology in blacks and whites: racial and gender disparities in incidence, mortality, survival rates and histology.

    PubMed Central

    Baquet, Claudia R.; Commiskey, Patricia; Mack, Kelly; Meltzer, Stephen; Mishra, Shiraz I.

    2005-01-01

    BACKGROUND: Esophageal cancer rate disparities are pronounced for blacks and whites. This study presents black-white esophageal cancer incidence, mortality, relative survival rates, histology and trends for two five-year time periods--1991-1995 and 1996-2000--and for the time period 1991-2000. METHODS: The study used data from the National Cancer Institute's population-based Surveillance Epidemiology End Results (SEER) program with submission dates 1991-2000. Age-adjusted incidence, mortality, relative survival rates and histology for esophageal carcinoma were calculated for nine SEER cancer registries for 1991-2000. Rates were analyzed by race and gender for changes over specified time periods. RESULTS: Esophageal cancer age-adjusted incidence of blacks was about twice that of whites (8.63 vs. 4.39/100,000, p < 0.05). Age-adjusted mortality for blacks, although showing a declining trend, was nearly twice that of whites (7.79 vs. 3.96, p < 0.05). Although survival was poor for all groups, it was significantly poorer in blacks than in whites. Squamous cell carcinoma was more commonly diagnosed in blacks and white females, whereas adenocarcinoma was more common among white males (p < 0.001). CONCLUSIONS: Racial disparities in esophageal cancer incidence, mortality, survival and histology exist. Survival rates from this disease have not significantly improved over the decade. These data support the need for advances in prevention, early detection biomarker research and research on new, more effective treatment modalities for this disease. Images Figure 1 PMID:16334494

  8. The medicinal fungus Antrodia cinnamomea regulates DNA repair and enhances the radiosensitivity of human esophageal cancer cells

    PubMed Central

    Liu, Yu-Ming; Liu, Yu-Kuo; Wang, Ling-Wei; Huang, Yu-Chuen; Huang, Pin-I; Tsai, Tung-Hu; Chen, Yu-Jen

    2016-01-01

    This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase. An immunofluorescence assay and a Western blotting assay showed that AC-MFB delayed the abrogation of γ-H2AX, upregulated p21 expression, and attenuated the radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. An in vivo validation study showed that AC-MFB treatment tended to have a synergistic effect with radiation on the tumor growth delay of CE81T/VGH cells in BALB/c mice. These data suggest that this edible fungus product could enhance the effect of radiotherapy against esophageal cancer. PMID:27826196

  9. Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy

    PubMed Central

    Liu, Ting; Wu, Hai-Jun; Liang, Yu; Liang, Xu-Jun; Huang, Hui-Chao; Zhao, Yan-Zhong; Liao, Qing-Chuan; Chen, Ya-Qi; Leng, Ai-Min; Yuan, Wei-Jian; Zhang, Gui-Ying; Peng, Jie; Chen, Yong-Heng

    2016-01-01

    AIM: To develop a potent and safe gene therapy for esophageal cancer. METHODS: An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. RESULTS: Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. CONCLUSION: The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy. PMID:27340350

  10. High incidence of esophageal cancer in central-western Brazil: a migrant effect?

    PubMed

    e Silva, Diego Rodrigues Mendonça; Curado, Maria-Paula; de Oliveira, José Carlos

    2013-05-01

    To determine the incidence and mortality rates of esophageal cancer in central-western Brazil: Goiânia, Brasília, Cuiabá, and Campo Grande, incidence data for Cuiabá (2000-2005) and Brasília (1999-2002) were obtained from the National Cancer Institute, and data from Goiânia (1995-2008) from the Population-Based Cancer Registry of Goiânia. Mortality data for the cities of central-western Brazil were obtained for the period 1980-2008 from the Ministry of Health. Age-standardized incidence and mortality rates were calculated using the world population of Segi. Mortality trends were assessed with the Joinpoint Regression Program and a P value less than 0.05 was defined as significant. The highest incidence of esophageal cancer among men was in Cuiabá (16.0/100 000); the lowest was in Goiânia (6.5/100 000). Among women, the incidence rates were similar in Brasília and Cuiabá, but in Goiânia, the incidence declined. There was a significant increase in mortality among men in Cuiabá (2.4%, P=0.03) and Campo Grande (1.2%, P=0.05), and in women (1.6%, P=0.04) in Goiânia. Mortality by age group increased significantly in Campo Grande by 1.9% for men aged at least 50 years and in Goiânia by 2.7% among women aged at least 50 years; the mortality decreased in Goiânia by 2.2% for women aged less than 50 years. The incidence of esophageal cancer in Brasília and Cuiabá was similar to that of southern Brazil in some periods. There was an increase in mortality trends for men in Cuiabá and Campo Grande, and for women in Goiânia.

  11. Tea and coffee consumption and risk of esophageal cancer: the European prospective investigation into cancer and nutrition study.

    PubMed

    Zamora-Ros, Raul; Luján-Barroso, Leila; Bueno-de-Mesquita, H Bas; Dik, Vincent K; Boeing, Heiner; Steffen, Annika; Tjønneland, Anne; Olsen, Anja; Bech, Bodil Hammer; Overvad, Kim; Boutron-Ruault, Marie-Christine; Racine, Antoine; Fagherazzi, Guy; Kuhn, Tilman; Katzke, Verena; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Tumino, Rosario; Panico, Salvatore; Vineis, Paolo; Grioni, Sara; Palli, Domenico; Weiderpass, Elisabete; Skeie, Guri; Huerta, José María; Sánchez, María-José; Argüelles, Marcial; Amiano, Pilar; Ardanaz, Eva; Nilsson, Lena; Wallner, Bengt; Lindkvist, Björn; Wallström, Peter; Peeters, Petra H M; Key, Timothy J; Khaw, Kay-Thee; Wareham, Nicholas J; Freisling, Heinz; Stepien, Magdalena; Ferrari, Pietro; Gunter, Marc J; Murphy, Neil; Riboli, Elio; González, Carlos A

    2014-09-15

    Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition. Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; p-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; p-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; p-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100 mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

  12. Chemoradiotherapy for Synchronous Multiple Primary Cancers with Esophageal Squamous Cell Carcinoma: a Case-control Study

    PubMed Central

    Li, Qi-Wen; Zhu, Yu-Jia; Zhang, Wen-Wen; Yang, Han; Liang, Yao; Hu, Yong-Hong; Qiu, Bo; Liu, Meng-Zhong; Liu, Hui

    2017-01-01

    Objective: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CRT) in multiple primary cancers (MPC) of the upper digestive tract in esophageal squamous cell carcinoma (ESCC). Methods: In a screening of 1193 consecutive patients diagnosed with ESCC and received radiotherapy, 53 patients presenting synchronous MPC in the upper digestive tract were retrospectively investigated. 53 consecutive patients with esophageal non-multiple primary cancer (NPC), matched by stage, age and sex, served as control. All of the patients received concurrent CRT. The median radiation dose was 60 Gy. Chemotherapy regimens were based on platinum and/or 5-fluorouracil. Clinical outcomes and treatment toxicities were compared. Results: Clinic-pathologic characteristics were well balanced between groups. MPC mostly located in esophagus (43, 81.8%), followed by hypopharynx (8, 15.1%) and stomach (2, 3.8%). In MPC and NPC patients, 94.3% and 96.2% completed the intended treatment. The immediate response rate was 73.6% vs 75.5%, with complete response rate of 11.3% vs 24.5% and partial response rate of 62.3% vs 51.0%. Two-year overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were 52.2% vs 68.9% (p=0.026), 32.9% vs 54.0% (p=0.032), 60.8% vs 87.8% (p=0.002) and 64.0% vs 70.8% (p=0.22), respectively. Acute grade 3-4 toxicities were observed in 64.2% vs 54.7%, significantly higher in radiation esophagitis (49.1% vs 28.3%, p<0.001), and mucositis (11.3% vs 00p=0.027). Conclusions: Compared with matched NPC, ESCC accompanied with synchronous MPC was related to significantly impaired survival, elevated risk of locoregional disease progression and higher incidence of severe esophagitis and mucositis, following concurrent chemoradiotherapy. Future study on reasons for decreased efficacy of chemoradiotherapy will help to optimize treatment. Advanced radiation techniques may play a role

  13. Minimally invasive Ivor-Lewis esophagectomy for esophageal cancer with right aortic arch

    PubMed Central

    Linson, Jeremy; Ahmed, Bestoun; Awad, Ziad

    2017-01-01

    Right aortic arch (RAA) is a rare congenital vascular abnormality in which the aorta descends in the right thorax and encircles the esophagus. Historically, esophagectomy for patients for RAA is done through a left thoracotomy as exposure and mobilization of the esophagus is difficult through a right thoracotomy. A 73-year-old male was found to have an esophageal adenocarcinoma. Endoscopic ultrasound showed a T3N0 lesion in the lower third of the esophagus. PET CT demonstrated a circumferential lesion without evidence of distant disease or involved lymph nodes and a RAA which was not associated with congenital heart disease or symptoms. The patient received neo-adjuvant chemoradiation (50.4 Gy) with carboplatin and paclitaxel. Minimally invasive Ivor-Lewis esophagectomy (MIE) utilizing conventional right thoracoscopy was done. Esophageal mobilization, transection and mediastinal lymph node dissection was performed through anteriorly placed trocars, thereby avoiding the right side descending aorta that is lying anterior and to the right of the esophagus. In this video we demonstrate MIE utilizing right thoracoscopy. Total operative time was 250 minutes and the patient was discharged home on post-operative day 8. Final pathology showed complete pathological response, with 0/22 involved lymph nodes and uninvolved surgical margins. Minimally invasive esophagectomy has been reported to deliver superior outcomes to the open approach. MIE can be performed in selected patients with RAA, and herein we demonstrate a minimally invasive option for the treatment of distal esophageal cancer in patients with RAA. To our knowledge this is the 1st reported case in the English literature utilizing this approach in patient with RAA.

  14. Detection of Occult Lymph Node Metastases in Esophageal Cancer by Minimally Invasive Staging Combined with Molecular Diagnostic Techniques

    PubMed Central

    Kassis, Edmund S.; Nguyen, Ninh; Shriver, Sharon P.; Siegfried, Jill M.; Schauer, Philip R.

    1998-01-01

    Background and Objectives: Lymph node metastases are the most important prognostic factor in patients with esophageal cancer. Histologic examination misses micrometastases in up to 20% of lymph nodes evaluated. In addition, non-invasive imaging modalities are not sensitive enough to detect small lymph nodes metastases. The objective of this study was to investigate the use of reverse transcriptase-polymerase chain reaction (RT-PCR) of messenger RNA (mRNA) for carcinoembryonic antigen (CEA) to increase the detection of micrometastases in lymph nodes from patients with esophageal cancer. Methods: RT-PCR of CEA mRNA was performed in lymph nodes from patients with malignant and benign esophageal disease. Each specimen was examined histopathologically and by RT-PCR and the results were compared. Results: Metastases were present in 29 of 60 (48%) lymph nodes sample by minimally invasive staging from 13 patients with esophageal cancer when examined histopathologically. RT-PCR identified nodal metastases in 46 of these 60 (77%) samples. RT-PCR detected CEA mRNA in all 29 histologically positive samples and in 17 histologically negative lymph nodes. All lymph nodes from patients with benign disease (n=15) were negative both histopathologically and by RT-PCR. The stage of two patients was reclassified based on the RT-PCR results, which identified lymph node spread undetected histopathologically. Both of these patients developed recurrent disease after resection of the primary tumor. Conclusions: RT-PCR is more sensitive than histologic examination in the detection of lymph node metastases in esophageal cancer and can lead to diagnosis of a more advanced stage in some patients. The combination of minimally invasive surgical techniques in combination with new molecular diagnostic techniques may improve our ability to stage cancer patients. PMID:10036123

  15. Effects of silencing the ATP-binding cassette protein E1 gene by electroporation on the proliferation and migration of EC109 human esophageal cancer cells.

    PubMed

    Li, Xiao-Rui; Yang, Liu-Zhong; Huo, Xiao-Qing; Wang, Ying; Yang, Qing-Hui; Zhang, Qing-Qin

    2015-07-01

    In the present study, the gene expression of ATP-binding cassette protein E1 (ABCE1) in the EC109 human esophageal cancer cell line was silenced using electroporation to examine the effect if the ABCE1 gene on the growth migration and cell cycle of cancer cells. The small interference (si)RNA sequence of ABCE1 was designed and synthesized to transfect the EC109 cells by electroporation. The mRNA and protein expression levels of ABCE1 were then detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The analysis of the cell cycle and apoptosis was performed using flow cytometry. The effect of silencing the ABCE1 gene on the proliferation, migration and invasive ability of the EC109 human esophageal cancer cells were assessed using a Cell counting kit-8 (CCK-8) and with proliferation, wound-healing and cell invasion assays. The mRNA and protein expression levels of ABCE1 were significantly lower in the experimental group compared with the control group (P<0.05). The apoptotic rate of the experimental group was markedly higher than the control group and blank group (P<0.01). The CCK-8 proliferation assay revealed that, compared with the control and blank groups, the proliferation of the EC109 cells in the experimental group was significantly inhibited (P<0.05). The wound healing assay revealed that the migration capacity of the cells in the experimental group was significantly decreased (P<0.05). The Transwell chamber assay demonstrated that the invasive ability of the EC109 cells in the experimental group was significantly decreased (P<0.01). These results revealed that ABCE1 is closely associated with cell proliferation, invasion and migration in esophageal cancer and silencing the ABCE1 gene by electroporation can significantly reduce the proliferation, invasion and migration capacity of EC109 cells in vitro.

  16. Cytochrome P450 1B1, a novel chemopreventive target for benzo[a]pyrene-initiated human esophageal cancer.

    PubMed

    Wen, Xia; Walle, Thomas

    2007-02-08

    Esophageal cancer is common worldwide, with poor prognosis. Smoking, including exposure to polyaromatic hydrocarbons like benzo[a]pyrene (BaP), is a major risk factor. In human esophageal HET-1A cells, we found that time-dependent BaP-DNA binding was associated with upregulation of CYP1B1, but not CYP1A1, mRNA and protein. The dietary flavonoid 5,7-dimethoxyflavone significantly inhibited BaP-DNA binding and down-regulated BaP-induced CYP1B1 mRNA and protein. 3',4'-Dimethoxyflavone was an even more potent inhibitor of CYP1B1 expression, while resveratrol had no effect. Thus, dietary methoxylated flavones inhibited BaP-induced CYP1B1 transcription in a cell-specific manner and hold promise as chemopreventive agents in esophageal carcinogenesis.

  17. Factors Influencing Compliance to Radical Treatment of Middle Thoracic Esophageal Cancer: An Audit from a Regional Cancer Centre

    PubMed Central

    Kapoor, Rakesh; Bansal, Anshuma; Kumar, Shikhar; Miriyala, Ravi Teja

    2016-01-01

    Background: The aim of this study is to identify the factors responsible for interruption of planned treatment in patients of carcinoma mid-thoracic esophagus and also discuss the strategies for improving treatment completion rates. Materials and Methods: Patients with nonmetastatic mid-thoracic esophageal cancer who received treatment by multimodality approach using chemotherapy, radiation, and/or surgery were retrospectively analyzed. Factors influencing compliance with planned treatment completion were evaluated, and their significance was determined using multivariate Cox regression analysis. Results: Ninety-one patients were reviewed. Median follow-up period was 11 months. Of 15 patients planned with neoadjuvant chemoradiation followed by surgery (Group 1), only 6 (40%) could complete the treatment. Similarly, only 19 out of 36 patients (52.8%) completed the planned definitive chemoradiation (Group 2). Furthermore, of forty patients planned with definitive radiotherapy (Group 3), 29 patients only (72.5%) completed this schedule. The rate of completion of therapy was worst in Group 1. The most common reason for noncompletion of planned treatment was nutritional inadequacy and excessive weight loss in all groups. In addition, chemotherapy-induced myelosuppression (P = 0.05) was the factor leading to treatment interruption in Group 2 and radiation-induced acute mucositis (P = 0.02) and lost to follow-up (P = 0.02) were the factors in Group 3. Conclusions: Rate of treatment completion significantly impacts survival rates. Nutritional inadequacy was the most common factor for noncompletion of planned treatment. A well-trained management team consisting of oncologist, dietitian, and psychotherapist can help overcome these factors and thereby improve the treatment completion rates. PMID:27559257

  18. Overexpression of miR-199a-5p decreases esophageal cancer cell proliferation through repression of mitogen-activated protein kinase kinase kinase-11 (MAP3K11)

    PubMed Central

    Byrnes, Kimberly A.; Phatak, Pornima; Mansour, Daniel; Xiao, Lan; Zou, Tongtong; Rao, Jaladanki N.; Turner, Douglas J.; Wang, Jian-Ying; Donahue, James M.

    2016-01-01

    Studies examining the oncogenic or tumor suppressive functions of dysregulated microRNAs (miRs) in cancer cells may also identify novel miR targets, which can themselves serve as therapeutic targets. Using array analysis, we have previously determined that miR-199a-5p was the most downregulated miR in two esophageal cancer cell lines compared to esophageal epithelial cells. MiR-199a-5p is predicted to bind mitogen-activated protein kinase kinase kinase 11 (MAP3K11) mRNA with high affinity. In this study, we observed that MAP3K11 is markedly overexpressed in esophageal cancer cell lines. Forced expression of miR-199a-5p in these cells leads to a decrease in the mRNA and protein levels of MAP3K11, due to decreased MAP3K11 mRNA stability. A direct binding interaction between miR-199a-5p and MAP3K11 mRNA is demonstrated using biotin pull-down assays and heterologous luciferase reporter constructs and confirmed by mutational analysis. Finally, forced expression of miR-199a-5p decreases proliferation of esophageal cancer cells by inducing G2/M arrest. This effect is mediated, in part, by decreased transcription of cyclin D1, due to reduced MAP3K11-mediated phosphorylation of c-Jun. These findings suggest that miR-199a-5p acts as a tumor suppressor in esophageal cancer cells and that its downregulation contributes to enhanced cellular proliferation by targeting MAP3K11. PMID:26717044

  19. Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during chemoradiation predict for survival and pathologic complete response in trimodality esophageal cancer patients

    PubMed Central

    Hyder, Jalal; Boggs, Drexell Hunter; Hanna, Andrew; Suntharalingam, Mohan

    2016-01-01

    Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multimodality therapy, the effect of therapy on the NLR and PLR is not well understood. We evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods We performed a retrospective analysis of nonmetastatic patients with esophageal cancer who received neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained for the following time points (TPs): (I) at diagnosis before CRT; (II) after CRT but prior to surgery; and (III) after surgery. We evaluated changes in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results This IRB-approved study included the records of 83 consecutive patients with stage II-IV esophageal cancer. The median age was 60 years, and median follow-up was 29.3 months. Patients were treated to a median prescription dose of 50.4 Gy (range, 50.4-56.4 Gy) in 28-33 fractions. Median NLR and PLR were 3.3 and 157.2, 12 and 645, and 11.5 and 391.7 at TPs 1, 2, and 3, respectively. On multivariate analysis, superior OS was associated with PLR ≥250 at TP3 (P=0.03), PLR decrease ≥609.2 between TP2 and TP3 (P=0.02), and PLR ratio (TP3/TP1) ≥1.08 (P=0.03). Inferior progression-free survival (PFS) was associated with NLR ≥36 at TP2 (P=0.0008), NLR increase ≥28.3 between TP1 and TP2 (P=0.0005), and PLR ratio (TP2/TP3) ≥0.38 (P=0.1). Pathologic complete response (PCR) was less likely for adenocarcinoma (AC) histology (P=0.03), NLR ≥10.6 at TP2 (P=0.04), and NLR increase ≥4.6 from TP1 to TP2 (P=0.03). Conclusions To our knowledge, this is the first

  20. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    SciTech Connect

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-03-15

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.

  1. The Antiproliferative Effect of Moringa oleifera Crude Aqueous Leaf Extract on Human Esophageal Cancer Cells.

    PubMed

    Tiloke, Charlette; Phulukdaree, Alisa; Chuturgoon, Anil A

    2016-04-01

    Esophageal cancer (EC) is commonly diagnosed in South Africa (SA), with high incidences occurring in SA's black population. Moringa oleifera (MO), a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of ailments, including cancer. We investigated the antiproliferative effect of MO crude aqueous leaf extract (MOE) on a cancerous esophageal cell line (SNO). SNO cells were exposed to a range of MOE dilutions to evaluate cytotoxicity (MTT assay). Oxidative stress was determined using the TBARS assay. The comet assay was used to assess DNA damage. We then determined cell death mechanisms by measuring phosphatidylserine (PS) externalization (flow cytometry), caspase-3/7 and caspase-9 activities, and adenosine triphosphate (ATP) levels (luminometry). Protein expression of Smac/DIABLO and PARP-1 was determined by western blotting. SNO cells were treated with a range of MOE dilutions to obtain an IC50 value of 389.2 μg/mL MOE (24 h), which was used in all subsequent assays. MOE significantly increased lipid peroxidation (P < .05) and DNA fragmentation (P < .0001) in SNO cells. The induction of apoptosis was confirmed by the increase in PS externalization (P < .0001), caspase-9 (P < .05) and caspase-3/7 (P = .22) activities, and decreased ATP levels (P < .0001). MOE significantly increased both the expression of Smac/DIABLO protein and cleavage of PARP-1, resulting in an increase in the 24-kDa fragment (P < .001). MOE possesses antiproliferative effects on SNO EC cells by increasing lipid peroxidation, DNA fragmentation, and induction of apoptosis.

  2. Dose-volume modeling of the risk of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery

    SciTech Connect

    Tucker, Susan L. . E-mail: sltucker@mdanderson.org; Liu, H. Helen; Wang, Shulian; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Mohan, Radhe

    2006-11-01

    Purpose: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. Methods and Materials: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. Results: Normal-tissue complication probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses {>=}5 Gy (VS5), that is, exposed to doses <5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving {>=}5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, {infinity}), m = 0.55 (0.22, 1.02), and D {sub 5} = 17.5 Gy (9.4 Gy, 102 Gy). Conclusions: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving <5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of Radiation dose distribution in the lung.

  3. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

    PubMed

    Liu, Wenjin; Snell, Jeff M; Jeck, William R; Hoadley, Katherine A; Wilkerson, Matthew D; Parker, Joel S; Patel, Nirali; Mlombe, Yohannie B; Mulima, Gift; Liomba, N George; Wolf, Lindsey L; Shores, Carol G; Gopal, Satish; Sharpless, Norman E

    2016-10-06

    Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

  4. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis

    PubMed Central

    Liu, Wenjin; Snell, Jeff M.; Jeck, William R.; Wilkerson, Matthew D.; Parker, Joel S.; Patel, Nirali; Mlombe, Yohannie B.; Mulima, Gift; Liomba, N. George; Wolf, Lindsey L.; Shores, Carol G.; Gopal, Satish; Sharpless, Norman E.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses. PMID:27734031

  5. The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study

    PubMed Central

    Hu, Dan; Peng, Feng; Lin, Xiandong; Chen, Gang; Liang, Binying; Li, Chao; Zhang, Hejun; Liao, Xuehong; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2016-01-01

    Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: P<0.001). In males, the survival was worse in patients with diabetes than those without (MST: 27.9 vs. 111.1 months, Log-rank test: P<0.001). In females, the survivor was improved in patients with diabetes (MST: 71.5 months), but was still worse than patients without diabetes (MST: 180+ months, Log-rank test: P<0.001). The overall multivariate hazard ratio for per unit increment in fasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, P<0.001) and 1.08 (95% CI: 1.03-1.13, P=0.002) in males and females, respectively. Further survival tree analysis consolidated the discrimination ability of fasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males. PMID:27533454

  6. The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

    PubMed

    Hu, Dan; Peng, Feng; Lin, Xiandong; Chen, Gang; Liang, Binying; Li, Chao; Zhang, Hejun; Liao, Xuehong; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2016-10-04

    Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: P<0.001). In males, the survival was worse in patients with diabetes than those without (MST: 27.9 vs. 111.1 months, Log-rank test: P<0.001). In females, the survivor was improved in patients with diabetes (MST: 71.5 months), but was still worse than patients without diabetes (MST: 180+ months, Log-rank test: P<0.001). The overall multivariate hazard ratio for per unit increment in fasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, P<0.001) and 1.08 (95% CI: 1.03-1.13, P=0.002) in males and females, respectively. Further survival tree analysis consolidated the discrimination ability of fasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males.

  7. Lithium Modulates Autophagy in Esophageal and Colorectal Cancer Cells and Enhances the Efficacy of Therapeutic Agents In Vitro and In Vivo

    PubMed Central

    O’Donovan, Tracey R.; Rajendran, Simon; O’Reilly, Seamus; McKenna, Sharon L.

    2015-01-01

    Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. However, known pharmacological inhibitors of autophagy could not enhance cytotoxicity. In this study, we have examined two well known, clinically approved autophagy inducers, rapamycin and lithium, for their effects on chemosensitivity in apoptosis incompetent cancer cells. Both lithium and rapamycin were shown to induce autophagosomes in esophageal and colorectal cancer cells by western blot analysis of LC3 isoforms, morphology and FACS quantitation of Cyto-ID or mCherry-GFP-LC3. Analysis of autophagic flux indicates inefficient autophagosome processing in lithium treated cells, whereas rapamycin treated cells showed efficient flux. Viability and recovery was assessed by clonogenic assays. When combined with the chemotherapeutic agent 5-fluorouracil, rapamycin was protective. In contrast, lithium showed strong enhancement of non-apoptotic cell death. The combination of lithium with 5-fluorouracil or oxaliplatin was then tested in the syngenic mouse (balb/c) colorectal cancer model—CT26. When either chemotherapeutic agent was combined with lithium a significant reduction in tumor volume was achieved. In addition, survival was dramatically increased in the combination group (p < 0.0001), with > 50% of animals achieving long term cure without re-occurrence (> 1 year tumor free). Thus, combination treatment with lithium can substantially improve the efficacy of chemotherapeutic agents in apoptosis deficient cancer cells. Induction of compromised autophagy may contribute to this cytotoxicity. PMID:26248051

  8. Problems and needs in patients with incurable esophageal and pancreaticobiliary cancer: a descriptive study.

    PubMed

    Uitdehaag, Madeleen J; Verschuur, Els M L; van Eijck, Casper H J; van der Gaast, Ate; van der Rijt, Carin C D; de Man, Rob A; Steyerberg, Ewout W; Kuipers, Ernst J; Siersema, Peter D

    2015-01-01

    Patients with incurable esophageal cancer (EC) or pancreaticobiliary cancer (PBC) often have multiple symptoms and their quality of life is poor. We investigated which problems these patients experience and how often care is expected for these problems to provide optimal professional care. Fifty-seven patients with incurable EC (N = 24) or PBC (N = 33) from our outpatient clinic completed the validated "Problems and Needs for Palliative Care" (PNPC) questionnaire and two disease-specific quality of life questionnaires, European Organization for Research and Treatment in Cancer (EORTC). Although patients in general had several problems, physical, emotional, and loss of autonomy (LOA) problems were most common. For these physical and emotional problems, patients also expected professional care, although to a lesser extent for LOA problems. Inadequate care was received for fatigue, fear, frustration, and uncertainty. We conclude that an individualized approach based on problems related to physical, emotional, and LOA issues and anticipated problems with healthcare providers has priority in the follow-up policy of patients with incurable upper gastrointestinal cancer. Caregivers should be alert to discuss needs for fatigue, feelings of fear, frustration, and uncertainty.

  9. Apnea in postsurgical hypnotherapy of an esophageal cancer patient: a brief communication.

    PubMed

    Jones, M M

    1994-07-01

    Use of clinical hypnosis in the postsurgical psychotherapy of an esophageal cancer patient who could not swallow involved reenactment of the successful surgery and producing hallucinations of taste and smell, as well as working through emotions relations to the surgery and her disease. An apnea that occurred in a late phase of the treatment was addressed with the familiar arm pumping technique that had been used as a deepening technique, resulting in the patient's resuming normal breathing. The experience reminds the practitioner of the possible unexpected professional demands when working in a medical environment. It also provides clues as to the underlying psychological mechanisms and their role in successful symptom removal. A 6-year follow-up confirmed the lasting effect of this brief psychotherapy.

  10. [Treatment approach to localized esophageal cancer--what have we learned so far?].

    PubMed

    Brenner, Baruch; Purim, Ofer; Sulkes, Aaron

    2005-07-01

    The treatment of localized esophageal cancer (LEC) is under extensive debate. Treatment approaches include surgery or radiation alone, surgery with preoperative or postoperative radiation, preoperative or postoperative chemotherapy and definitive or preoperative chemoradiation. In fact, the type of therapy patients receive is often dependent on the actual medical field of the treating physician (surgery, oncology, etc.). The use of multiple treatment approaches toward LEC primarily reflects the scarcity of data that is derived from controlled randomized trials and the poor results of current therapies. In spite of the above, the cumulative data suggest that surgery and chemoradiation are the two treatment options in LEC and that their combined approach, i.e. preoperative chemoradiation, has not been proven to have a survival advantage over each one of these methods, and should therefore still be considered investigational. This article will review the available data on the various treatment approaches that are being used against LEC.

  11. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Warren, Samantha; Partridge, Mike; Carrington, Rhys; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  12. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    SciTech Connect

    Kordes, Sil; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.; Bergman, Jacques J.G.H.M.; Vliet, Hans J. van der; Kapiteijn, Ellen; Laarhoven, Hanneke W.M. van; Richel, Dick J.; Klinkenbijl, Jean H.G.; Meijer, Sybren L.; Wilmink, Johanna W.

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  13. Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer

    PubMed Central

    Hansen, Jorgen L.; Bhagwat, Mandar S.; O'Farrell, Desmond A.; Friesen, Scott; Harris, Thomas C.; Damato, Antonio L.; Cormack, Robert A.; Martin, Neil E.; Devlin, Phillip M.

    2016-01-01

    Purpose In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator. Material and methods Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well. Results The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. Conclusions The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved

  14. Heredity, diet and lifestyle as determining risk factors for the esophageal cancer on Nanao Island in Southern China.

    PubMed

    Liu, Min; Su, Min; Tian, Dong-Ping; Zhang, Guo-Hong; Yang, He-Lin; Gao, Yu-Xia

    2010-06-01

    In this case-control study we evaluated contribution of environmental and genetic factors for risk of esophageal cancer (EC) by studying populations on Nanao Island (highest risk area for EC in China) and Shanwei (low risk region). Data on lifestyle, diet and family history were collected from the 166 newly diagnosed EC patients on Nanao between 2003 and 2004, from their 1450 first degree relatives and from controls on Nanao and Shanwei. Univariate and logistic regression analysis, family aggregation patterns, standardized incidence ratio (SIR), segregation ratio and heritability index were evaluated. The family cancer history was a significant risk factor for the two scenarios; Nanao cases versus Nanao controls, and Nanao controls versus Shanwei controls. Other risk factors included smoking, alcohol and fermented fish sauce. After adjusting for confounding variables, family history was independently associated with the occurrence of EC in Nanao cases versus Nanao controls. The incidence in the first degree relatives of Nanao cases was 0.86%, significantly higher than that of the public (0.12%) and SIR value was 1.44 in the first degree relatives of the 166 EC cases. The segregation ratio was 0.11 and the heritability index among first degree relatives was 40%. Our study indicates that there are steady pathogenic risk factors in the Nanao population's lifestyle but genetic factors also play an important role for EC onset.

  15. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2012-03-01

    in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR (C) for esophageal...microscopy and morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants...most highly associated variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor

  16. Response Assessment and Prediction in Esophageal Cancer Patients via F-18 FDG PET/CT Scans

    NASA Astrophysics Data System (ADS)

    Higgins, Kyle J.

    Purpose: The purpose of this study is to utilize F-18 FDG PET/CT scans to determine an indicator for the response of esophageal cancer patients during radiation therapy. There is a need for such an indicator since local failures are quite common in esophageal cancer patients despite modern treatment techniques. If an indicator is found, a patient's treatment strategy may be altered to possibly improve the outcome. This is investigated with various standard uptake volume (SUV) metrics along with image texture features. The metrics and features showing the most promise and indicating response are used in logistic regression analysis to find an equation for the prediction of response. Materials and Methods: 28 patients underwent F-18 FDG PET/CT scans prior to the start of radiation therapy (RT). A second PET/CT scan was administered following the delivery of ~32 Gray (Gy) of dose. A physician contoured gross tumor volume (GTV) was used to delineate a PET based GTV (GTV-pre-PET) based on a threshold of >40% and >20% of the maximum SUV value in the GTV. Deformable registration was used in VelocityAI software to register the pre-treatment and intra-treatment CT scans so that the GTV-pre-PET contours could be transferred from the pre to intra scans (GTV-intra-PET). The fractional decrease in the maximum, mean, volume to the highest intensity 10%-90%, and combination SUV metrics of the significant previous SUV metrics were compared to post-treatment pathologic response for an indication of response. Next for the >40% threshold, texture features based on a neighborhood gray-tone dimension matrix (NGTDM) were analyzed. The fractional decrease in coarseness, contrast, busyness, complexity, and texture strength were compared to the pathologic response of the patients. From these previous two types of analysis, SUV and texture features, the two most significant results were used in logistic regression analysis to find an equation to predict the probability of a non

  17. Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer

    PubMed Central

    Speicher, Paul J.; Englum, Brian R.; Ganapathi, Asvin M.; Wang, Xiaofei; Hartwig, Matthew G.; D’Amico, Thomas A.; Berry, Mark F.

    2016-01-01

    Background An association between volume and outcomes has been observed for esophagectomy, though little is known about why or how patients choose low- or high-volume centers. The purpose of this study was to evaluate how travel burden and hospital volume influence treatment and outcomes of patients with locally advanced esophageal cancer. Methods Predictors of receiving esophagectomy for patients with T1-3N1M0 mid or distal esophageal cancer in the National Cancer Data Base from 2006 to 2011 were identified using multivariable logistic regression. Survival was compared using propensity score-matched groups: patients in the bottom quartile of travel distance who underwent treatment at low-volume facilities (Local) and patients in the top quartile of travel distance who underwent treatment at high-volume facilities (Travel). Results Of 4979 patients who met inclusion criteria, we identified 867 Local patients who traveled 2.7 [interquartile range (IQR): 1.6–4 miles] miles to centers that treated 2.6 (IQR: 1.9–3.3) esophageal cancers per year, and 317 Travel patients who traveled 107.1 (IQR: 65–247) miles to centers treating 31.9 (IQR: 30.9–38.5) cases. Travel patients were more likely to undergo esophagectomy (67.8% vs 42.9%, P < 0.001) and had significantly better 5-year survival (39.8% vs 20.6%, P < 0.001) than Local patients. Conclusions Patients who travel longer distances to high-volume centers have significantly different treatment and better outcomes than patients who stay close to home at low-volume centers. Strategies that support patient travel for treatment at high-volume centers may improve esophageal cancer outcomes. PMID:28266965

  18. Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal cancer

    PubMed Central

    Klimczak-Bitner, Anna Agnieszka; Kordek, Radzisław; Bitner, Jan; Musiał, Jacek; Szemraj, Janusz

    2016-01-01

    Esophageal cancer (EC) is a malignant tumor with a typically poor prognosis for patients. It is well known that certain microRNA (miRNA/miR) genes can regulate other genes responsible for carcinogenesis. In the present study, a group of these genes (miR-21, miR-134, miR-205 and miR-495) and genes connected with cancer-related pathways (MET, MMP9, PDGFA and SERPINE1) were chosen for analysis in order to find a potential correlation between their expression and the clinicopathological factors of EC. Esophageal tumors and adjacent non-cancerous tissue specimens were collected from a total of 63 patients and embedded in paraffin. Commercial arrays were used on KYSE-30, KYSE-150 and KYSE-270 EC cell lines in order to find genes of different expression profiles compared with those acquired from the control Het-1A cell line. Quantitative polymerase chain reaction was used on formalin-fixed, paraffin-embedded samples in order to analyze the expression of the genes chosen in the earlier step. The results were analyzed by the Kruskal-Wallis and Mann-Whitney U tests, Spearman's rank correlation coefficient, Kaplan-Meier methods and the long-rank test. Only miR-495 was not expressed in the analyzed samples. The expression of MMP9 and SERPINE1 was significantly coefficient with age range (P=0.011 and P=0.044, respectively) according to the Kruskal-Wallis test. The Spearman's rank-order correlation measurement showed that there was a coefficient correlation between age and miR-134 expression. The same measurement demonstrated a correlation between age range and MMP9 expression. The expression of miR-134 and MMP9 were also found to be correlated. In all cases, a value of P<0.049 was recorded. Overall, the present study demonstrated that MMP9, SERPINE1 and miR-134 were the most prognostic genes in Caucasian patients with EC. PMID:27895782

  19. Case Report: Detection and quantification of tumor cells in peripheral blood and ascitic fluid from a metastatic esophageal cancer patient using the CellSearch ® technology

    PubMed Central

    Tu, Qian; Bittencourt, Marcelo De Carvalho; Cai, Huili; Bastien, Claire; Lemarie-Delaunay, Camille; Bene, Marie C; Faure, Gilbert C

    2014-01-01

    Analysis of ascitic fluid should help to identify and characterize malignant cells in gastrointestinal cancer. However, despite a high specificity, the sensitivity of traditional ascitic fluid cytology remains insufficient, at around 60%. Since 2004 the CellSearch ® technology has shown its advantages in the detection of circulating tumor cells (CTCs) in peripheral blood, which can perform an accurate diagnosis and molecular analysis at the same time. To our knowledge, no previous study has explored the potential utility of this technology for the detection and quantification of tumor cells in ascitic fluid samples. Herein we report a case of metastatic esophageal adenocarcinoma in a 70-year-old man presenting with dysphagia and a large amount of fluid in the peritoneal cavity. Analysis of a peripheral blood sample and ascites sample with the CellSearch ® technology both revealed the presence of putative tumor cells that were positive for epithelial cell adhesion molecule (EpCAM) and cytokeratin (CK) expression. This study confirmed the hematogenous dissemination of esophageal cancer by the detection of circulating tumor cells in the peripheral blood, and is the first to demonstrate that tumor cells can be identified in ascitic fluid by using CellSearch ® technology. PMID:25075284

  20. Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy

    PubMed Central

    Baird, Andrew; Lee, Jisook; Podvin, Sonia; Kurabi, Arwa; Dang, Xitong; Coimbra, Raul; Costantini, Todd; Bansal, Vishal; Eliceiri, Brian P

    2014-01-01

    In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to 14, ten, eight, six, four, and two KDa peptides, depending on the cell in which the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4 gene expression in many epithelial cancers, several investigators have speculated that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4 inhibits cell proliferation in vitro, but it also has a wide range of effects in vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis, senescence, cell migration, inflammation, injury, and infection responsiveness. ECRG4 activities also depend on its cellular localization, secretion, and post-translational processing. These cytokine/chemokine-like characteristics argue that ECRG4 is not a traditional candidate tumor suppressor gene, as originally predicted by its downregulation in cancer. We review how insights into the regulation of ECRG4 gene expression, knowledge of its primary structure, and the study of its emerging physiological functions come together to support a much more complex role for ECRG4 at the interface of inflammation, infection, and malignancy. PMID:25580077

  1. Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy

    PubMed Central

    Wang, Lu; Wang, Cong; Wang, Jiangfeng; Huang, Xiaochen; Cheng, Yufeng

    2016-01-01

    Vitamin D can exert anticancer effect beyond bone and calcium metabolism. We aimed to investigate whether postoperative vitamin D supplementation affects quality of life (QOL) and survival in esophageal cancer (EC) patients. We utilized the widely used EORTC QLQ-C30 and QLQ-OES18 to assess QOL at EC diagnosis and 24 months after surgery. Generalized estimating equations (GEEs) were used to analysis the association of vitamin D supplement use with QOL. Kaplan-Meier method and Cox regression model were used to evaluate the prognostic value of vitamin D supplementation. The notably improved QOL were found among vitamin D supplementation users compared with non-users (p < 0.05). Kaplan-Meier analysis revealed that vitamin D supplement use was significantly associated with improved disease-free survival (DFS) (p = 0.030), but not related to overall survival (OS) (p = 0.303). The multivariable analysis further demonstrated vitamin D supplement use as an independent prognostic factor for DFS (p = 0.040; HR 0.610; 95% CI 0.381–0.978). In conclusion, these results showed that vitamin D supplement use could serve as a promising intervention to enhancing QOL and prolonging DFS in EC. PMID:27958342

  2. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.

  3. miR-625 down-regulation promotes proliferation and invasion in esophageal cancer by targeting Sox2.

    PubMed

    Wang, Zhiqiang; Qiao, Qiao; Chen, Min; Li, Xianhua; Wang, Zhenjun; Liu, Chuanxin; Xie, Zongtao

    2014-03-18

    miR-625 has been reported to exhibit abnormal expression in esophageal cancer (EC), but the mechanism and functions of miR-625 in esophageal cancer remain unclear. miR-625 down-regulation and Sox2 up-regulation were validated by qRT-PCR in 158 EC samples. Low expression of miR-625 promotes cell proliferation and invasion, while high expression of miR-625 has the opposite effect. Sox2, a target gene of miR-625, was examined by luciferase assay and western blot. Our data suggest that miR-625 may regulate the biological processes of EC via controlling Sox2 expression.

  4. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

    PubMed Central

    Jin, Zhaohui

    2016-01-01

    Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6–7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14–24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10–20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified. Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery. PMID

  5. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1.

    PubMed

    Jin, Zhaohui; Yoon, Harry H

    2016-10-01

    Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14-24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10-20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified. Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery.

  6. Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer

    PubMed Central

    Zhang, Jin-Liang; Wang, Hui-Yun; Yang, Qing; Lin, Shi-Yong; Luo, Guang-Yu; Zhang, Rong; Xu, Guo-Liang

    2015-01-01

    AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC. PMID:25892874

  7. Analysis of cancer patients admitted to intensive care unit

    PubMed Central

    Aksoy, Yakup; Kaydu, Ayhan; Sahin, Omer Fatih; Kacar, Cem Kivilcim

    2016-01-01

    OBJECTIVE: The present study is an analysis of cancer patients who received follow-up treatment for either cancer-related complications or treatment-associated side effects while hospitalized in the intensive care unit (ICU). METHODS: Records of cancer patients treated at Dr. Lütfi Kırdar Kartal Training and Research Hospital ICU between January 1, 2011 and December 31, 2012 were retrospectively reviewed. Demographic data and type of cancer were recorded in prepared forms and subsequently analyzed. RESULTS: Among 2240 ICU patients treated and hospitalized between January 1, 2011 and December 31, 2012, 482 cancer patients were identified and included in the study. Percentage of cancer patients in ICU was 23.9%. Male to female ratio was determined to be 1.55. First 3 most common cancers found were colorectal (19.7%), lung (15.7%), and stomach cancers (11.6%). Mortality rate of cancer patients hospitalized in ICU was 46.6%. Larynx, lung, urinary bladder, skin, rectosigmoid, hematological, and kidney cancer were more prevalent in male patients, whereas esophageal cancer was seen in more female patients than male patients. Incidence of stomach, brain, and pancreatic cancers, as well as unclassified tumors, was found to be unrelated to gender. CONCLUSION: Rectosigmoid cancer was most common type of cancer observed in our ICU. Esophageal cancer was observed in more females than males, while larynx cancer was more frequently present in males. PMID:28275754

  8. Mithramycin represses basal and cigarette smoke-induced expression of ABCG2 and inhibits stem cell signaling in lung and esophageal cancer cells.

    PubMed

    Zhang, Mary; Mathur, Aarti; Zhang, Yuwei; Xi, Sichuan; Atay, Scott; Hong, Julie A; Datrice, Nicole; Upham, Trevor; Kemp, Clinton D; Ripley, R Taylor; Wiegand, Gordon; Avital, Itzak; Fetsch, Patricia; Mani, Haresh; Zlott, Daniel; Robey, Robert; Bates, Susan E; Li, Xinmin; Rao, Mahadev; Schrump, David S

    2012-08-15

    Cigarette smoking at diagnosis or during therapy correlates with poor outcome in patients with lung and esophageal cancers, yet the underlying mechanisms remain unknown. In this study, we observed that exposure of esophageal cancer cells to cigarette smoke condensate (CSC) led to upregulation of the xenobiotic pump ABCG2, which is expressed in cancer stem cells and confers treatment resistance in lung and esophageal carcinomas. Furthermore, CSC increased the side population of lung cancer cells containing cancer stem cells. Upregulation of ABCG2 coincided with increased occupancy of aryl hydrocarbon receptor, Sp1, and Nrf2 within the ABCG2 promoter, and deletion of xenobiotic response elements and/or Sp1 sites markedly attenuated ABCG2 induction. Under conditions potentially achievable in clinical settings, mithramycin diminished basal as well as CSC-mediated increases in AhR, Sp1, and Nrf2 levels within the ABCG2 promoter, markedly downregulated ABCG2, and inhibited proliferation and tumorigenicity of lung and esophageal cancer cells. Microarray analyses revealed that mithramycin targeted multiple stem cell-related pathways in vitro and in vivo. Collectively, our findings provide a potential mechanistic link between smoking status and outcome of patients with lung and esophageal cancers, and support clinical use of mithramycin for repressing ABCG2 and inhibiting stem cell signaling in thoracic malignancies.

  9. SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy

    SciTech Connect

    Liao, L; Yu, J; Zhu, X; Li, H; Zhang, X; Li, Y; Lim, G

    2015-06-15

    Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used to evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.

  10. High-dose-rate intraluminal brachytherapy prior to external radiochemotherapy in locally advanced esophageal cancer: preliminary results

    PubMed Central

    Safaei, Afsaneh Maddah; Ghalehtaki, Reza; Khanjani, Nezhat; Farazmand, Borna; Babaei, Mohammad

    2017-01-01

    Purpose Dysphagia is a common initial presentation in locally advanced esophageal cancer and negatively impacts patient quality of life and treatment compliance. To induce fast relief of dysphagia in patients with potentially operable esophageal cancer high-dose-rate (HDR) brachytherapy was applied prior to definitive radiochemotherapy. Material and methods In this single arm phase II clinical trial between 2013 to 2014 twenty patients with locally advanced esophageal cancer (17 squamous cell and 3 adenocarcinoma) were treated with upfront 10 Gy HDR brachytherapy, followed by 50.4 Gy external beam radiotherapy (EBRT) and concurrent chemotherapy with cisplatin/5-fluorouracil. Results Tumor response, as measured by endoscopy and/or computed tomography scan, revealed complete remission in 16 and partial response in 4 patients (overall response rate 100%). Improvement of dysphagia was induced by brachytherapy within a few days and maintained up to the end of treatment in 80% of patients. No differences in either response rate or dysphagia resolution were found between squamous cell and adenocarcinoma histology. The grade 2 and 3 acute pancytopenia or bicytopenia reported in 4 patients, while sub-acute adverse effects with painful ulceration was seen in five patients, occurring after a median of 2 months. A perforation developed in one patient during the procedure of brachytherapy that resolved successfully with immediate surgery. Conclusions Brachytherapy before EBRT was a safe and effective procedure to induce rapid and durable relief from dysphagia, especially when combined with EBRT. PMID:28344601

  11. The efficacy of oral glutamine in prevention of acute radiotherapy-induced esophagitis in patients with lung cancer

    PubMed Central

    Tutanc, Oznur Donmez; Aydogan, Akin; Sunbul, Ahmet Taner; Zincircioglu, Seyit Burhanedtin; Alpagat, Gulistan; Erden, Ersin Sukru

    2013-01-01

    Aim of the study This study explores the efficacy of oral glutamine in the prevention of acute radiotherapy-induced esophagitis in patients with lung cancer who are treated with thoracic radiotherapy. Material and methods This study was planned as a retrospective randomized experimental study. Forty-six patients with lung cancer, who were treated and kept under control between January 2008 and January 2010, were included in the study by the Department of Radiation Oncology, Faculty of Medicine, Dicle University. The patients were divided into two groups. The first group (n = 21) was given prophylactic oral powder glutamine (daily 30 g), while the second group (n = 25) was not given oral glutamine. Results There were 21 patients in Group 1 (45.7%) and 25 patients in Group 2 (54.3%). No significant statistical difference was observed between the two groups in terms of age, gender, stage, histopathological type, treatment choice, received radiation doses, esophagus length in RT field, or location of the tumor (p > 0.05). A significant statistical difference was observed between the glutamine-supplemented group (first group) and the glutamine-free group (second group) according to the grade of esophagitis (p < 0.0001). Conclusions In our retrospective randomized experimental study, we determined that the severity of acute radiotherapy-induced esophagitis might be decreased with oral glutamine in patients with lung cancer who were treated with thoracic radiotherapy. PMID:24592140

  12. LOI of IGF2 is associated with esophageal cancer and linked to methylation status of IGF2 DMR.

    PubMed

    Xu, W; Fan, H; He, X; Zhang, J; Xie, W

    2006-12-01

    In the present study, IGF2 mRNA expression was examined by semi-quantitative RT-PCR in 46 esophageal cancer cases. LOI of IGF2 was detected in informative samples, which were determined as heterozygote with ApaI polymorphism in exon 9 of IGF2 by PCR-RFLP and RT-PCR-RFLP. Methylation status of IGF2 DMR in informative samples was analyzed by sodium bisulfite treatment and PCR and the following cloning sequencing. The results showed that there was over-expression of IGF2 mRNA in tumor tissues (T) compared to their matched normal tissues (N) (P < 0.05). The expression level of IGF2 in tumor tissues was associated with pathological grades (P < 0.05), but proved irrelevant to clinical stages (P > 0.05). Of all informative samples, 21% (5/24) of cases showed there were IGF2 LOI; however, there was IGF2 LOI in the tumor tissue and not in its matched normal tissue in a special case. Methylation level of IGF2 DMR was average 29.7% in normal imprinting samples and 50.6% (P < 0.01) in IGF2 LOI separate samples. These data suggested that IGF2 may participate in carcinogenesis of esophageal cancer through its over-expression. IGF2 LOI may be one of the factors that lead to overexpression of IGF2 and may be at least partly due to aberrant methylation of IGF2 DMR in esophageal cancer.

  13. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    SciTech Connect

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-07-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m{sup 2}) on Days 1-4 and either mitomycin C (10 mg/m{sup 2}) or cisplatin (75 mg/m{sup 2}) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m{sup 2}) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age {<=}64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

  14. Self-expanding plastic esophageal stents versus jejunostomy tubes for the maintenance of nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer: a retrospective study.

    PubMed

    Siddiqui, A A; Glynn, C; Loren, D; Kowalski, T

    2009-01-01

    In patients undergoing chemoradiotherapy for esophageal cancer, the inability to eat may severely impair nutritional status. We conducted a retrospective study to compare the efficacy of the Polyflex self-expanding silicone stent (PS) versus a jejunostomy tube (JT) for maintaining nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer who were scheduled for resectional surgery. Thirty-six patients were treated either with PS placement (12 patients) or JT placement (24 patients) prior to receiving an 8-week course of chemoradiation therapy. Patients were interviewed weekly until cessation of therapy. Patient data were collected on procedural success and complication rates, nutritional status, and dysphagia scores. PS placement was successful in 11 of 12 patients (92%), and those 11 patients were able to resume oral nutrition. Dysphagia scores improved from a mean of 3 to 1 in the PS group (P < 0.005) but did not change significantly in the JT group. PS were removed endoscopically without complications prior to the esophagectomies. Albumin levels and weight increased significantly in both the PS and JT groups. There were no significant differences between groups in the procedural success rates (PS 92% vs. JT 100%, P = 0.33), complication rates (PS 22% vs. JT 4%, P = 0.11), mean increase in weight (PS 4.4 kg vs. JT 4.2 kg, P = 0.59), and mean increase in serum albumin (PS 0.62 g/dL vs. JT 0.44 g/dL, P = 0.05). PS is a safe and effective alternative to a surgical JT for maintaining nutrition in this subset of patients.

  15. Shp2 Inhibits Proliferation of Esophageal Squamous Cell Cancer via Dephosphorylation of Stat3.

    PubMed

    Qi, Chen; Han, Tao; Tang, Hua; Huang, Kenan; Min, Jie; Li, Jing; Ding, Xinyu; Xu, Zhifei

    2017-01-12

    Shp2 (Src-homology 2 domain-containing phosphatase 2) was originally reported as an oncogene in kinds of solid tumors and hematologic malignancies. However, recent studies indicated that Shp2 may act as tumor suppressors in several tumor types. We investigated the function of Shp2 in esophageal squamous cell cancer (ESCC). The expression level of Shp2 was analyzed in tumor tissues in comparison with adjacent normal tissues of ESCC patients by immunohistochemistry and Western blot. Shp2 was knocked down by Short hairpin RNA to evaluate its function in ESCC cell lines. The relationship between Shp2 and p-Stat3 (signal transducer and activator of transcription 3) in human ESCC tissues was statistically examined. A significant low expression of Shp2 was found in ESCC tissues. Low expression of Shp2 was related to poorer overall survival in patients from The Cancer Genome Atlas (TCGA) dataset. Knockdown of Shp2 increased the growth of ESCC cell lines both in vivo and vitro. Activation of Stat3 (p-Stat3) was induced by Shp2 depletion. Expression of p-Stat3 was negatively correlated with Shp2 expression in ESCC tissues. Furthermore, knockdown of Shp2 attenuated cisplatin-sensitivity of ESCC cells. Shp2 might suppress the proliferation of ESCC by dephosphorylation of p-Stat3 and represents a novel research field for targeted therapy.

  16. Shp2 Inhibits Proliferation of Esophageal Squamous Cell Cancer via Dephosphorylation of Stat3

    PubMed Central

    Qi, Chen; Han, Tao; Tang, Hua; Huang, Kenan; Min, Jie; Li, Jing; Ding, Xinyu; Xu, Zhifei

    2017-01-01

    Shp2 (Src-homology 2 domain-containing phosphatase 2) was originally reported as an oncogene in kinds of solid tumors and hematologic malignancies. However, recent studies indicated that Shp2 may act as tumor suppressors in several tumor types. We investigated the function of Shp2 in esophageal squamous cell cancer (ESCC). The expression level of Shp2 was analyzed in tumor tissues in comparison with adjacent normal tissues of ESCC patients by immunohistochemistry and Western blot. Shp2 was knocked down by Short hairpin RNA to evaluate its function in ESCC cell lines. The relationship between Shp2 and p-Stat3 (signal transducer and activator of transcription 3) in human ESCC tissues was statistically examined. A significant low expression of Shp2 was found in ESCC tissues. Low expression of Shp2 was related to poorer overall survival in patients from The Cancer Genome Atlas (TCGA) dataset. Knockdown of Shp2 increased the growth of ESCC cell lines both in vivo and vitro. Activation of Stat3 (p-Stat3) was induced by Shp2 depletion. Expression of p-Stat3 was negatively correlated with Shp2 expression in ESCC tissues. Furthermore, knockdown of Shp2 attenuated cisplatin-sensitivity of ESCC cells. Shp2 might suppress the proliferation of ESCC by dephosphorylation of p-Stat3 and represents a novel research field for targeted therapy. PMID:28085101

  17. Thapsigargin sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation

    PubMed Central

    Ma, Zhiqiang; Fan, Chongxi; Yang, Yang; Di, Shouyin; Hu, Wei; Li, Tian; Zhu, Yifang; Han, Jing; Xin, Zhenlong; Wu, Guiling; Zhao, Jing; Li, Xiaofei; Yan, Xiaolong

    2016-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent for esophageal squamous cell carcinoma (ESCC). Forced expression of CHOP, one of the key downstream transcription factors during endoplasmic reticulum (ER) stress, upregulates the death receptor 5 (DR5) levels and promotes oxidative stress and cell death. In this study, we show that ER stress mediated by thapsigargin promoted CHOP and DR5 synthesis thus sensitizing TRAIL treatment, which induced ESCC cells apoptosis. These effects were reversed by DR5 siRNA in vitro and CHOP siRNA both in vitro and in vivo. Besides, chemically inhibition of AMPK by Compound C and AMPK siRNA weakened the anti-cancer effect of thapsigargin and TRAIL co-treatment. Therefore, our findings suggest ER stress effectively sensitizes human ESCC to TRAIL-mediated apoptosis via the TRAIL-DR5-AMPK signaling pathway, and that activation of ER stress may be beneficial for improving the efficacy of TRAIL-based anti-cancer therapy. PMID:27731378

  18. Usefulness of Intraluminal Brachytherapy Combined With External Beam Radiation Therapy for Submucosal Esophageal Cancer: Long-Term Follow-Up Results

    SciTech Connect

    Ishikawa, Hitoshi; Nonaka, Tetsuo; Sakurai, Hideyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi; Ebara, Takeshi; Shioya, Mariko; Noda, Shin-Ei; Shirai, Katsuyuki; Suzuki, Yoshiyuki; Takahashi, Takeo; Nakano, Takashi

    2010-02-01

    Purpose: To assess the efficacy of radiation therapy (RT) by using intraluminal brachytherapy (IBT) combined with external beam RT (EBRT) for submucosal esophageal cancer. Methods and Materials: Between 1991 and 2005, 59 consecutive patients received definitive RT without chemotherapy. IBT was performed after patients completed EBRT as a booster therapy for 17 patients, using low-dose-rate Cs-137 sources until 1997, and for 19 patients, using high-dose-rate Ir-192 sources thereafter. The long-term outcomes were investigated with a median follow-up time of 61 months. Results: Logoregional recurrences and distant metastases were observed in 14 patients and in 2 patients in the lung, respectively, and 5 patients were rescued by salvage treatments. The 5-year logoregional control and cause-specific survival rates were 75% and 76%, respectively. The 5-year cause-specific survival rate in the EBRT group was 62%, whereas the corresponding rate in the IBT group was 86% (p = 0.04). Multivariate analysis revealed that IBT was the most powerful predictor of survival but did not reach a significant level (p = 0.07). There were five esophageal ulcers in the IBT group, but no ulcers developed with small fractions of 3 Gy. Grade 2 or higher cardiorespiratory complications developed in 2 patients (5.6%) in the IBT group and in 3 patients (13.0%) in the EBRT group. Conclusions: Combining IBT with EBRT is suggested to be one of the preferable treatment modalities for medically inoperable submucosal esophageal cancer because of its preferable local control and survival probabilities, with appreciably less morbidity.

  19. Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer

    PubMed Central

    2012-01-01

    Background Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer. Methods This phase I, laser dose escalation study used a fixed dose (40 mg/m2) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm2, with an escalation plan to 75 J/cm2 and 100 J/cm2. Results 9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT. Conclusions PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm2. PMID:22824179

  20. SU-E-J-248: Comparative Study of Two Image Registration for Image-Guided Radiation Therapy in Esophageal Cancer

    SciTech Connect

    Shang, K; Wang, J; Liu, D; Li, R; Cao, Y; Chi, Z

    2014-06-01

    Purpose: Image-guided radiation therapy (IGRT) is one of the major treatment of esophageal cancer. Gray value registration and bone registration are two kinds of image registration, the purpose of this work is to compare which one is more suitable for esophageal cancer patients. Methods: Twenty three esophageal patients were treated by Elekta Synergy, CBCT images were acquired and automatically registered to planning kilovoltage CT scans according to gray value or bone registration. The setup errors were measured in the X, Y and Z axis, respectively. Two kinds of setup errors were analysed by matching T test statistical method. Results: Four hundred and five groups of CBCT images were available and the systematic and random setup errors (cm) in X, Y, Z directions were 0.35, 0.63, 0.29 and 0.31, 0.53, 0.21 with gray value registration, while 0.37, 0.64, 0.26 and 0.32, 0.55, 0.20 with bone registration, respectively. Compared with bone registration and gray value registration, the setup errors in X and Z axis have significant differences. In Y axis, both measurement comparison results of T value is 0.256 (P value > 0.05); In X axis, the T value is 5.287(P value < 0.05); In Z axis, the T value is −5.138 (P value < 0.05). Conclusion: Gray value registration is recommended in image-guided radiotherapy for esophageal cancer and the other thoracic tumors. Manual registration could be applied when it is necessary. Bone registration is more suitable for the head tumor and pelvic tumor department where composed of redundant interconnected and immobile bone tissue.

  1. Phase I trial of escalating-dose cisplatin with 5-fluorouracil and concurrent radiotherapy in Chinese patients with esophageal cancer.

    PubMed

    Lin, Qiang; Gao, Xian-Shu; Qiao, Xue-Ying; Zhou, Zhi-Guo; Zhang, Ping; Chen, Kun; Zhao, Yan-Nan; Asaumi, Junichi

    2008-02-01

    We defined the maximum-tolerated dose (MTD) of chemoradiotherapy (cisplatin (CDDP) with 5-fluorouracil (5-FU) and concurrent chemoradiotherapy) for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR) of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

  2. Acute Cardiac Impairment Associated With Concurrent Chemoradiotherapy for Esophageal Cancer: Magnetic Resonance Evaluation

    SciTech Connect

    Hatakenaka, Masamitsu; Yonezawa, Masato; Nonoshita, Takeshi; Nakamura, Katsumasa; Yabuuchi, Hidetake; Shioyama, Yoshiyuki; Nagao, Michinobu; Matsuo, Yoshio; Kamitani, Takeshi; Higo, Taiki; Nishikawa, Kei; Setoguchi, Taro; Honda, Hiroshi

    2012-05-01

    Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference

  3. Influence of socioeconomic environment on survival in patients diagnosed with esophageal cancer: a population-based study.

    PubMed

    Launay, L; Dejardin, O; Pornet, C; Morlais, F; Guittet, L; Launoy, G; Bouvier, V

    2012-01-01

    The influence of social environment on survival in patients with cancer has been demonstrated in many studies, subjects living in the most deprived areas having a poorer prognosis. Geographic remoteness and limited access to specialized care centers are often associated with socioeconomic deprivation. The aim was to assess the influence of social environment and geographic remoteness on the relative survival of patients diagnosed with esophageal cancer between 1997 and 2004 in the department of Calvados in France. The study population, which was provided by the Calvados digestive cancer registry, included 629 patients. Relative survival was used to estimate the influence of social environment and geographic remoteness on patient survival. Five-year survival rates were 14.1%, 15.1%, 11.8%, 8.8%, and 11.4%, respectively, for patients living in the least to the most deprived areas (P= 0.39). The influence of social environment was significant after adjustment for clinical variables, patients living in the most deprived areas having the worst survival. These discrepancies cannot totally be explained by differences in access to care, cancer extension, or morphology at diagnosis. No association was observed between distance to the nearest cancer center and survival. Social environment appears to induce disparities among patients diagnosed with esophageal cancer, with a worse prognosis for patients living in the most deprived areas.

  4. Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer

    SciTech Connect

    Jayachandran, Priya; Pai, Reetesh K.; Quon, Andrew; Graves, Edward; Krakow, Trevor E.; La, Trang; Loo, Billy W.; Koong, Albert C.; Chang, Daniel T.

    2012-10-01

    Purpose: To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer. Materials and Methods: The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum Multiplication-Sign 50%. The total glycolytic activity (TGA{sub x}) was defined as the mean SUV Multiplication-Sign MTV{sub x}. The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale. Results: The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV{sub 2.5Post} and TGA{sub 2.5Post} had the greatest correlation. The MTV{sub 2} ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001). Conclusion: The maximum SUV was not a predictive or prognostic parameter. The MTV{sub 2.5} and TGA{sub 2.5} were useful markers for predicting the response and

  5. SU-E-J-12: A New Stereological Method for Tumor Volume Evaluation for Esophageal Cancer

    SciTech Connect

    Feng, Y; Pan, R; Lin, W; Sa, Y; Wang, P; Yang, C

    2014-06-01

    Purpose: Stereological method used to obtain three dimensional quantitative information from two dimensional images is a widely used tool in the study of cells and pathology. But the feasibility of the method for quantitative evaluation of volumes with 3D image data sets for radiotherapy clinical application has not been explored. On the other hand, a quick, easy-to-use and reliable method is highly desired in image-guided-radiotherapy(IGRT) for tumor volume measurement for the assessment of response to treatment. To meet this need, a stereological method for evaluating tumor volumes for esophageal cancer is presented in this abstract. Methods: The stereology method was optimized by selecting the appropriate grid point distances and sample types. 7 patients with esophageal cancer were selected retrospectively for this study, each having pre and post treatment computed tomography (CT) scans. Stereological measurements were performed for evaluating the gross tumor volume (GTV) changes after radiotherapy and the results was compared with the ones by planimetric measurements. Two independent observers evaluated the reproducibility for volume measurement using the new stereological technique. Results: The intraobserver variation in the GTV volume estimation was 3.42±1.68cm3 (the Wilcoxon matched-pairs test Resultwas Z=−1.726,P=0.084>0.05); the interobserver variation in the GTV volume estimation was 22.40±7.23 cm3 (Z=−3.296,P=0.083>0.05), which showed the consistency in GTV volume calculation with the new method for the same and different users. The agreement level between the results from the two techniques was also evaluated. Difference between the measured GTVs was 20.10±5.35 cm3 (Z=−3.101,P=0.089>0.05). Variation of the measurement results using the two techniques was low and clinically acceptable. Conclusion: The good agreement between stereological and planimetric techniques proves the reliability of the stereological tumor volume estimations. The

  6. Synergistic effects of puerarin combined with 5-fluorouracil on esophageal cancer.

    PubMed

    Wang, Jun; Yang, Zi-Rong; Guo, Xu-Feng; Song, Jia; Zhang, Ji-Xiang; Wang, Jing; Dong, Wei-Guo

    2014-11-01

    Puerarin is an isoflavone derived from kudzu roots with a wide range of biological and medicinal properties. The aim of the present study was to investigate the inhibitive effects of puerarin combined with 5‑fluorouracil (5‑FU) on Eca‑109 esophageal cancer cells in vitro and in vivo. Inhibitive effects of the treatments on Eca‑109 cells were detected by cell counting kit‑8, Hoechst 33258 staining and flow cytometry. A tumor xenograft model was established in nude mice. Puerarin and 5‑FU, administered either in combination or individually, were injected into mice and the inhibitive effects along with any side effects were observed. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Puerarin and 5‑FU, administered as combined treatment or individual drugs, significantly inhibited proliferation and induced marked apoptosis. The mean growth inhibition rate (± standard deviation) reached 87.27±5.37% and the apoptotic rate at 48 h reached 36.18±1.24% in the combined treatment group. The percentages of apoptotic cells induced by puerarin and 5‑FU (combined or alone) were significantly higher than those of the control group (P<0.05). Puerarin or 5‑FU alone significantly inhibited the growth of xenograft tumors in comparison to the control group (P<0.05), with inhibition rates of 76.93 and 72.21%, respectively. The drugs combined exhibited a significantly greater effect than either drug alone (P<0.05), with the tumor inhibition rate reaching 89.06%. During the course of chemotherapy, no evident side effects were observed. The results suggested that the combined inhibitive effects of puerarin and 5‑FU were greater than the effects of the agents used individually. In addition, puerarin combined with 5‑FU exhibited synergistic effects at lower concentrations and promoted apoptosis, but did not increase the side effects of chemotherapy, which indicated that puerarin may be a safe and effective

  7. Phase II study of preoperative paclitaxel/cisplatin with radiotherapy in locally advanced esophageal cancer

    SciTech Connect

    Kim, Dong W.; Blanke, Charles D.; Wu, Huiyun; Shyr, Yu; Berlin, Jordan; Beauchamp, R. Daniel; Chakravarthy, Bapsi . E-mail: bapsi.chak@vanderbilt.edu

    2007-02-01

    Purpose: Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival. Methods and Materials: Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m{sup 2} and cisplatin 75 mg/m{sup 2} on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m{sup 2} on Day 1 and 5-fluorouracil 350 mg/m{sup 2} and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy. Results: Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p <0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%. Conclusion: Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.

  8. Propensity Score-based Comparison of Long-term Outcomes With 3-Dimensional Conformal Radiotherapy vs Intensity-Modulated Radiotherapy for Esophageal Cancer

    SciTech Connect

    Lin, Steven H.; Wang Lu; Myles, Bevan; Thall, Peter F.; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao Zhongxing

    2012-12-01

    Purpose: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide standard for the treatment of esophageal cancer, intensity modulated radiotherapy (IMRT) improves dose conformality and reduces the radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared with 3D-CRT. Methods and Materials: An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002) esophageal cancers treated with chemoradiotherapy at a single institution from 1998-2008. An inverse probability of treatment weighting and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival time, interval to local failure, and interval to distant metastasis, while accounting for the effects of other clinically relevant covariates. The propensity scores were estimated using logistic regression analysis. Results: A fitted multivariate inverse probability weighted-adjusted Cox model showed that the overall survival time was significantly associated with several well-known prognostic factors, along with the treatment modality (IMRT vs 3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying (72.6% vs 52.9%, inverse probability of treatment weighting, log-rank test, P<.0001) and of locoregional recurrence (P=.0038). No difference was seen in cancer-specific mortality (Gray's test, P=.86) or distant metastasis (P=.99) between the 2 groups. An increased cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT group, Gray's test, P=.0029). Conclusions: Overall survival, locoregional control, and noncancer-related death were significantly better after IMRT than after 3D-CRT. Although these results need

  9. Influence of Irradiated Lung Volumes on Perioperative Morbidity and Mortality in Patients After Neoadjuvant Radiochemotherapy for Esophageal Cancer

    SciTech Connect

    Daehn, Doreen; Martell, Joachim; Vorwerk, Hilke; Hess, Clemens F.; Becker, Heinz; Jung, Klaus; Hilgers, Reinhard; Wolff, Hendrik Andreas; Hermann, Robert Michael; Christiansen, Hans

    2010-05-01

    Purpose: In some randomized trials, the treatment outcome of locally advanced esophageal cancer has been significantly improved by neoadjuvant radiochemotherapy (RCT). However, increased perioperative pulmonary toxicity in terms of acute respiratory distress syndrome (ARDS) has been linked to radiation exposure of the lungs. In our study we evaluated perioperative morbidity and mortality in patients with cancer Stages IIA-IVA treated with curative intent either with surgery alone (S) or with neoadjuvant RCT followed by surgery (RCTS). Patients and Methods: Between 1996 and 2003, 55 patients received S, and 98 received RCTS. In the RCTS group, most patients received two cycles of 5-fluorouracil plus cisplatinum simultaneously with normofractionated radiotherapy (40Gy). Four weeks later they underwent surgery. Endpoints were the incidence of acute lung injury (ALI), ARDS, other postoperative complications, and mortality within 31 days. Results: Between both groups there were no significant differences between the incidence and severity of ALI and ARDS (RCTS: 42.9%, 42.9%; S: 45.5%, 38.2%). Furthermore, there were no significant differences in the incidences of pneumonia, pleural effusion, and pneumothorax (RCTS 29.6% vs. S 16.4%, p = 0.07). Perioperative complication rates and mortality did not vary significantly (mortality after RCTS 5.1% vs. S 3.6%). A detailed analysis of 54 RCTS patients according to lung dose-volume histograms did not show any correlation between ARDS and pulmonary exposure. In univariate analysis, only respiratory comorbidity correlated with ARDS. Conclusion: Neoadjuvant cisplatinum and 5-fluorouracil-based RCT apparently has no detrimental impact on the postoperative course.

  10. High Intake of Folate from Food Sources Is Associated with Reduced Risk of Esophageal Cancer in an Australian Population12

    PubMed Central

    Ibiebele, Torukiri I.; Hughes, Maria Celia; Pandeya, Nirmala; Zhao, Zhen; Montgomery, Grant; Hayward, Nick; Green, Adèle C.; Whiteman, David C.; Webb, Penelope M.

    2011-01-01

    Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett’s esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC. PMID:21178085

  11. Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid.

    PubMed

    Peiffer, Daniel S; Zimmerman, Noah P; Wang, Li-Shu; Ransom, Benjamin W S; Carmella, Steven G; Kuo, Chieh-Ti; Siddiqui, Jibran; Chen, Jo-Hsin; Oshima, Kiyoko; Huang, Yi-Wen; Hecht, Stephen S; Stoner, Gary D

    2014-06-01

    Diets containing either freeze-dried black raspberries (BRBs) or their polyphenolic anthocyanins (ACs) have been shown to inhibit the development of N-nitrosomethylbenzylamine (NMBA)-induced esophageal cancer in rats. The present study was conducted to determine whether PCA, a major microbial metabolite of black raspberry (BRB) ACs, also prevents NMBA-induced esophageal cancer in rats. F344 rats were injected with NMBA three times a week for 5 weeks and then fed control or experimental diets containing 6.1% BRBs, an anthocyanin (AC)-enriched fraction derived from BRBs, or protocatechuic acid (PCA). Animals were exsanguinated at weeks 15, 25, and 35 to quantify the development of preneoplastic lesions and tumors in the esophagus, and to relate this to the expression of inflammatory biomarkers. At weeks 15 and 25, all experimental diets were equally effective in reducing NMBA-induced esophageal tumorigenesis, as well as in reducing the expression of pentraxin-3 (PTX3), a cytokine produced by peripheral blood mononuclear cells in response to interleukin (IL)-1β and TNF-α. All experimental diets were also active at reducing tumorigenesis at week 35; however, the BRB diet was significantly more effective than the AC and PCA diets. Furthermore, all experimental diets inhibited inflammation in the esophagus via reducing biomarker (COX-2, iNOS, p-NF-κB, and sEH) and cytokine (PTX3) expression. Overall, our data suggest that BRBs, their component ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis, at least in part, by their inhibitory effects on genes associated with inflammation.

  12. Objective assessment of tracheoesophageal and esophageal speech using acoustic analysis of voice.

    PubMed

    Sirić, Ljiljana; Sos, Dario; Rosso, Marinela; Stevanović, Sinisa

    2012-11-01

    The aim of this study was to analyze the voice quality of alaryngeal tracheoesophageal and esophageal speech, and to determine which of them is more similar to laryngeal voice production, and thus more acceptable as a rehabilitation method of laryngectomized persons. Objective voice evaluation was performed on a sample of 20 totally laryngectomized subjects of both sexes, average age 61.3 years. Subjects were divided into two groups: 10 (50%) respondents with built tracheoesophageal prosthesis and 10 (50%) who acquired esophageal speech. Testing included 6 variables: 5 parameters of acoustic analysis of voice and one parameter of aerodynamic measurements. The obtained data was statistically analyzed by analysis of variance. Analysis of the data showed a statistically significant difference between the two groups in the terms of intensity, fundamental frequency and maximum phonation time of vowel at a significance level of 5% and confidence interval of 95%. A statistically significant difference was not found between the values of jitter, shimmer, and harmonic-to-noise ratio between tracheoesophageal and esophageal voice. There is no ideal method of rehabilitation and every one of them requires an individual approach to the patient, but the results shows the advantages of rehabilitation by means of installing voice prosthesis.

  13. Serum concentrations of antibiotics during severe invasive surgery such as esophagectomy for esophageal cancer.

    PubMed

    Owaki, Tetsuhiro; Okumura, Hiroshi; Uchikado, Yasuto; Sasaki, Ken; Matsumoto, Masataka; Omoto, Itaru; Setoyama, Tetsuro; Kita, Yoshiaki; Sakurai, Toshihide; Matsushita, Daisuke; Ishigami, Sumiya; Ueno, Shinichi; Natsugoe, Shoji

    2013-01-01

    This study was performed to confirm the antibiotic regimen during a severe invasive surgery, such as esophagectomy, with a long procedure and a large amount of normal volumes of infusion. Ten patients with esophageal cancer were enrolled in this study, and cefmetazole sodium concentrations in serum were measured during esophagectomy. The ranges of minimum inhibitory concentrations for 90% of isolates of cefmetazole sodium for microorganisms in our institutions for 8 years were investigated. The maximum concentration was 83.9 μg/mL just after the completion of infusion, and its half-life was 1.5 hours. Serum concentration of cefmetazole sodium was kept above 16 μg/mL for 4 hours during esophagectomy. It was kept above 32 μg/mL for 2.5 hours after injection. There are almost no differences in the pharmacokinetics of cefmetazole sodium between common use and during esophagectomy. In addition, additive infusion of antibiotics 4 hours after the first infusion was recommended during esophagectomy.

  14. Serum Concentrations of Antibiotics During Severe Invasive Surgery Such as Esophagectomy for Esophageal Cancer

    PubMed Central

    Owaki, Tetsuhiro; Okumura, Hiroshi; Uchikado, Yasuto; Sasaki, Ken; Matsumoto, Masataka; Omoto, Itaru; Setoyama, Tetsuro; Kita, Yoshiaki; Sakurai, Toshihide; Matsushita, Daisuke; Ishigami, Sumiya; Ueno, Shinichi; Natsugoe, Shoji

    2013-01-01

    This study was performed to confirm the antibiotic regimen during a severe invasive surgery, such as esophagectomy, with a long procedure and a large amount of normal volumes of infusion. Ten patients with esophageal cancer were enrolled in this study, and cefmetazole sodium concentrations in serum were measured during esophagectomy. The ranges of minimum inhibitory concentrations for 90% of isolates of cefmetazole sodium for microorganisms in our institutions for 8 years were investigated. The maximum concentration was 83.9 μg/mL just after the completion of infusion, and its half-life was 1.5 hours. Serum concentration of cefmetazole sodium was kept above 16 μg/mL for 4 hours during esophagectomy. It was kept above 32 μg/mL for 2.5 hours after injection. There are almost no differences in the pharmacokinetics of cefmetazole sodium between common use and during esophagectomy. In addition, additive infusion of antibiotics 4 hours after the first infusion was recommended during esophagectomy. PMID:23438269

  15. Quantifying the Interfractional Displacement of the Gastroesophageal Junction During Radiation Therapy for Esophageal Cancer

    SciTech Connect

    Wang Jingya; Lin, Steven H.; Dong Lei; Balter, Peter; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Starkschall, George

    2012-06-01

    Purpose: Accounting for interfractional changes in tumor location improves the accuracy of radiation treatment delivery. The purpose of this study was to quantify the interfractional displacement of the gastroesophageal junction (GEJ) based on standard treatment setup in patients with esophageal cancer undergoing radiation therapy. Methods and Materials: Free-breathing four-dimensional computed tomography (4D-CT) datasets were acquired weekly from 22 patients during treatment for esophageal adenocarcinoma. Scans were registered to baseline (simulation) 4D-CT scans by using bony landmarks. The distance between the center of the GEJ contour on the simulation scan and the mean location of GEJ centers on subsequent scans was used to assess changes in GEJ location between fractions; displacement was also correlated with clinical and respiratory variables. Results: The mean absolute random error was 1.69 mm (range, 0.11-4.11 mm) in the lateral direction, 1.87 mm (range, 0.51-4.09 mm) in the anterior-posterior (AP) direction, and 3.09 mm (range, 0.99-6.16 mm) in the superior-inferior (SI) direction. The mean absolute systemic GEJ displacement between fractions was 2.88 mm lateral ({>=}5 mm in 14%), mostly leftward; 2.90 mm ({>=}5 mm in 14%) AP, mostly anterior; and 6.77 mm ({>=}1 cm in 18%) SI, mostly inferior. Variations in tidal volume and diaphragmatic excursion during treatment correlated strongly with systematic SI GEJ displacement (r = 0.964, p < 0.0001; and r = 0.944, p < 0.0001, respectively) and moderately with systematic AP GEJ displacement (r = 0.678, p = 0.0005; r = 0.758, p < 0.0001, respectively). Systematic displacement in the inferior direction resulted in higher-than-intended doses ({>=}60 Gy) to the GEJ, with increased hot-spot to the adjacent stomach and lung base. Conclusion: We found large (>1-cm) interfractional displacements in the GEJ in the SI (especially inferior) direction that was not accounted for when skeletal alignment alone was used for

  16. Complete Pathologic Response After Neoadjuvant Chemoradiotherapy for Esophageal Cancer Is Associated With Enhanced Survival

    PubMed Central

    Donahue, James M.; Nichols, Francis C.; Li, Zhuo; Schomas, David A.; Allen, Mark S.; Cassivi, Stephen D.; Jatoi, Aminah; Miller, Robert C.; Wigle, Dennis A.; Shen, K. Robert; Deschamps, Claude

    2010-01-01

    Background Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has become the standard of care for patients with locally advanced esophageal cancer. This report analyzes our experience with this treatment approach. Methods From January 1998 through December 2003, all patients from a single institution receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were reviewed for operative mortality, morbidity, long-term survival, and factors affecting survival. Only patients preoperatively staged with both computed tomographic scans and endoscopic ultrasound were included. Results There were 162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to 81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in 19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%), and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9% and 37%, respectively. Pathologic response was complete in 42 patients (26%), near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five-year survival for overall, complete, near complete, and partial response patients was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes were rendered free of cancer showed improved overall and disease-free survival compared with patients having persistently positive lymph nodes (p = 0.019). Conclusion Esophagogastrectomy after neoadjuvant chemoradiotherapy can be performed with low mortality and morbidity. Patients with complete pathologic response have significantly improved long-term survival compared with patients with near complete and partial responses. Future efforts should be directed at understanding determinants of complete responses. PMID:19161745

  17. MiR-203 suppresses tumor growth and invasion and down-regulates MiR-21 expression through repressing Ran in esophageal cancer.

    PubMed

    Zhang, Fang; Yang, Zhiping; Cao, Minjun; Xu, Yinsheng; Li, Jintao; Chen, Xuebin; Gao, Zhi; Xin, Jing; Zhou, Shaomei; Zhou, Zhixiang; Yang, Yishu; Sheng, Wang; Zeng, Yi

    2014-01-01

    The expression of miR-203 has been reported to be significantly down-regulated in esophageal cancer. We showed here that overexpression of miR-203 in esophageal cancer cells dramatically increased cell apoptosis and inhibited cell proliferation, migration and invasion as well as tumor growth and down-regulated miR-21 expression. We subsequently identified that small GTPase Ran was a target gene of miR-203. Furthermore, Ran restoration partially counteracted the tumor suppressive effects of miR-203 and increased miR-21 expression. Taken together, our findings suggest that miR-203 may act as novel tumor suppressor in esophageal cancer through down-regulating the expression of Ran and miR-21.

  18. Palliative stenting for relief of dysphagia in patients with inoperable esophageal cancer: impact on quality of life.

    PubMed

    Madhusudhan, Chinthakandhi; Saluja, Sundeep S; Pal, Sujoy; Ahuja, Vineet; Saran, Pratap; Dash, Nihar R; Sahni, Peush; Chattopadhyay, Tushar K

    2009-01-01

    The aim of palliation in patients with inoperable esophageal cancer is to relieve dysphagia with minimal morbidity and mortality, and thus improve quality of life (QOL). The use of a self-expanding metal stent (SEMS) is a well-established modality for palliation of dysphagia in such patients. We assessed the QOL after palliative stenting in patients with inoperable esophageal cancer. Thirty-three patients with dysphagia due to inoperable esophageal cancer underwent SEMS insertion between October 2004 and December 2006. All patients had grade III/IV dysphagia and locally advanced unresectable cancer (n = 13), distant metastasis (n = 14), or comorbid conditions/poor general health status precluding a major surgical procedure (n = 6). Patients with grade I/II dysphagia and those with carcinoma of the cervical esophagus were excluded. The QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3) and EORTC QLQ-Esophagus (OES) 18 questionnaire (a QOL scale specifically designed for esophageal diseases) before and at 1, 4, and 8 weeks after placement of the stent. The mean age of the patients was 56 (range 34-78) years, and 22 were men. A covered SEMS was used in all patients. The most common site of malignancy was the lower third of the esophagus (n = 18, 55%). In 23 (77%) patients, the stent crossed the gastroesophageal junction. Seven patients required a reintervention for stent block (n = 5) and stent migration (n = 2). Dysphagia improved significantly immediately after stenting, and this improvement persisted until 8 weeks (16.5 vs. 90.6; P < 0.01). The global health status (5.8 vs. 71.7; P < 0.01) and all functional scores improved significantly after stenting from baseline until 8 weeks. Except pain (14.1 vs. 17.7; P = 0.67), there was significant improvement in deglutition (22.7 vs. 2.0; P < 0.01), eating (48 vs. 12.6; P < 0.01), and other symptom scales (19.7 vs. 12.1; P = 0.04) following stenting. The

  19. Traditional home-brewed beer consumption and iron status in patients with esophageal cancer and healthy control subjects from Transkei, South Africa.

    PubMed

    Matsha, Tandi; Brink, Lucy; van Rensburg, Susan; Hon, Dinie; Lombard, Carl; Erasmus, Rajiv

    2006-01-01

    Consumption of home-brewed beer is associated with dietary iron excess and a high incidence of esophageal cancer in Transkei, South Africa. We examined the relationship between home-brewed beer consumption and body iron status in 234 patients with esophageal squamous cell carcinoma and 595 control subjects residing in Transkei. Subjects were screened for iron overload using transferrin saturation >45%, and/or serum ferritin >200 microg/l for women and >300 microg/l for men. A questionnaire was administered to all subjects, and iron content of randomly selected home-brewed beer samples was determined. The iron content of home-brewed beer was 258-fold higher than the commercial Castle Lager beer produced by South African Breweries. The prevalence of home-brewed beer consumption was 30.1% in esophageal cancer patients and 15.5% in control subjects and was found not to be a risk factor for esophageal cancer after adjustment for age, sex, and tobacco consumption (male subjects, odds ratio= 1.6 (95% confidence interval [CI]: 0.7-4.5); female subjects, odds ratio=1.7 (95% CI: 0.7-4.5). Iron overload as determined by transferrin saturation and elevated serum ferritin was observed in 4.3% of patients with esophageal cancer and 0.7% of control subjects and was not associated with the consumption of home-brewed beer. Consumption of home-brewed beer is not a risk factor for esophageal cancer and is not linked with iron overload in either cancer patients or control subjects; however, iron overload is likely to result from a combination of dietary intake and a genetic component.

  20. Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers

    PubMed Central

    Panettieri, Vanessa; Ruben, Jeremy D.; Senthi, Sashendra

    2016-01-01

    Background Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Methods Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. Results IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Conclusions Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses. PMID:27162670

  1. CXCR4 mRNA expression in colon, esophageal and gastric cancers and hepatitis C infected liver.

    PubMed

    Mitra, P; Shibuta, K; Mathai, J; Shimoda, K; Banner, B F; Mori, M; Barnard, G F

    1999-05-01

    We have recently demonstrated by Northern blot and RT-PCR that the mRNA expression of the alpha-chemokine hIRH/SDF-1alpha is reduced in hepatocellular carcinoma (HCC), several digestive tract cancers and premalignant colon adenomas, and that its receptor CXCR4 mRNA expression is reduced in HCC. Here we investigate the expression of CXCR4 mRNA expression in several digestive tract cancers and hepatitis C viral (HCV) infected liver, a premalignant condition. There was no difference in the CXCR4 mRNA expression in colon, esophageal or gastric cancers compared to non-cancerous tissues. This is significantly different from the reduced expression we have seen with hepatocellular carcinoma (p<0.05). To better refine regional tumor or hepatic cytokine mRNA analysis within a biopsy sample we describe a micro-isolation technique for RNA extraction from portal and triad areas of liver biopsies or other small malignant or non-malignant biopsy samples suitable for use in RT-PCR and differential display reactions. In HCV liver biopsies, the expression of hIRH and its receptor CXCR4 mRNA, corrected for G3PDH, was not significantly different from that of control non-HCV (steatosis) biopsies. CXCR4 is expressed on leukocytes and its expression was predicted to correlate with hepatic inflammation. CXCR4 receptor mRNA expression did correlate significantly with that of its ligand hIRH/SDF-1alpha (p=0.001), and with the severity of fibrosis (p<0.05), but not with portal inflammation (p<0.10), piecemeal necrosis (p<0.10), lobular inflammation (p>0.10), the presence of lymphoid aggregates (p>0.10), or the total histological activity index (p=0.07). There was no difference in expression of hIRH or CXCR4 between responders and non-responders to interferon (IFN) treatment, while as a control, the responder group of patients did show a higher expression of IFNalpha receptor than the non-responder group (p=0.05).

  2. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  3. Patterns of Care and Locoregional Treatment Outcomes in Older Esophageal Cancer Patients: The SEER-Medicare Cohort

    SciTech Connect

    Smith, Grace L.; Smith, Benjamin D.; Buchholz, Thomas A.; Liao Zhongxing; Jeter, Melenda; Swisher, Stephen G. M.D.; Hofstetter, Wayne L.; Ajani, Jaffer A.; McAleer, Mary F.; Komaki, Ritsuko; Cox, James D.

    2009-06-01

    Purpose: Optimal management of elderly patients with nonmetastatic esophageal cancer is unclear. Outcomes data after locoregional treatment are lacking for this group. Methods: We assessed outcomes associated with standard locoregional treatments in 2,626 patients (age > 65 years) from the Surveillance Epidemiology and End Results (SEER)-Medicare cohort diagnosed with nonmetastatic esophageal cancer from 1992 to 2002. In patients treated with radiotherapy alone (RT), surgery alone (S), chemoradiotherapy (CRT), or preoperative chemotherapy followed by surgery (CRT + S), overall and disease-free survival were compared using proportional hazards regression. Postoperative complications were compared using logistic regression. Results: Mean age was 76 {+-} 6 years. Seven percent underwent CRT + S, 39% CRT, 30% S, and 24% RT. One-year survival was 68% (CRT + S), 52% (CRT), 53% (S), and 16% (RT), respectively (p < 0.001). Patients who underwent CRT + S demonstrated improved overall survival compared with S alone (hazard ratio [HR] = 0.81; 95% confidence interval [CI], 0.66-0.98; p = 0.03) and RT (HR = 0.44; 95% CI, 0.35-0.55; p < 0.0001); and comparable survival to CRT (HR = 0.82; 95% CI, 0.67-1.01; p = 0.06). Patients who underwent CRT + S also had comparable postoperative mortality (HR = 0.96; 95% CI, 0.87-1.07; p = 0.45) and complications (OR = 0.89; 95% CI, 0.70-1.14; p = 0.36) compared with S alone. Conclusions: Preoperative chemoradiotherapy may be an acceptable treatment option in appropriately selected older esophageal cancer patients. This treatment modality did not appear to increase surgical complications and offered potential therapeutic benefit, particularly compared with surgery alone.

  4. Preoperative blood-routine markers and prognosis of esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

    PubMed

    Hu, Dan; Lin, Xiandong; Chen, Yan; Chang, Qing; Chen, Gang; Li, Chao; Zhang, Hejun; Cui, Zhaolei; Liang, Binying; Jiang, Wenhui; Ji, Kaida; Huang, Jun; Peng, Feng; Zheng, Xiongwei; Niu, Wenquan

    2016-11-11

    This prospective study was designed to investigate the prognosis of preoperative blood-routine markers for esophageal cancer mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients who received three-field lymphadenectomy for esophageal cancer between 2000 and 2010 were enrolled. Of 2535 patients with complete survival data, esophageal squamous cell carcinoma (ESCC) accounted for 94.5% (n = 2396). Here, only ESCC patients were analyzed, with the median follow-up time of 38.2 months (range: 0.5 to 180 months). Of 10 blood-routine markers evaluated, platelet count and red cell distribution width (RDW) were two significant predictors for ESCC mortality in men (adjusted hazard ratio or HR = 1.25 and 0.84, 95% confidence interval or CI: 1.08-1.22 and 0.75-0.93, P < 0.001 and P = 0.001, respectively), while in women only lymphocyte showed marginal significance. Based on individual results, a new derivate calculated as platelet count to RDW ratio (PRR) was created, and it was superior over other widely-evaluated derivates in men after adjustment (HR = 1.21, 95% CI: 1.13-1.30, P < 0.001), while there was no observable significance in women. In further stratified analyses, the prognosis of PRR for ESCC mortality was reinforced in men with tumor-node-metastasis stage III (HR, 95% CI, P: 1.18, 1.09-1.28, 0.001), invasion depth T3-T4 (1.17, 1.08-1.26, <0.001) or positive lymph node metastasis (1.37, 1.18-1.59, <0.001). Taken together, we created a new derivate PRR that was proven to be superior over other blood-routine markers and exhibited strong prognostic capability for ESCC mortality in Chinese men.

  5. Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three-field lymph node dissection for stage II/III N1, 2 esophageal cancer.

    PubMed

    Hashiguchi, Tadasuke; Nasu, Motomi; Hashimoto, Takashi; Kuniyasu, Tetsuji; Inoue, Hirohumi; Sakai, Noritaka; Ouchi, Kazutomo; Amano, Takayuki; Isayama, Fuyumi; Tomita, Natsumi; Iwanuma, Yoshimi; Tsurumaru, Masahiko; Kajiyama, Yoshiaki

    2014-09-01

    To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and

  6. Clinical study assessing the photosensitizer accumulation and light penetration for esophageal cancer prior to treatment by PDT

    NASA Astrophysics Data System (ADS)

    Bargo, Paulo R.; Jacques, Steven L.

    2001-07-01

    The FDA has approved PDT using Photofrin for certain esophageal and lung cancers, specifying an approved prescription of administered drug (mg/kg body weight) and administered light (J/linear cm of cylindrical fiber). This paper describes our development of a multi-optical fiber catheter for endoscopic use which documents the drug accumulated in the target tissues and the light penetration into the target tissues. The catheter uses reflectance to specify the light penetration depth and uses reflectance- corrected fluorescence to document drug accumulation. The goal is to document the variation in drug and light received by patients who are administered the FDA-approved prescription.

  7. Hydroferrate fluid, MRN-100, provides protection against chemical-induced gastric and esophageal cancer in Wistar rats.

    PubMed

    Ghoneum, Mamdooh H; Badr El-Din, Nariman K; Abdel Fattah, Salma M; Pan, Deyu; Tolentino, Lucilene

    2015-01-01

    In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.

  8. Hydroferrate Fluid, MRN-100, Provides Protection against Chemical-Induced Gastric and Esophageal Cancer in Wistar Rats

    PubMed Central

    Ghoneum, Mamdooh H.; Badr El-Din, Nariman K.; Abdel Fattah, Salma M.; Pan, Deyu; Tolentino, Lucilene

    2015-01-01

    In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma. PMID:25678848

  9. Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients

    PubMed Central

    Zheng, Xiao; Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients. Our results showed that the density of the infiltrating NK cells in tumor stroma was significantly associated with nodal status. In addition, the densities of the infiltrating NK cells in tumor nest, and the infiltrating macrophages in tumor nest as well as in tumor stroma, were significantly associated with patients' postoperative prognoses. Furthermore, the combination of infiltrating NK cells in tumor nest and stroma, or the combination of infiltrating macrophages in tumor nest and stroma, could also be used as important prognostic tool in predicting the survival of the stage II+III esophageal cancer patients. PMID:27736796

  10. MicroRNA-20b (miR-20b) Promotes the Proliferation, Migration, Invasion, and Tumorigenicity in Esophageal Cancer Cells via the Regulation of Phosphatase and Tensin Homologue Expression

    PubMed Central

    Xiao, Bin

    2016-01-01

    Increasing evidence has indicated that many microRNAs participate in the development and progression of esophageal cancer and gene expression regulation. MicroRNA-20b (miR-20b) has been reported to be aberrantly expressed in various cancers, but its exact role in esophageal cancer cells remains unclear so far. Therefore, we detected the levels of miR-20b in esophageal tumor tissues and their adjacent normal tissues, and various esophageal cancer cell lines by qRT-PCR. We also explored the effects of miR-20b on cell proliferation, migration, invasion and tumorigenicity of esophageal carcinoma cells through transfection with miR-20b mimics or inhibitor to upregulate or downregulate miR-20b expression in the esophageal cancer cells Eca-109 and KYSE-150, respectively. Additionally, the 3'-untranslated region (3'-UTR) of phosphatase and tensin homologue (PTEN) binding with miR-20b was analyzed by dual-luciferase reporter assays. The results indicated that miR-20b expression level in esophageal tumor tissues was significantly increased compared with their neighboring normal tissues, but its expression was inverse with PTEN protein expression. Luciferase assays confirmed that the 3'-UTR of PTEN was a target of miR-20b in esophageal cancer cells. MiR-20b upregulation promoted cell proliferation, migration, invasiveness, and tumor growth, and decreased apoptosis, and reduced PTEN protein level but not mRNA expression in Eca-109 cells. Conversely, downregulation of miR-20b suppressed these processes in KYSE-150 cells, and enhanced PTEN protein expression. These data indicate that miR-20b plays important roles in tumorigenesis of esophageal cancer possibly via regulation of PTEN expression, and it may be a potential therapeutic target for esophageal cancer treatment. PMID:27701465

  11. Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

    SciTech Connect

    Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng; Ping, Yu; Liu, Shasha; Shi, Xiaojuan; Li, Lifeng; Wang, Liping; Huang, Lan; Zhang, Bin; and others

    2015-08-01

    Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells.

  12. Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

    PubMed Central

    Yu, Jing-Ping; Sun, Su-Ping; Sun, Zhi-Qiang; Ni, Xin-Chu; Wang, Jian; Li, Yi; Hu, Li-Jun; Li, Dong-Qing

    2014-01-01

    AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients. PMID:24803825

  13. Rare tumors of esophageal squamous mucosa.

    PubMed

    Tripathi, Monika; Swanson, Paul E

    2016-10-01

    In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.

  14. Magnitude of Missed Esophageal Adenocarcinoma After Barrett's Esophagus Diagnosis: A Systematic Review and Meta-analysis

    PubMed Central

    Visrodia, Kavel; Singh, Siddharth; Krishnamoorthi, Rajesh; Ahlquist, David A.; Wang, Kenneth K.; Iyer, Prasad G.; Katzka, David A.

    2016-01-01

    Background & Aims A proportion of patients with Barrett's esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE. Methods We searched MEDLINE, EMBASE, and Web of Science from their inception to May 31, 2015 to identify cohort studies of adults with BE (baseline nondysplastic BE ± BE with low-grade dysplasia) and at least a 3-year follow-up period, providing data on missed and incident EACs (diagnosed within 1 year and diagnosed more than 1 year after the initial endoscopy in which BE was diagnosed, respectively). The main outcome measure was pooled proportion of missed and incident EACs (of all EACs detected after initial endoscopy) among BE cohorts, using a random effects model. Results In a metaanalysis of 24 studies reporting on 820 missed and incident EACs, 25.3% were classified as missed (95% confidence interval: 16.4%–36.8%) and 74.7% as incident EACs (95% CI: 63.2%–83.6%), although there was substantial heterogeneity among studies (I2 = 74%). When the analysis was restricted to nondysplastic BE cohorts (15 studies), 23.9% of EACs were classified as missed (95% confidence interval: 15.3%–35.4%; I2 = 0%). In a meta-analysis of 10 studies with follow-up periods of ≥5 years (a total of 239 EACs), 22.0% were classified as missed (95% confidence interval: 8.7%–45.5%), with substantial heterogeneity (I2 = 68%). Conclusions Among adults with nondysplastic BE (or BE with low-grade dysplasia) at their index endoscopy and at least a 3-year follow-up period, 25% of EACs are diagnosed within 1 year after the index endoscopy. Additional resources should be allocated to detect missed EAC. PMID:26619962

  15. Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells.

    PubMed

    Puspitasari, Irma M; Yamazaki, Chiho; Abdulah, Rizky; Putri, Mirasari; Kameo, Satomi; Nakano, Takashi; Koyama, Hiroshi

    2017-01-01

    The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0

  16. Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells

    PubMed Central

    Puspitasari, Irma M.; Yamazaki, Chiho; Abdulah, Rizky; Putri, Mirasari; Kameo, Satomi; Nakano, Takashi; Koyama, Hiroshi

    2017-01-01

    The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0

  17. CEP3 and CEP17 DNA probe potential in the genetic diagnosis and prognostic prediction of esophageal squamous cell cancer

    PubMed Central

    NIYAZ, MADINIYAT; ABDURAHMAN, ABLAJAN; TURGHUN, ABDUGHENI; AWUT, IDIRIS

    2016-01-01

    The aim of the present study was to investigate the clinical application of molecular pathological diagnosis for the prognosis of Kazakh patients with esophageal squamous cell carcinoma (ESCC) using centromere enumeration probes (CEPs) for chromosomes 3 and 17. A total of 40 patients with ESCC that had received radical surgical treatment and 10 healthy control participants were enrolled in the present study. Touch preparations of fresh cancerous and normal tissues were completed and fluorescence in situ hybridization (FISH) was performed to count the copy numbers of CEP 3 and 17, and abnormalities were analyzed, in comparison with routine pathological diagnoses. FISH analysis demonstrated that abnormal copy numbers of CEP 3 and 17 (aneuploidy) were detected in all 40 patients with ESCC. CEP 3 and 17 polyploidy rates differed significantly between poorly differentiated, moderately differentiated and well-differentiated ESCC groups (P<0.05): Well-differentiated, 35.38 and 30.92%; moderately differentiated, 55.81 and 44.43%; and poorly differentiated, 76.26 and 71.90%, respectively. Furthermore, polyploidy rates were significantly increased in the group with lymph node metastasis, as compared with the group without (CEP 3, P=0.0001; CEP 17, P=0.012). Variations in the copy numbers of CEP 3 and 17 were demonstrated to be correlated with the level of differentiation and lymph node metastasis in patients with ESCC. Therefore, the present results indicate that DNA probes may be used to predict prognostic factors in patients with ESCC. Furthermore, FISH technology is an objective and qualitative method that is capable of detecting variations in CEP 3 and 17; therefore, FISH may be used in the genetic diagnosis of ESCC in Kazakh patients. PMID:27073452

  18. Long non-coding RNA MEG3 induces cell apoptosis in esophageal cancer through endoplasmic reticulum stress.

    PubMed

    Huang, Zhen-Lun; Chen, Rui-Pei; Zhou, Xiao-Tao; Zhan, Hao-Lian; Hu, Min-Min; Liu, Bin; Wu, Guan-Di; Wu, Ling-Fei

    2017-05-01

    Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. Although downregulation of lncRNA MEG3 has been identified in several cancers, little is known about its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to detect MEG3 expression in clinical ESCC tissues, investigate its biological functions and the endoplasmic reticulum (ER) stress-relative mechanism. MEG3 expression levels were detected by qRT-PCR in both tumor tissues and adjacent non-tumor tissues from 28 ESCC patients. PcDNA3.1-MEG3 recombinant plasmids were constructed and transfected to EC109 cells. Cell growth was analyzed by CCK-8 assay. Cell apoptosis was analyzed by fluorescence microscope and Annexin V/PI assay. The protein expression was determined by western blot analysis. The results showed that MEG3 decreased significantly in ESCC tissues relative to adjacent normal tissues. PcDNA3.1-MEG3 plasmids were successfully constructed and the expression level of MEG3 significantly increased after MEG3 transfection to EC109 cells. Ectopic expression of MEG3 inhibited EC109 cell proliferation and induced apoptosis in vitro. MEG3 overexpression increased the expression of ER stress‑related proteins (GRP78, IRE1, PERK, ATF6, CHOP and cleaved‑caspase-3). Our results first demonstrate that MEG3 is downregulated in ESCC tissues. MEG3 was able to inhibit cell growth and induced apoptosis in EC109 cells, most probably via activation of the ER stress pathway.

  19. Esophageal surgery in minimally invasive era

    PubMed Central

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-01

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  20. Determination of Internal Target Volume for Radiation Treatment Planning of Esophageal Cancer by Using 4-Dimensional Computed Tomography (4DCT)

    SciTech Connect

    Chen, Xiaojian; Lu, Haijun; Tai, An; Johnstone, Candice; Gore, Elizabeth; Li, X. Allen

    2014-09-01

    Purpose: To determine an efficient strategy for the generation of the internal target volume (ITV) for radiation treatment planning for esophageal cancer using 4-dimensional computed tomography (4DCT). Methods and Materials: 4DCT sets acquired for 20 patients with esophageal carcinoma were analyzed. Each of the 4DCT sets was binned into 10 respiratory phases. For each patient, the gross tumor volume (GTV) was delineated on the 4DCT set at each phase. Various strategies to derive ITV were explored, including the volume from the maximum intensity projection (MIP; ITV{sub M}IP), unions of the GTVs from selected multiple phases ITV2 (0% and 50% phases), ITV3 (ITV2 plus 80%), and ITV4 (ITV3 plus 60%), as well as the volumes expanded from ITV2 and ITV3 with a uniform margin. These ITVs were compared to ITV10 (the union of the GTVs for all 10 phases) and the differences were measured with the overlap ratio (OR) and relative volume ratio (RVR) relative to ITV10 (ITVx/ITV10). Results: For all patients studied, the average GTV from a single phase was 84.9% of ITV10. The average ORs were 91.2%, 91.3%, 94.5%, and 96.4% for ITV{sub M}IP, ITV2, ITV3, and ITV4, respectively. Low ORs were associated with irregular breathing patterns. ITV3s plus 1 mm uniform margins (ITV3+1) led to an average OR of 98.1% and an average RVR of 106.4%. Conclusions: The ITV generated directly from MIP underestimates the range of the respiration motion for esophageal cancer. The ITV generated from 3 phases (ITV3) may be used for regular breathers, whereas the ITV generated from 4 phases (ITV4) or ITV3 plus a 1-mm uniform margin may be applied for irregular breathers.

  1. Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan.

    PubMed

    Lee, Chien-Hung; Lee, Jang-Ming; Wu, Deng-Chyang; Hsu, Hon-Ki; Kao, Ein-Long; Huang, Hsiao-Ling; Wang, Tsu-Nai; Huang, Meng-Chuan; Wu, Ming-Tsang

    2005-01-20

    A multicenter case-control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospital-matched controls were included. We found a significant dose-response relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR = 13.9) being for those who consumed more than 900 g/day-year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8-19.7 fold and, to all 3 substances, to 41.2-fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

  2. Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity.

    PubMed

    Hongo, Michio; Nagasaki, Yutaka; Shoji, Tomotaka

    2009-05-01

    Esophageal adenocarcinoma (EAC) has been rapidly increasing in Western countries during the past half century, especially in white men. Esophageal squamous cell carcinoma (ESCC) used to be the dominant type of esophageal malignancy both in Western and Asian countries. The rapid increase of EAC in Western countries has occurred in parallel with an increased prevalence of gastroesophageal reflux disease (GERD) and its major determinant, obesity. Such an increase in EAC has not yet been observed in Asia, despite a recent increase in prevalence of GERD. In this mini-review, we analyze possible factors influencing such east-west ('Orient to Occident') differences, particularly possible roles of ethnicity and environmental factors, such as Helicobacter pylori infection and nutritional factors, and how these might interact with socioeconomic differences. Development of Barrett's esophagus and esophageal adenocarcinoma appears to be strongly affected by ethnic factors, with populations resident at the west end of the Eurasian continent, such as Anglo-Celtics, being more prone to both conditions. On the other hand, ethnic groups from the eastern and southern ends of Eurasia, such as Chinese, Koreans and Japanese, and Africans might be more prone to developing esophageal squamous cell carcinoma. Future trends will also be discussed.

  3. Peroral endoscopic myotomy for the treatment of esophageal achalasia: systematic review and pooled analysis.

    PubMed

    Patel, K; Abbassi-Ghadi, N; Markar, S; Kumar, S; Jethwa, P; Zaninotto, G

    2016-10-01

    Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy for the treatment of achalasia. This review aims to assess subjective and objective metrics of achalasia treatment efficacy, perioperative adverse events and the incidence of postoperative gastroesophageal reflux disease in patients treated with POEM. Secondary aims include a pooled analysis comparison of the clinical outcomes and procedural safety of POEM versus laparoscopic Heller's myotomy (LHM). A systematic review of the literature, up to and including January 15, 2015, was conducted for studies reporting POEM outcomes. Studies comparing POEM to LHM were also included for the purpose of pooled analysis. Outcomes from 1122 POEM patients, from 22 studies, are reported in this systematic review. Minor operative adverse events included capno/pneumo-peritoneum (30.6%), capno/pneumo-thorax (11.0%) and subcutaneous emphysema (31.6%). Major operative adverse events included mediastinal leak (0.3%), postoperative bleeding (1.1%) and a single mortality (0.09%). There was an improvement in lower esophageal sphincter pressure and timed barium esophagram column height of 66% and 80% post-POEM, respectively. Symptom improvement was demonstrated with a pre- and post-POEM Eckardt score ± standard deviation of 6.8 ± 1.0 and 1.2 ± 0.6, respectively. Pre- and post-POEM endoscopy showed esophagitis in 0% and 19% of patients, respectively. The median (interquartile range) points scored for study quality was 15 (14-16) out of total of 32. Pooled analysis of three comparative studies between LHM and POEM showed similar results for adverse events, perforation rate, operative time and a nonsignificant trend toward a reduced length of hospital stay in the POEM group. In conclusion, POEM is a safe and effective treatment for achalasia, showing significant improvements in objective metrics and achalasia-related symptoms. Randomized comparative studies of LHM and POEM are required to determine the

  4. Induction of autophagy counteracts the anticancer effect of cisplatin in human esophageal cancer cells with acquired drug resistance.

    PubMed

    Yu, Le; Gu, Chunping; Zhong, Desheng; Shi, Lili; Kong, Yi; Zhou, Zhitao; Liu, Shuwen

    2014-12-01

    Cisplatin-based chemotherapy frequently resulted in acquired resistance. The underpinning mechanism of such resistance remains obscure especially in relation to autophagic response. This study thus investigated the role of autophagy in the anticancer activity of cisplatin in human esophageal cancer cells with acquired cisplatin resistance. In response to cisplatin treatment, EC109 cells exhibited substantial apoptosis and senescence whereas cisplatin-resistant EC109/CDDP cells exhibited resistance. In this respect, cisplatin increased ERK phosphorylation whose inhibition by MEK inhibitor significantly attenuated the cytotoxic and cytostatic effect of cisplatin. Notably, cisplatin preferentially induces autophagy in EC109/CDDP cells but not in EC109 cells. Moreover, the induction of autophagy was accompanied by the suppression of mTORC1 activity. Abolition of autophagy by pharmacological inhibitors or knockdown of ATG5/7 re-sensitized EC109/CDDP cells. Co-administration of an autophagy inhibitor chloroquine and cisplatin significantly suppressed tumor growth whereas cisplatin monotherapy failed to elicit anticancer activity in nude mice xenografted with EC109/CDDP cells. To conclude, our data implicate autophagic response as a key mechanism of acquired resistance to cisplatin, suggesting that autophagy is a novel target to improve therapy efficiency of cisplatin toward human esophageal cancers with acquired resistance.

  5. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2011-03-01

    staining for major basic protein in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR... morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants on chromosome 4q26-27...variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor- expressing cells within

  6. Preliminary clinical data on a new photodynamic therapy photosensitizer: 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) for treatment of obstructive esophageal cancer

    NASA Astrophysics Data System (ADS)

    Dougherty, Thomas J.; Pandey, R. K.; Nava, Hector R.; Smith, Judy L.; Douglass, Harold O.; Edge, Stephen B.; Bellnier, David A.; O'Malley, Linda; Cooper, Michele

    2000-03-01

    The hexyl ether derivative or HPPH, has been identified as an optimal active in vivo photosensitizer in pre-clinical studies and has been evaluated clinically in obstructive esophageal cancer in five patients to date. The photosensitizer appears to have no systemic toxicity and be effective at low drug and light doses. Further, cutaneous photosensitivity appears to persist only 5-7 days.

  7. Downregulation of O-linked N-acetylglucosamine transferase by RNA interference decreases MMP9 expression in human esophageal cancer cells

    PubMed Central

    QIAO, ZHE; DANG, CHENGXUE; ZHOU, BIN; LI, SHAOMIN; ZHANG, WEI; JIANG, JIANTAO; ZHANG, JIN; MA, YUEFENG; KONG, RANRAN; MA, ZHENCHUAN

    2016-01-01

    O-linked N-acetylglucosamine transferase (OGT) catalyzes O-linked glycosylation (O-GlcNAcylation). O-GlcNAcylation is a post-translational carbohydrate modification of diverse nuclear and cytosolic proteins by the addition of O-linked β-N-acetylglucosamine. It was recently demonstrated that OGT and the level of O-GlcNAcylation are upregulated in esophageal cancer; however, the physiological consequences of this upregulation remain unknown. The current study reports that OGT knockdown by short hairpin RNA (shRNA) did not affect cell viability; however, cell migration in esophageal cancer Eca-109 cells was significantly reduced. OGT-specific shRNA vectors efficiently decreased the protein and mRNA levels of OGT and the RL2 level (a marker of O-GlcNAcylation levels) in Eca-109 esophageal cancer cells. In addition, colony formation and cell proliferation assays demonstrated that OGT-specific shRNA decreased the proliferation of Eca-109 cells; however, there was no significant statistical difference between OGT-specific shRNA and control shRNA. Notably, transwell assays demonstrated that the migratory ability of Eca-109 cells was significantly suppressed following knockdown of the OGT gene. Correspondingly, western blot analyses demonstrated that OGT knockdown significantly downregulated the expression of matrix metalloproteinase 9 (MMP9) in Eca-109 cells. These results suggest that OGT may promote the migration, invasion and metastasis of esophageal cancer cells by enhancing the stability or expression of MMP9. PMID:27123109

  8. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  9. Prognostic value of right upper mediastinal lymphadenectomy in Sweet procedure for esophageal cancer

    PubMed Central

    Wang, Zhi-Qiang; Deng, Han-Yu; Hu, Yang; Yuan, Yong; Wang, Wen-Ping; Wang, Yun-Cang

    2016-01-01

    Background The prognostic value of the right upper mediastinal lymph node dissection (RUMLND) for patients with middle or lower thoracic esophageal squamous cell carcinoma (ESCC-MLT) is still not well established yet. Our objective is to evaluate the prognostic role of the Sweet procedure plus right upper mediastinal lymph node dissection (MS) by comparing with the Sweet procedure with standard lymph node dissection (SS) in terms of long-term survival. Methods Totally 1,477 ESCC-MLT patients underwent radical intent surgery (186 with MS, 1,291 with SS) at our department between January 2007 and September 2013. After propensity score matching (PSM), 186 patients from each group were matched and analyzed. The 5-year survival rates in two groups were compared by detailed stratifications in terms of clinical characteristics. Results As for the prognostic role of RUMLND, patients treated with MS tended to obtain higher 5-year survival rate than patients treated with SS in univariate analysis (48.1% vs. 37.4%). Moreover, in multivariate analysis, MS yielded significant higher 5-year survival rate compared with SS (P=0.041). In addition, subgroup analyses of the survival between the MS and SS patients by detailed stratifications demonstrated the survival superiority in the MS group with age <60 years old, TNM stage III, number of lymph node dissection (LND) ≥15, as well as no using of postoperative adjuvant treatment. Conclusions The RUMLND in Sweet procedure is an independent prognostic factor for ESCC-MLT patients, especially for those with thoracic middle segment-located tumor, stage III or younger. PMID:28149557

  10. Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

    PubMed

    Hori, Masakazu; Someya, Masanori; Matsumoto, Yoshihisa; Nakata, Kensei; Kitagawa, Mio; Hasegawa, Tomokazu; Tsuchiya, Takaaki; Fukushima, Yuki; Gocho, Toshio; Sato, Yasushi; Ohnuma, Hiroyuki; Kato, Junji; Sugita, Shintaro; Hasegawa, Tadashi; Sakata, Koh-Ichi

    2017-03-01

    DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.

  11. Long Term Outcome in Patients with Esophageal Stenting for Cancer Esophagus - Our Experience at a Rural Hospital of Punjab, India

    PubMed Central

    Singh, Abhitesh; Singh, Anantbir; Sharma, Ghansham; Bhatia, Parmod Kumar; Grover, Amarjeet Singh

    2016-01-01

    Introduction Cancer of the esophagus is among the leading cause of cancer deaths in Punjab, India. Patients generally present with dysphagia as their first symptom and more often they have advanced disease at the time of presentation to a tertiary care centre. Palliative procedures have important roles in this setting. Stenting is the best option to palliate the symptoms of dysphagia, from which patient is suffering the most. Aim To know the success rate, early and long term complications and mortality in esophageal stenting, when it was done in malignant esophageal stricture patients. Materials and Methods One hundred patients, who had undergone esophageal stenting from January 2012 to January 2015, were included in the study. We retrospectively analysed the data for patient characteristics, causes of non-operability, early and long term complications, re-interventions, efficacy and mortality. Results Out of 100 patients, indications for stenting were locally advanced disease not amenable to surgery (52%), metastatic disease (35%), CVA (1%), cardiac and respiratory problem (8%), un-willing for surgery in 5% of patients. Majority of patients (94%) had squamous cell carcinoma, while only 6% had adenocarcinoma. 84% of patients presented with dysphagia with or without chest pain and recurrent cough while 16% had recurrent vomiting. 58% had dysphagia to liquids and solids and 17% had complete dysphagia. After stenting 93% had significant improvement in dysphagia score from median of 3 to 1. Post procedure stay was 3.61±1.0 days. One patient had procedure related major complication in the form of post procedural bleed (after 16 days of stenting) leading to death of that patient. Minor complications were present in 52 patients treated conservatively not affecting the efficacy of procedure. These include pain after stenting (38%), stent obstruction (23%) and stent migration (6%). All the minor complications were treated conservatively except in six patients in whom re

  12. Cancer-associated fibroblasts mediated chemoresistance by a FOXO1/TGFβ1 signaling loop in esophageal squamous cell carcinoma.

    PubMed

    Zhang, Hongfang; Xie, Conghua; Yue, Jing; Jiang, Zhenzhen; Zhou, Rongjing; Xie, Ruifei; Wang, Yan; Wu, Shixiu

    2017-03-01

    Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively. The association of CAFs and chemoresistance was assessed in esophageal carcinoma cells, in xenograft tumor models and in clinical specimens of ESCC patients. We found CAFs conferred ESCC cells significant resistance to several common chemotherapeutic drugs including cisplatin, taxol, irinotecan (CPT-11), 5-fluorouracil (5-Fu), carboplatin, docetaxel, pharmorubicin, and vincristine. Mechanism studies revealed that blockage of CAFs-secreted TGFβ1 signaling by its receptor TGFβR1 inhibitor LY2157299 significantly reversed the chemoresistance in vitro and in vivo. Furthermore, the crosstalk of CAFs and ESCC cells enhanced the expression and activation of FOXO1, a member of the forkhead transcription factors in the O-box sub-family, inducing TGFβ1 expression in an autocrine/paracrine signaling loop. In 130 ESCC patients, the expression of TGFβ1 in CAFs was significantly associated with overall survival of patients treated with chemoradiotherapy. Together, our study highlighted TGFβ1 expressed in CAFs as an attractive target to reverse tumor chemoresistance, and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy. © 2016 Wiley Periodicals, Inc.

  13. miR-30b inhibits cancer cell growth, migration, and invasion by targeting homeobox A1 in esophageal cancer.

    PubMed

    Li, Qing; Zhang, Xuan; Li, Ning; Liu, Qin; Chen, Dongfeng

    2017-02-09

    Emerging evidence has shown that microRNAs (miRNAs) play important roles in tumor development and progression. In particular, miR-30b is thought to be closely related to the migration, invasion, proliferation, communication, and drug resistance of tumor cells. However, the potential value of miR-30b in human esophageal cancer (EC) remains unclear. In this study, we investigated the biological functions of miR-30b and its potential role in EC. The results indicated that the expression levels of miR-30b were decreased in EC tissues and were correlated with invasion classification (P < 0.01), lymph node metastasis (P < 0.01), and pathological stage (P < 0.05). Log-rank tests demonstrated that low expression of miR-30bwas strongly correlated with poor overall survival in patients with EC (P < 0.05). Moreover, overexpression of miR-30b markedly inhibited the growth, migration, and invasion of ECA109 and TE-1 cells by directly downregulating homeobox A1 (HOXA1). When HOXA1 was reintroduced into miR-30b-transfected ECA109 or TE-1 cells, the inhibitory effects of miR-30b on EC cell growth, migration, and invasion were markedly reversed. In conclusion, our findings demonstrated that miR-30b could inhibit tumor cell growth, migration, and invasion by directly targeting HOXA1 in EC cells.

  14. Impact of hybrid fluorodeoxyglucose positron-emission tomography/computed tomography on radiotherapy planning in esophageal and non-small-cell lung cancer

    SciTech Connect

    Gondi, Vinai; Bradley, Kristin; Mehta, Minesh . E-mail: mehta@humonc.wisc.edu; Howard, Andy; Khuntia, Deepak; Ritter, Mark; Tome, Wolfgang

    2007-01-01

    Purpose: The aim of this study was to investigate the impact of a hybrid fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) scanner in radiotherapy planning for esophageal and non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 30 patients (16 with esophageal cancer, 14 with NSCLC) underwent an FDG-PET/CT for radiotherapy planning purposes. Noncontrast total-body spiral CT scans were obtained first, followed immediately by FDG-PET imaging which was automatically co-registered to the CT scan. A physician not involved in the patients' original treatment planning designed a gross tumor volume (GTV) based first on the CT dataset alone, while blinded to the FDG-PET dataset. Afterward, the physician designed a GTV based on the fused PET/CT dataset. To standardize PET GTV margin definition, background liver PET activity was standardized in all i