MiR-328 suppresses the survival of esophageal cancer cells by targeting PLCE1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Na; Zhao, Wenchao; Zhang, Zhongmian

2016-01-29

Esophageal cancer (EC) is the sixth leading cause of death worldwide. Recent studies have highlighted the vital role of microRNAs (miRNAs) in EC development and diagnosis. In our study, qPCR analysis showed that miRNA-328 was expressed at significantly low levels in EC109 and EC9706 cells. The results also showed that overexpression of miR-328 by lentivirus-mediated gene transfer markedly inhibited cell proliferation and invasion, and enhanced apoptosis; whereas, inhibition of miR-328 significantly promoted cell proliferation and invasion, and suppressed apoptosis in EC109 and EC9706 cells. Dual-luciferase reporter assay confirmed that miR-328 directly targeted phospholipase C epsilon 1 (PLCE1) by binding to target sequencesmore » in the 3′-UTR. qPCR and Western blot analysis showed that the PLCE1 was overexpressed in EC109 and EC9706 cells. Additionally, we found that miR-328 overexpression decreased PLCE1 mRNA and protein levels, while miR-328 inhibition enhanced the PLCE1 expression. Further analysis showed that PLCE1 overexpression rescued the inhibitory effect of miR-328 on cell proliferation and invasion, and repressed the promotive effect of miR-328 on cell apoptosis. In conclusion, our results suggest that miR-328 suppresses the survival of EC cells by regulating PLCE1 expression, which might be a potential therapeutic method for EC. - Highlights: • PLCE1 was a target gene of miR-328. • MiR-328 overexpression decreased PLCE1 expression. • PLCE1 overexpression rescued the inhibitory effect of miR-328 on the survival of EC cells.« less

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

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

PubMed

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

2017-02-07

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Yi; Zhou, Yajuan; Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071

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, wemore » 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.« less

Cancer stem cells with increased metastatic potential as a therapeutic target for esophageal cancer.

PubMed

Wang, D; Plukker, J Th M; Coppes, R P

2017-06-01

Esophageal cancers (EC) are highly aggressive tumors, commonly presented in a locally advanced stage with a poor prognosis and survival. Up to 50% of the patients are eligible for treatment with curative intent and receive the standard treatment with neoadjuvant chemoradiotherapy (nCRT) and surgery. Currently, pathologic complete response to nCRT is 20-30%, with a partial or no response in about 50% and 20%, respectively. EC recurrences occur frequently even after successful anti-cancer treatment, suggesting high aggressiveness with increased metastatic potential. A tumor sub-population of so-called cancer stem cells (CSCs), is known to display a high metastatic potential and resistance to conventional anti-cancer therapy, hereby being responsible for the unbeneficial clinical features. In this review, a concise overview will be given of the current literature on esophageal CSCs and related metastases. Esophageal CSC markers will be discussed followed by the pathways that initiate and sustain these cells. In addition, the cellular processes, epithelial-mesenchymal transition (EMT), hypoxia and autophagy, known to contribute to cancer stemness and metastasis will be explained. Finally, potential options for treatment also related to cancer genome atlas (TCGA) data on EC will be discussed. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intervention and follow-up on human esophageal precancerous lesions in Henan, northern China, a high-incidence area for esophageal cancer.

PubMed

Wang, Li Dong; Zhou, Qi; Feng, Chang Wei; Liu, Bin; Qi, Yi Jun; Zhang, Yan Run; Gao, Shan Shan; Fan, Zong Min; Zhou, Yun; Yang, Chang S; Wei, Jun Ping; Zheng, Shu

2002-02-01

Esophageal cancer (EC) remains a leading cause of cancer-related deaths in Linzhou (formerly Linxian) and Huixian of Henan province, northern China, which has been well recognized as the highest incidence area for EC. The lack of useful chemoprevention agents and early detection methods is the key factors for stable EC incidence in these areas. Human esophageal carcinogensis has been considered as a multistep progressive process. The natural history for EC, however is not very clear. Follow-up studies with linear repeated biopsies and histopathological examination were performed on 778 subjects from Linzhou and Huixian. Of these subjects, 578 subjects were followed for 11 years (1989-2000), 400 subjects with different severity of esophageal precancerous lesions were randomly divided into 2 groups for intervention studies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 subjects for treatment, and 100 subjects for placebo). In calcium group, each subject received an oral supplementation of 1,200 mg of calcium daily for 11 months. In DGT group, each subject received 5 mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calcium group) and 12 month (DGT group). At the entry and the end of the trial, esophageal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic lesions, if only, of each subject. DGT trail did not show apparent difference between the treatment and placebo group in alleviating the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years' follow-up, 10 subjects had developed into cancers in the calcium group (10%, 8 EC and 2 GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n = 23, 4.3%) and gastric

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.

Intakes of citrus fruit and risk of esophageal cancer: A meta-analysis.

PubMed

Zhao, Wenyue; Liu, Lu; Xu, Shun

2018-03-01

Esophageal cancer (EC) is the eighth most common cancer and the sixth most frequent cause of cancer death in the whole world. Many studies have investigated the association between citrus fruit intake and the risk of EC, but the results are inconsistent and not analyzed by category. We aimed to perform a meta-analysis of studies to evaluate the incidence between citrus fruit consumption and subtypes of esophageal cancer and derive a more precise estimation.Through searches of PubMed, OVID, and Web of Science we updated 1988 systematic review up to April 2016. Based on an inclusion and exclusion criteria, conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. Random-effect models were used to calculate subgroups.Twenty-five English articles (20 case-control studies and 5 cohort studies) comprising totally 5730 patients of esophageal cancer would be suitable for use in this study. The result indicated the inverse associations between intakes of citrus fruit and EC (relative risk [RR] = 0.65, 95% confidence interval [CI] 0.56-0.75, I  = 51.1%, P = .001), Esophageal squamous cell carcinoma (ESCC) (RR = 0.59, 95% CI 0.47-0.76, I  = 60.7%, P = .002), no significant relationship between citrus fruit and esophageal adenocarcinoma (EAC) (RR = 0.86, 95% CI 0.74-1.01, I  = 0.0%, P = .598).This meta-analysis indicates that intakes of citrus fruit significantly reduce the risk of ESCC and is no obvious relationship with EAC. Further studies about constituents in citrus fruit and its mechanism are warranted.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PubMed

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

To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. 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. 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). 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. Copyright © 2012 Elsevier Inc. All rights reserved.

PD-L1 Expression Promotes Epithelial to Mesenchymal Transition in Human Esophageal Cancer.

PubMed

Chen, Lujun; Xiong, Yuqi; Li, Jing; Zheng, Xiao; Zhou, Qi; Turner, Abbey; Wu, Changping; Lu, Binfeng; Jiang, Jingting

2017-01-01

PD-L1 (Programmed cell death 1 ligand 1, PD-L1), an essential immune checkpoint molecule in the tumor microenvironment, is an important target for cancer immunotherapy. We have previously reported that its expression in human gastric and esophageal cancer tissues is significantly associated with cancer progression and patients' postoperative prognoses. Its expression in cancer cells is well known to inhibit the T cell-mediated anti-tumor response, and this mechanism of action has been targeted for cancer immunotherapy. As of now, the autonomous effect of PD-L1 on cancer cells is not well understood, thus our present study aimed to examine the role of PD-L1 intervention in cellular biological functions, especially epithelial to mesenchymal transition (EMT), of the human esophageal cancer cell line, Eca-109 cells. Immunohistochemistry assay was used to investigate the correlation between expression of PD-L1 and EMT markers in human esophageal cancer tissues. Intervention of PD-L1 by using RNAi and over-expression methods were used to study the role of PD-L1 in regulation of biological behaviors and EMT in Eca-109 cells. Our clinical and pathological data demonstrated that tumor samples in the EMT positive subgroup had higher PD-L1 expression than those in the EMT negative subgroup. By manipulating PD-L1 expression in Eca-109 cells either through ablation or overexpression of wild type and the cytoplasmic domain-truncated mutant, we demonstrated that PD-L1 expression significantly promoted the cell viability, migration and EMT phenotype. Furthermore, our study also indicated that PD-1 fusion protein mediated stimulation of PD-L1 and the cytoplasmic domain of PD-L1 played a critical role in promoting EMT phenotype of Eca-109 cells, thereby suggesting that PD-1 receptor usually by triggering the reverse signaling can effect PD-L1 mediated regulation of esophageal cancer cell response. Our present study reveals a tumor cell-autonomous role of PD-L1 signaling in promoting

Differential role of microRNAs in the pathogenesis and treatment of Esophageal cancer.

PubMed

Hemmatzadeh, Maryam; Mohammadi, Hamed; Karimi, Mohammad; Musavishenas, Mohammad Hossein; Baradaran, Behzad

2016-08-01

Esophageal cancer (EC) is the most invasive disease associated with inclusive poor prognosis. EC usually is found as either adenocarcinoma (EAC) or squamous cell carcinomas (ESCC). ESCC forms in squamous cells and highly occurs in the upper third of the esophagus. EAC appears in glandular cells and ordinarily develops in the lower one third of the esophagus near the stomach. Barrett's esophagus (BE) is a metaplastic precursor of EAC. There is a persistent need for improving our understanding of the molecular basis of this disease. MicroRNAs (miRNAs) demonstrate an uncovered class of small, non-coding RNAs that can negatively regulate the protein coding gene, and are associated with approximately all known physiological and pathological processes, especially cancer. MiRNAs can affect cancer pathogenesis, playing a crucial role as either oncogenes or tumor suppressors. The recent emergence of observations on the role of miRNAs in cancer and their functions has induced many investigations to examine their relevance to esophageal cancer. In esophageal cancer, miRNA dysregulation plays a crucial role in cancer prognosis and in patients' responsiveness to neo-adjuvant and adjuvant therapies. In this review, the oncogenic, tumor suppressive, and drug resistance related roles of miRNAs, and their involvement in the pathogenesis and treatment of esophageal cancer were summarized. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Esophageal Cancer: Genomic and Molecular Characterization, Stem Cell Compartment and Clonal Evolution

PubMed Central

Testa, Ugo; Castelli, Germana; Pelosi, Elvira

2017-01-01

Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett’s esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC. EAC is a heterogeneous cancer dominated by copy number alterations, a high mutational burden, co-amplification of receptor tyrosine kinase, frequent TP53 mutations. The cellular origins of BE and EAC are still not understood: animal models supported a cellular origin either from stem cells located in the basal layer of esophageal epithelium or from progenitors present in the cardia region. Many studies support the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. The exact identification of these CSCs, as well as their role in the pathogenesis of EAC and ESCC remain still to be demonstrated. The reviewed studies suggest that current molecular and cellular characterization of EAC and ESCC should serve as background for development of new treatment strategies. PMID:28930282

[Effect of EMP-1 gene on human esophageal cancer cell line].

PubMed

Wang, Hai-tao; Liu, Zhi-hua; Wang, Xiu-qin; Wu, Min

2002-03-01

EMP-1 was selected from a series of differential expressed genes obtained from cDNA microarray in the authors' lab. Epithelial membrane pnteiu-1 gene (EMP-1) was expressed 6 fold lower in esophageal cancer than in normal tissue. The authors further designed the experiment to study the effect of human EMP-1 gene on human esophageal cancer cell line in order to explain the function of this gene on the carcinogensis and progression esophageal cancer. EMP-1 gene was cloned into eukaryotic vector and transfected into the human esophageal cancer cell line. The transfection effect was qualified by Western blot and RT-PCR method. The cell growth curve was observed and the cell cycle was checked by FACS method. EMP-1 was transfected into EC9706 cell line and its expression was up-regulated. The cell growth is accelerated and expression of EMP-1 is linked to induction of S phase arrest. EMP-1 gene has some relationship with carcinogenesis of esophagus.

Dual effects of 8-Br-cAMP on differentiation and apoptosis of human esophageal cancer cell line Eca-109

PubMed Central

Wang, Hong-Mei; Zheng, Nai-Gang; Wu, Jing-Lan; Gong, Cui-Cui; Wang, Yi-Ling

2005-01-01

AIM: To investigate the effects of 8-Br-cAMP on differentiation and apoptosis of human esophageal cancer cell line Eca-109, and the related gene expression. METHODS: The cultured Eca-109 cells were divided into four groups: E1 group (co-cultured with 8-Br-cAMP for 24 h); E2 group (co-cultured with 8-Br-cAMP for 48 h); C1 group (treated without 8-Br-cAMP for 24 h); and C2 group (treated without 8-Br-cAMP for 48 h). The same concentration of cell suspension of each group was dropped separately onto the slides and nitrocellulose membranes (NCM). The biotin-labeled cDNA probes for c-myc, wild-type (wt) p53, bcl-2 and iNOS were prepared for in situ hybridization. The expressions of epidermal growth factor receptor (EGFR), p38 kinase, FAS, FasL and caspase-3 were detected using immunocytochemistry, and the NOS activity and the ratio of differentiated cells/proliferating cells were examined by cytochemistry. Immunocytochemistry, cytochemistry, and in situ hybridization were separately carried out on both slides and NCM specimens for each group. In addition, TUNEL was used to detect the cell apoptosis rate in each group. RESULTS: The apoptotic rate of E2 group was significantly higher compared to E1 group, while there was no difference in the ratio of differentiated cells/proliferating cells between E1 and E2 groups. The signals of wt p53 and iNOS were markedly stronger, while the signals of c-myc and EGFR were obviously weaker in E1 group than those in C1 group (P<0.05). Moreover, the signals of wt p53, iNOS, p38 kinase, caspase-3 and NOS activity were significantly stronger, whereas, the signals of bcl-2, c-myc and Fas/FasL were markedly weaker in E2 group than those in C2 group (P<0.05). CONCLUSION: The differentiation and apoptosis of human esophageal cancer cell Eca-109 can be induced after 24- and 48-h treatment with 8-Br-cAMP, respectively. Upregulation of wt p53, iNOS and downregulation of c-myc may be associated with differentiation and apoptosis of Eca-109 cells

Early diagnostic potential of APC hypermethylation in esophageal cancer.

PubMed

Wang, Bujiang; Song, Haojun; Jiang, Haizhong; Fu, Yangbo; Ding, Xiaoyun; Zhou, Chongchang

2018-01-01

The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE ( P = 0.052), it was not associated with tumor stage ( P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

Advances in Radiotherapy Management of Esophageal Cancer.

PubMed

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

2016-10-21

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.

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

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 ...

Esophageal cancer

MedlinePlus

... old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types look different from each other under the microscope. Squamous cell esophageal cancer is linked to smoking and drinking too much ...

Esophageal Cancer.

PubMed

Short, Matthew W; Burgers, Kristina G; Fry, Vincent T

2017-01-01

Esophageal cancer has a poor prognosis and high mortality rate, with an estimated 16,910 new cases and 15,910 deaths projected in 2016 in the United States. Squamous cell carcinoma and adenocarcinoma account for more than 95% of esophageal cancers. Squamous cell carcinoma is more common in nonindustrialized countries, and important risk factors include smoking, alcohol use, and achalasia. Adenocarcinoma is the predominant esophageal cancer in developed nations, and important risk factors include chronic gastroesophageal reflux disease, obesity, and smoking. Dysphagia alone or with unintentional weight loss is the most common presenting symptom, although esophageal cancer is often asymptomatic in early stages. Physicians should have a low threshold for evaluation with endoscopy if any symptoms are present. If cancer is confirmed, integrated positron emission tomography and computed tomography should be used for initial staging. If no distant metastases are found, endoscopic ultrasonography should be performed to determine tumor depth and evaluate for nodal involvement. Localized tumors can be treated with endoscopic mucosal resection, whereas regional tumors are treated with esophagectomy, neoadjuvant chemotherapy, chemoradiotherapy, or a combination of modalities. Nonresectable tumors or tumors with distant metastases are treated with palliative interventions. Specific prevention strategies have not been proven, and there are no recommendations for esophageal cancer screening.

[Current status and future prospect of internal medicine treatment for advanced esophageal cancer].

PubMed

Wang, F; Fan, Q X

2016-09-23

Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research. Molecular targeted drugs have become a new developmental direction in cancer treatment because of their high specificity and antitumor activity, but the effects on esophageal cancer remain controversial. With the development of immune check point blockade treatment, breakthrough has been made in tumor immunotherapy, which has become an important means in cancer comprehensive treatment and shown a good prospect of treatment.

Outcomes of nutritional interventions to treat dysphagia in esophageal cancer: a population-based study.

PubMed

Modi, R M; Mikhail, S; Ciombor, K; Perry, K A; Hinton, A; Stanich, P P; Zhang, C; Conwell, D L; Krishna, S G

2017-11-01

Esophageal cancer (EC) is increasing in prevalence due to rising incidence and improved treatment strategies. Dysphagia is a significant morbidity in patients with EC requiring nutritional intervention. We sought to evaluate outcomes of nutritional interventions for EC patients hospitalized with dysphagia at a population level. The National Inpatient Sample (2002-2012) was utilized to include all adult inpatients (≥18 years of age) with EC and presence of dysphagia and stricture that underwent nutritional interventions including feeding tube (FT) placement, esophageal stenting, or parenteral nutrition (PN). Temporal trends were examined with multivariate analysis performed for mortality, length of stay (LOS), and cost of hospitalization. A total of 509,593 EC patients had 12,205 hospitalizations related to dysphagia. The hospitalization rates doubled over the study period (1.52% vs. 3.28%, p < 0.001). The most common nutritional intervention was FT (27%), followed by esophageal stenting (13%), and PN (11%). PN was more frequently associated with a diagnosis of sepsis (6.1%, p = 0.023) compared to FT (2.5%) or esophageal stenting (1.8%). Multivariate analysis demonstrated FT and esophageal stenting had comparable mortality (OR 1.06, 95% CI: 0.49, 2.32); however, PN was associated with higher mortality (OR 2.37, 95% CI: 1.22, 4.63), cost of hospitalization ($5,510, 95% CI: 2,262, 8,759), and LOS (2.13 days, 95% CI: 0.72, 3.54). This study shows that hospitalizations for EC with dysphagia and related nutritional interventions are increasing. As a single modality, parenteral nutrition should be avoided. Among our esophageal stent and FT population, further studies are necessary to determine adequate interventions based on disease stage. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pro-Apoptotic Effects of JDA-202, a Novel Natural Diterpenoid, on Esophageal Cancer Through Targeting Peroxiredoxin I

PubMed Central

Shi, Xiao-Jing; Ding, Lina; Zhou, Wenjuan; Ji, Yage; Wang, Junwei; Wang, Huimin; Ma, Yongcheng; Jiang, Guozhong; Tang, Kai

2017-01-01

Abstract Aims: Esophageal cancer (EC) is an aggressive malignancy and the most common solid tumor of gastrointestinal tract all over the world, with high incidence in Asia. The current study was designed to investigate the anticancer efficacy and mechanism that is involved in the action of a natural ent-kaurene diterpenoid, JDA-202, targeting EC. Results: We found that an antioxidant protein peroxiredoxin I (Prx I) was upregulated in human EC tissues as well as in EC cell lines. JDA-202, a novel natural compound isolated from Isodon rubescens (Labiatae), was proved to possess strong anti-proliferative activities on those cell lines. Importantly, JDA-202 does not only bind to Prx I directly and markedly inhibit the activity of Prx I in vitro, but it also significantly induces hydrogen peroxide (H2O2)-related cell death. Furthermore, overexpression of Prx I significantly reversed EC109 cell apoptosis caused by JDA-202, whereas short interfering RNA (siRNA)-induced Prx I knockdown resulted in marked cell death even without JDA-202 pretreatment. On the other hand, the increased phosphorylation of mitogen-activated protein kinase (MAPK) proteins (c-Jun N-terminal kinase [JNK], p38, and extracellular signal-regulated kinase [ERK]) by JDA-202 was suppressed by N-acetylcysteine (NAC) or catalase, a known reactive oxygen species (ROS) or H2O2 scavenger. JDA-202 also significantly inhibited the growth of EC109 tumor xenograft, without significant body weight loss and multi-organ toxicities. Innovation and Conclusion: Our findings, for the first time, demonstrated that JDA-202 may serve as a lead compound, targeting the overexpressed Prx I in EC cell lines and ROS accumulation as well as inhibiting the activation of their downstream targets in MAPKs. Antioxid. Redox Signal. 27, 73–92. PMID:27650197

LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway.

PubMed

He, Qing; Li, Jing; Dong, Feng; Cai, Chuanshu; Zou, Xi

2017-08-01

Liver kinase B (LKB) 1 acts as a tumor suppressor in a broad spectrum of human cancers, and is important in chemoradiotherapy treatment of various tumor types. However, the potential function of LKB1 in esophageal cancer radiotherapy remains to be elucidated. The aim of the present study was to investigate the role of LKB1 in radiosensitivity of esophageal cancer in vivo and in vitro, and to explore its molecular mechanism. Eca‑109 cells transfected with LKB1 overexpression plasmid were xenografted into nude mice and subjected to irradiation and it was observed that the tumor volume was significantly increased in LKB1‑overexpressed tumors compared with that of the control tumors. The in vitro study revealed that LKB1 overexpression led to the radioresistance of Eca‑109 cells, as determined by MTT and colony formation assays. Furthermore, it was demonstrated that LKB1 overexpression inhibited apoptosis and activated autophagy of Eca‑109 cells following radiation treatment, as determined by flow cytometry and western blot analyses. AMP‑activated protein kinase (AMPK) inhibition attenuated LKB1‑induced radioresistance of Eca‑109 cells. To the best of our knowledge, the present study, for the first time, confirmed that LKB1 induces radioresistance of esophageal cancer cells to irradiation via suppression of apoptosis and activation of autophagy, and AMPK mediates this function of LKB1 in esophageal cancer radiotherapy. These findings suggest that LKB1 may act as a novel target in the future, to maximize the efficiency of esophageal cancer radiotherapy.

Esophageal Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... stage . There is no standard or routine screening test for esophageal cancer. Screening for esophageal cancer is under study with screening clinical trials taking place in many ...

Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC).

PubMed

Overholser, Jay; Ambegaokar, Kristen Henkins; Eze, Siobhan M; Sanabria-Figueroa, Eduardo; Nahta, Rita; Bekaii-Saab, Tanios; Kaumaya, Pravin T P

2015-07-06

Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety. Specifically, we postulate that novel combination treatments targeting members of the EGFR family and IGF-1R will yield significant anti-tumor effects in in vitro models of EC and TNBC possibly overcoming mechanisms of resistance. We show that the combination of HER-1 and HER-2 or HER-1 and IGF-1R peptide mimics/vaccine antibodies exhibited enhanced antitumor properties with significant inhibition of tumorigenesis in OE19 EC and MDA-MB-231 TNBC cell lines. Our work elucidates the mechanisms of HER-1/IGF-1R and HER-1/HER-2 signaling in these cancer cell lines, and the promising results support the rationale for dual targeting with HER-1 and HER-2 or IGF-1R as an improved treatment regimen for advanced therapy tailored to difference types of cancer.

[Effects and its mechanism of Nimotuzumab on radiosensitivity of esophageal carcinoma ECA-109 and TE-13 cell lines].

PubMed

Wang, J; Wang, W; Guo, Y; Jing, S W; Shang, K; Miao, M C; Wang, J; Wu, Y J; Liu, L N; Yu, J M

2016-10-23

expression in the combined group were decreased significantly ( P <0.05), while γH2AX protein expression was significantly increased ( P <0.05). Conclusions: Nimotuzumab can enhance the radiosensitivity of esophageal cancer ECA-109 and TE-13 cells. The potential mechanism may be related to the inhibition of EGFR phosphorylation and down-regulation of DNA damage repair proteins. The radiosensitizing effect of nimotuzumab is greater on poorly differentiated esophageal cancer cells.

Increased expression of HSP27 inhibits invasion and metastasis in human esophageal squamous cell carcinoma.

PubMed

Xue, Lin; Yang, Lei; Jin, Zhi-an; Gao, Fei; Kang, Jian-qin; Xu, Guang-hui; Liu, Bing; Li, Hong; Wang, Xiao-juan; Liu, Li-juan; Wang, Biao-luo; Liang, Shu-hui; Ding, Jie

2014-07-01

Previous studies have indicated that heat shock protein 27 (HSP27) had high correlation with the development and progression in several tumors. However, the roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The aim in this study is to investigate the potential roles of HSP27 in the metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human esophageal cancer cell lines were examined by immunohistochemistry and Western blotting, respectively. Wound healing assays, transwell assays, and in vivo assays were used to identify the differences of metastasis potential between normal and HSP27 overexpressed cells. HSP27 expression was downregulated in cancer tissue compared to the matched normal tissue. And the positive staining was mainly located in the cytoplasm. Statistical analyses showed that the expression of HSP27 in ESCC was significantly correlated with the tumor differentiation (P = 0.023), the patient's TNM stage (P = 0.013), lymph metastasis (P = 0.020), and distant metastasis (P = 0.017). HSP27 expression was significantly lower in highly metastatic cells than the less ones. The metastatic potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly metastatic cells dramatically decreased their metastatic capacity. This study indicated that the expression level of HSP27 may be inversely correlated with the metastasis behavior of ESCC, and HSP27 may play an important role in this progression. HSP27 may be a potential molecular target for the therapy and prognosis of patients with ESCC.

Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

PubMed Central

Rosenberg, Ari J.; Wainwright, Derek A.; Rademaker, Alfred; Galvez, Carlos; Genet, Matthew; Zhai, Lijie; Lauing, Kristen L.; Mulcahy, Mary F.; Hayes, John P.; Odell, David D.; Horbinski, Craig; Komanduri, Srinadh; Tetreault, Marie-Pier; Kim, Kwang-Youn A.; Villaflor, Victoria M.

2018-01-01

Background Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis. PMID:29805749

APIO-EE-9 is a novel Aurora A and B antagonist that suppresses esophageal cancer growth in a PDX mouse model.

PubMed

Jin, Guoguo; Yao, Ke; Guo, Zhiping; Zhao, Zhenjiang; Liu, Kangdong; Liu, Fangfang; Chen, Hanyong; Gorja, Dhilli Rao; Reddy, Kanamata; Bode, Ann M; Dong, Ziming; Dong, Zigang

2017-08-08

Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied. Here, we identified a novel compound, referred to as APIO-EE-9, which inhibits growth and colony formation and induces apoptosis of esophageal cancer cells. Using computer modeling, we found that APIO-EE-9 interacted with both Aurora A and B in the ATP-binding pocket. APIO-EE-9 inhibited both Aurora A and B kinase activities in a dose-dependent manner. Treatment with APIO-EE-9 substantially reduced the downstream Aurora kinase phosphorylation of histone H3 (Ser10), resulting in formation of multiple nuclei and centrosomes. Additionally, esophageal cancer cells expressing shAurora A or shAurora B kinase exhibited a dramatic reduction in proliferation and colony formation. Injection of these cells as xenografts in mice reduced tumor formation compared to wildtype cells. Importantly, APIO-EE-9 significantly decreased the size of esophageal patient-derived xenograft (PDX) tumors implanted in SCID mice. These results demonstrated that APIO-EE-9 is a specific Aurora kinase inhibitor that could be developed as a therapeutic agent against esophageal cancer.

Surface modification of esophageal stent materials by a polyethylenimine layer aiming at anti-cancer function.

PubMed

Zhang, Kun; Bai, Yuxin; Wang, Xiaofeng; Li, Qian; Guan, Fangxia; Li, Jingan

2017-08-01

Esophageal cancer is difficult to cure globally and possesses high mortality rate, and it is generally accepted that palliative care such as stent implantation is the main therapy method for esophageal cancer in later period. However, the restenosis caused by tumor cells and inflammatory cells seriously interferes the stent clinical application and limits its long-term services. To solve this problem, series of drug delivery stents were developed and proven rather effective in the early stage of implantation, but more serious restenosis occurred after the drug delivery was over, which endangered the patients' life. Therefore, endowing the esophageal stent continuous anti-cancer function become an ideal strategy for inhibiting the restenosis. In this contribution, the functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10 3 , 1 × 10 4 , 2.5 × 10 4 and 7 × 10 4  Da) were fabricated onto the esophageal stent material 317L stainless steel (317L SS) surface. The surface characterization including amine quantitative, atomic force microscopy (AFM) and water contact angle measurement indicated successful preparation of the PDA/PEI layer. The Eca109 cells culture results proved that the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis, suggesting excellent anti-cancer function. In addition, we also found that the anti-cancer function of the PDA/PEI layers was positively correlated to the immobilized PEIs' MW. All the results demonstrated the potential application of the PDA/PEI layers on the surface modification of esophageal stent for continuous anti-cancer function. It is generally accepted that the restenosis caused by tumor cells seriously interferes the esophageal stent clinical application. Thus, endowing the esophageal stent continuous anti-cancer function is the ideal strategy for inhibiting the restenosis. In this work, we fabricated functional layers

Poultry and fish intake and risk of esophageal cancer: A meta-analysis of observational studies.

PubMed

Jiang, Gengxi; Li, Bailing; Liao, Xiaohong; Zhong, Chongjun

2016-03-01

Mixed results regarding the association between white meat (including poultry and fish) intake and the risk of esophageal cancer (EC) have been reported. We performed a meta-analysis to provide a quantitative assessment of this association. Relevant studies were identified in MEDLINE until December 31, 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. A total of 20 articles, including 3990 cases with EC, were included in this meta-analysis. Compared to individuals with the lowest level of fish intake, individuals with the highest fish intake were found to have reduced risk of EC (SRRs = 0.69; 95% CIs: 0.57-0.85), while poultry intake was not associated with EC (SRRs = 0.83; 95% CIs: 0.62-1.12). Total fish consumption is associated with reduced esophageal squamous cell carcinoma (ESCC) risk, while poultry consumption was not associated with ESCC risk. Additionally, neither poultry nor fish consumption was associated with esophageal adenocarcinoma risk. Our results suggest that fish consumption may have a potential role in EC prevention, while poultry intake has no effect. However, because the majority of data was from case-control studies, further well-designed prospective studies are warranted. © 2013 Wiley Publishing Asia Pty Ltd.

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. © Springer Science+Business Media B.V. 2011

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

PubMed

Gao, Xue-Xin; Gao, Lei; Wang, Jiu-Qiang; Qu, Su-Su; Qu, Yue; Sun, Hong-Lei; Liu, Si-Dang; Shang, Ying-Li

2016-07-12

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.

Dietary habits and esophageal cancer.

PubMed

Palladino-Davis, A G; Mendez, B M; Fisichella, P M; Davis, C S

2015-01-01

Cancer of the esophagus is an underestimated, poorly understood, and changing disease. Its overall 5-year survival is less than 20%, even in the United States, which is largely a function of a delay in diagnosis until its more advanced stages. Additionally, the epidemiologic complexities of esophageal cancer are vast, rendering screening and prevention limited at best. First, the prevalence of esophageal cancer is unevenly distributed throughout the world. Second, the two histological forms (squamous cell and adenocarcinoma) vary in terms of their geographic prevalence and associated risk factors. Third, some populations appear at particular risk for esophageal cancer. And fourth, the incidence of esophageal cancer is in continuous flux among groups. Despite the varied prevalence and risks among populations, some factors have emerged as consistent associations while others are only now becoming more fully recognized. The most prominent, scientifically supported, and long-regarded risk factors for esophageal cancer are tobacco, alcohol, and reflux esophagitis. Inasmuch as the above are regarded as important risk factors for esophageal cancer, they are not the sole contributors. Dietary habits, nutrition, local customs, and the environment may be contributory. Along these lines, vitamins, minerals, fruits, vegetables, meats, fats, salted foods, nitrogen compounds, carcinogens, mycotoxins, and even the temperature of what we consume are increasingly regarded as potential etiologies for this deadly although potentially preventable disease. The goal of this review is to shed light on the less known role of nutrition and dietary habits in esophageal cancer. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

APIO-EE-9 is a novel Aurora A and B antagonist that suppresses esophageal cancer growth in a PDX mouse model

PubMed Central

Liu, Kangdong; Liu, Fangfang; Chen, Hanyong; Gorja, Dhilli Rao; Reddy, Kanamata; Bode, Ann M.; Dong, Ziming; Dong, Zigang

2017-01-01

Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied. Here, we identified a novel compound, referred to as APIO-EE-9, which inhibits growth and colony formation and induces apoptosis of esophageal cancer cells. Using computer modeling, we found that APIO-EE-9 interacted with both Aurora A and B in the ATP-binding pocket. APIO-EE-9 inhibited both Aurora A and B kinase activities in a dose-dependent manner. Treatment with APIO-EE-9 substantially reduced the downstream Aurora kinase phosphorylation of histone H3 (Ser10), resulting in formation of multiple nuclei and centrosomes. Additionally, esophageal cancer cells expressing shAurora A or shAurora B kinase exhibited a dramatic reduction in proliferation and colony formation. Injection of these cells as xenografts in mice reduced tumor formation compared to wildtype cells. Importantly, APIO-EE-9 significantly decreased the size of esophageal patient-derived xenograft (PDX) tumors implanted in SCID mice. These results demonstrated that APIO-EE-9 is a specific Aurora kinase inhibitor that could be developed as a therapeutic agent against esophageal cancer. PMID:28881819

Synchronous second primary cancers in patients with squamous esophageal cancer: clinical features and survival outcome.

PubMed

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

2016-03-01

Unexpected diagnosis of synchronous second primary cancers (SPC) complicates physicians' decision-making because clinical details of squamous esophageal cancer (EC) patients with SPC have been limited. We evaluated clinical features and treatment outcomes of patients with synchronous SPC detected during the initial staging of squamous EC. We identified a total of 317 consecutive patients diagnosed with squamous EC. Relevant clinical and cancer-specific information were reviewed retrospectively. EC patients with synchronous SPC were identified in 21 patients (6.6%). There were significant differences in median age (70 years vs. 63 years, p = 0.01), serum albumin level (3.3 g/dL vs. 3.9 g/dL, p < 0.01) and body mass index (20.4 kg/m(2) vs. 22.8 kg/m(2), p = 0.01) between EC patients with and without SPC. Head and neck, lung and gastric cancers accounted for 18.2%, 22.7%, and 18.2% of SPC, respectively. Positron emission tomography-computed tomography (PET-CT) detected four cases (18.2%) of SPC that were missed on CT. Management plans were altered in 13 of 21 patients (61.9%) with detected SPC. Curative esophagectomy was attempted in 28.6% of EC patients with SPC (vs. 59.1% of patients without SPC; p = 0.006). EC patients with SPC had significantly lower 5-year survival than patients without SPC (10.6% vs. 36.7%, p = 0.008). Synchronous SPC were found in 6.6% of squamous EC patients, and PET-CT contributed substantially to the detection of synchronous SPC. EC patients with SPC had poor survival due to challenges of providing stage-appropriate treatment.

High-temperature beverages and Foods and Esophageal Cancer Risk -- A Systematic Review

PubMed Central

Islami, Farhad; Boffetta, Paolo; Ren, JianSong; Pedoeim, Leah; Khatib, Dara; Kamangar, Farin

2009-01-01

Coffee, tea, and maté may cause esophageal cancer (EC) by causing thermal injury to the esophageal mucosa. If so, the risk of EC attributable to thermal injury could be large in populations in which these beverages are commonly consumed. In addition, these drinks may cause or prevent EC via their chemical constituents. Therefore, a large number of epidemiologic studies have investigated the association of an indicator of amount or temperature of use of these drinks or other hot foods and beverages with risk of EC. We conducted a systematic review of these studies, and report the results for amount and temperature of use separately. By searching PubMed and the ISI, we found 59 eligible studies. For coffee and tea, there was little evidence for an association between amount of use and EC risk; however, the majority of studies showed an increased risk of EC associated with higher drinking temperature which was statistically significant in most of them. For maté drinking, the number of studies was limited, but they consistently showed that EC risk increased with both amount consumed and temperature, and these two were independent risk factors. For other hot foods and drinks, over half of the studies showed statistically significant increased risks of EC associated with higher temperature of intake. Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data, and results should be reported by histological subtypes of EC. PMID:19415743

Risk of treatment-related esophageal cancer among breast cancer survivors.

PubMed

Morton, L M; Gilbert, E S; Hall, P; Andersson, M; Joensuu, H; Vaalavirta, L; Dores, G M; Stovall, M; Holowaty, E J; Lynch, C F; Curtis, R E; Smith, S A; Kleinerman, R A; Kaijser, M; Storm, H H; Pukkala, E; Weathers, R E; Linet, M S; Rajaraman, P; Fraumeni, J F; Brown, L M; van Leeuwen, F E; Fossa, S D; Johannesen, T B; Langmark, F; Lamart, S; Travis, L B; Aleman, B M P

2012-12-01

Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Targeted therapy in esophageal cancer.

PubMed

Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

2016-01-01

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

ABT-263 induces G1/G0-phase arrest, apoptosis and autophagy in human esophageal cancer cells in vitro.

PubMed

Lin, Qing-Huan; Que, Fu-Chang; Gu, Chun-Ping; Zhong, De-Sheng; Zhou, Dan; Kong, Yi; Yu, Le; Liu, Shu-Wen

2017-12-01

Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC 50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 μmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 μmol/L) dose-dependently induced G 1 /G 0 -phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21 Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G 1 /G 0 -phase arrest. Knockdown of p21 Waf1/Cip1 attenuated ABT-263-induced G 1 /G 0 -phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.

Risk of treatment-related esophageal cancer among breast cancer survivors

PubMed Central

Morton, L. M.; Gilbert, E. S.; Hall, P.; Andersson, M.; Joensuu, H.; Vaalavirta, L.; Dores, G. M.; Stovall, M.; Holowaty, E. J.; Lynch, C. F.; Curtis, R. E.; Smith, S. A.; Kleinerman, R. A.; Kaijser, M.; Storm, H. H.; Pukkala, E.; Weathers, R. E.; Linet, M. S.; Rajaraman, P.; Fraumeni, J. F.; Brown, L. M.; van Leeuwen, F. E.; Fossa, S. D.; Johannesen, T. B.; Langmark, F.; Lamart, S.; Travis, L. B.; Aleman, B. M. P.

2012-01-01

Background Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. Design Nested case–control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. Results The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (Ptrend < 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7–28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2–0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). Conclusions Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up. PMID:22745217

Stage-directed individualized therapy in esophageal cancer.

PubMed

Goense, Lucas; van Rossum, Peter S N; Kandioler, Daniela; Ruurda, Jelle P; Goh, Khean-Lee; Luyer, Misha D; Krasna, Mark J; van Hillegersberg, Richard

2016-10-01

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

PubMed

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

2016-06-21

To develop a potent and safe gene therapy for esophageal cancer. 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. 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. The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

Risks of Esophageal Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... stage . There is no standard or routine screening test for esophageal cancer. Screening for esophageal cancer is under study with screening clinical trials taking place in many ...

General Information about Esophageal Cancer

MedlinePlus

... Research Esophageal Cancer Treatment (PDQ®)–Patient Version General Information About Esophageal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Nutrition therapy in esophageal cancer-Consensus statement of the Gastroenterological Society of Taiwan.

PubMed

Chen, M-J; Wu, I-C; Chen, Y-J; Wang, T-E; Chang, Y-F; Yang, C-L; Huang, W-C; Chang, W-K; Sheu, B-S; Wu, M-S; Lin, J-T; Chu, C-H

2018-05-31

A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits

The potential of photodynamic therapy to treat esophageal candidiasis coexisting with esophageal cancer.

PubMed

Qiu, Haixia; Mao, Yongping; Gu, Ying; Zhu, Jianguo; Wang, Ying; Zeng, Jing; Huang, Naiyan; Liu, Qingsen; Yang, Yunsheng

2014-01-05

Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2017-02-28

To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. 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. 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). 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.

Lymphocyte Nadir and Esophageal Cancer Survival Outcomes After Chemoradiation Therapy.

PubMed

Davuluri, Rajayogesh; Jiang, Wen; Fang, Penny; Xu, Cai; Komaki, Ritsuko; Gomez, Daniel R; Welsh, James; Cox, James D; Crane, Christopher H; Hsu, Charles C; Lin, Steven H

2017-09-01

Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival. 504 patients with stage I-III EC (2007-2013) treated with neoadjuvant or definitive CRT with weekly ALC determinations made during treatment were analyzed. Grade of lymphopenia from ALC nadir during CRT was based on Common Terminology Criteria for Adverse Events version 4.0. Associations of ALC nadir with survival were examined using multivariate Cox proportional hazards analysis (MVA) and competing risks regression analysis. The median follow-up time was 36 months. The incidences of grade 1, 2, 3, and 4 ALC nadir during CRT were 2%, 12%, 59%, and 27%, respectively. The impact was lymphocyte-specific because this was not seen for monocyte or neutrophil count. On MVA, grade 4 ALC nadir (G4 nadir) was significantly associated with worse overall and disease-specific survival outcomes. Predictors of G4 nadir included distal tumor location, definitive CRT, taxane/5-fluorouracil chemotherapy, and photon-based radiation type (vs proton-based). Radiation type strongly influenced the mean body dose exposure, which was a strong predictor for G4 nadir (odds ratio 1.22 per Gray, P<.001). G4 nadir during CRT for EC was associated with poor outcomes, suggesting a role of host immunity in disease control. This observation provides a rationale to prospectively test chemotherapeutic and radiation treatment strategies that may have a lower impact on host immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

PubMed

Luu, Carrie; Amaral, Marisa; Klapman, Jason; Harris, Cynthia; Almhanna, Khaldoun; Hoffe, Sarah; Frakes, Jessica; Pimiento, Jose M; Fontaine, Jacques P

2017-12-14

To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center. A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student's t test and Fisher's exact test or χ 2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy. Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement. EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

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.

TP53, PIK3CA, FBXW7 and KRAS Mutations in Esophageal Cancer Identified by Targeted Sequencing.

PubMed

Zheng, Huili; Wang, Yan; Tang, Chuanning; Jones, Lindsey; Ye, Hua; Zhang, Guangchun; Cao, Weihai; Li, Jingwen; Liu, Lifeng; Liu, Zhencong; Zhang, Chao; Lou, Feng; Liu, Zhiyuan; Li, Yangyang; Shi, Zhenfen; Zhang, Jingbo; Zhang, Dandan; Sun, Hong; Dong, Haichao; Dong, Zhishou; Guo, Baishuai; Yan, H E; Lu, Qingyu; Huang, Xue; Chen, Si-Yi

2016-01-01

Esophageal cancer (EC) is a common malignancy with significant morbidity and mortality. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in EC that may serve as biomarkers might help predict patient outcome and guide treatment. Traditionally, personalized cancer DNA sequencing was impractical and expensive. Recent technological advancements have made targeted DNA sequencing more cost- and time-effective with reliable results. This technology may be useful for clinicians to direct patient treatment. The Ion PGM and AmpliSeq Cancer Panel was used to identify mutations at 737 hotspot loci of 45 cancer-related genes in 64 EC samples from Chinese patients. Frequent mutations were found in TP53 and less frequent mutations in PIK3CA, FBXW7 and KRAS. These results demonstrate that targeted sequencing can reliably identify mutations in individual tumors that make this technology a possibility for clinical use. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Hospital of Diagnosis Influences the Probability of Receiving Curative Treatment for Esophageal Cancer.

PubMed

van Putten, Margreet; Koëter, Marijn; van Laarhoven, Hanneke W M; Lemmens, Valery E P P; Siersema, Peter D; Hulshof, Maarten C C M; Verhoeven, Rob H A; Nieuwenhuijzen, Grard A P

2018-02-01

The aim of this article was to study the influence of hospital of diagnosis on the probability of receiving curative treatment and its impact on survival among patients with esophageal cancer (EC). Although EC surgery is centralized in the Netherlands, the disease is often diagnosed in hospitals that do not perform this procedure. Patients with potentially curable esophageal or gastroesophageal junction tumors diagnosed between 2005 and 2013 who were potentially curable (cT1-3,X, any N, M0,X) were selected from the Netherlands Cancer Registry. Multilevel logistic regression was performed to examine the probability to undergo curative treatment (resection with or without neoadjuvant treatment, definitive chemoradiotherapy, or local tumor excision) according to hospital of diagnosis. Effects of variation in probability of undergoing curative treatment among these hospitals on survival were investigated by Cox regression. All 13,017 patients with potentially curable EC, diagnosed in 91 hospitals, were included. The proportion of patients receiving curative treatment ranged from 37% to 83% and from 45% to 86% in the periods 2005-2009 and 2010-2013, respectively, depending on hospital of diagnosis. After adjustment for patient- and hospital-related characteristics these proportions ranged from 41% to 77% and from 50% to 82%, respectively (both P < 0.001). Multivariable survival analyses showed that patients diagnosed in hospitals with a low probability of undergoing curative treatment had a worse overall survival (hazard ratio = 1.13, 95% confidence interval 1.06-1.20; hazard ratio = 1.15, 95% confidence interval 1.07-1.24). The variation in probability of undergoing potentially curative treatment for EC between hospitals of diagnosis and its impact on survival indicates that treatment decision making in EC may be improved.

Role of silis in esophageal cancer

PubMed Central

Jabbari, Ali; Besharat, Sima; Semnani, Shahryar

2008-01-01

Association of silica with diseases like cancers has been determined previously. This study was designed to determine the quantity of silis in flour produced in Golestan Province, and its relation to esophageal cancer (EC). We took flour samples from all flour millings in Golestan Province. Base-melting method in nickel cruise was used at 550°C. The extract was reduced with acids. Different silis concentrations in various regions were compared. P < 0.05 was considered statistically significant. The median silis concentration was 0.0030 g, the mean silis concentration was 0.008760 ± 0.004265 g in each 100 g flour. The difference of mean silis concentrations in various regions was not significant. No high level of silica was found in the flour of Golestan Province. We could not find any significant difference in various areas between silica contaminations. Studies on the consumed bread and rice in various regions of Golestan Province can be helpful. PMID:18494071

Does neoadjuvant therapy for esophageal cancer increase postoperative morbidity or mortality?

PubMed

Mungo, B; Molena, D; Stem, M; Yang, S C; Battafarano, R J; Brock, M V; Lidor, A O

2015-10-01

Neoadjuvant therapy has proven to be effective in the reduction of locoregional recurrence and mortality for esophageal cancer. However, induction treatment has been reported to be associated with increased risk of postoperative complications. We therefore compared outcomes after esophagectomy for esophageal cancer for patients who underwent neoadjuvant therapy and patients treated with surgery alone. Using the American College of Surgeons National Surgical Quality Improvement Program database (2005-2011), we identified 1939 patients who underwent esophagectomy for esophageal cancer. Seven hundred and eight (36.5%) received neoadjuvant therapy, while 1231 (63.5%) received no neoadjuvant therapy within 90 days prior to surgery. Primary outcome was 30-day mortality, and secondary outcomes included overall and serious morbidity, length of stay, and operative time. Patients who underwent neoadjuvant treatment were younger (62.3 vs. 64.7, P < 0.001), were more likely to have experienced recent weight loss (29.4% vs. 15.9%, P < 0.001), and had worse preoperative hematological cell counts (white blood cells <4.5 or >11 × 10(9) /L: 29.3% vs. 15.0%, P < 0.001; hematocrit <36%: 49.7% vs. 30.0%, P < 0.001). On unadjusted analysis, 30-day mortality, overall, and serious morbidity were comparable between the two groups, with the exception of the individual complications of venous thromboembolic events and bleeding transfusion, which were significantly lower in the surgery-only patients (5.71% vs. 8.27%, P = 0.027; 6.89% vs. 10.57%, P = 0.004; respectively). Multivariable and matched analysis confirmed that 30-day mortality, overall, and serious morbidity, as well as prolonged length of stay, were comparable between the two groups of patients. An increasing trend of preoperative neoadjuvant therapy for esophageal cancer was observed through the study years (from 29.0% in 2005-2006 to 44.0% in 2011, P < 0.001). According to our analysis, preoperative neoadjuvant therapy for

Esophageal Motility after Extensive Circumferential Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

PubMed

Kuribayashi, Yasutaka; Iizuka, Toshiro; Nomura, Kosuke; Furuhata, Tsukasa; Yamashita, Satoshi; Matsui, Akira; Kikuchi, Daisuke; Mitani, Toshifumi; Kaise, Mitsuru; Hoteya, Shu

2018-06-05

Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is sometimes extensive, and in our experience, patients not infrequently present with dysphagia after ESD even in the absence of esophageal stricture. The aim of this study was to evaluate esophageal motility using high-resolution manometry (HRM) in patients with and without dysphagia after extensive circumferential ESD. HRM was performed in a total of 52 patients who had undergone ESD for superficial esophageal cancer and a mucosal defect after ESD exceeded more than two-thirds of the esophageal circumference. The frequency and type of esophageal dysmotility and the relationship between esophageal motility and dysphagia were evaluated. Esophageal dysmotility was observed in 13 patients (25%): jackhammer esophagus in 4, esophagogastric junction outflow obstruction in 4, absent contractility in 2, and distal esophageal spasm, ineffective esophageal motility, and fragmented peristalsis in 1 patient each. Of the 22 patients with dysphagia after ESD, 9 (41%) had esophageal dysmotility. Of the 30 patients without dysphagia after ESD, 4 (13%) had esophageal dysmotility. The relationship between dysmotility and dysphagia was significant (p = 0.025). Esophageal dysmotility exists in approximately one-quarter of patients after extensive circumferential ESD, which is associated with dysphagia in the absence of esophageal stricture. © 2018 S. Karger AG, Basel.

Updates on esophageal and gastric cancers.

PubMed

Gallo, Amy; Cha, Charles

2006-05-28

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

The tumor microenvironment in esophageal cancer.

PubMed

Lin, E W; Karakasheva, T A; Hicks, P D; Bass, A J; Rustgi, A K

2016-10-13

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 (TME), 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. Antitumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells and regulatory T cells, as well as immune checkpoints like programmed death-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 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.

Androgens and esophageal cancer: What do we know?

PubMed

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

2015-05-28

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.

Nutrition in peri-operative esophageal cancer management.

PubMed

Steenhagen, Elles; van Vulpen, Jonna K; van Hillegersberg, Richard; May, Anne M; Siersema, Peter D

2017-07-01

Nutritional status and dietary intake are increasingly recognized as essential areas in esophageal cancer management. Nutritional management of esophageal cancer is a continuously evolving field and comprises an interesting area for scientific research. Areas covered: This review encompasses the current literature on nutrition in the pre-operative, peri-operative, and post-operative phases of esophageal cancer. Both established interventions and potential novel targets for nutritional management are discussed. Expert commentary: To ensure an optimal pre-operative status and to reduce peri-operative complications, it is key to assess nutritional status in all pre-operative esophageal cancer patients and to apply nutritional interventions accordingly. Since esophagectomy results in a permanent anatomical change, a special focus on nutritional strategies is needed in the post-operative phase, including early initiation of enteral feeding, nutritional interventions for post-operative complications, and attention to long-term nutritional intake and status. Nutritional aspects of pre-optimization and peri-operative management should be incorporated in novel Enhanced Recovery After Surgery programs for esophageal cancer.

Role of MLH1 methylation in esophageal cancer carcinogenesis and its clinical significance.

PubMed

Li, Jinyun; Ye, Dong; Wang, Lei; Peng, Yingying; Li, Qun; Deng, Hongxia; Zhou, Chongchang

2018-01-01

The mutL homolog-1 ( MLH1 ) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20-2.66), advanced tumor grade (OR=3.7; 95% CI =2.37-5.77), lymph node metastasis (OR=2.65; 95% CI =1.81-3.88), distant metastasis (OR=7.60; 95% CI =1.23-47.19), advanced clinical stage (OR=4.46; 95% CI =2.88-6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00-2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC.

Video-assisted mediastinoscopic resection compared with video-assisted thoracoscopic surgery in patients with esophageal cancer.

PubMed

Wang, Qian-Yun; Tan, Li-Jie; Feng, Ming-Xiang; Zhang, Xiao-Ying; Zhang, Lei; Jiang, Nan-Qing; Wang, Zhong-Lin

2014-06-01

The purpose of this study was to explore the indications of radical vedio-assisted mediastinoscopic resection for esophageal cancer. The data of 109 patients with T1 esophageal cancer who underwent video-assisted mediastinoscopic resection (VAMS group) in Third Affiliated Hospital of Soochow University Hospital from December 2005 to December 2011 were collected in the study for comparison with the 58 patients with T1 esophageal cancer who underwent video-assisted thoracoscopic surgery (VATS group) in Zhongshan Hospital, Fudan University. The perioperative safety and survival were compared between the two groups. All operations were successful in both groups. One perioperative death was noted in the VATS group. The incidences of post-operative complications were not significantly different between these two groups, whereas the VAMS group was favorable in terms of operative time (P<0.001) and blood loss (P<0.001), and a significantly larger number of chest lymph nodes were dissected in the VATS group compared with the VAMS group (P<0.001). Long-term follow-up showed that the overall survival was not significantly different between these two groups (P=0.876). T1N0M0 esophageal cancer can be as the indication of VAMS radical resection. VAMS radical resection can be considered as the preferred option for patients with poor pulmonary and cardiac function or a history of pleural disease.

Video-assisted mediastinoscopic resection compared with video-assisted thoracoscopic surgery in patients with esophageal cancer

PubMed Central

Wang, Qian-Yun; Tan, Li-Jie; Feng, Ming-Xiang; Zhang, Xiao-Ying; Zhang, Lei; Jiang, Nan-Qing

2014-01-01

Objective The purpose of this study was to explore the indications of radical vedio-assisted mediastinoscopic resection for esophageal cancer. Methods The data of 109 patients with T1 esophageal cancer who underwent video-assisted mediastinoscopic resection (VAMS group) in Third Affiliated Hospital of Soochow University Hospital from December 2005 to December 2011 were collected in the study for comparison with the 58 patients with T1 esophageal cancer who underwent video-assisted thoracoscopic surgery (VATS group) in Zhongshan Hospital, Fudan University. The perioperative safety and survival were compared between the two groups. Results All operations were successful in both groups. One perioperative death was noted in the VATS group. The incidences of post-operative complications were not significantly different between these two groups, whereas the VAMS group was favorable in terms of operative time (P<0.001) and blood loss (P<0.001), and a significantly larger number of chest lymph nodes were dissected in the VATS group compared with the VAMS group (P<0.001). Long-term follow-up showed that the overall survival was not significantly different between these two groups (P=0.876). Conclusions T1N0M0 esophageal cancer can be as the indication of VAMS radical resection. VAMS radical resection can be considered as the preferred option for patients with poor pulmonary and cardiac function or a history of pleural disease. PMID:24976988

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.

Incidence of Esophageal Cancer in Iran, a Population-Based Study: 2001-2015.

PubMed

Moradzadeh, Rahmatollah; Golmohammadi, Parvaneh; Ghaitasi, Bahman; Nadrian, Haidar; Najafi, Athareh

2018-05-09

Even though Kurdistan, the western province of Iran, has a cancer surveillance system, a detailed analysis of incidence rate has not been yet performed. We describe Age Standardized Incidence Rates (ASRs) for esophageal cancer (EC) in Kurdistan Province of Iran in 2001-2015. Incidence cases of EC were obtained from a population-based cancer registry. We obtained ASRs and 95% confidence intervals (CI) per 100,000 populations for each calendar year group. Between 2001 and 2015, 1362 incidence cases with EC were reported to the cancer registry. Annual ASRs in 2006-2010 were more than the other years in both men and women, respectively. Most ASRs were reported among women in Divandarreh (18.95, 95% CI 14.76, 23.92), Saqez (12.75, 95% CI 10.73, 15.01), Sanandaj (8.84, 95% CI 7.64, 10.17), and Qorveh (8.19, 95% CI 6.54, 10.12), and among men in Divandarreh (19.38, 95% CI 15.38, 24.06), Saqez (13.64, 95% CI 11.49, 16.05), Sanandaj (8.70, 95% CI 7.56, 9.96), and Marivan (7.93, 95% CI 6.26, 9.88). It was concluded that EC in Divandarreh, Saqez, and Sanandaj has the highest ASRs, and these areas are considered as high-risk areas for this disease in the Iranian province of Kurdistan. Therefore, to understand the reasons of these problems, a considerable work is needed.

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.

Esophageal Cancer Prevention (PDQ®)—Patient Version

Cancer.gov

Esophageal cancer prevention strategies include avoiding risk factors like alcohol and tobacco. Learn more about risk factors and possible protective factors for esophageal cancer in this expert-reviewed summary.

Association between genetic variants and esophageal cancer risk.

PubMed

Yue, Chenli; Li, Miao; Da, Chenxing; Meng, Hongtao; Lv, Shaomin; Zhao, Xinhan

2017-07-18

We investigated whether single nucleotide polymorphisms (SNPs) in the nuclear assembly factor 1 (NAF1) and TNFAIP3-interacting protein 1 (TNIP1) gene were associated with susceptibility to esophageal cancer in a Chinese Han population. Five SNPs were genotyped and their relationship with esophageal cancer risk was analyzed in a sample of 386 esophageal cancer patients and 495 unrelated healthy controls recruited from the First Affiliated Hospital of Xi'an Jiaotong University. Patients with the AG genotype of rs2320615 were at lower risk of developing esophageal cancer than those with the GG genotype (adjusted odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.46-0.90, P = 0.009). The rs2320615 SNP was found to be associated with a decreased the risk of esophageal cancer in the dominant model (adjusted OR = 0.70, 95% CI = 0.51-0.96, P = 0.026). These results provide the first evidence that the rs2320615 in NAF1 was associated with reduced risk of esophageal cancer. Further studies with larger samples are warranted to confirm our findings.

Esophageal Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Esophageal cancer screening is not currently considered to be a routine part of cancer screening. Not all screening tests are helpful, and many have risks. Learn more about esophageal cancer risk factors and tests to detect it in this expert-reviewed summary.

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

Consumption of hot beverages and foods and the risk of esophageal cancer: a meta-analysis of observational studies.

PubMed

Chen, Yawen; Tong, Yeqing; Yang, Chen; Gan, Yong; Sun, Huilian; Bi, Huashan; Cao, Shiyi; Yin, Xiaoxv; Lu, Zuxun

2015-06-02

Previous studies have mostly focused on the effects of specific constituents of beverages and foods on the risk of esophageal cancer (EC). An increasing number of studies are now emerging examining the health consequences of the high temperature of beverages and foods. We conducted a meta-analysis to summarize the evidence and clarify the association between hot beverages and foods consumption and EC risk. We searched the PubMed, Embase, and Web of Science databases for relevant studies, published before May 1, 2014, with the aim to estimate the association between hot beverage and food consumption and EC risk. A random-effect model was used to pool the results from the included studies. Publication bias was assessed by using the Begg test, the Egger test, and funnel plot. Thirty-nine studies satisfied the inclusion criteria, giving a total of 42,475 non-overlapping participants and 13,811 EC cases. Hot beverage and food consumption was significantly associated with EC risk, with an odds ratio (OR) of 1.82 (95% confidence interval [CI], 1.53-2.17). The risk was higher for esophageal squamous cell carcinoma, with a pooled OR of 1.60 (95% CI, 1.29-2.00), and was insignificant for esophageal adenocarcinoma (OR: 0.79; 95% CI: 0.53-1.16). Subgroup analyses suggests that the association between hot beverage and food consumption and EC risk were significant in Asian population (OR: 2.06; 95% CI: 1.62-2.61) and South American population (OR: 1.52; 95% CI: 1.25-1.85), but not significant in European population (OR: 0.95; 95% CI: 0.68-1.34). Hot beverage and food consumption is associated with a significantly increased risk of EC, especially in Asian and South American populations, indicating the importance in changing people's dietary habits to prevent EC.

The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer.

PubMed

Reeh, Matthias; Metze, Johannes; Uzunoglu, Faik G; Nentwich, Michael; Ghadban, Tarik; Wellner, Ullrich; Bockhorn, Maximilian; Kluge, Stefan; Izbicki, Jakob R; Vashist, Yogesh K

2016-02-01

Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.

Definitive radiotherapy for cervical esophageal cancer.

PubMed

Cao, Caineng; Luo, Jingwei; Gao, Li; Xu, Guozhen; Yi, Junlin; Huang, Xiaodong; Wang, Kai; Zhang, Shiping; Qu, Yuan; Li, Suyan; Xiao, Jianping; Zhang, Zhong

2015-02-01

The role of contemporary radiotherapy (RT) has not yet been elucidated, mainly because of the low incidence of cervical esophageal cancer. The purpose of this study was to analyze the outcome in patients with cervical esophageal cancer treated with definitive RT. A total of 115 patients with cervical esophageal cancer treated with definitive RT during January 2001 through April 2012 in our center were analyzed. Eighty patients received RT alone and 35 patients received concurrent chemoradiotherapy with cisplatin administered either weekly (30 mg/m2) or every 3 weeks (80 mg/m2). The median follow-up time was 17.1 months. For all patients, the overall 2-year local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) rate was 68.3%, 83.3%, 75.7%, and 47.6%, respectively. Definitive RT accomplished a satisfactory local control rate and contributed to organ preservation for patients with cervical esophageal cancer. 2015. © 2014 Wiley Periodicals, Inc.

18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

PubMed Central

Anderegg, Maarten C. J.; de Groof, Elisabeth J.; Gisbertz, Suzanne S.; Bennink, Roel J.; Lagarde, Sjoerd M.; Klinkenbijl, Jean H. G.; Dijkgraaf, Marcel G. W.; Bergman, Jacques J. G. H. M.; Hulshof, Maarten C. C. M.; van Laarhoven, Hanneke W. M.; van Berge Henegouwen, Mark I.

2015-01-01

Background Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. Methods From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. Results 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). Conclusion In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery. PMID:26529313

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

Water Carcinogenicity and Prevalence of HPV Infection in Esophageal Cancer Patients in Huaihe River Basin, China

PubMed Central

Li, Jintao; Khodahemmati, Sara; Wang, Minglian; Wang, Yangjunqi; Zhao, Lijiao; Jia, Runqing; Chen, Su

2018-01-01

Objective The incidence of the upper gastrointestinal tumor has increased rapidly during recent decades. The relationship between local water pollution and the tumor is still not much clear, so this study was conducted to further investigate the local water pollution and its influence on the malignant cell transformation. Prevalence of human papillomavirus (HPV) in local esophageal cancer (EC) patients was also analyzed in Shenqiu County for the first time. Methods Two-step cell transformation was used to study different sources of water in the malignant cell transformation, and the existence of 3-methylcholanthrene (3-MC) in water was analyzed from the river and shallow and deep wells. HPV DNA in tissue samples of EC patients was detected by polymerase chain reaction (PCR) and HPV diagnostic kit. Results The river water has higher cytotoxicity than the shallow well water and induced significant cell malignant transformation, while deep well water has not shown the malignant cell transformation. In Huaihe River water, the 3-MC concentration was found higher than shallow and deep wells. An HPV infection rate was found high in patients with esophageal cancer. Conclusion Long-term consumption of polluted water can induce malignant cell transformation, and the presence of HPV may be an important cause of cancer. PMID:29853858

Esophageal Cancer Clinical Presentation: Trends in the Last 3 Decades in a Large Italian Series.

PubMed

Cavallin, Francesco; Scarpa, Marco; Cagol, Matteo; Alfieri, Rita; Ruol, Alberto; Sileni, Vanna Chiarion; Ancona, Ermanno; Castoro, Carlo

2018-01-01

The aim of this study was to investigate trends in patients' characteristics and comorbidities in esophageal cancer (EC) patients. Identifying changing pattern is essential to understand and predict further changes and to plan surgical procedures and resource allocation. Trends in patients' characteristics and comorbidities were evaluated in 4440 EC patients at the Center for Esophageal Diseases in Padova, Italy, during 1980 to 2011. Joinpoint regression analysis was performed to evaluate trends and to estimate annual percentage changes (APCs). During the study period, there has been a statistically significant increment of the rate of esophageal adenocarcinoma (APC 3.70). The rates of elderly and of asymptomatic patients increased over time (APCs 0.98 and 6.24), whereas the rates of malnutrition, alcoholic drinking, and gastric ulcer decreased (APCs -1.50, -1.72, and -5.20). Reflux rate increased until 1997 and decreased thereafter (APCs 6.96 and -4.48), whereas the rate of Barrett esophagus increased until 1992 (APC 35.84) and then leveled. The rates of patients with previous neoplasms increased over time (APCs 3.22 and 4.86). There have been significant changes in systemic comorbidities, with an increase of hypertension and cardiac disease (APCs 7.56 and 1.86) and a decrease of advanced liver disease and pulmonary disease (APCs -2.67 and -1.74). The current EC patient has more often an esophageal adenocarcinoma and is more frequently elderly, asymptomatic, a survivor of previous neoplasms, and a patient with hypertension and cardiac disease than 30 years ago. On the contrary, malnutrition, alcoholic drinking, gastric ulcer, pulmonary disease, and advanced liver disease decreased.

Clinical application and prognostic assessment of serum Tumor Associated Material (TAM) from esophageal cancer patients.

PubMed

Zhou, K; Yan, Y; Zhao, S; Li, B

2014-01-01

To explore the correlation between serum levels of Tumor Associated Materials (TAM) and clinicopathological parameters and prognosis in patients with esophageal cancer (EC). The levels of TAM were determined by chemical colorimetry in 100 EC patients and 100 healthy controls. Serum TAM levels were significantly higher in patients with esophageal carcinoma than in the control group (p < 0.001). High levels of TAM were associated with tumor size (p = 0.004), tumor depth (p < 0.001), stage (p < 0.001), lymph node metastases (p < 0.001), tumor differentiation (p = 0.001), tumor respectability (p = 0.002) and disease progression (p < 0.001). The poor prognostic outcomes were correlated with an elevated level of TAM (p = 0.001). Kaplan-Meier analysis showed patients with increased levels of TAM after operation had an lower overall survival (p < 0.001) and disease-free survival (p < 0.001). In addition, multivariate Cox proportional hazard analyses revealed that TAM may be an independent factor affecting the overall survival and disease-free survival (p < 0.001). The detection of TAM could be used to screen for tumor and assess unfavorable prognosis in patients with EC.

Role of MLH1 methylation in esophageal cancer carcinogenesis and its clinical significance

PubMed Central

Li, Jinyun; Ye, Dong; Wang, Lei; Peng, Yingying; Li, Qun; Deng, Hongxia

2018-01-01

The mutL homolog-1 (MLH1) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20–2.66), advanced tumor grade (OR=3.7; 95% CI =2.37–5.77), lymph node metastasis (OR=2.65; 95% CI =1.81–3.88), distant metastasis (OR=7.60; 95% CI =1.23–47.19), advanced clinical stage (OR=4.46; 95% CI =2.88–6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00–2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC. PMID:29440913

Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met

PubMed Central

Chen, Guang-Zong; Dai, Wang-Shu; Zhu, Hong-Cheng; Song, Hong-Mei; Yang, Xi; Wang, Yuan-Dong; Min, Hua; Lu, Qian; Liu, Shu; Sun, Xin-Chen; Zeng, Xiao-Ning

2017-01-01

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer. PMID:28529610

Esophageal Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Esophageal cancer screening is not currently recommended as a part of routine cancer screening. Get detailed information about risk factors and the possible benefits and harms related to screening for esophageal cancer in this clinician summary.

Biomarkers Predict Prognosis of Esophageal Cancer Patients | Center for Cancer Research

Cancer.gov

New treatment strategies are needed to improve outcomes for patients with esophageal cancer. With five-year survival rates less than 25 percent, this is one of the deadliest forms of cancer. There are two main types of esophageal cancer—squamous cell carcinoma and adenocarcinoma. Esophageal adenocarcinoma is frequently preceded by Barrett’s esophagus, a chronic inflammatory

Radiation techniques for esophageal cancer.

PubMed

Zhang, Minsi; Wu, Abraham J

2017-10-01

Radiotherapy plays a crucial role in the curative management of localized esophageal cancer, both as definitive and preoperative therapy. For definitive therapy, the standard radiation dose is 50.4 Gy in 28 fractions and should be delivered with concurrent chemotherapy. Chemoradiotherapy also has a wellestablished benefit in the preoperative setting, as established in the CROSS randomized trial. Radiation fields are typically generous, to account for subclinical extension of disease along the esophagus and to regional nodes. Three-dimensional conformal radiation is the current standard technique for esophageal cancer, though intensity-modulated radiation therapy is increasingly utilized and may improve the outcomes of esophageal radiotherapy by reducing radiation dose to critical normal tissues.

Treatments for esophageal cancer: a review.

PubMed

Kato, Hiroyuki; Nakajima, Masanobu

2013-06-01

Esophageal cancer is the eighth most common form of cancer worldwide. The treatments for esophageal cancer depend on its etiology. For mucosal cancer, endoscopic mucosal resection and endoscopic submucosal dissection are standard, while for locally advanced cancer, esophagectomy remains the mainstay. The three most common techniques for thoracic esophagectomy are the transhiatal approach, the Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown technique (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis). Surgery for carcinoma of the cervical esophagus requires an extensive procedure with laryngectomy in many cases. When the tumor is more advanced, neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is added. The theoretical advantages of adding chemotherapy to the treatment of esophageal cancer are potential tumor down-staging prior to surgery, as well as targeting micrometastases and, thus, decreasing the risk of distant metastasis. Cisplatin- and 5-fluorouracil-based regimes are used worldwide. Chemoradiotherapy is the standard for unresectable esophageal cancer and could also be considered as an option for resectable tumors. For patients who are medically or technically inoperable, concurrent chemoradiotherapy should be the standard of care. Although neoadjuvant chemoradiotherapy followed by surgery or salvage surgery after definitive chemoradiotherapy is a practical treatment; judicious patient selection is crucial. It is important to have a thorough understanding of these therapeutic modalities to assist in this endeavor.

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.

PAQR3 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer Cells.

PubMed

Zhou, Fang; Wang, Shunchang; Wang, Jianjun

2017-05-24

Progestin and adipoQ receptor family member III (PAQR3), a member of the PAQR family, is frequently downregulated in different types of human cancer. However, its expression and functions in esophageal cancer are still unknown. This study aimed to explore the expression of PAQR3 in esophageal cancer cell lines and to investigate the role of PAQR3 in the development of esophageal cancer. Our data showed that PAQR3 is expressed in low amounts in human esophageal cancer cell lines. Overexpression of PAQR3 significantly suppressed the proliferation, migration, and invasion of esophageal cancer cells. In addition, overexpression of PAQR3 downregulated the protein expression levels of RAF1, p-MEK1, and p-ERK1/2 in esophageal cancer cells. Furthermore, overexpression of PAQR3 attenuated the tumor growth in a tumor xenograft model. In conclusion, we demonstrated that overexpression of PAQR3 suppresses cell proliferation, migration, and invasion in esophageal cancer in vitro and in vivo. Therefore, PAQR3 may act as a therapeutic target for human esophageal cancer.

Association between diet and esophageal cancer in Taiwan.

PubMed

Hung, Hsin-Chia; Huang, Meng-Chuan; Lee, Jang-Ming; Wu, Deng-Chyang; Hsu, Hon-Ki; Wu, Ming-Tsang

2004-06-01

Several studies have reported the importance of dietary factors in the development of esophageal cancer. The purpose of the present study was to evaluate the effects of several common dietary factors on the risk of squamous cell carcinoma of the esophagus in a Taiwanese population. The association between diet and esophageal cancer was examined in 284 male patients and 480 male controls, who were recruited during 6 year period. Consumption of preserved and overheated foods was found to be associated with increased risk of esophageal cancer, whereas intake of fresh fruits, vegetables, and tea was inversely associated with this risk. Men who consumed fermented bean products, salted food and preserved/pickled vegetables more than once a week after age 40 years had a 3.4-fold risk (95% confidence interval (CI): 1.9-6.2), 2.3-fold risk (95%CI: 1.2-4.2), and 2.5-fold risk (95%CI: 1.3-4.5), respectively, compared to men eating these items less than once a week. It was further found that these preserved foods were more strongly associated with esophageal cancer among men who consumed fruit less than once per day than those who consumed fruits one or more times per day. These results suggest that a high intake of preserved foods and overheated drinks might increase the risk of esophageal cancer, and intake of fruit, vegetables, and tea might be negatively associated with risk of esophageal cancer. The results also suggest that diet is an important factor in the development of esophageal cancer in Taiwan.

Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway.

PubMed

Hu, Xue; Ma, Jingjing; Vikash, Vikash; Li, Jiao; Wu, Dandan; Liu, Ya; Zhang, Jixiang; Dong, Weiguo

2018-01-01

Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC). To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo. The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis. TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP. TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.

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.

Biomarkers Predict Prognosis of Esophageal Cancer Patients | Center for Cancer Research

Cancer.gov

New treatment strategies are needed to improve outcomes for patients with esophageal cancer. With five-year survival rates less than 25 percent, this is one of the deadliest forms of cancer. There are two main types of esophageal cancer—squamous cell carcinoma and adenocarcinoma. Esophageal adenocarcinoma is frequently preceded by Barrett’s esophagus, a chronic inflammatory condition caused by gastroesophageal reflux. It is known that communication between tumor cells and the immune system can alter the behavior of tumor cells, and chronic inflammation has been implicated in several types of human cancers, including cancer of the esophagus.

Long telomere length predicts poor clinical outcome in esophageal cancer patients.

PubMed

Lv, Yanyan; Zhang, Yong; Li, Xinru; Ren, Xiaojuan; Wang, Meichen; Tian, Sijia; Hou, Peng; Shi, Bingyin; Yang, Qi

2017-02-01

Abnormal telomere length is widely reported in various human cancers, and it is considered to be an important hallmark of cancer. However, there is remarkably little consensus on the value of telomere length in the prognostic evaluation of esophageal cancers. Here, we attempted to determine the association of variable telomere length with clinical outcome of esophageal cancer patients. Using real-time quantitative PCR, we examined relative telomere lengths (RTL) in a cohort of esophageal cancer and normal esophageal tissues, and statistically investigated the association between RTL and clinical outcomes of esophageal cancer patients. The majority of esophageal cancers in this study had longer RTLs as compared to adjacent non-tumor tissues. Enhanced tumor RTL was associated with smoking habit, poor differentiation, advanced tumor stage, lymph node metastasis and cancer related death. In particular, a close relationship between longer RTL and poor survival was fully demonstrated by using cox regression and Kaplan-Maier survival curves. We found frequent telomere elongation in esophageal cancer tissues, and demonstrated longer RTL may be an independent poor prognostic factor for esophageal cancer patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Prognosis was not deteriorated by multiple primary cancers in esophageal cancer patients treated by radiotherapy

PubMed Central

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

2013-01-01

Esophageal cancer patients are often associated with multiple primary cancers (MPC). The aim of this study is to evaluate the effect of MPC on prognosis in esophageal cancer patients treated by radiotherapy. Between 2001 and 2008, esophageal cancer patients treated by definitive radiotherapy at Gunma Cancer Center were retrospectively reviewed. Exclusion criteria were preoperative or postoperative radiotherapy, palliative radiotherapy, follow-up of <6 months, radiation dose of <50 Gy and no information on MPC. We analyzed 167 esophageal cancer patients and 56 (33.5%) were associated with MPC. Gastric cancer was the most frequent tumor (38.2%), followed by head and neck cancer (26.5%). Median follow-up time was 31.5 months (range 6.1–87.3 months). Patients with MPC included more stage I/II esophageal cancer than those without MPC (66.1% vs. 36.9%, P < 0.01). The 5-year overall survival rate for esophageal cancer with MPC was relatively better than those without MPC (46.1% vs. 26.7%), although the difference did not reach statistical significance in univariate analysis (P = 0.09). Stage I/II esophageal cancer patients had a significantly better overall survival than stage III/IV patients (P < 0.01). Among esophageal cancer patients with MPC, there was no difference in overall survival between antecedent and synchronous cancer (P = 0.59). Our study indicated that the prognosis of esophageal cancer patients treated by radiotherapy was primarily determined by the clinical stage itself, but not the presence of MPC. PMID:23381956

Genetic polymorphisms in TERT are associated with increased risk of esophageal cancer.

PubMed

Wu, Yifei; Yan, Mengdan; Li, Jing; Li, Jingjie; Chen, Zhengshuai; Chen, Peng; Li, Bin; Chen, Fulin; Jin, Tianbo; Chen, Chao

2017-02-07

Single nucleotide polymorphisms (SNPs) in TERT may be associated with susceptibility to esophageal cancer. In this study, we analyzed the association between TERT SNPs and risk of esophageal cancer in 386 esophageal cancer patients and 495 healthy subjects from the Xi'an area of China. Of the four SNPs examined, rs10069690 and rs2242652 were correlated with esophageal cancer risk. Additionally, after adjusting for age and gender, the "Trs10069690Ars2242652", "Trs10069690Grs2242652" haplotypes were associated with an increased risk of esophageal cancer, while the and "Crs10069690Grs2242652" haplotype was associated with a decreased risk of esophageal cancer. These findings suggest that TERT polymorphisms may contribute to the development of esophageal cancer.

Esophageal Cancer Prevention (PDQ®)—Health Professional Version

Cancer.gov

Esophageal cancer prevention strategies include avoiding risk factors like tobacco and alcohol. Get detailed information about factors that influence the risk of esophageal cancer and research aimed at preventing it in this summary for clinicians.

Methylation of DACT2 accelerates esophageal cancer development by activating Wnt signaling

PubMed Central

Zhang, Meiying; Linghu, Enqiang; Zhan, Qimin; He, Tao; Cao, Baoping; Brock, Malcolm V.; Herman, James G.; Xiang, Rong; Guo, Mingzhou

2016-01-01

Esophageal cancer is one of the most common malignancies worldwide. DACT2 is frequently methylated in human lung, hepatic, gastric and thyroid cancers. The methylation status and function of DACT2 remain to be elucidated in human esophageal cancer. Ten esophageal cancer cell lines, 42 cases of dysplasia and 126 cases of primary esophageal cancer samples were analyzed in this study. The expression of DACT2 was detected in YES2 cells, while reduced DACT2 expression levels were found in TE8 and KYSE70 cells, and complete loss of DACT2 expression was found in KYSE30, KYSE140, KYSE150, KYSE410, KYSE450, TE3 and TE7 cells. Loss of expression or reduced expression of DACT2 correlated with promoter region hypermethylation in esophageal cancer cells. Restoration of DACT2 expression was induced by 5-aza-2′-deoxycytidine. In human primary esophageal squamous carcinoma, 69% (87/126) of samples were methylated. Methylation of DACT2 was significantly associated with tumor stage and metastasis (P < 0.01, P < 0.05). DACT2 suppressed colony formation, cell migration and invasion in esophageal cancer cells, and it also suppressed esophageal cancer cell xenograft growth. DACT2 inhibited Wnt signaling in human esophageal cancer cells. In conclusion, DACT2 is frequently methylated in human esophageal cancer and its expression is regulated by promoter region methylation. DACT2 suppresses esophageal cancer growth by inhibiting Wnt signaling. PMID:26919254

Esophageal Cancer: Associations with pN+

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Hofstetter, Wayne L.; Schipper, Paul H.; Kesler, Kenneth A.; Law, Simon; Lerut, Toni E.M.R.; Denlinger, Chadrick E.; Salo, Jarmo A.; Scott, Walter J.; Watson, Thomas J.; Allen, Mark S.; Chen, Long-Qi; Rusch, Valerie W.; Cerfolio, Robert J.; Luketich, James D.; Duranceau, Andre; Darling, Gail E.; Pera, Manuel; Apperson-Hansen, Carolyn; Blackstone, Eugene H.

2017-01-01

Objectives 1) To identify the association of positive lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and 2) to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Summary Background Data Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Methods Data on 5,806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration (WECC) were analyzed by Random Forest machine learning techniques. Results pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. Conclusions In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status. PMID:28009736

Comparing Treatment Plan in All Locations of Esophageal Cancer

PubMed Central

Lin, Jang-Chun; Tsai, Jo-Ting; Chang, Chih-Chieh; Jen, Yee-Min; Li, Ming-Hsien; Liu, Wei-Hsiu

2015-01-01

Abstract The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations. This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle3 with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume. In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques. IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted. PMID:25929910

Identification of intramural metastasis in esophageal cancer using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Xu, Jian; Kang, Deyong; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, jiangbo; Chen, Jianxin

2017-02-01

Intramural metastasis (IM) of esophageal cancer is defined as metastasis from a primary lesion to the esophageal wall without intraepithelial cancer extension. Esophageal cancer with IM is more common and such cases indicate a poor prognosis. In esophageal surgery, if curative resection is possible, the complete removal of both primary tumor and associated IMs is required. Therefore, accurate diagnosis of IMs in esophageal cancer prior to surgery is of particular importance. Multiphoton microscopy (MPM) with subcellular resolution is well-suited for deep tissue imaging since many endogenous fluorophores of fresh biological tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Here, a study to identify IM in fresh tissue section using MPM is reported. In this study, the morphological and spectral differences between IM and surrounding tissue are described. These results show that MPM has the ability to accurately identify IM in esophageal tissues. With improvement of the penetration depth of MPM and the development of multiphton microendoscope, MPM may be a promising imaging technique for preoperative diagnosis of IMs in esophageal cancer in the future.

1H-NMR based metabonomic profiling of human esophageal cancer tissue

PubMed Central

2013-01-01

Background The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research. Methods In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers. Results The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different

Esophageal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Esophageal cancer treatment options include surgery alone for very early disease and add chemotherapy and radiation therapy for more advanced cases. Get detailed information about the treatment of newly diagnosed and recurrent esophageal cancer in this summary for clinicians.

Emerging immunotherapy for the treatment of esophageal cancer.

PubMed

Jackie Oh, SeungJu; Han, Songhee; Lee, Wooin; Lockhart, A Craig

2016-06-01

Esophageal cancer is the third most common cancer of the gastrointestinal tract. Despite new therapies, the prognosis for patients with these cancers remains poor with 5-year survival rates lower than 15%. Recently, immunotherapy has increasingly gained attention as a novel treatment strategy for advanced esophageal cancer. Recent success of immunotherapy in treating other solid tumors has shed light on the utility of these approaches for esophageal cancers. Here, the authors focus on antibody-based, adoptive-cell-therapy-based, and vaccine-based immunotherapies, and briefly address their rationale, clinical data, and implications. Immunotherapy is now established to be a key treatment modality that can improve the outcomes of many cancer patients and appears to be ushering in a new era in cancer treatment. Checkpoint inhibitor drugs have shown preliminary favorable results in esophageal cancer treatment. Adoptive cell therapy and vaccine studies have also shown some promise in various clinical studies. Future endeavors will need to focus on identifying patients who are likely to benefit from immunotherapy, monitoring and managing immune responses and designing optimal combination strategies where immunotherapy agents are combined with other traditional treatment modalities.

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

PubMed Central

Vaclavikova, Radka; Neoral, Cestmir; Vrba, Jiri; Aujesky, Rene; Matzenauer, Marcel; Melichar, Bohuslav

2018-01-01

The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome. PMID:29543757

[Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer].

PubMed

Ye, Minhua; Ye, Penghui; Zhang, Weizhu; Rao, Jiaqi; Xie, Zijun

2014-06-01

To evaluate the diagnostic value of salivary and plasma miR-21 in patients with esophageal cancer (EC). Total RNA was extracted from saliva and plasma samples from 50 stage I and 50 stage II patients with EC and 50 healthy controls for measurement of miR-21 levels using qPCR. The diagnostic values of salivary and plasma miR-21 levels were assessed for stage I, stage II, and stage I+II EC. Salivary and plasma miR-21 were significantly higher in the EC patients than in the control group. The diagnostic sensitivities of plasma miR-21 for stage I, stage II, and stage I+II EC were 96%, 64% and 97%, with specificities of 44%, 84%, and 56%, respectively; the sensitivities of salivary miR-21 were 90%, 88%, and 89%, respectively, with the same specificities of 64%. Regardless of EC staging, the expression of plasma miR-21 showed a significant positive correlation with that of salivary miR-21, and their diagnostic values were comparable. Both salivary and plasmatic miR-21 can be sensitive biomarkers for EC, and salivary miR-21 detection has the potential to replace plasma detection for EC diagnosis.

Utility of double endoscopic intraluminal operation for esophageal cancer.

PubMed

Sohda, Makoto; Saito, Hideyuki; Yoshida, Tomonori; Kumakura, Yuji; Honjyo, Hiroaki; Hara, Keigo; Ozawa, Daigo; Suzuki, Shigemasa; Tanaka, Naritaka; Sakai, Makoto; Miyazaki, Tatsuya; Fukuchi, Minoru; Kuwano, Hiroyuki

2017-08-01

Endoscopic submucosal dissection (ESD) is a more difficult technique for esophageal cancer than for gastric cancer because the working space for esophageal ESD is small. Further, the difficulty level gradually increases depending on the size of the carcinoma. To overcome these difficulties, double endoscopic intraluminal operation (DEILO), which enables the resection of mucosal lesions using two fine endoscopes and monopolar shears, was reported previously. Here, we report the utility of DEILO for esophageal cancer. A total of 26 esophageal cancer patients (19 men and seven women) with 26 lesions treated using DEILO between 2011 and 2014 at Gunma University Hospital were included. We evaluated the utility and safety of DEILO for early esophageal cancer. For all patients (100%), the DEILO procedure was performed successfully, and en bloc resection was achieved. The median operation time, postoperative hospital stay, and the longitudinal dimension of resected specimens were 123 min (range 45-236 min), 5 days, and 32 mm, respectively. Perioperative perforation, pneumothorax, and mediastinal emphysema were not recognized. Only one patient was diagnosed with a postoperative hemorrhage, but the bleeding was successfully treated by bleeding vessel coagulation. DEILO has good utility as a technique of ESD for early esophageal cancers. Additional improvement and advancement of the procedure will increase the indication of DEILO.

Basis for molecular diagnostics and immunotherapy for esophageal cancer

PubMed Central

Abdo, Joe; Agrawal, Devendra K.; Mittal, Sumeet K.

2017-01-01

Introduction Esophageal cancer is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field’s most dire survival statistics. Areas covered Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for esophageal cancer. Expert commentary Of the 12 FDA-approved therapies in esophageal cancer, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy. PMID:27838937

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model

PubMed Central

Dedja, Arben; Giacometti, Cinzia; Francia, Simona; Fabris, Federico; Zaramella, Alice; Gallagher, Emily J.; Cassaro, Mauro; Rugge, Massimo; LeRoith, Derek; Alberti, Alfredo; Realdon, Stefano

2018-01-01

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett’s Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side—to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis. PMID:29662006

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model.

PubMed

Arcidiacono, Diletta; Dedja, Arben; Giacometti, Cinzia; Fassan, Matteo; Nucci, Daniele; Francia, Simona; Fabris, Federico; Zaramella, Alice; Gallagher, Emily J; Cassaro, Mauro; Rugge, Massimo; LeRoith, Derek; Alberti, Alfredo; Realdon, Stefano

2018-04-14

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

Clinical value of integrated-signature miRNAs in esophageal cancer.

PubMed

Zhang, Heng-Chao; Tang, Kai-Fu

2017-08-01

MicroRNAs (miRNAs) are crucial regulators of gene expression in tumorigenesis and are of great interest to researchers, but miRNA profiles are often inconsistent between studies. The aim of this study was to confirm candidate miRNA biomarkers for esophageal cancer from integrated-miRNA expression profiling data and TCGA (The Cancer Genome Atlas) data in tissues. Here, we identify five significant miRNAs by a comprehensive analysis in esophageal cancer, and two of them (hsa-miR-100-5p and hsa-miR-133b) show better prognoses with significant difference for both 3-year and 5-year survival. Additionally, they participate in esophageal cancer occurrence and development according to KEGG and Panther enrichment analyses. Therefore, these five miRNAs may serve as miRNA biomarkers in esophageal cancer. Analysis of differential expression for target genes of these miRNAs may also provide new therapeutic alternatives in esophageal cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer.

PubMed

Morimoto, J; Tanaka, H; Ohira, M; Kubo, N; Muguruma, K; Sakurai, K; Yamashita, Y; Maeda, K; Sawada, T; Hirakawa, K

2014-01-01

Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N-status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total

Comparable Molecular Alterations in 4-Nitroquinoline 1-Oxide-induced Oral and Esophageal Cancer in Mice and in Human Esophageal Cancer, Associated with Poor Prognosis of Patients

PubMed Central

YANG, ZHENGDUO; GUAN, BAOXIANG; MEN, TAOYAN; FUJIMOTO, JUNYA; XU, XIAOCHUN

2013-01-01

Background The murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced oral and esophageal cancer is frequently used to assess the effects of different cancer prevention/therapy agents in vivo, but the molecular mechanisms in those 4-NQO-induced carcinogenesis are unknown. This study investigated aberrant expression of cell growth-critical genes in 4-NQO-induced oral and esophageal cancer tissues in mice compared to human disease for association with survival of patients. Materials and Methods C57LB6/129Sv mice were given 4-NQO in their drinking water to induce oral and esophageal cancer. Quantitative-reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry were used to detect gene expression in the cancer tissues from mice and in 4-NQO-treated human esophageal cancer cell lines and esophageal cancer tissues. Methylation-specific PCR and DNA sequencing were performed to assess methylation of Rarb2 promoter in murine tissues. Kaplan-Meier analysis was performed to associate gene expression in esophageal cancer tissues with survival data for patients with esophageal cancer. Results 4-NQO dose-dependently induced pre-malignant and malignant lesions in oral cavity and esophagus in mice that pathologically and morphologically mimicked human oral and esophageal cancer. Molecularly, 4-NQO inhibited Rarβ2 but induced expression of phosphorylated extracellular-signal-regulated kinase 1 and 2 (p-ERK1/2) and Cox2 proteins and Rarβ2 gene promoter methylation in murine tumors. In vitro treatment with 4-NQO altered expression of RARβ2, p-ERK1/2, and COX2 in human esophageal cancer cells. In tissues from 90 patients with esophageal cancer, expression of p-ERK1/2 and COX2 was up-regulated, and p-ERK1/2 expression was associated with advanced clinical tumor stage and consumption of hot beverages, while COX2 expression was associated with tumor de-differentiation in esophageal cancer. Furthermore, expression of p-ERK1/2 was associated

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

PubMed

Chen, Yongshun; Li, Xiaohong; Guo, Leiming; Wu, Xiaoyuan; He, Chunyu; Zhang, Song; Xiao, Yanjing; Yang, Yuanyuan; Hao, Daxuan

2015-08-01

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.

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

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

ClinicalTrials.gov

2018-06-22

Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Stage IB Esophageal Cancer AJCC v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7

Outcomes in the management of esophageal cancer.

PubMed

Paul, Subroto; Altorki, Nasser

2014-10-01

Esophageal cancer rates have continued to rise in the Western World. Esophageal cancer will be responsible for an estimated 15,450 deaths in the United States in 2014 alone. Esophageal resection with or without preoperative therapy remains the mainstay of treatment. Advances in surgical technique and perioperative care have improved short-term outcomes considerably by decreasing operative mortality. Despite these advances though, esophagectomy remains a procedure associated with considerable morbidity from a wide range of complications. Prompt recognition and treatment of complications can lower overall morbidity and mortality. Unfortunately, long-term outcomes remain poor as the vast majority of patients present with loco-regionally advanced or metastatic disease. Surgery by itself provides poor loco-regional control and fails to address micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation provides a modest survival advantage compared to surgical resection alone. Future gains in understanding the molecular biology of esophageal cancer will hopefully lead to improved therapeutics and resultant outcomes. © 2014 Wiley Periodicals, Inc.

Current treatment options for the management of esophageal cancer

PubMed Central

Mawhinney, Mark R; Glasgow, Robert E

2012-01-01

In recent years, esophageal cancer characteristics and management options have evolved significantly. There has been a sharp increase in the frequency of esophageal adenocarcinoma and a decline in the frequency of squamous cell carcinoma. A more comprehensive understanding of prognostic factors influencing outcome has also been developed. This has led to more management options for esophageal cancer at all stages than ever before. A multidisciplinary, team approach to management in a high volume center is the preferred approach. Each patient should be individually assessed based on type of cancer, local or regional involvement, and his or her own functional status to determine an appropriate treatment regimen. This review will discuss management of esophageal cancer relative to disease progression and patient functional status. PMID:23152702

Berberine displays antitumor activity in esophageal cancer cells in vitro.

PubMed

Jiang, Shu-Xian; Qi, Bo; Yao, Wen-Jian; Gu, Cheng-Wei; Wei, Xiu-Feng; Zhao, Yi; Liu, Yu-Zhen; Zhao, Bao-Sheng

2017-04-14

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting. Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G 2 /M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner. Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment

Berberine displays antitumor activity in esophageal cancer cells in vitro

PubMed Central

Jiang, Shu-Xian; Qi, Bo; Yao, Wen-Jian; Gu, Cheng-Wei; Wei, Xiu-Feng; Zhao, Yi; Liu, Yu-Zhen; Zhao, Bao-Sheng

2017-01-01

AIM To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. METHODS Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting. RESULTS Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G2/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner. CONCLUSION Berberine is an inhibitor of human EC cell growth and could be considered as a

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

PubMed

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

2016-12-14

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.

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

Multidisciplinary approach for patients with esophageal cancer

PubMed Central

Villaflor, Victoria M; Allaix, Marco E; Minsky, Bruce; Herbella, Fernando A; Patti, Marco G

2012-01-01

Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett’s esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations. PMID:23239911

Nano Let‑7b sensitization of eliminating esophageal cancer stem‑like cells is dependent on blockade of Wnt activation of symmetric division.

PubMed

Pang, Yamei; Liu, Jian; Li, Xiang; Zhang, Yiwen; Zhang, Boxiang; Zhang, Jing; Du, Ning; Xu, Chongwen; Liang, Rui; Ren, Hong; Tang, Shou-Ching; Sun, Xin

2017-10-01

The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence. Higher ratios of cancer stem cells indicated later clinical stages, and Wnt signaling activation was more frequent in later esophageal carcinoma. Further in bench studies, we explored the suppressive roles and the mechanisms involved in Let‑7 on self-renewal in ECA‑109 and ECA‑9706 esophageal cancer stem cells. Isolated cancer stem cells naturally divide symmetrically and are therapy resistant. Therapy of fluorouracil and docetaxel both enriched the stem cells, proving the resistant characteristics of cancer stem cells. Wnt activation stimulated more symmetric division of stem cells, resulting in self-renewal promotion, which could be blocked by Let‑7 overexpression. Furthermore, enforced Let‑7 sensitized the stem cells to chemotherapies in a Wnt pathway inhibition-dependent manner, contributing to Let‑7 sensitization of chemotherapeutic response. Wnt activation weakened the suppressive Let‑7b through the sponge functions of CCAT-1, forming the negative feedback loop of Let‑7b/Wnt/CCAT1. These results identified the crucial participation of stem cells in esophageal cancer occurrence and progression as the potent indicator, and also indicate the potential powerful agent of Let‑7 nano-particles in treatment of cancer.

Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy Between Hypopharyngeal Cancer and Cervical Esophageal Cancer.

PubMed

Takebayashi, Katsushi; Tsubosa, Yasuhiro; Kamijo, Tomoyuki; Iida, Yoshiyuki; Imai, Atsushi; Nagaoka, Masato; Kitani, Takashi; Niihara, Masahiro; Booka, Eisuke; Shimada, Ayako; Nakagawa, Masahiro; Onitsuka, Tetsuro

2017-03-01

Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after chemoradiotherapy remains a challenge because of the high rate of complications and few available data on outcomes and safety. The purpose of this study was to evaluate the clinical significance of salvage TPLCE and to compare treatment outcomes between hypopharyngeal cancer and cervical esophageal cancer. Data from 37 consecutive patients who were diagnosed with potentially resectable hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were retrospectively analyzed. The survival and surgical outcomes were investigated between the hypopharyngeal cancer and cervical esophageal cancer groups. Twenty-six patients were included in hypopharyngeal cancer group and 11 patients were included in cervical esophageal cancer group. The baseline characteristics were balanced between the two groups. Compared to the hypopharyngeal cancer group, the cervical esophageal cancer group had significantly more frequent tracheal-related complications (p < 0.05) and stronger association of distal margin of the cervical esophagus and radiation field with tracheal ischemia after salvage surgery. Salvage TPLCE can offer the exclusive chance of prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen more frequently for cervical esophageal cancer. Therefore, the indication for salvage TPLCE must be carefully considered to maintain the balance between curability and safety.

Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study.

PubMed

Chen, Jianzhou; Guo, Hong; Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

2016-04-19

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

PubMed Central

Ren, Zhipeng; Zhang, Guoliang

2017-01-01

Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer. PMID:28388588

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer.

PubMed

Hou, Xiaobin; Wen, Jiaxin; Ren, Zhipeng; Zhang, Guoliang

2017-06-27

Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.

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

ClinicalTrials.gov

2018-02-23

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

Management of esophageal stenting-associated esophagotracheal fistula, tracheal stenosis and tracheal rupture: a case report and review of the literature.

PubMed

Ji, Fanceng; Nie, Peihe; Yi, Fuxia; Zhang, Limin

2015-01-01

Although the placement of esophageal self-expandable stents (SES) can effectively relieve dysphagia after radiotherapy in patients with esophageal cancer (EC), it may induce severe esophageal complications. This article reports a case of emergency endotracheal intubation in an EC patient who suddenly developed severe dyspnea two months after SES placement. Electronic bronchoscopy of the patient's airway confirmed the diagnosis of esophagotracheal fistula, tracheal stenosis and tracheal rupture. Endotracheal intubation was successfully performed under the guidance of electronic bronchoscopy. Dyspnea due to tracheal stenosis was relieved effectively by inserting the tracheal catheter to a proper place under the guidance of electronic bronchoscopy. Bronchoscopic examination is strongly recommended in EC patients who are highly suspected as having airway stenosis associated with esophageal stenting, for which endotracheal intubation under the guidance of bronchoscopy is suggested.

Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer

PubMed Central

Tsushima, Takahiro; Mizusawa, Junki; Sudo, Kazuki; Honma, Yoshitaka; Kato, Ken; Igaki, Hiroyasu; Tsubosa, Yasuhiro; Shinoda, Masayuki; Nakamura, Kenichi; Fukuda, Haruhiko; Kitagawa, Yuko

2016-01-01

Abstract Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated. We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models. Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45–171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13–5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation. Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma. PMID:27196482

cDNA microarray analysis of esophageal cancer: discoveries and prospects.

PubMed

Shimada, Yutaka; Sato, Fumiaki; Shimizu, Kazuharu; Tsujimoto, Gozoh; Tsukada, Kazuhiro

2009-07-01

Recent progress in molecular biology has revealed many genetic and epigenetic alterations that are involved in the development and progression of esophageal cancer. Microarray analysis has also revealed several genetic networks that are involved in esophageal cancer. However, clinical application of microarray techniques and use of microarray data have not yet occurred. In this review, we focus on the recent developments and problems with microarray analysis of esophageal cancer.

Esophageal diverticula and cancer.

PubMed

Herbella, F A M; Dubecz, A; Patti, M G

2012-02-01

Esophageal diverticula are rare. The association of cancer and diverticula has been described. Some authors adopt a conservative non-surgical approach in selected patients with diverticula whereas others treat the symptoms by diverticulopexy or myotomy only, leaving the diverticulum in situ. However, the risk of malignant degeneration should be may be taken in account if the diverticulum is not resected. The correct evaluation of the possible risk factors for malignancy may help in the decision making process. We performed a literature review of esophageal diverticula and cancer. The incidence of cancer in a diverticulum is 0.3-7, 1.8, and 0.6% for pharyngoesophageal, midesophageal, and epiphrenic diverticula, respectively. Symptoms may mimic those of the diverticulum or underlying motor disorder. Progressive dysphagia, unintentional weight loss, the presence of blood in the regurgitated material, regurgitation of peaces of the tumor, odynophagia, melena, hemathemesis, and hemoptysis are key symptoms. Risk factors for malignancy are old age, male gender, long-standing history, and larger diverticula. A carcinoma may develop in treated diverticula, even after resection. Outcomes are usually quoted as dismal because of a delayed diagnosis but several cases of superficial carcinoma have been described. The treatment follows the same principals as the therapy for esophageal cancer; however, diverticulectomy is enough in cases of superficial carcinomas. Patients must be carefully evaluated before therapy and a long-term follow-up is advisable. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

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

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.

Clinical application of oral meglumine diatrizoate esophagogram in screening esophageal fistula during radiotherapy for esophageal cancer.

PubMed

Geng, Lidan; Wu, Rong; Hu, He; Zhao, Yu; Fan, Lingli; Zhao, Zhenhua; Liao, Dongbiao; Li, Musheng; Xiang, Miao; Ma, Ying; Du, Xiaobo

2018-05-01

Esophageal fistula is a serious and common complication of radiotherapy for esophageal cancer. Therefore, early diagnosis and treatment is necessary. Because of side effect of barium esophagography, it cannot be used to screening esophageal fistula during radiotherapy. Meglumine diatrizoate is an ionic contrast agent, its adverse reactions were rarely seen when it was used in the body cavity. The purpose of this trial is identified the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. This trial was a prospective, multicenter, diagnostic clinical trial. A total of 105 patients with esophageal cancer will swallowed meglumine diatrizoate and underwent a radiographic examination weekly during radiotherapy, medical personnel observed the esophageal lesions to determine whether an esophageal fistula formed. If an esophageal fistula was observed, esophagofiberoscopy and/or computer tomography was used to further confirm the diagnosis. And the sensitivity and specificity of meglumine diatrizoate should be calculated for screening esophageal fistula during radiotherapy. To our knowledge, this study protocol is the first to identify the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. If oral meglumine diatrizoate can be used to screening esophageal fistula, more patients will benefit from early detection and treatment.

Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells.

PubMed

Wu, Dengpan; Liu, Zhen; Fu, Yanni; Zhang, Yuan; Tang, Nan; Wang, Qin; Tao, Liang

2013-10-01

The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell survival and in vivo tumor growth derived from human esophageal squamous cancer cells (Eca109). A cell counting kit 8 (CCK8) assay was used to assess the phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of tumor growth was determined by the changes in the relative tumor volume (RTV) and tumor weight. The results revealed that HPPH, in the range of 0.005-1 μg/ml, exhibited no cytotoxicity in the Eca109 cells without light exposure and that the in vitro efficiency of HPPH-mediated PDT was higher compared with that of Photofrin ® -mediated PDT. The in vivo results indicated that graded doses of HPPH-mediated PDT significantly inhibited the xenograft tumor growth derived from the Eca109 cells in a dose-dependent manner. The inhibition efficacy of 0.6 and 1.0 mg/kg HPPH-mediated PDT was similar to that of 10 mg/kg Photofrin-mediated PDT. Furthermore, HPPH possessed a lower toxicity than Photofrin at the dose that achieved the same efficacy in mice bearing Eca109 subcutaneous tumors. The histopathological findings indicated that the tumor tissues in the photosensitizer (PS)-treated mice demonstrated varying degrees of necrosis. HPPH and Photofrin exhibited vascular cytotoxicity on the treated tumors. In conclusion, the present study demonstrated that the phototoxicity of HPPH-mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH possessed lower toxicity than Photofrin at the dose that achieved the same efficacy. Therefore, HPPH may be a promising agent for treating human esophageal squamous cell cancer (ESCC).

Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells

PubMed Central

WU, DENGPAN; LIU, ZHEN; FU, YANNI; ZHANG, YUAN; TANG, NAN; WANG, QIN; TAO, LIANG

2013-01-01

The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell survival and in vivo tumor growth derived from human esophageal squamous cancer cells (Eca109). A cell counting kit 8 (CCK8) assay was used to assess the phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of tumor growth was determined by the changes in the relative tumor volume (RTV) and tumor weight. The results revealed that HPPH, in the range of 0.005–1 μg/ml, exhibited no cytotoxicity in the Eca109 cells without light exposure and that the in vitro efficiency of HPPH-mediated PDT was higher compared with that of Photofrin®-mediated PDT. The in vivo results indicated that graded doses of HPPH-mediated PDT significantly inhibited the xenograft tumor growth derived from the Eca109 cells in a dose-dependent manner. The inhibition efficacy of 0.6 and 1.0 mg/kg HPPH-mediated PDT was similar to that of 10 mg/kg Photofrin-mediated PDT. Furthermore, HPPH possessed a lower toxicity than Photofrin at the dose that achieved the same efficacy in mice bearing Eca109 subcutaneous tumors. The histopathological findings indicated that the tumor tissues in the photosensitizer (PS)-treated mice demonstrated varying degrees of necrosis. HPPH and Photofrin exhibited vascular cytotoxicity on the treated tumors. In conclusion, the present study demonstrated that the phototoxicity of HPPH-mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH possessed lower toxicity than Photofrin at the dose that achieved the same efficacy. Therefore, HPPH may be a promising agent for treating human esophageal squamous cell cancer (ESCC). PMID:24137473

Advanced esophageal cancer with tracheobronchial fistula successfully treated by　esophageal bypass surgery.

PubMed

Kimura, Masahiro; Ishiguro, Hideyuki; Tanaka, Tatsuya; Takeyama, Hiromitsu

2015-01-01

When esophageal cancer infiltrates the respiratory tract and forms a fistula, a patient's quality of life falls remarkably. Abstinence from oral feeding is necessary to prevent respiratory complications including pneumonia. Surgery is sometimes necessary to maintain quality of life. The aim of this study was to examine clinical outcomes of esophageal cancer complicated by tracheobronchial fistula. Twelve patients who underwent esophageal bypass between 2006 and 2011 in our hospital were studied. Patient characteristics, therapeutic course, outcome, and operation type were compared. Six patients among 8 who could not tolerate oral feeding could do so after bypass surgery. Ten patients were able to enjoy oral intake up until the last few days of life. Three patients survived for more than 10 months. In spite of undergoing an operation, 1 patient survived for only 2 months and another for 4 months. The only complication was postoperative delirium in 1 patient. While surgical bypass is more invasive than procedures such as endoscopic stenting, we had few complications after operative intervention and were able to maintain quality of life in our patients. This bypass procedure is a treatment option for patients with tracheobronchial fistula from advanced esophageal cancer. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preoperative therapy in locally advanced esophageal cancer.

PubMed

Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

2016-10-21

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

Protamine sulfate-nanodiamond hybrid nanoparticles as a vector for MiR-203 restoration in esophageal carcinoma cells

NASA Astrophysics Data System (ADS)

Cao, Minjun; Deng, Xiongwei; Su, Shishuai; Zhang, Fang; Xiao, Xiangqian; Hu, Qin; Fu, Yongwei; Yang, Burton B.; Wu, Yan; Sheng, Wang; Zeng, Yi

2013-11-01

We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ΔNp63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy.We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ΔNp63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy. Electronic supplementary information (ESI) available: (1) Experimental section; (2) Results: serum stability of miR-203/PS@NDs and miR-203 release curve (Fig. S1). Cytotoxicity assay of PS@NDs to Ec-109 cells (Fig. S2); confocal image and FACS analysis of intracellular uptake of cy3-labeled miR-203 (Fig. S3 and S4); real-time PCR analysis of miR-203 restoration (Fig. S5); Ran and ΔNp63 expression (Fig. S6); the sizes and zeta potentials of miRNA/PS@NDs (Table S1); the sequences of the microRNA mimics and primers (Table S2, S3 and S4). See DOI: 10.1039/c3nr04056a

High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion.

PubMed

Liu, Xinyang; Wang, Zhichao; Zhang, Guoliang; Zhu, Qikun; Zeng, Hui; Wang, Tao; Gao, Feng; Qi, Zhan; Zhang, Jinwen; Wang, Rui

2017-04-14

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population.

PubMed

Geng, Ting-Ting; Xun, Xiao-Jie; Li, Sen; Feng, Tian; Wang, Li-Ping; Jin, Tian-Bo; Hou, Peng

2015-06-14

To investigate the association between colorectal cancer (CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population. A case-control study was conducted including 360 esophageal cancer patients and 310 healthy controls. Thirty-one single-nucleotide polymorphisms (SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from Hardy-Weinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ(2) test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models (codominant, dominant, recessive, overdominant, and additive). ORs and 95%CIs were calculated by unconditional logistic regression with adjustments for age and sex. The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold (95%CI: 1.15-2.06; P = 0.004) and 1.28-fold (95%CI: 1.03-1.60; P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model (OR = 0.52, 95%CI: 0.31-0.88; P = 0.033) and recessive model (OR = 0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827 C/T-T/T genotype was associated with a 0.67-fold (95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition, rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold (95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model. These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

PubMed Central

Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

2017-01-01

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy

[Interpretation of update on The AJCC Esophageal Cancer Staging System, Eighth Edition].

PubMed

Yuan, Y; Chen, L Q

2017-02-01

The recently published AJCC Esophageal Cancer Staging System, 8(th) Edition will be implemented on Januray 1, 2018, which was developed by Worldwide Esophageal Cancer Collaboration based on 22 654 esophageal cancer patients from 33 worldwide centers. The definition of T, N, M, G stage and regional lymph nodes were optimized in the 8(th) edition. And the new "2 cm" principle has simplified the definition for the cancer of esophagogastric junction. In addition to pathologic staging, the 8(th) edition also provided clinical staging and pathologic staging after neoadjuvant therapy, making the new esophageal cancer staging system more practicable and reasonable.

[A comparison between 3.0 T MRI and histopathology for preoperative T staging of potentially resectable esophageal cancer].

PubMed

Wang, Z Q; Zhang, F G; Guo, J; Zhang, H K; Qin, J J; Zhao, Y; Ding, Z D; Zhang, Z X; Zhang, J B; Yuan, J H; Li, H L; Qu, J R

2017-03-21

Objective: To explore the value of 3.0 T MRI using multiple sequences (star VIBE+ BLADE) in evaluating the preoperative T staging for potentially resectable esophageal cancer (EC). Methods: Between April 2015 and March 2016, a total of 66 consecutive patients with endoscopically proven resectable EC underwent 3.0T MRI in the Affiliated Cancer Hospital of Zhengzhou University.Two independent readers were assigned a T staging on MRI according to the 7th edition of UICC-AJCC TNM Classification, the results of preoperative T staging were compared and analyzed with post-operative pathologic confirmation. Results: The MRI T staging of two readers were highly consistent with histopathological findings, and the sensitivity, specificity and accuracy of preoperative T staging MR imaging were also very high. Conclusion: 3.0 T MRI using multiple sequences is with high accuracy for patients of potentially resectable EC in T staging. The staging accuracy of T1, T2 and T3 is better than that of T4a. 3.0T MRI using multiple sequences could be used as a noninvasive imaging method for pre-operative T staging of EC.

Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer.

PubMed

Wang, Xingwei; Cao, Yan; Zhang, Shirong; Chen, Zhihui; Fan, Ling; Shen, Xiaochun; Zhou, Shiwen; Chen, Dongfeng

2017-05-30

Esophageal cancer is one of the most common malignant tumors of the digestive tract. The greatest obstacle to the curing of esophageal cancer is its propensity to spread and metastasize. Esophageal cancer stem cells are considered the source for recurrence and metastasis of the tumors. While clinical evidence suggested that continuous up-regulation of CXCL12/CXCR4 was significantly associated with poor prognosis in patients with esophageal cancer, but the role and mechanism of CXCL12/CXCR4 in the invasion and metastasis of esophageal cancer has not been reported by far. This study found that esophageal cancer stem cells not only autocrine a great amount of CXCL12, but also high expression of its corresponding receptor CXCR4. Most importantly, the ability of esophageal cancer stem cells to spread and metastasize could be inhibited by blockage of CXCR4 with inhibitors or shRNA approaches both in vivo and in vitro studies. The important role of CXCL12 in the invasion and metastasis of esophageal cancer stem cells was also confirmed by loss-of-function and gain-of-function strategies. Mechanistically, we demonstrated that CXCL12/CXCR4 activated the ERK1/2 pathway and thereby ultimately maintained the characteristics of high-level invasion and metastasis of esophageal cancer stem cells. Taken together, our findings suggested that autocrine CXCL12/CXCR4 was one of the major mechanisms underlying the metastatic property of esophageal cancer stem cells through ERK1/2 signaling pathway, and might serve as a therapeutic target for esophageal cancer patients.

Concurrent chemoradiotherapy with or without surgery for patients with resectable esophageal cancer: An analysis of the National Cancer Data Base.

PubMed

Naik, Kushal B; Liu, Yuan; Goodman, Michael; Gillespie, Theresa W; Pickens, Allan; Force, Seth D; Steuer, Conor E; Owonikoko, Taofeek K; Ramalingam, Suresh S; Higgins, Kristin; Beitler, Jonathan J; Shin, Dong M; Willingham, Field F; El-Rayes, Bassel; Landry, Jerome C; Fernandez, Felix G; Saba, Nabil F

2017-09-15

Patients with resectable esophageal cancer (rEC) are managed with either concurrent chemoradiotherapy followed by surgery (CRSx) or concurrent chemoradiotherapy alone (cCR). To the authors' knowledge, there is insufficient evidence comparing the overall survival of patients treated with these 2 options. The National Cancer Data Base was queried for rEC cases diagnosed from 2003 through 2011. Patients with previous cancers, cervical rEC, clinical stage T1N0 disease, or metastasis were excluded. cCR was defined as radiotherapy administered within 30 days of chemotherapy. CRSx was defined as cCR followed by esophagectomy within 90 days. Overall survival was compared using Kaplan-Meier methods, propensity score matching, and extended Cox proportional hazards models. Of the 11,122 eligible patients, 8091 (72.7%) received cCR and 3031 (27.3%) received CRSx. The odds of receiving CRSx were higher among patients with American Joint Committee on Cancer stage II disease (vs stage III), adenocarcinoma (vs squamous cell carcinoma), lesions of the lower one-third of the esophagus, private insurance, and those living >25 miles from the treating facility or in areas with a higher median income or a greater percentage of high school-educated residents. Patients aged >70 years, female patients, African-American patients, those with ≥2 comorbidities, or those treated at community programs were more likely to receive cCR. After propensity score matching, the median and 10-year survival rates were found to be significantly better with CRSx (32.5 months [95% confidence interval (95% CI), 29.6-34.8 months] and 23.8% months [95% CI, 20.0-27.9 months], respectively) compared with cCR (14.2 months [95% CI, 13.4-15.5 months] and 6.1% months [95% CI, 3.9-9.0 months], respectively). Data from the National Cancer Data Base support the inclusion of surgery after concurrent chemoradiotherapy for patients with locally advanced rEC. Cancer 2017;123:3476-85. © 2017 American Cancer Society. �

Statin use after esophageal cancer diagnosis and survival: A population based cohort study.

PubMed

Cardwell, Chris R; Spence, Andrew D; Hughes, Carmel M; Murray, Liam J

2017-06-01

A recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients. Newly diagnosed [2009-2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders. 1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99). In this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decoy receptor 3 polymorphisms are not associated with the risk of esophageal cancer in a Chinese population.

PubMed

Ren, Zhengbing; Zhu, Jingfeng; Gu, Haiyong; Liu, Ruiping; Chen, Suocheng; Rong, Guoxiang; Sun, Bin

2014-06-01

Esophageal cancer (EC) is the sixth most common cancer worldwide, and esophageal squamous-cell carcinoma (ESCC) accounts for more than 90% of ECs. We hypothesized that genetic factors might play an important role in ESCC carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between two single nucleotide polymorphisms of decoy receptor 3 (DcR3), namely, rs2297441 G > A and rs2257440 T > C, on the ESCC risk. In all, 629 ESCC cases and 686 controls were included. Genotypes were determined using the ligation detection reaction method. When the DcR3 rs2297441 GG homozygote genotype was used as the reference group, the GA genotype showed no association with the ESCC risk (GA versus GG: adjusted OR = 1.11, 95% CI = 0.88-1.40, p = 0.396); similarly, even the TT genotype showed no association with the ESCC risk (AA versus GG: adjusted OR = 0.80, 95% CI = 0.55-1.18, p = 0.268). Logistic regression analyses revealed that the DcR3 rs2257440 T > C polymorphism was not associated with the ESCC risk. DcR3 rs2297441 G > A and DcR3 rs2257440 T > C polymorphisms may not contribute to the ESCC risk, and additional, larger studies are required to confirm our results.

Coffee consumption and risk of esophageal cancer incidence: A meta-analysis of epidemiologic studies.

PubMed

Zhang, Juan; Zhou, Bin; Hao, Chuanzheng

2018-04-01

In epidemiologic studies, association between coffee consumption and esophageal cancer risk is inconsistent. The aim of tjis study was to evaluate the effect of coffee on esophageal cancer by combining several similar studies. We conducted a meta-analysis for association of coffee intake and esophageal cancer incidence. Eleven studies, including 457,010 participants and 2628 incident cases, were identified. A relative risk (RR, for cohort study) or odds ratio (OR, for case-control study) of heavy coffee drinkers was calculated, compared with light coffee drinkers or non-drinkers. The analysis was also stratified by cancer types (esophageal squamous cell carcinoma and esophageal adenocarcinoma), sex, and geographic region. The summarized OR of having esophageal cancer in heavy coffee drinkers was 0.93 (95% confidence interval [CI]: 0.73-1.12), compared with light coffee drinkers. When stratified by sex, pathologic type of esophageal cancer, and type of epidemiologic study, we did not find any association of coffee consumption and esophageal cancer incidence. However, an inverse association between coffee consumption and incidence of esophageal cancer was found in East Asia participants with OR of 0.64 (95% CI: 0.44-0.83), but not in Euro-America participants (OR = 1.05; 95% CI: 0.81-1.29). There is a protective role of coffee consumption against esophageal cancer in East Asians, but not in Euro-Americans.

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

PubMed

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

2016-09-27

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.

Prognostic value of circulating tumor cells in esophageal cancer.

PubMed

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

2017-02-21

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. 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. 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. 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.

Current and future treatment options for esophageal cancer in the elderly.

PubMed

Bollschweiler, Elfriede; Plum, Patrick; Mönig, Stefan P; Hölscher, Arnulf H

2017-07-01

Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

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. Copyright 2010 Elsevier Ltd. All rights reserved.

Polycyclic Aromatic Hydrocarbons and Esophageal Squamous Cell Carcinoma-A Review

PubMed Central

Roshandel, Gholamreza; Semnani, Shahryar; Malekzadeh, Reza; Dawsey, Sanford M.

2018-01-01

Esophageal cancer (EC) is the 8th most common cancer and the 6th most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC. PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC. Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas. PMID:23102250

The bidirectional association between oral cancer and esophageal cancer: A population-based study in Taiwan over a 28-year period

PubMed Central

Lu, Chang-Hsien; Huang, Cih-En; Chen, Min-Chi

2017-01-01

Previous studies have revealed that patients with oral or esophageal cancer are at higher risk for subsequently developing a second primary malignancy. However, it remains to be determined what association exists between oral cancer and esophageal cancer particularly in Asian countries where squamous cell carcinoma is the predominant type of esophageal cancer. A population-based study was carried out in Taiwan, where the incidence rates of both oral and esophageal squamous cell carcinomas are high, to test the hypothesis that oral cancer or esophageal cancer predisposes an individual to developing the other form of cancer. Our results showed that patients with primary oral cancer (n=45,859) had ten times the risk of second esophageal cancer compared to the general population. Within the same cohort, the reciprocal risk of oral cancer as a second primary in primary esophageal cancer patients (n=16,658) was also increased seven-fold. The bidirectional relationship suggests common risk factors between these two cancers. The present study is not only the first population-based study in Asia to validate the reciprocal relationship between oral and esophageal squamous cell carcinomas, but also will aid in the appropriate selection of high-risk patients for a future follow-up surveillance program. PMID:28562351

The bidirectional association between oral cancer and esophageal cancer: A population-based study in Taiwan over a 28-year period.

PubMed

Lee, Kuan-Der; Wang, Ting-Yao; Lu, Chang-Hsien; Huang, Cih-En; Chen, Min-Chi

2017-07-04

Previous studies have revealed that patients with oral or esophageal cancer are at higher risk for subsequently developing a second primary malignancy. However, it remains to be determined what association exists between oral cancer and esophageal cancer particularly in Asian countries where squamous cell carcinoma is the predominant type of esophageal cancer. A population-based study was carried out in Taiwan, where the incidence rates of both oral and esophageal squamous cell carcinomas are high, to test the hypothesis that oral cancer or esophageal cancer predisposes an individual to developing the other form of cancer. Our results showed that patients with primary oral cancer (n=45,859) had ten times the risk of second esophageal cancer compared to the general population. Within the same cohort, the reciprocal risk of oral cancer as a second primary in primary esophageal cancer patients (n=16,658) was also increased seven-fold. The bidirectional relationship suggests common risk factors between these two cancers. The present study is not only the first population-based study in Asia to validate the reciprocal relationship between oral and esophageal squamous cell carcinomas, but also will aid in the appropriate selection of high-risk patients for a future follow-up surveillance program.

Safety and benefit of curative surgical resection for esophageal squamous cell cancer associated with multiple primary cancers.

PubMed

Otowa, Y; Nakamura, T; Takiguchi, G; Yamamoto, M; Kanaji, S; Imanishi, T; Oshikiri, T; Suzuki, S; Tanaka, K; Kakeji, Y

2016-03-01

Enhancements in surgical techniques have led to improved outcomes for esophageal cancer. Recent findings have showed that esophageal cancer is frequently associated with multiple primary cancers, and surgical resection is usually complicated in such cases. The aim of this study was to clarify the clinical significance of surgery for patients with esophageal squamous cell cancer associated with multiple primary cancers. The clinical outcomes of surgical resection for esophageal cancer were compared among 79 patients with antecedent and/or synchronous cancers (Multiple cancer group) and 194 patients without antecedent and/or synchronous cancers (Single cancer group). The most common site of multiple primary cancers was the pharynx (36 patients; 29.7%), followed by the stomach (24 patients; 19.8%). The reconstruction method was more complicated in the Multiple cancer group as a result of the prolonged surgery time and increased blood loss. However, postoperative morbidity and overall survival (OS) did not differ between the two groups. After esophagectomy, metachronous cancers were observed in 26 patients, with 30 regions in total, and 93.1% were found to be curable. Sex was the only independent risk factors for developing metachronous cancer after esophagectomy. The presence of antecedent and synchronous cancers complicates the surgical resection of esophageal cancer; however, no differences were found in the OS and postoperative morbidity between the two groups. Therefore, surgical intervention should be selected as a first-line treatment. Because second primary cancers are often observed in esophageal cancer, we recommend a close follow-up using esophagogastroduodenoscopy and contrast-enhanced computed tomography. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine

PubMed Central

Ahrens, Theresa D; Timme, Sylvia; Hoeppner, Jens; Ostendorp, Jenny; Hembach, Sina; Follo, Marie; Hopt, Ulrich T; Werner, Martin; Busch, Hauke; Boerries, Melanie; Lassmann, Silke

2015-01-01

Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach. PMID:25923331

[Eight Cases of Esophagus and Tracheobronchial Stenting for Advanced Esophageal Cancer].

PubMed

Nakahara, Yujiro; Takachi, Ko; Tsujimura, Naoto; Wakasugi, Masaki; Hirota, Masaki; Matsumoto, Takashi; Takemoto, Hiroyoshi; Nishioka, Kiyonori; Oshima, Satoshi

2017-11-01

Malignant stricture and fistula of the esophagus and tracheobronchus adversely affect the quality of life(QOL)in patients with advanced esophageal cancer. Stenting is one ofthe therapies available for these patients. We investigated the outcomes ofesophagus and tracheobronchial stenting in our institution. Eight patients with advanced esophageal cancer underwent double stenting from 2010 to 2016. Among them, 4 patients underwent double stenting as planned. One patient underwent an emergency tracheal stenting because ofstenosis ofthe trachea caused by esophageal stenting. Three patients underwent tracheobronchial stenting later on because ofan increase in the tumor size after esophageal stenting. Dysphagia score was improved in 5(67.5%)out ofthe 8 patients. Respiratory symptoms were improved in all patients, and 4 patients(50.0%) were discharged. The median survival time after esophageal stenting was 70.5 days. Esophagus and tracheobronchial stenting for advanced esophageal cancer was useful for the improvement of the QOL.

Advances in radiotherapy for esophageal cancer

PubMed Central

Deng, Wei

2018-01-01

Esophageal cancer is a common type of malignancy worldwide and usually requires multidisciplinary care. Radiotherapy plays an important part in management of the disease. During the past few years, researchers have made much progress about radiotherapy for esophageal cancer, which was revealed in every aspect of clinical practice. Neoadjuvant chemoradiotherapy remains the standard treatment for locally advanced esophageal cancer, whereas neoadjuvant chemotherapy appears to show less toxicities and non-inferior prognosis. What’s more, definitive chemoradiotherapy could be an option for non-surgical candidates and good responders to chemoradiotherapy. Advances in radiation techniques result in higher conformity, homogeneity, more normal tissue sparing and less treatment time. Promising prognoses and less toxicities were also seen in advanced techniques. As radiation dose higher than 50 Gy obtains better local control and survival, simultaneously integrated boost is designed to increase primary tumor dosage and keep prophylactic dose to subclinical areas. Elective nodal irradiation brings about better local control but do not show advantages in survival compared with involved field irradiation (IFI). As a trend, more tolerable chemoradiotherapy regimen would be taken into account in dealing with elderly patients. PMID:29666802

Expandable metallic stents for tracheobronchial stenoses in esophageal cancer.

PubMed

Takamori, S; Fujita, H; Hayashi, A; Tayama, K; Mitsuoka, M; Ohtsuka, S; Shirouzu, K

1996-09-01

Tracheobronchial stenosis in patients with esophageal cancer can be life threatening. Few reports have discussed use of expandable metallic stents for central airway stenoses in patients with esophageal cancer. Twelve patients with esophageal cancer underwent placement of expandable metallic stents for respiratory distress caused by tracheobronchial stricture. Single or double metallic stents were placed in the stenotic airways under fluoroscopic guidance. Improvement in respiratory symptoms and clinical outcome were assessed. Most stenoses were located in the trachea or the left main bronchus. From one to four expandable metallic stents were placed in each stricture site, with immediate relief of respiratory symptoms in 8 patients. One patient with tracheomalacia in alive 3 years after stent placement and another is alive 6 months after stent insertion. The other 10 patients lived from 10 to 70 days (mean; survival, 35 days) after stent placement. Death was due to progression of disease. Although metallic stents are useful for relieving respiratory distress in patients with advanced esophageal cancer, additional therapies should be considered.

An Update on Modern Approaches to Localized Esophageal Cancer

PubMed Central

Welsh, James; Amini, Arya; Likhacheva, Anna; Erasmus, Jeremy; Gomez, Daniel; Davila, Marta; Mehran, Reza J; Komaki, Ritsuko; Liao, Zhongxing; Hofstetter, Wayne L; Bhutani, Manoop; Ajani, Jaffer A

2014-01-01

Esophageal cancer treatment continues to be a topic of wide debate. Based on improvements in chemotherapy drugs, surgical techniques, and radiotherapy advances, esophageal cancer treatment approaches are becoming more specific to the stage of the tumor and the overall performance status of the patient. While surgery continues to be the standard treatment option for localized disease, the current direction favors multimodality treatment including both radiation and chemotherapy with surgery. In the next few years, we will continue to see improvements in radiation techniques and proton treatment, with more minimally invasive surgical approaches minimizing postoperative side effects, and the discovery of molecular biomarkers to help deliver more specifically targeted medication to treat esophageal cancers. PMID:21365188

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

PubMed

Sheng, Yuqiao; Liu, Kangdong; Wu, Qiong; 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

2016-05-24

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.

Esophageal cancer in high-risk areas of China: research progress and challenges.

PubMed

Lin, Yingsong; Totsuka, Yukari; Shan, Baoen; Wang, Chaochen; Wei, Wenqiang; Qiao, Youlin; Kikuchi, Shogo; Inoue, Manami; Tanaka, Hideo; He, Yutong

2017-03-01

The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad. We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013). Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type. Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of histology on recurrence patterns in esophageal cancer treated with definitive chemoradiotherapy.

PubMed

Xi, Mian; Xu, Cai; Liao, Zhongxing; Hofstetter, Wayne L; Blum Murphy, Mariela; Maru, Dipen M; Bhutani, Manoop S; Lee, Jeffrey H; Weston, Brian; Komaki, Ritsuko; Lin, Steven H

2017-08-01

To assess the impact of histology on recurrence patterns and survival outcomes in patients with esophageal cancer (EC) treated with definitive chemoradiotherapy (CRT). We analyzed 590 consecutive EC patients who received definitive CRT from 1998 to 2014, including 182 patients (30.8%) with squamous cell carcinoma (SCC) and 408 (69.2%) with adenocarcinoma. Recurrence pattern and timing, survival, and potential prognostic factors were compared. After a median follow-up time of 58.0months, the SCC group demonstrated a comparable locoregional recurrence rate (42.9% vs. 38.0%, P=0.264) but a significantly lower distant failure rate (27.5% vs. 48.0%, P<0.001) than adenocarcinoma group. No significant difference was found in overall survival or locoregional failure-free survival between groups, whereas the SCC group was associated with significantly more favorable recurrence-free survival (P=0.009) and distant metastasis-free survival (P<0.001). The adenocarcinoma group had higher hematogenous metastasis rates of bone, brain, and liver, whereas the SCC group had a marginally higher regional recurrence rate. Among patients who received salvage surgery after locoregional recurrence, no significant difference in survival was found between groups (P=0.12). The patterns and sites of recurrence, survival outcomes, and prognostic factors were significantly different between esophageal SCC and adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence and management of colorectal neoplasia in surgically treated esophageal cancer patients.

PubMed

Takeuchi, Daisuke; Koide, Naohiko; Komatsu, Daisuke; Suzuki, Akira; Miyagawa, Shinichi

2015-05-01

The existence of other primary tumors during the treatment of esophageal cancer patients has been an important issue. Our aim is to investigate the prevalence and management of colorectal neoplasia (CRN) in surgically treated esophageal cancer patients. Between 2002 and 2008, 93 patients with esophageal cancer were surgically treated. Seventy-three patients underwent subtotal esophagectomy and 20 underwent lower esophagectomy for esophageal cancer. Colonoscopy was available for detecting CRN before and after surgery. Eighty-nine (95.7%) of the 93 patients were screened by colonoscopy preoperatively or within a year from the operation. Thirty-nine patients (43.8%) with CRN were synchronously identified: adenoma in 34 (38.2%) and adenocarcinoma in 5 patients (5.6%). Eleven adenomas with high grade-dysplasia and 8 adenomas with low grade-dysplasia were removed endoscopically. Three superficial adenocarcinomas were endoscopically removed before surgery, and 2 adenocarcinomas were surgically removed. Seventy-four patients (83.1%) were followed using colonoscopy, and 11 subsequent CRN, including 2 superficial adenocarcinomas, were endoscopically detected in 8 patients (10.8%). The size of esophageal cancer was larger in the patients with than without CRN (p = 0.036). The body mass index in esophageal cancer patients with CRN tended to be higher than in those without CRN (p = 0.065). We noted that esophageal cancer is frequently associated with synchronous and/or metachronous colorectal cancer and adenomas. Colonoscopy is useful to detect and manage CRN before and after esophagectomy, although a few limitations exist. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer.

PubMed

Watanabe, Seishiro; Sasahara, Katsuyuki; Kinekawa, Fumihiko; Uchida, Naohito; Masaki, Tsutomu; Kurokohchi, Kazutaka; Murota, Masayuki; Touge, Tetsuo; Kawauchi, Kazuyoshi; Oda, Syuji; Kuriyama, Shigeki

2002-01-01

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.

Atlas of the thoracic lymph nodal delineation and recommendations for lymph nodal CTV of esophageal squamous cell cancer in radiation therapy from China.

PubMed

Huang, Wei; Huang, Yong; Sun, Jujie; Liu, Xibin; Zhang, Jian; Zhou, Tao; Zhang, Baijiang; Li, Baosheng

2015-07-01

To construct an anatomical atlas of thoracic lymph node regions of esophageal cancer (EC) based on definitions from The Japan Esophageal Society (JES) and generate a consensus to delineate the nodal clinical target volume (CTVn) for elective nodal radiation (ENI) of esophageal squamous cell carcinoma (ESCC). An interdisciplinary group including two dedicated radiation oncologists, an experienced radiologist, a pathologist and two thoracic surgeons were gathered to generate a three-dimensional radiological description for the mediastinal lymph node regions of EC on axial CT scans. Then the radiological boundaries of lymph node regions were validated by a relatively large number of physicians in multiple institutions. An atlas of detailed anatomic boundaries of lymph node station No. 105-114 was defined on axial CT, along with illustrations. From the previous work, the study provided a guide of CTVn contouring for ENI of thoracic ESCC from a single center. It is feasible to use such an atlas of thoracic lymph node stations for radiotherapy planning. A phase III study based on the atlas is ongoing in China to measure quantitatively the ENI received by patients with ESCC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Hofstetter, Wayne L; Schipper, Paul H; Kesler, Kenneth A; Law, Simon; Lerut, E M R; Denlinger, Chadrick E; Salo, Jarmo A; Scott, Walter J; Watson, Thomas J; Allen, Mark S; Chen, Long-Qi; Rusch, Valerie W; Cerfolio, Robert J; Luketich, James D; Duranceau, Andre; Darling, Gail E; Pera, Manuel; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2017-01-01

To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Self-Expandable Metallic Stent Placement for the Palliation of Esophageal Cancer.

PubMed

Kim, Kun Yung; Tsauo, Jiaywei; Song, Ho Young; Kim, Pyeong Hwa; Park, Jung Hoon

2017-07-01

Esophageal stents have been used to palliate patients with dysphagia caused by esophageal cancer. Early rigid plastic prostheses have been associated with a high risk of complications. However, with the development of self-expanding stents, it has developed into a widely accepted method for treating malignant esophageal strictures and esophagorespiratory fistulas (ERFs). The present review covers various aspects of self-expanding metallic stent placement for palliating esophageal cancer, including its types, placement procedures, indications, contraindications, complications, and some of innovations that will become available in the future. © 2017 The Korean Academy of Medical Sciences.

Self-Expandable Metallic Stent Placement for the Palliation of Esophageal Cancer

PubMed Central

2017-01-01

Esophageal stents have been used to palliate patients with dysphagia caused by esophageal cancer. Early rigid plastic prostheses have been associated with a high risk of complications. However, with the development of self-expanding stents, it has developed into a widely accepted method for treating malignant esophageal strictures and esophagorespiratory fistulas (ERFs). The present review covers various aspects of self-expanding metallic stent placement for palliating esophageal cancer, including its types, placement procedures, indications, contraindications, complications, and some of innovations that will become available in the future. PMID:28581260

Measuring Cell Free DNA During the Course of Treatment for Esophageal Cancer as a Marker of Response and Recurrence

ClinicalTrials.gov

2017-10-09

Esophageal Neoplasm; Esophageal Neoplasms Malignancy Unspecified; Esophageal Neoplasms Malignant; Cancer of Esophagus; Cancer of the Esophagus; Esophageal Cancer; Esophagus Cancer; Neoplasm, Esophageal

[Optimal lymphadenectomy for thoracic esophageal cancer: three-field or modified two-field lymphadenectomy].

PubMed

Liu, Shuoyan; Wang, Zhen; Wang, Feng

2016-09-25

Differences in operative procedure and knowledge of esophageal cancer exist among surgeons from different countries and regions. There is controversy in the surgical treatment of esophageal cancer, especially in the extent of lymphadenectomy. Until now, results of the three-field lymphadenectomy and two-field lymphadenectomy are mostly reported by retrospective studies from Japan and China. Three-field lymphadenectomy has been initiated in Fujian Provincial Cancer Hospital since 1990s. After evaluating our database, we found that three-field was superior to two-field lymphadenectomy in terms of long-term survival for patients with upper thoracic esophageal cancer, whereas for those with middle or lower thoracic esophageal cancer, the survival benefit of three-field lymphadenectomy was reduced. Therefore, we propose to perform three-field lymphadenectomy for upper thoracic esophageal cancer. In middle or lower thoracic esophageal cancer, we suggest to perform modified two-field lymphadenectomy in most cases, and three-field lymphadenectomy in selective cases. Video-assisted two-field lymphadenectomy is feasible. Based on the national condition of China, we advise to perform thoracic duct removal only in patients with posterior mediastinal or peri-ductus node metastasis to achieve curative effect.

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.

Influence of preoperative radiation field on postoperative leak rates in esophageal cancer patients after trimodality therapy.

PubMed

Juloori, Aditya; Tucker, Susan L; Komaki, Ritsuko; Liao, Zhongxing; Correa, Arlene M; Swisher, Stephen G; Hofstetter, Wayne L; Lin, Steven H

2014-04-01

Postoperative morbidities, such as anastomotic leaks, are common after trimodality therapy (chemoradiation followed by surgery) for esophageal cancer. We investigated for factors associated with an increased incidence of anastomotic leaks. Data from 285 esophageal cancer patients treated from 2000 to 2011 with trimodality therapy were analyzed. Anastomotic location relative to preoperative radiation field was assessed using postoperative computed tomographic imaging. Logistic regression was used to evaluate for factors associated with any or clinically relevant (CR) (≥ grade 2) leaks. Overall anastomotic leak rate was 11% (31 of 285), and CR leak rate was 6% (17 of 285). Multivariable analysis identified body mass index (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.00-1.17; OR, 1.11, 95% CI, 1.01-1.22), three-field surgery (OR, 10.01; 95% CI, 3.83-26.21; OR, 4.83; 95% CI, 1.39-16.71), and within radiation field ("in-field") anastomosis (OR, 5.37; 95% CI, 2.21-13.04; OR, 8.63; 95% CI, 2.90-25.65) as independent predictors of both all grade and CR leaks, respectively. While patients with distal esophageal tumors and Ivor-Lewis surgery had the lowest incidence of all grade (6.5%) and CR leaks (4.2%), most of the leaks were associated with the anastomosis constructed within the field of radiation (in-field: 39% and 30% versus out-of-field: 2.6% and 1.0%, respectively, for total and CR leaks, p less than 0.0001, Fisher's exact test). Esophagogastric anastomosis placed within the preoperative radiation field was a very strong predictor for anastomotic leaks in esophageal cancer patients treated with trimodality therapy, among other factors. Surgical planning should include a critical evaluation of the preoperative radiation fields to ensure proper anastomotic placement after chemoradiation therapy.

The current status of neoadjuvant therapy for esophageal cancer.

PubMed

Lin, Daniel; Leichman, Lawrence

2014-01-01

Through the contribution of a very large number of single-arm phase II trials and many less randomized phase III trials, the standard of care for locally advanced esophageal cancer has evolved to either combination chemotherapy plus radiation or combination chemotherapy. In this review, we focus on the key findings of these studies and selected meta-analyses that have led to this evolution. We note differences in outcomes for adenocarcinomas of the esophagus when compared to squamous cell esophageal cancers. Despite progress in developing a consensus for therapy, the outcome for patients with locally advanced remains poor. We complete the review by noting newer areas of investigation seeking to provide targeted and more personalized therapy to patients with esophageal cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics.

PubMed

Yokoyama, A; Muramatsu, T; Omori, T; Yokoyama, T; Matsushita, S; Higuchi, S; Maruyama, K; Ishii, H

2001-03-01

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investigated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After adjustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52 with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and 40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it was not observed for those with stomach cancer alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.

Bypass laparoscopic procedure for palliation of esophageal cancer.

PubMed

Siosaki, Marcos Duarte; Lacerda, Croider Franco; Bertulucci, Paulo Anderson; da Costa Filho, José Orlando; de Oliveira, Antônio Talvane Torres

2013-03-26

Esophageal cancer is a devastating disease with rapidly increasing incidence in Western countries. Dysphagia is the most common complication, causing severe malnutrition and reduced quality of life. A 69-year-old male with persistent esophageal cancer after radiation therapy was subjected to palliative by-pass surgery using a laparoscopic approach. Due to the advanced stage at diagnosis, palliative treatment was a more realistic option. Dysphagia is a most distressing symptom of this disease, causing malnutrition and reducing quality of life. The goal of palliation is to improve swallowing. The most common methods applied are endoscopic stenting, radiation therapy (external or brachytherapy), chemotherapy, yttrium-aluminum-garnet laser rechanneling or endoscopic dilatation. Palliative surgery is rarely proposed due to morbidity and complications. This paper demonstrates an update in the technique proposed by Postlethwait in 1979 for palliation of esophageal cancer. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

Shared susceptibility loci at 2q33 region for lung and esophageal cancers in high-incidence areas of esophageal cancer in northern China.

PubMed

Zhao, Xue Ke; Mao, Yi Min; Meng, Hui; Song, Xin; Hu, Shou Jia; Lv, Shuang; Cheng, Rang; Zhang, Tang Juan; Han, Xue Na; Ren, Jing Li; Qi, Yi Jun; Wang, Li Dong

2017-01-01

Cancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population. A total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson's Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival. Four of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107-1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100-1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098-1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089-1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with gender, TNM stage, histopathological type

Esophageal bypass operation prior to definitive chemoradiotherapy in advanced esophageal cancer with tracheobronchial invasion.

PubMed

Hihara, Jun; Hamai, Yoichi; Emi, Manabu; Aoki, Yoshiro; Taomoto, Junya; Miyata, Yoshihiro; Okada, Morihito

2014-01-01

In T4 esophageal cancer with tracheobronchial invasion, an esophagorespiratory fistula (ERF) often occurs during or after chemoradiotherapy. We have performed esophageal bypass operations prior to definitive chemoradiotherapy for these patients to increase the chemoradiotherapy completion rate by minimizing the potential effect of an ERF. The aim of this study was to examine the clinical outcome of esophageal bypass surgery prior to chemoradiotherapy. Between 1997 and 2010, 17 patients underwent esophageal bypass surgery followed by definitive chemoradiotherapy for esophageal cancer with tracheobronchial invasion (bypass group). Ten patients in the same circumstances were treated with chemoradiotherapy alone (control group). Overall survival, the clinical effect of chemoradiotherapy, the ERF incidence rate, and the safety of esophageal bypass surgery were assessed. The overall response rate to chemoradiotherapy was 64.7% in the bypass group and 90.0% in the control group. Except for 2 patients with ERF at initial diagnosis, 4 (26.7%) of the 15 patients developed ERF in the bypass group, and 3 (30.0%) of the 10 patients developed ERF in the control group during or after chemoradiotherapy. The 2-year and 3-year overall survival rates were 17.6% and 17.6% in the bypass group and 20.0% and 0% in the control group, respectively (p = 0.924); long-term survival of more than 3 years was seen only in the bypass group. Esophageal bypass surgery prior to definitive chemoradiotherapy could be performed safely, and this strategy contributed to long-term survival in the patients who achieved a good response to chemoradiotherapy but developed an ERF. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Humoral response against sialyl-Le(a) glycosylated protein species in esophageal cancer: Insights for immunoproteomic studies.

PubMed

Fernandes, Elisabete; Peixoto, Andreia; Neves, Manuel; Afonso, Luís Pedro; Santos, Lúcio Lara; Ferreira, José Alexandre

2015-12-01

Esophageal cancers (ECs) show poor prognosis and decreased overall survival due to late diagnosis and ineffective therapeutics, urging the introduction of novel biomarkers to aid disease management. The levels of sialyl-Lewis(a) antigen (sLe(a) ) are frequently increased in digestive tumours, which has been explored in serological non-invasive prognostication (CA19-9 test); however, with low sensitivity and specificity. Autoantibodies against cancer antigens are considered the next generation biomarkers, as they are present in circulation long before tumour-associated proteins. Based on these observations we have mined the serum of EC patients (n = 7) for antibodies against sLe(a) -glycosylated protein species. All EC were positive for sLe(a) , irrespectively of their histological nature but only two patients showed elevated CA19-9. Moreover, IgG titers, with emphasis on IgG1, were elevated in EC patients in comparison to the control group. SLe(a) -glycoproteins were then extracted from tumours of patients with negative CA19-9, isolated by immunoprecipitation and blotted with patients IgG. Autoantibodies against sLe(a) -glycosylated proteins were detected in all cases. Different SLe(a) -glycoproteins were observed for tumours of distinct histological natures, which now require identification and validation in larger patient sets. This preliminary data suggests that antoantibodies against sLe(a) glycosylated proteins hold potential for non-invasive diagnosis in CA19-9 negative cases and sets the rational for future immunoproteomic studies envisaging highly specific EC biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association between ambient ultraviolet radiation and risk of esophageal cancer.

PubMed

Tran, Bich; Lucas, Robyn; Kimlin, Michael; Whiteman, David; Neale, Rachel

2012-12-01

Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC. PMID:24886123

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.

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

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

Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.

PubMed

Li, Shuying; Shen, Haie; Li, Ji; Hou, Xiaoli; Zhang, Ke; Li, Jintao

2018-03-01

To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection. Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients. Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC). A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.

Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Nakamura, Katsumasa; Nomoto, Satoshi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Ueda, Masanobu; Hirata, Hideki; Honda, Hiroshi

2010-01-01

The purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stage II-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3,50-75%; 4,75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n = 14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p = 0.0006, p = 0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful.

[Incidence and survival of esophageal cancer with different histological types in Linzhou between 2003 and 2012].

PubMed

Liu, S Z; Yu, L; Chen, Q; Quan, P L; Cao, X Q; Sun, X B

2017-05-06

Objective: To investigate the incidence and survival of esophageal cancer with different histological types and to understand the incidence trend and burden of esophageal cancer in Linzhou during 2003-2012. Methods: All incidence records of esophageal cancer and population reported were collected from Linzhou Cancer Registry during 2003-2012. Incidence rate was calculated using gender and histological types. Age standardized incidence rate was calculated according to world Segi's population and Chinese census data in 2000. Age standardized incidence rate by world population between 2003 and 2012 was analyzed with JoinPoint regression model and estimated annual percentage change (EAPC) was calculated. 5-year survival rate was calculated with Kaplan-Meier model. Results: There were 8 229 esophageal cancer cases in Linzhou during 2003-2012. The average annual incidence rate was 80.08/100 000 (8 229/10 276 481). Among all esophageal cancer cases, 7 019 (85.3%) were diagnosed as esophageal squamous cell carcinoma (ESCC). In Linzhou, the age standardized incidence rate by Chinese standard population and by world standard population was 80.92/100 000 and 81.85/100 000 in 2003, 67.97/100 000 and 68.63/100 000 in 2012. JoinPoint regression model showed that EAPC was-12.9% (95 %CI: -16.4%--9.1%) for other and unspecified histological type between 2003 and 2012. The EAPC was-5.5% (95 %CI: -9.2%--1.6%) for esophageal cancer between 2007 and 2012,-5.4% (95 %CI: -7.0%--3.9%) for esophageal cancer in female between 2006 and 2012,-4.9% (95 %CI: -9.5%--0.1%) for ESCC between 2007 and 2012. The 5-year prevalence of esophageal cancer was 215.49 per 100 000 (2 337/1 084 493), and 5 489 died within 5 years after incidence. 5-year survival rate of esophageal cancer was 34.6% (95 %CI: 33.5%-35.6%). Conclusion: Esophageal cancer had a decreasing trend in Linzhou. The survival rate was increasing. But, esophageal cancer was still a major burden in Linzhou. The major histological type was

Curcumin Induces Cell Death in Esophageal Cancer Cells through Modulating Notch Signaling

PubMed Central

Subramaniam, Dharmalingam; Ponnurangam, Sivapriya; Ramamoorthy, Prabhu; Standing, David; Battafarano, Richard J.; Anant, Shrikant; Sharma, Prateek

2012-01-01

Background Curcumin inhibits the growth of esophageal cancer cell lines; however, the mechanism of action is not well understood. It is becoming increasingly clear that aberrant activation of Notch signaling has been associated with the development of esophageal cancer. Here, we have determined that curcumin inhibits esophageal cancer growth via a mechanism mediated through the Notch signaling pathway. Methodology/Principal Findings In this study, we show that curcumin treatment resulted in a dose and time dependent inhibition of proliferation and colony formation in esophageal cancer cell lines. Furthermore, curcumin treatment induced apoptosis through caspase 3 activation, confirmed by an increase in the ratio of Bax to Bcl2. Cell cycle analysis demonstrated that curcumin treatment induced cell death and down regulated cyclin D1 levels. Curcumin treatment also resulted in reduced number and size of esophagospheres. Furthermore, curcumin treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1. This reduction in Notch-1 activation was determined to be due to the down-regulation of critical components of the γ-secretase complex proteins such as Presenilin 1 and Nicastrin. The combination of a known γ-secretase inhibitor DAPT and curcumin further decreased proliferation and induced apoptosis in esophageal cancer cells. Finally, curcumin treatment down-regulate the expressions of Notch-1 specific microRNAs miR-21 and miR-34a, and upregulated tumor suppressor let-7a miRNA. Conclusion/Significance Curcumin is a potent inhibitor of esophageal cancer growth that targets the Notch-1 activating γ-secretase complex proteins. These data suggest that Notch signaling inhibition is a novel mechanism of action for curcumin during therapeutic intervention in esophageal cancers. PMID:22363450

Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic stent placement

PubMed Central

Yu, You-Tao; Yang, Guang; Liu, Yan; Shen, Bao-Zhong

2004-01-01

AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement. METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement. RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases. CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients’ survival and reduce occurrence of re-stenosis. PMID:15237455

Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

PubMed

Wang, Yao-Kuang; Chuang, Yun-Shiuan; Wu, Tzung-Shiun; Lee, Ka-Wo; Wu, Che-Wei; Wang, Hsiang-Chen; Kuo, Chie-Tong; Lee, Chien-Hung; Kuo, Wen-Rei; Chen, Chung-Ho; Wu, Deng-Chyang; Wu, I-Chen

2017-11-15

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx. © 2017 UICC.

Chemoradiotherapy for esophageal squamous cell cancer.

PubMed

Sasaki, Yusuke; Kato, Ken

2016-09-01

Chemoradiotherapy has been clinically indicated for patients with resectable esophageal squamous cell carcinoma who refuse surgical resection and in locally advanced unresectable esophageal squamous cell carcinoma patients. Concurrent chemoradiotherapy prolongs survival than radiation therapy alone when given as definitive treatment. Therefore, chemoradiotherapy is recognized as the standard non-invasive treatment for patients with localized esophageal cancer who opt for non-surgical treatment. JCOG9906 showed promising outcomes for stage II/III ESCC patients. But there are some problems about chemoradiotherapy for esophageal squamous cell carcinoma. Late toxicities are sometimes lethal for patients who achieved complete response even after years. Salvage treatment for residual or recurrent disease is unestablished. Modified Radiation Therapy Oncology Group regimen at the dose of 50.4 Gy reduced late toxicities without reducing efficacy. Optimal timings and procedure of salvage surgery and endoscopic therapy is evaluated in JCOG0909. Strategy including salvage therapy after chemoradiotherapy should be considered at the time of starting the treatment. Targeted therapy has not shown adding effect for chemoradiotherapy for esophageal squamous cell carcinoma yet. New agents, such as immune checkpoint inhibitors, are expected to show synergistic effect with chemoradiotherapy for esophageal squamous cell carcinoma. Further investigation is needed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

PubMed Central

Abdo, Joe; Bertellotti, Carrie A.; Cornell, David L.; Agrawal, Devendra K.; Mittal, Sumeet K.

2017-01-01

There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients. PMID:28770168

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy

PubMed Central

Greenwald, Bruce D.; Dumot, John A.; Abrams, Julian A.; Lightdale, Charles J.; David, Donald S.; Nishioka, Norman S.; Yachimski, Patrick; Johnston, Mark H.; Shaheen, Nicholas J.; Zfass, Alvin M.; Smith, Jenny O.; Gill, Kanwar Rupinder S.; Burdick, J. Steven; Mallat, Damien; Wolfsen, Herbert C.

2011-01-01

Background Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. Objective To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Design Multicenter, retrospective cohort study. Setting Ten academic and community medical centers between 2006 and 2009. Patients Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Interventions Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Main Outcome Measurements Complete eradication of luminal cancer and adverse events. Results Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1–15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Limitations Retrospective study design, short follow-up. Conclusions Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

PubMed

Greenwald, Bruce D; Dumot, John A; Abrams, Julian A; Lightdale, Charles J; David, Donald S; Nishioka, Norman S; Yachimski, Patrick; Johnston, Mark H; Shaheen, Nicholas J; Zfass, Alvin M; Smith, Jenny O; Gill, Kanwar Rupinder S; Burdick, J Steven; Mallat, Damien; Wolfsen, Herbert C

2010-04-01

Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Multicenter, retrospective cohort study. Ten academic and community medical centers between 2006 and 2009. Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Complete eradication of luminal cancer and adverse events. Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Retrospective study design, short follow-up. Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All

Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer.

PubMed

Lin, Steven H; Zhang, Ning; Godby, Joy; Wang, Jingya; Marsh, Gary D; Liao, Zhongxing; Komaki, Ritsuko; Ho, Linus; Hofstetter, Wayne L; Swisher, Stephen G; Mehran, Reza J; Buchholz, Thomas A; Elting, Linda S; Giordano, Sharon H

2016-03-15

It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. © 2015 American Cancer Society.

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

PubMed

Shiraishi, Yutaka; Fang, Penny; Xu, Cai; Song, Juhee; Krishnan, Sunil; Koay, Eugene J; Mehran, Reza J; Hofstetter, Wayne L; Blum-Murphy, Mariela; Ajani, Jaffer A; Komaki, Ritsuko; Minsky, Bruce; Mohan, Radhe; Hsu, Charles C; Hobbs, Brian P; Lin, Steven H

2017-12-13

Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16-0.52; P < 0.0001). PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Shared susceptibility loci at 2q33 region for lung and esophageal cancers in high-incidence areas of esophageal cancer in northern China

PubMed Central

Song, Xin; Hu, Shou Jia; Lv, Shuang; Cheng, Rang; Zhang, Tang Juan; Han, Xue Na; Ren, Jing Li; Qi, Yi Jun

2017-01-01

Background Cancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population. Methods A total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson’s Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival. Results Four of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107–1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100–1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098–1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089–1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with

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

ClinicalTrials.gov

2017-10-17

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

The low IGFBP-3 level is associated with esophageal cancer patients: a meta-analysis.

PubMed

Song, Guiqin; Liu, Kang; Zhu, Xiaoyan; Yang, Xiaolin; Shen, Yuewu; Wang, Wan; Shi, Guidong; Li, Qing; Duan, Yi; Zhao, Yunxia; Feng, Gang

2016-12-15

Esophageal cancer was a vital cause of cancer-related mortality worldwide, and the insulin-like growth factor-binding proteins (IGFBPs) has been proved to be an important factor of multiple types of tumors. There is a controversy that whether the IGFBP-3 level is associated with the clinical pathological characteristics and overall survival of esophageal cancer patients. Herein, we aimed to comprehensively assess the association between the low IGFBP-3 level and the risk, overall survival and clinical pathological characteristics of esophageal cancer. We conducted a meta-analysis using seven eligible studies. The overall odds ratios (OR)/relative risk (RR) and their corresponding 95% confidence interval (CI) were calculated for each parameter. For the risk of esophageal cancer, the OR was 2.342 (p = 0.000), indicating that individuals with lower IGFBP-3 level were more likely to suffer from esophageal cancer, compared to those with relatively high IGFBP-3 level. With respect to the 3-year survival rate, the RR was 2.163 (p = 0.027), which demonstrated that esophageal cancer patients with low IGFBP-3 level had significantly lower 3-year survival rate; in terms of clinical pathological characteristics, significantly lower IGFBP-3 level was found for patients in all categories; for survival status, patients in low IGFBP-3 level are more likely to be in the dead survival status (OR = 4.480, p = 0.000). Our meta-analysis suggests that for esophageal cancer, the low IGFBP-3 level is associated with high cancer risk, poor prognosis, and unfavorable tumor stage and metastasis.

The incidence and mortality of esophageal cancer and their relationship to development in Asia.

PubMed

Pakzad, Reza; Mohammadian-Hafshejani, Abdollah; Khosravi, Bahman; Soltani, Shahin; Pakzad, Iraj; Mohammadian, Mahdi; Salehiniya, Hamid; Momenimovahed, Zohre

2016-01-01

Esophageal cancer is the most common cancer in less developed countries. It is necessary to understand epidemiology of the cancer for planning. The aim of this study was to evaluate the incidence and mortality of esophageal cancer, and its relationship with Human Development Index (HDI) and its components in Asia in 2012. This study was an Ecological study, which conducted based on GLOBOCAN project of WHO for Asian counters. We assess the correlation between standardized incidence rates (SIR) and standardized mortality rates (SMR) of esophageal cancer with HDI and its components with using of SPSS18. A total of 337,698 incidence (70.33% were males and 29.87% females. Sex ratio was 2.37) and 296,734 death (69.45% in men and 30.54% in women. The sex ratio was 2.27) esophageal cancer was recorded in Asian countries in 2012. Five countries with the highest SIR and SMR of esophageal cancer were Turkmenistan, Mongolia and Tajikistan, Bangladesh and China respectively. Correlation between HDI and SIR was -0.211 (P=0.159), in men -0.175 (P=0.244) and in women -0.231 (P=0.123). Also between HDI and SMR -0.250 (P=0.094) in men -0.226 (P=0.131) and in women -0.251 (P=0.037). The incidence of esophageal cancer is more in less developed and developing countries. Statistically significant correlation was not found between standardized incidence and mortality rates of esophageal cancer, and HDI and its dimensions, except for life expectancy at birth.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy.

PubMed

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-11-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929-1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

PubMed Central

Ozgen, Aytul; Hayran, Mutlu; Kahraman, Fatih

2012-01-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy. PMID:22915782

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

PubMed

Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

2017-06-01

Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

miR-34a inhibits the in vitro cell proliferation and migration in human esophageal cancer.

PubMed

Shi, Hui; Zhou, Shengluan; Liu, Junhua; Zhu, Jun; Xue, Jianhua; Gu, Luo; Chen, Yijiang

2016-05-01

Increasing studies demonstrate that reduced expression of miR-34a is involved in the initiation and progression of cancers, and it has been characterized as a tumor suppressor in various types of cancers. In present study, we investigated the expression and role of miR-34a in esophageal cancer. qRT-PCR assays were performed to analyze the expression of miR-34a in human esophageal cancer tissues and adjacent esophageal tissues. CCK8 assay, flow cytometry analysis and in vitro migration assays were performed to analyze the role of miR-34a in human esophageal cancer cell. MSP assay was performed to analyze the DNA methylation of the miR-34a promoter. The expression of miR-34a was down-regulated in human esophageal cancer tissues. miR-34a ectopic expression affected esophageal cancer cells survival, proliferation and capabilities of migration in vitro. p53 status was not correlated with miR-34a. Subsequently, aberrant DNA methylation of the miR-34a promoter was found in human esophageal cancer, and 5-AZA-dC inhibited DNA methylation of the miR-34a promoter. our data showed that miR-34a acted as a tumor suppressor in human esophageal cancer. Copyright © 2016. Published by Elsevier GmbH.

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.

Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

PubMed Central

Uemura, Norihisa; Kondo, Tadashi

2014-01-01

Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients (60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice. PMID:25133032

NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer: screening in 1969 patients with various cancers.

PubMed

Oshima, Yoko; Shimada, Hideaki; Yajima, Satoshi; Nanami, Tatsuki; Matsushita, Kazuyuki; Nomura, Fumio; Kainuma, Osamu; Takiguchi, Nobuhiro; Soda, Hiroaki; Ueda, Takeshi; Iizasa, Toshihiko; Yamamoto, Naoto; Yamamoto, Hiroshi; Nagata, Matsuo; Yokoi, Sana; Tagawa, Masatoshi; Ohtsuka, Seiko; Kuwajima, Akiko; Murakami, Akihiro; Kaneko, Hironori

2016-01-01

Although serum NY-ESO-1 antibodies (s-NY-ESO-1-Abs) have been reported in patients with esophageal carcinoma, this assay system has not been used to study a large series of patients with various other cancers. Serum samples of 1969 cancer patients [esophageal cancer (n = 172), lung cancer (n = 269), hepatocellular carcinoma (n = 91), prostate cancer (n = 358), gastric cancer (n = 313), colorectal cancer (n = 262), breast cancer (n = 365)] and 74 healthy individuals were analyzed using an originally developed enzyme-linked immunosorbent assay system for s-NY-ESO-1-Abs. The optical density cut-off value, determined as the mean plus three standard deviations for serum samples from the healthy controls, was fixed at 0.165. Conventional tumor markers were also evaluated in patients with esophageal carcinoma. The positive rate of s-NY-ESO-1-Abs in patients with esophageal cancer (31 %) was significantly higher than that in the other groups: patients with lung cancer (13 %), patients with hepatocellular carcinoma (11 %), patients with prostate cancer (10 %), patients with gastric cancer (10 %), patients with colorectal cancer (8 %), patients with breast cancer (7 %), and healthy controls (0 %). The positive rate of s-NY-ESO-1-Abs was comparable to that of serum p53 antibodies (33 %), squamous cell carcinoma antigen (36 %), carcinoembryonic antigen (26 %), and CYFRA 21-1 (18 %) and gradually increased with the tumor stage. The positive rate of s-NY-ESO-1-Abs was significantly higher in patients with esophageal cancer than in patients with the other types of cancers. On the basis of its high specificity and sensitivity, even in patients with stage I tumors, s-NY-ESO-1-Abs may be one of the first choices for esophageal cancer.

Nutrition therapy issues in esophageal cancer.

PubMed

Miller, Keith R; Bozeman, Matthew C

2012-08-01

Esophageal cancer has traditionally been a disease with poor long term outcomes in terms of both survival and quality of life. In combination with surgical and pharmacologic therapy, nutrition support has been demonstrated to improve patient tolerance of treatment, quality of life, and longterm outcomes. An aggressive multi-disciplinary approach is warranted with nutrition support remaining a cornerstone in management. Historically, nutrition support has focused on adequate caloric provision to prevent weight loss and allow for tolerance of treatment regimens. Alterations in metabolism occur in these patients making their use of available calories inefficient and the future of nutritional support may lie in the ability to alter this deranged metabolism. The purpose of this article is to review the current literature surrounding the etiology, treatment, and role of nutrition support in improving outcomes in esophageal cancer.

Biology of telomeres: importance in etiology of esophageal cancer and as therapeutic target.

PubMed

Pal, Jagannath; Gold, Jason S; Munshi, Nikhil C; Shammas, Masood A

2013-12-01

The purpose of this review is to highlight the importance of telomeres, the mechanisms implicated in their maintenance, and their role in the etiology as well as the treatment of human esophageal cancer. We will also discuss the role of telomeres in the maintenance and preservation of genomic integrity, the consequences of telomere dysfunction, and the various factors that may affect telomere health in esophageal tissue predisposing it to oncogenesis. There has been growing evidence that telomeres, which can be affected by various intrinsic and extrinsic factors, contribute to genomic instability, oncogenesis, as well as proliferation of cancer cells. Telomeres are the protective DNA-protein complexes at chromosome ends. Telomeric DNA undergoes progressive shortening with age leading to cellular senescence and/or apoptosis. If senescence/apoptosis is prevented as a consequence of specific genomic changes, continued proliferation leads to very short (ie, dysfunctional) telomeres that can potentially cause genomic instability, thus, increasing the risk for activation of telomere maintenance mechanisms and oncogenesis. Like many other cancers, esophageal cancer cells have short telomeres and elevated telomerase, the enzyme that maintains telomeres in most cancer cells. Homologous recombination, which is implicated in the alternate pathway of telomere elongation, is also elevated in Barrett's-associated esophageal adenocarcinoma. Evidence from our laboratory indicates that both telomerase and homologous recombination contribute to telomere maintenance, DNA repair, and the ongoing survival of esophageal cancer cells. This indicates that telomere maintenance mechanisms may potentially be targeted to make esophageal cancer cells static. The rate at which telomeres in healthy cells shorten is determined by a number of intrinsic and extrinsic factors, including those associated with lifestyle. Avoidance of factors that may directly or indirectly injure esophageal tissue

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

PubMed Central

Gao, Mai-cang; Jia, Xiao-di; Wu, Qi-fei; Cheng, Yan; Chen, Fen-rong; Zhang, Jun

2011-01-01

Aim: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). Methods: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. Results: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. Conclusion: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi. PMID:21468086

Failure-to-rescue in patients undergoing surgery for esophageal or gastric cancer.

PubMed

Busweiler, L A; Henneman, D; Dikken, J L; Fiocco, M; van Berge Henegouwen, M I; Wijnhoven, B P; van Hillegersberg, R; Rosman, C; Wouters, M W; van Sandick, J W

2017-10-01

Complex surgical procedures such as esophagectomy and gastrectomy for cancer are associated with substantial morbidity and mortality. The purpose of this study was to evaluate trends in postoperative morbidity, mortality, and associated failure-to-rescue (FTR), in patients who underwent a potentially curative resection for esophageal or gastric cancer in the Netherlands, and to investigate differences between the two groups. All patients with esophageal or gastric cancer who underwent a potentially curative resection, registered in the Dutch Upper GI Cancer Audit (DUCA) between 2011 and 2014, were included. Primary outcomes were (major) postoperative complications, postoperative mortality and FTR. To investigate groups' effect on the outcomes of interest a mixed model was used. Overall, 2644 patients with esophageal cancer and 1584 patients with gastric cancer were included in this study. In patients with gastric cancer, postoperative mortality (7.7% in 2011 vs. 3.8% in 2014) and FTR (38% in 2011 and 19% in 2014) decreased significantly over the years. The adjusted risk of developing a major postoperative complication was lower (OR 0.54; 95% CI 0.42-0.70), but the risk of FTR was higher (OR 1.85; 95% CI 1.05-3.27) in patients with gastric cancer compared to patients with esophageal cancer. Once a postoperative complication occurred, patients with gastric cancer were more likely to die compared to patients with esophageal cancer. Underlying mechanisms like patient selection, and differences in structure and organization of care should be investigated. Next to morbidity and mortality, failure-to-rescue should be considered as an important outcome measure after esophagogastric cancer resections. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Fruit Consumption Reduces the Risk of Esophageal Cancer in Yanting, People's Republic of China.

PubMed

Song, Qingkun; Zhao, Lin; Li, Jun; Ren, Jun

2015-05-01

This study aimed to investigate the contribution of fruit and family history to esophageal cancer, among residents with abnormal esophagus discovered in screening. The study was a frequency-matched case-control design in groups of normal esophagus, abnormal esophagus but not carcinoma, and esophageal squamous cell carcinoma. Odds ratio (OR) was estimated by unconditional logistic regression. Fruit intake (OR = 0.19, 95% CI = 0.06-0.56) and positive family history of esophageal cancer (OR = 3.87, 95% CI = 1.41-10.63) were associated with esophageal cancer compared to individuals with abnormal conditions of the esophagus. In individuals who consumed fruits at least once per week, the OR for family cancer history is reduced to a nonsignificant level (OR = 1.06, 95% CI = 0.07-15.91). In the individuals with abnormal esophagus at screening, fruit intake was possibly protective against esophageal cancer, even in the ones with positive family history. Local public health strategies should focus on the improvement in fruit intake. © 2014 APJPH.

Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors.

PubMed

Chiou, C C; Groll, A H; Gonzalez, C E; Callender, D; Venzon, D; Pizzo, P A; Wood, L; Walsh, T J

2000-08-01

Little is known about the epidemiology and clinical features of esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of esophageal candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of esophageal candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/microl), representing a frequency of EC of 8.0%. Concurrent oropharyngeal candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P<0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. EC in pediatric AIDS is a debilitating infection, which develops in the

The incidence and mortality of esophageal cancer and their relationship to development in Asia

PubMed Central

Pakzad, Reza; Mohammadian-Hafshejani, Abdollah; Khosravi, Bahman; Soltani, Shahin; Pakzad, Iraj; Mohammadian, Mahdi; Momenimovahed, Zohre

2016-01-01

Background Esophageal cancer is the most common cancer in less developed countries. It is necessary to understand epidemiology of the cancer for planning. The aim of this study was to evaluate the incidence and mortality of esophageal cancer, and its relationship with Human Development Index (HDI) and its components in Asia in 2012. Methods This study was an Ecological study, which conducted based on GLOBOCAN project of WHO for Asian counters. We assess the correlation between standardized incidence rates (SIR) and standardized mortality rates (SMR) of esophageal cancer with HDI and its components with using of SPSS18. Results A total of 337,698 incidence (70.33% were males and 29.87% females. Sex ratio was 2.37) and 296,734 death (69.45% in men and 30.54% in women. The sex ratio was 2.27) esophageal cancer was recorded in Asian countries in 2012. Five countries with the highest SIR and SMR of esophageal cancer were Turkmenistan, Mongolia and Tajikistan, Bangladesh and China respectively. Correlation between HDI and SIR was −0.211 (P=0.159), in men −0.175 (P=0.244) and in women −0.231 (P=0.123). Also between HDI and SMR −0.250 (P=0.094) in men −0.226 (P=0.131) and in women −0.251 (P=0.037). Conclusions The incidence of esophageal cancer is more in less developed and developing countries. Statistically significant correlation was not found between standardized incidence and mortality rates of esophageal cancer, and HDI and its dimensions, except for life expectancy at birth. PMID:26889482

Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

ClinicalTrials.gov

2018-03-05

Esophageal Cancer; Radiation Pneumonitis; Pulmonary Fibrosis; Respiratory Failure; Pneumonia; Surgery; Chemotherapy Effect; Radiation Fibrosis; Radiation Toxicity; Adenocarcinoma; Squamous Cell Carcinoma

Hot Food and Beverage Consumption and the Risk of Esophageal Cancer: A Meta-Analysis.

PubMed

Andrici, Juliana; Eslick, Guy D

2015-12-01

Esophageal cancer is a neoplasm with a poor prognosis. Its two histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have been associated with different risk factors. The possibility of an association between the consumption of hot food and beverages and esophageal cancer, especially ESCC, has long been suspected, presenting a potentially modifiable risk factor. A meta-analysis of existing observational studies was performed to provide a quantitative estimate of the risk of esophageal cancer associated with the consumption of hot food and drink. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to November 11, 2014. Pooled ORs and 95% CIs were calculated using a random effects model for the risk of esophageal cancer associated with the consumption of hot food and drink. Subgroup analyses were conducted for ESCC and EAC, as well as for studies that adjusted for tobacco smoking and alcohol consumption, two well-recognized risk factors for ESCC. Consumption of hot food and drink was associated with an increased risk of any esophageal cancer (OR=1.90, 95% CI=1.46, 2.48). Heterogeneity was observed. There was an increased risk of ESCC (OR=2.29, 95% CI=1.79, 2.93), which remained even after adjusting for significant confounding variables (OR=2.39, 95% CI=1.71, 3.33). The relationship was not significant for EAC. The consumption of hot food and beverages was associated with an increased risk of esophageal cancer, particularly ESCC. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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

A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandes, Annemarie, E-mail: Annemarie.fernandes@gmail.com; Berman, Abigail T.; Mick, Rosemarie

Purpose: Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. Methods and Materials: Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. Results: The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients receivedmore » concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. Conclusions: Our data demonstrate

A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer.

PubMed

Fernandes, Annemarie; Berman, Abigail T; Mick, Rosemarie; Both, Stefan; Lelionis, Kristi; Lukens, John N; Ben-Josef, Edgar; Metz, James M; Plastaras, John P

2016-05-01

Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients received concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control

Silencing NKD2 by Promoter Region Hypermethylation Promotes Esophageal Cancer Progression by Activating Wnt Signaling.

PubMed

Cao, Baoping; Yang, Weili; Jin, Yongshuai; Zhang, Meiying; He, Tao; Zhan, Qimin; Herman, James G; Zhong, Guanglin; Guo, Mingzhou

2016-11-01

Naked cuticle homolog 2 (NKD2) was found to be frequently methylated in human breast and gastric cancers. However, the epigenetic changes and mechanisms of NKD2 in human esophageal cancer remain unclear. Nine esophageal cancer cell lines and 154 cases of primary esophageal cancer samples were analyzed using methylation-specific polymerase chain reaction, immunohistochemical analysis, Western blot, and xenograft mouse models. Loss of NKD2 expression and complete methylation were found in KYSE150 and TE1 cells. Reduced NKD2 expression and partial methylation of the promoter region were observed in KYSE30, KYSE70, KYSE410, KYSE140, and COLO680 cells. High levels of NKD2 expression and unmethylation were detected in KYSE450 and TE8 cells. Reexpression of NKD2 was induced by 5-aza-2'-deoxycytidine in cells in which NKD2 was not expressed or cells in which NKD2 expression was reduced. NKD2 was methylated in 53.2% of human primary esophageal cancer samples (82 of 154), and promoter region hypermethylation was significantly associated with reduced expression of NKD2 (p < 0.01). NKD2 methylation was associated with tumor, node, and metastasis stage and lymph node metastasis (p < 0.01). Our results suggest that NKD2 is regulated by promoter region methylation and that methylation of NKD2 may serve as a prognostic marker in esophageal cancer. Our further studies demonstrate that NKD2 suppresses cell proliferation, colony formation, cell invasion, and migration and also induces G1/S checkpoint arrest in esophageal cancer cells. NKD2 suppressed xenograft tumor growth and inhibited Wnt signaling in human esophageal cancer cells. NKD2 is frequently methylated in human esophageal cancer, and the expression of NKD2 is regulated by promoter region methylation. NKD2 suppresses esophageal cancer progression by inhibiting Wnt signaling both in vitro and in vivo. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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.

Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.

PubMed

Hu, Li-Yu; Ku, Fan-Chen; Wang, Yen-Po; Shen, Cheng-Che; Hu, Yu-Wen; Yeh, Chiu-Mei; Chen, Pan-Ming; Chiang, Huey-Ling; Lu, Ti; Chen, Tzeng-Ji; Teng, Chung-Jen; Liu, Chia-Jen

2015-03-01

The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients. To assess the risk of comorbid anxiety and depressive disorders after the diagnosis of esophageal cancer compared with a matched cohort by using the Taiwan National Health Insurance Research Database (NHIRD). We conducted a retrospective study of 28,454 patients (14,227 patients with esophageal cancer and 14,227 matched patients) who were selected from the NHIRD. Patients were observed for a maximum of 12 years to determine the incidence of new-onset anxiety and depressive disorders for which antidepressants had been prescribed. A Cox regression analysis was performed to identify the risk factors associated with anxiety and depressive disorders in esophageal cancer patients. The cumulative incidence of anxiety and depressive disorders in the esophageal cancer patients was significantly higher than that in the matched cohort (P < .001). The adjusted hazard ratio (HR) was 2.24 (95 % confidence interval, CI = 1.95-2.56, P < .001) in the esophageal cancer cohort compared with the matched cohort. Independent risk factors for developing anxiety and depressive disorders among the patients with esophageal cancer included cirrhosis, cerebrovascular disease, and surgical treatment. Esophageal cancer may be a prominent risk factor for anxiety and depressive disorders. Based on our data, we suggest that attention should be focused on esophageal cancer patients with comorbid cirrhosis and cerebrovascular disease and those who have received surgical interventions.

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.

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.

Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks.

PubMed

Wu, Xuping; Smavadati, Shirin; Nordfjäll, Katarina; Karlsson, Krister; Qvarnström, Fredrik; Simonsson, Martin; Bergqvist, Michael; Gryaznov, Sergei; Ekman, Simon; Paulsson-Karlsson, Ylva

2012-12-01

Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1 week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Late esophageal toxicity after radiation therapy for head and neck cancer.

PubMed

Chen, Allen M; Li, Bao-Qing; Jennelle, Richard L S; Lau, Derick H; Yang, Claus C; Courquin, Jean; Vijayakumar, Srinivasan; Purdy, James A

2010-02-01

The aim of this study was to determine the incidence of esophageal toxicity after radiation therapy for head and neck cancer. The records of 211 patients treated by radiation therapy for head and neck cancer were reviewed to identify those with dysphagia lasting more than 90 days after therapy. Late toxicity criteria established by the Radiation Therapy Oncology Group were used to score the symptoms. The incidence of grade 3+ esophageal toxicity at 3 and 6 months was 30% and 19%, respectively. The rate of gastrotomy-tube dependence at 3 and 6 months was 20% and 11%, respectively. Hypopharyngeal and unknown primary site (p = .01, for both), T4 disease (p = .01), and the use of concurrent chemotherapy (p = .001) were associated with grade 3+ esophageal toxicity and stricture formation. A significant proportion of patients exhibit symptoms of esophageal toxicity after radiation therapy for head and neck cancer. Therefore, preventive strategies need further investigation. Copyright 2009 Wiley Periodicals, Inc.

Recurrence risk model for esophageal cancer after radical surgery.

PubMed

Lu, Jincheng; Tao, Hua; Song, Dan; Chen, Cheng

2013-10-01

The aim of the present study was to construct a risk assessment model which was tested by disease-free survival (DFS) of esophageal cancer after radical surgery. A total of 164 consecutive esophageal cancer patients who had undergone radical surgery between January 2005 and December 2006 were retrospectively analyzed. The cutpoint of value at risk (VaR) was inferred by stem-and-leaf plot, as well as by independent-samples t-test for recurrence-free time, further confirmed by crosstab chi-square test, univariate analysis and Cox regression analysis for DFS. The cutpoint of VaR was 0.3 on the basis of our model. The rate of recurrence was 30.3% (30/99) and 52.3% (34/65) in VaR <0.3 and VaR ≥0.3 (chi-square test, (χ) (2) =7.984, P=0.005), respectively. The 1-, 3-, and 5-year DFS of esophageal cancer after radical surgery was 70.4%, 48.7%, and 45.3%, respectively in VaR ≥0.3, whereas 91.5%, 75.8%, and 67.3%, respectively in VaR <0.3 (Log-rank test, (χ) (2) =9.59, P=0.0020), and further confirmed by Cox regression analysis [hazard ratio =2.10, 95% confidence interval (CI): 1.2649-3.4751; P=0.0041]. The model could be applied for integrated assessment of recurrence risk after radical surgery for esophageal cancer.

Recurrence risk model for esophageal cancer after radical surgery

PubMed Central

Tao, Hua; Song, Dan; Chen, Cheng

2013-01-01

Objective The aim of the present study was to construct a risk assessment model which was tested by disease-free survival (DFS) of esophageal cancer after radical surgery. Methods A total of 164 consecutive esophageal cancer patients who had undergone radical surgery between January 2005 and December 2006 were retrospectively analyzed. The cutpoint of value at risk (VaR) was inferred by stem-and-leaf plot, as well as by independent-samples t-test for recurrence-free time, further confirmed by crosstab chi-square test, univariate analysis and Cox regression analysis for DFS. Results The cutpoint of VaR was 0.3 on the basis of our model. The rate of recurrence was 30.3% (30/99) and 52.3% (34/65) in VaR <0.3 and VaR ≥0.3 (chi-square test, χ2 =7.984, P=0.005), respectively. The 1-, 3-, and 5-year DFS of esophageal cancer after radical surgery was 70.4%, 48.7%, and 45.3%, respectively in VaR ≥0.3, whereas 91.5%, 75.8%, and 67.3%, respectively in VaR <0.3 (Log-rank test, χ2 =9.59, P=0.0020), and further confirmed by Cox regression analysis [hazard ratio =2.10, 95% confidence interval (CI): 1.2649-3.4751; P=0.0041]. Conclusions The model could be applied for integrated assessment of recurrence risk after radical surgery for esophageal cancer. PMID:24255579

Expert consensus contouring guidelines for IMRT in esophageal and gastroesophageal junction cancer

PubMed Central

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.

2015-01-01

Purpose/Objective(s) Current guidelines for esophageal cancer contouring are derived from traditional two-dimensional fields based on bony landmarks, and do not provide sufficient anatomical detail to ensure consistent contouring for more conformal radiotherapy 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 CT simulation datasets and an accompanying diagnostic PET-CT were distributed to each expert, and he/she 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 generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results Kappa statistics indicated substantial agreement between panelists for each of the three test cases. A consensus CTV atlas was generated for the three 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 utilizing these guidelines may require modification in the future. PMID:26104943

Protective Effect of Dietary Calcium Intake on Esophageal Cancer Risk: A Meta-Analysis of Observational Studies.

PubMed

Li, Qianwen; Cui, Lingling; Tian, Yalan; Cui, Han; Li, Li; Dou, Weifeng; Li, Haixia; Wang, Ling

2017-05-18

Although several epidemiological studies have investigated the association between dietary calcium intake and the risk of esophageal cancer, the results are inconsistent. This study aimed to make a comprehensive evaluation regarding the association between calcium intake and risk of esophageal cancer through a meta-analysis approach. We searched for all relevant articles from the inception to April 2017, using PUBMED, EMBASE, and Web of Knowledge. The pooled odds ratio (ORs) with the 95% confidence interval (95% CI) for the highest versus the lowest categories of calcium intake was calculated using a Mantel-Haenszel fixed-effect model. In total, 15 articles reporting 17 studies including 3396 esophageal cancer cases and 346,815 controls were selected for the meta-analysis. By comparing the highest vs. the lowest levels of dietary calcium intake, we found that dietary calcium intake was inversely associated with the risk of esophageal cancer (OR = 0.80, 95% CI: 0.71-0.91, I ² = 33.6%). The subgroup analysis indicated that the protective function of dietary calcium intake were observed in esophageal squamous cell cancer, but not in esophageal adenocarcinoma in the studies conducted in Asia, but not those in Europe and America. In conclusion, our results suggest that higher dietary calcium intake is associated with a lower risk of esophageal cancer-especially esophageal squamous cell cancer-in Asian populations, though more data from prospective cohort studies are needed.

Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer?

PubMed

Beukema, Jannet C; van Luijk, Peter; Widder, Joachim; Langendijk, Johannes A; Muijs, Christina T

2015-01-01

In recent years several papers have been published on radiation-induced cardiac toxicity, especially in breast cancer patients. However, in esophageal cancer patients the radiation dose to the heart is usually markedly higher. To determine whether radiation-induced cardiac toxicity is also a relevant issue for this group, we conducted a review of the current literature. A literature search was performed in Medline for papers concerning cardiac toxicity in esophageal cancer patients treated with radiotherapy with or without chemotherapy. The overall crude incidence of symptomatic cardiac toxicity was as high as 10.8%. Toxicities corresponded with several dose-volume parameters of the heart. The most frequently reported complications were pericardial effusion, ischemic heart disease and heart failure. Cardiac toxicity is a relevant issue in the treatment of esophageal cancer. However, valid Normal Tissue Complication Probability models for esophageal cancer are not available at present. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of coriolus versicolor polysaccharide-B on the biological characteristics of human esophageal carcinoma cell line eca109.

PubMed

Wang, Dao-Feng; Lou, Ning; Li, Xiao-Dong

2012-09-01

To investigate the effect of Coriolus versicolor polysaccharide-B (CVPs-B) on the biological characteristics of human esophageal carcinoma cell line Eca109 in vitro. The cells of experimental group (EG) were cultured in DMEM with 10% FCS and 150µg/mL CVPs-B, the cells of control group (CG) were cultured in DMEM with 10% FCS without CVPs-B. MTT reduction assay was performed to detect the effect of CVPs-B on the proliferation of Eca109 cells after the compound was administrated in varying concentrations. The living conditions of the Eca109 cells were determined using trypan blue exclusion. Then, cell growth curves were drawn. Flow cytometry was performed to detect the effect of CVPs-B on the apoptosis and cell cycle of Eca109. In comparison with the CG, a marked decrease in the proliferation of Eca09 cells was observed in the EG, after incubation with CVPs-B. The survival rate of Eca09 cells decreased as the time of CVPs-B incubation prolonged. Comparing the cell cycles and apoptotic rates between the two groups, the proportions of cells in the G0/G1, S, and G2/M phases in the EG were found to be (68.4±3.7)%, (13.9±2.1)%, and (17.7±1.4)%, respectively, after 24 h incubation with CVPs-B. The cells had an apoptotic rate of (9.7±0.7)%. On the other hand, the proportions of the G0/G1, S, and G2/M cells of the CG were found to be (53.9±3.6)%, (26.6±2.8)%, and (19.5±2.3)%, respectively, with an apoptotic rate of (5.7±1.4)%. In comparison with the CG cells, significant cell growth in the G0/G1 phase was observed in the EG (P<0.05). Furthermore, a significant decrease in the number of cells in the S phase was observed (P<0.05) in the EG. CVPs-B can inhibit proliferation and enhance apoptosis of Eca109 cells and may be useful in the treatment of esophageal carcinoma.

Effect of Coriolus Versicolor Polysaccharide-B on the Biological Characteristics of Human Esophageal Carcinoma Cell Line Eca109

PubMed Central

Wang, Dao-feng; Lou, Ning; Li, Xiao-dong

2012-01-01

Objective To investigate the effect of Coriolus versicolor polysaccharide-B (CVPs-B) on the biological characteristics of human esophageal carcinoma cell line Eca109 in vitro. Methods The cells of experimental group (EG) were cultured in DMEM with 10% FCS and 150µg/mL CVPs-B, the cells of control group (CG) were cultured in DMEM with 10% FCS without CVPs-B. MTT reduction assay was performed to detect the effect of CVPs-B on the proliferation of Eca109 cells after the compound was administrated in varying concentrations. The living conditions of the Eca109 cells were determined using trypan blue exclusion. Then, cell growth curves were drawn. Flow cytometry was performed to detect the effect of CVPs-B on the apoptosis and cell cycle of Eca109. Results In comparison with the CG, a marked decrease in the proliferation of Eca09 cells was observed in the EG, after incubation with CVPs-B. The survival rate of Eca09 cells decreased as the time of CVPs-B incubation prolonged. Comparing the cell cycles and apoptotic rates between the two groups, the proportions of cells in the G0/G1, S, and G2/M phases in the EG were found to be (68.4±3.7)%, (13.9±2.1)%, and (17.7±1.4)%, respectively, after 24 h incubation with CVPs-B. The cells had an apoptotic rate of (9.7±0.7)%. On the other hand, the proportions of the G0/G1, S, and G2/M cells of the CG were found to be (53.9±3.6)%, (26.6±2.8)%, and (19.5±2.3)%, respectively, with an apoptotic rate of (5.7±1.4)%. In comparison with the CG cells, significant cell growth in the G0/G1 phase was observed in the EG (P<0.05). Furthermore, a significant decrease in the number of cells in the S phase was observed (P<0.05) in the EG. Conclusions CVPs-B can inhibit proliferation and enhance apoptosis of Eca109 cells and may be useful in the treatment of esophageal carcinoma. PMID:23691473

Incidence and risk factors of synchronous colorectal cancer in patients with esophageal cancer: an analysis of 480 consecutive colonoscopies before surgery.

PubMed

Yoshida, Naoya; Tamaoki, Yuka; Baba, Yoshifumi; Sakamoto, Yasuo; Miyamoto, Yuji; Iwatsuki, Masaaki; Shono, Takashi; Miyamoto, Hideaki; Imuta, Masanori; Kurashige, Junji; Sawayama, Hiroshi; Tokunaga, Ryuma; Watanabe, Masayuki; Sasaki, Yutaka; Yamashita, Yasuyuki; Baba, Hideo

2016-12-01

The precise incidence rates of multiple primary colorectal cancers in esophageal cancer patients are unknown. In total, 480 consecutive patients with esophageal cancers surgically resected in the Kumamoto University Hospital received preoperative total colonoscopy for the assessment of colorectal disease between April 2005 and February 2016. We retrospectively investigated the occurrence of synchronous colorectal cancer with esophageal cancer. In addition, we examined the risk factors for the incidence of multiple primary colorectal cancers. Of the 480 patients, 14 (2.9 %) had synchronous colorectal cancers, 13 had well-differentiated tubular adenocarcinomas, and 1 had papillary adenocarcinoma. Other 14 patients had metachronous colorectal cancer. The current incidence rates of synchronous and total (both synchronous and metachronous) colorectal cancers outnumbered those in normal healthy population and those in esophageal cancer patients which previously reported by The Japan Esophageal Society. The age ≥70 years (hazard ratio 4.82, 95 % confidence interval 1.473-15.78; p = 0.009) and Brinkman index ≥800 (hazard ratio 3.47, 95 % confidence interval 1.056-11.37; p = 0.040) were the independent risk factors for the incidence of synchronous colorectal cancer. They were also the independent risk factors for the incidence of total colorectal cancer. The results of the present study suggested that pretreatment screening with total colonoscopy is meaningful for patients with esophageal cancer, because the frequency of synchronous colorectal cancer was not negligible. Particularly, in patients >70 years and with history of heavy smoking, pretreatment colonoscopy might be necessary.

Cigarette Smoking and Risk of Lung Metastasis from Esophageal Cancer

PubMed Central

Abrams, Julian A.; Lee, Paul C.; Port, Jeffrey L.; Altorki, Nasser K.; Neugut, Alfred I.

2008-01-01

Background While extensive research has explored the impact of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer. Methods We performed a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association. Results We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39/53) were ever smokers, versus 47.8% (144/301) of patients without lung metastases (p=0.001) (summary OR 2.52, 95%CI 1.17-5.45; stratified by histology). Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR 1.89, 95%CI 0.80-4.46). Upper esophageal subsite (OR 4.71, 95%CI 1.20-18.5) but not histology (squamous OR 0.65,95%CI 0.27-1.60) was associated with lung metastasis. Compared to the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR 2.35, 95%CI 1.11-4.97). There was no association between liver metastasis and smoking (OR 0.88, 95%CI 0.42-1.83) Conclusions Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship appears to be site-specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome. PMID:18843013

Cigarette smoking and risk of lung metastasis from esophageal cancer.

PubMed

Abrams, Julian A; Lee, Paul C; Port, Jeffrey L; Altorki, Nasser K; Neugut, Alfred I

2008-10-01

Whereas extensive research has explored the effect of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer. We conducted a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association. We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39 of 53) were ever smokers, versus 47.8% (144 of 301) of patients without lung metastases [P=0.001; summary odds ratio (OR), 2.52; 95% confidence interval (95% CI), 1.17-5.45; stratified by histology]. Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR, 1.89; 95% CI, 0.80-4.46). Upper esophageal subsite (OR, 4.71; 95% CI, 1.20-18.5), but not histology (squamous OR 0.65,95% CI 0.27-1.60), was associated with lung metastasis. Compared with the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR, 2.35; 95% CI, 1.11-4.97). There was no association between liver metastasis and smoking (OR, 0.88; 95% CI, 0.42-1.83). Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship seems to be site specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome.

Assessment of safety and efficacy of an indigenous self-expandable fully covered esophageal metal stent for palliation of esophageal cancer.

PubMed

Padhan, R K; Nongthombam, S K; Venuthurimilli, A; Dhingra, R; Sahni, P; Garg, P K

2016-01-01

Patients with unresectable esophageal cancer require palliation for dysphagia. Placement of a self-expandable metal stent (SEMS) is the procedure of choice for palliation of dysphagia. To evaluate the safety and efficacy of an indigenous fully-covered SEMS in patients with esophageal cancer. Eligible patients with unresectable esophageal cancer requiring palliation for dysphagia were included in the study. An indigenous fully covered SEMS of appropriate length was placed under endoscopic and fluoroscopic guidance. Outcome measures assessed were adverse events and improvement in dysphagia. Twenty one patients (mean age 57.71±13.14 years; 17 males) were included. After stenting, dysphagia score decreased from 3.2+0.4 to 0.35+0.74 at 4 weeks. Adverse events included retrosternal pain, respiratory distress and aspiration pneumonia in 12, 2 and 1 patients respectively. Five patients required repeat stenting due to stent migration in 4 (following radiotherapy in 3) and tumour ingrowth in 1. There was primary stent malfunction in one patient. The median survival of patients was 140 (76-199) days, which was higher in those who received radiotherapy. The stent was reasonably safe and effective to relieve dysphagia due to unresectable esophageal cancer.

A genome-wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer.

PubMed

Liu, Wenjia; Zhang, Yiyang; Chen, Min; Shi, Liangliang; Xu, Lei; Zou, Xiaoping

2018-06-21

Esophageal cancer is one of the most common cancers and a leading cause of cancer-related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence-free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein-coding genes involve with many known biological processes, such as cell cycle and cell-cell adherens junction. Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer: A treatment planning comparison

PubMed Central

Yin, Li; Wu, Hao; Gong, Jian; Geng, Jian-Hao; Jiang, Fan; Shi, An-Hui; Yu, Rong; Li, Yong-Heng; Han, Shu-Kui; Xu, Bo; Zhu, Guang-Ying

2012-01-01

AIM: To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC). METHODS: Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported. RESULTS: Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs 7F 24.59 Gy and 9F 24.16 Gy) and V

Volumetric-modulated arc therapy vs. c-IMRT in esophageal cancer: a treatment planning comparison.

PubMed

Yin, Li; Wu, Hao; Gong, Jian; Geng, Jian-Hao; Jiang, Fan; Shi, An-Hui; Yu, Rong; Li, Yong-Heng; Han, Shu-Kui; Xu, Bo; Zhu, Guang-Ying

2012-10-07

To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC). Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported. Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs. 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs. 5F

Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth

PubMed Central

KANO, YOSHIHIRO; KONNO, MASAMITSU; OHTA, KATSUYA; HARAGUCHI, NAOTSUGU; NISHIKAWA, SHIMPEI; KAGAWA, YOSHINORI; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; OGAWA, HISATAKA; FUKUSUMI, TAKAHITO; NOGUCHI, YUKO; OZAKI, MIYUKI; KUDO, TOSHIHIRO; SAKAI, DAISUKE; SATOH, TAROH; ISHII, MASARU; MIZOHATA, EIICHI; INOUE, TAKESHI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

2013-01-01

Although esophageal cancer is highly heterogeneous and the involvement of epigenetic regulation of cancer stem cells is highly suspected, the biological significance of epigenetically modified molecules that regulate different subpopulations remains to be firmly established. Using esophageal cancer cells, we investigated the functional roles of the H3K4 demethylase Jumonji/Arid1b (Jarid1b) (Kdm5b/Plu-1/Rbp2-h1), an epigenetic factor that is required for continuous cell growth in melanoma. JARID1B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial marker expression. However, these inhibitory effects observed on tumor formation were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that JARID1B plays a role in maintaining cancer stem cells in the esophagus and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer. PMID:24649241

Clinicopathological Features of Cervical Esophageal Cancer: Retrospective Analysis of 63 Consecutive Patients Who Underwent Surgical Resection.

PubMed

Saeki, Hiroshi; Tsutsumi, Satoshi; Yukaya, Takafumi; Tajiri, Hirotada; Tsutsumi, Ryosuke; Nishimura, Sho; Nakaji, Yu; Kudou, Kensuke; Akiyama, Shingo; Kasagi, Yuta; Nakashima, Yuichiro; Sugiyama, Masahiko; Sonoda, Hideto; Ohgaki, Kippei; Oki, Eiji; Yasumatsu, Ryuji; Nakashima, Torahiko; Morita, Masaru; Maehara, Yoshihiko

2017-01-01

The objectives of this retrospective study were to elucidate the clinicopathological features and recent surgical results of cervical esophageal cancer. Cervical esophageal cancer has been reported to have a dismal prognosis. Accurate knowledge of the clinical characteristics of cervical esophageal cancer is warranted to establish appropriate therapeutic strategies. The clinicopathological features and treatment results of 63 consecutive patients with cervical esophageal cancer (Ce group) who underwent surgical resection from 1980 to 2013 were analyzed and compared with 977 patients with thoracic or abdominal esophageal cancer (T/A group) who underwent surgical resection during that time. Among the patients who received curative resection, the 5-year overall and disease-specific survival rates of the Ce patients were significantly better than those of the T/A patients (overall: 77.3% vs 46.5%, respectively, P = 0.0067; disease-specific: 81.9% vs 55.8%, respectively, P = 0.0135). Although total pharyngo-laryngo-esophagectomy procedures were less frequently performed in the recent period, the rate of curative surgical procedures was markedly higher in the recent period (2000-1013) than that in the early period (1980-1999) (44.4% vs 88.9%, P = 0.0001). The 5-year overall survival rate in the recent period (71.5%) was significantly better than that in the early period (40.7%, P = 0.0342). Curative resection for cervical esophageal cancer contributes to favorable outcomes compared with other esophageal cancers. Recent surgical results for cervical esophageal cancer have improved, and include an increased rate of curative resection and decreased rate of extensive surgery.

Esophageal Cancer: New Insights into a Heterogenous Disease.

PubMed

Krug, Sebastian; Michl, Patrick

2017-01-01

Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols. With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved. Several trials confirmed a survival benefit for perioperative chemotherapy or neoadjuvant chemoradiation, respectively, for patients with resectable locally advanced adenocarcinomas. However, the question of whether perioperative chemotherapy or neoadjuvant chemoradiation is more effective for the long-term survival in this population has yet to be fully elucidated. In SCCs, neoadjuvant chemoradiation followed by surgery or definitive chemoradiation in case of functional inoperability represent the preferred treatment options. Compared to neoadjuvant protocols, adjuvant chemotherapy or chemoradiation have only minor effects and are associated with enhanced toxicities. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming to modulate immune check-points and dual inhibition of HER2. In this "to-the-point" article, we review the current standard and summarize the most recent and encouraging therapeutic advances in esophageal cancer. Multimodal treatment approaches for esophageal cancer should be discussed in a multidisciplinary team based on histology, tumor localization, and patient performance status. Neoadjuvant chemoradiation is beneficial for patients with locally advanced SCC and adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ), with perioperative chemotherapy representing a valid

Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

PubMed

Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

2017-08-01

Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12,more » every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.« less

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.

miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4.

PubMed

Zhang, Y H; Wang, Q Q; Li, H; Ye, T; Gao, F; Liu, Y C

2016-06-03

Radiotherapy is one of the most important treatments for esophageal cancer, but radioresistance remains a major challenge. Previous studies have shown that microRNAs (miRNAs or miRs) are involved in human cancers. miR-124 has been widely reported in various cancers and it is intimately involved in proliferation, cell cycle regulation, apoptosis, migration, and invasion of cancer cells. The aim of this study was to explore the relationship between the miR-124/cyclin-dependent kinase 4 (CDK4) axis and the radiosensitivity of esophageal cancer cells. In this study, we identified the reduced expression of miR-124 in 18 paired esophageal cancer tissues compared to their matched normal tissues. In order to investigate the physiological role of miR-124 in esophageal cancer, the cell counting kit-8 (CCK-8) assay and wound healing assay were performed, and the results suggest that miR-124 overexpression decreases tumor growth and aggression. Next, we detected the effects of ectopic miR-124 expression on the apoptosis of an esophageal cancer cell line (TE-1) following radiotherapy. Using the CCK-8 assay and Hoechst 332528 stain, we found that ectopic expression of miR-124 led to a higher percentage of apoptotic cells. Finally, we identified that CDK4 is a direct target of miR-124 in TE-1 cells using target prediction algorithms and a luciferase reporter assay. Moreover, western blot assay confirmed that CDK4 was downregulated during miR-124 transfection. Taken together, we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4.

Cancer Stem Cell Radioresistance and Enrichment: Where Frontline Radiation Therapy May Fail in Lung and Esophageal Cancers

PubMed Central

Nguyen, Giang Huong; Murph, Mandi M.; Chang, Joe Y.

2011-01-01

Many studies have highlighted the role cancer stem cells (CSC) play in the development and progression of various types of cancer including lung and esophageal cancer. More recently, it has been proposed that the presence of CSCs affects treatment efficacy and patient prognosis. In reviewing this new area of cancer biology, we will give an overview of the current literature regarding lung and esophageal CSCs and radioresistance of CSC, and discuss the potential therapeutic applications of these findings. PMID:21603589

[A case-control study on the risk factors of esophageal cancer in Linzhou].

PubMed

Lu, J; Lian, S; Sun, X; Zhang, Z; Dai, D; Li, B; Cheng, L; Wei, J; Duan, W

2000-12-01

To explore the characteristics of prevalence and influencing factors on the genesis of esophageal cancer. A population-based 1:1 matched case-control study was conducted in Linzhou. A total number of 352 pairs of cases and controls matched on sex, age and neighborhoods. Data was analysed by SAS software to calculate the odds ratio of and to evaluate the relative risks. It was found that lower socio-economic status, environmental pollution around the residential areas, lampblack in room, lower body mass index (BMI), more pickled food intake, cigarette smoking, alcoholic drinking, vigor mental-trauma and depression were risk factors of esophageal cancer. It also showed that the subjects having had history of upper digestive tract operation, dysplasia of esophagus and family history of carcinoma markedly increased the risks of developing esophageal cancer. Esophageal cancer seemed to be resulted from the combination of genetic and environmental factor, hence called for of medical surveillance and comprehensive prevention.

Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.

PubMed

Meyer, Armando; Alexandre, Pedro Celso Braga; Chrisman, Juliana de Rezende; Markowitz, Steven B; Koifman, Rosalina Jorge; Koifman, Sergio

2011-03-01

Several studies suggest that agricultural workers are at higher risk to develop and die by certain types of cancer. Esophageal cancer is not commonly listed among these types. However, some recent studies indicated that if there is an association between agricultural working and esophageal cancer, it s more likely to be observed among workers highly exposed to pesticides. In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Cases were individuals from both genders, 30-59 years old, for whom basic cause of death was ascertained as cancer of the esophagus. For each case, one control was randomly selected from all possible controls for which the basic cause of death was ascertained as different from neoplasm and diseases of the digestive system. In addition, controls matched their cases by sex, age, year of death, and state of residence. Crude and adjusted odds ratios were then calculated to estimate the magnitude of the risk. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working. Copyright © 2010 Elsevier GmbH. All rights reserved.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

PubMed

Song, Guiqin; Liu, Kang; Yang, Xiaolin; Mu, Bo; Yang, Junbao; He, Lang; Hu, Xin; Li, Qiujiang; Zhao, Yunxia; Cai, Xiaoming; Feng, Gang

2017-03-14

Esophageal cancer is a highly aggressive malignancy with very poor overall prognosis. Given the strong clinical relevance of SATB1 in esophagus cancer and other cancers suggested by previous studies, the exact function of SATB1 in esophagus cancer development is still unknown. Here we showed that the knockdown of SATB1 in esophageal cancer cell lines diminished the cell proliferation, survival and invasion. Whole genome transcriptome analysis of SATB1 knockdown cells revealed the different gene expression profiles between TE-1 cells and MDA-MB-231 cells. Network analysis and functional experiments further identified FN1 and PDGFRB to be key downstream genes regulated by SATB1 in esophageal cancer cells. Importantly, FN1 and PDGFRB were found to be highly expressed in human esophageal cancer. In summary, we provided the first molecular evidence that SATB1 played an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

Perspectives of HER2-targeting in gastric and esophageal cancer.

PubMed

Gerson, James N; Skariah, Sam; Denlinger, Crystal S; Astsaturov, Igor

2017-05-01

The blockade of HER2 signaling has significantly improved the outlook for esophagogastric cancer patients. However, targeting HER2 still remains challenging due to complex biology of this receptor in gastric and esophageal cancers. Areas covered: Here, we review complex HER2 biology, current methods of HER2 testing and tumor heterogeneity of gastroesophageal cancer. Ongoing and completed clinical research data are discussed. Expert opinion: HER2 overexpression is a validated target in gastroesophageal cancer, with therapeutic implications resulting in prolonged survival when inhibited in the front-line setting. With standardized HER2 testing in gastro-esophageal cancer, the ongoing trials are testing newer agents and combinations including combination of anti-HER2 antibodies with immunotherapy. Clonal heterogeneity and emergence of resistance will challenge our approach to treating these patients beyond the frontline settings.

Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer.

PubMed

Khushalani, Nikhil I; Leichman, Cynthia Gail; Proulx, Gary; Nava, Hector; Bodnar, Lisa; Klippenstein, Donald; Litwin, Alan; Smith, Judy; Nava, Enriqueta; Pendyala, Lakshmi; Smith, Patrick; Greco, William; Berdzik, Joanne; Douglass, Harold; Leichman, Lawrence

2002-06-15

To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.

Effect of Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer.

PubMed

Van Daele, E; Ceelen, W; Boterberg, T; Varinl, O; Van Nieuwenhove, Y; Putte, D Van de; Geboes, K; Pattyn, P

2015-01-01

Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

Lapatinib in combination with paclitaxel plays synergistic antitumor effects on esophageal squamous cancer.

PubMed

Guo, Xiao-Fang; Li, Sai-Sai; Zhu, Xiao-Fei; Dou, Qiao-Hua; Liu, Duan

2018-06-16

Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), combined with paclitaxel on the esophageal squamous cancer. MTT assays were used to evaluate the effects of the combination of lapatinib and paclitaxel on the growth of esophageal squamous cancer cell lines (KYSE150, KYSE450, KYSE510 and TE-7). The activity of the combination of two agents on cell invasion, migration and apoptosis was measured by wound healing assay, transwell assay and Annexin V-FITC/PI stain assay. Western blot assay was used to analyze the effects of the two agents on the EGFR/HER2 signaling. The in vivo efficacy was evaluated in KYSE450 xenograft nude mouse model. The combination of lapatinib and paclitaxel was highly synergistic in inhibiting cell growth with a combination index of < 1, and suppressed significantly the invasion and migration capability of esophageal squamous cancer cells. Esophageal squamous cancer cells displayed increased rates of apoptosis after treatment with lapatinib plus paclitaxel. The phosphorylated EGFR and HER2 as well as the activation of downstream molecules MAPKs and AKT significantly decreased when exposed to lapatinib and paclitaxel. In vivo studies showed that the combination of two agents had greater antitumor efficacy than either agent alone. The combination of lapatinib with paclitaxel showed synergistic antitumor activity, suggesting their potential in treating patients with esophageal squamous cancer.

Effects of food insecurity on the women esophageal cancer in the Zanjan Province.

PubMed

Najafi, Amir

2018-01-01

Nowadays one of the principal challenges of any country is improving the chronic disease and cancers. One of the most important of cancers is esophageal cancer in Iran. No doubt, esophageal cancer is an outcome of the interaction and combination of different factors. Cancer of the esophagus is one of the most common causes of death in adults (especially women) in Iran, where the incidence of this cancer is among the highest in the world. The main aim of this cross-sectional study was to test the hypothesis that food insecurity could create esophageal cancer among women in Iran (Zanjan Province). The method of this paper has been based on the analytical and descriptive research using fuzzy cognitive maps (FCMs) method. The subjects were 580 women aged 40-70 years (150 women have esophageal cancer), and they are selected randomly in the Zanjan Province of Iran. The food insecurity (such as hunger and hidden hunger) in the Zanjan Province, according to the 24 h food-recall questionnaire was 23% and 38%, respectively. Only 39% of the study population was secure in terms of having access to all key nutrients. The accuracy of the questionnaire for screening for hunger in the population was 88.78%, respectively, and the corresponding value for hidden hunger was 83.4%. The average value of esophageal cancer predicted using fuzzy cognitive maps is equal to 75.43% (for 36 months). Our findings showed an association of food insecurity and body mass index (BMI) in the study population. Food insecurity increased the rate of underweight and decreased the rates of overweight and obesity.

Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function.

PubMed

Shi, Huijuan; Shi, Dongxuan; Wu, Yansong; Shen, Qiang; Li, Jing

2016-09-28

Qigesan (QGS), a well-known traditional Chinese medicinal formula, has long been used to treat patients with esophageal cancer. However, the anticancer mechanisms of action of QGS remain unknown. This study aims to determine whether QGS regulates gap junction (GJ) function and affects the invasiveness of esophageal cancer cells. Our results demonstrate that QGS markedly inhibits the migration and invasion of esophageal cancer cells in vitro. We further show that QGS enhances the function of GJ in esophageal cancer cells. We therefore hypothesized that enhanced connexin expression leads to enhanced GJ function and inhibition of metastasis. We found that QGS enhances expression of connexin 26 and connexin 43 in esophageal cancer cells. This study suggests that QGS increases GJ function via enhancing the expression of connexins, resulting in reduced esophageal cancer cell migration and invasion. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Flavonoid consumption and esophageal cancer among Black and White men in the United States

USDA-ARS?s Scientific Manuscript database

Flavonoids and proanthocyanidins are bioactive polyphenolic components of fruits and vegetables that may account for part of the protective effect of raw fruit and vegetable consumption in esophageal cancer. We studied the relationship between esophageal cancer and dietary proanthocyanidins, flavon...

Esophageal Cancer—Patient Version

Cancer.gov

The most common types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. These forms of esophageal cancer develop in some parts of the esophagus and are driven by genetic changes. Start here to find information on esophageal cancer treatment, causes and prevention, screening, research, and statistics.

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. © 2015 UICC.

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

PubMed Central

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

2016-01-01

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. PMID:27338463

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

Molecular Diagnostics in Esophageal and Gastric Neoplasms: 2018 Update.

PubMed

Zulfiqar, Muhammad; Bluth, Martin H; Bhalla, Amarpreet

2018-06-01

Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Recent advances in intensity modulated radiotherapy and proton therapy for esophageal cancer.

PubMed

Xi, Mian; Lin, Steven H

2017-07-01

Radiotherapy is an important component of the standard of care for esophageal cancer. In the past decades, significant improvements in the planning and delivery of radiation techniques have led to better dose conformity to the target volume and improved normal tissue sparing. Areas covered: This review focuses on the advances in radiotherapy techniques and summarizes the availably dosimetric and clinical outcomes of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, proton therapy, and four-dimensional radiotherapy for esophageal cancer, and discusses the challenges and future development of proton therapy. Expert commentary: Although three-dimensional conformal radiotherapy is the standard radiotherapy technique in esophageal cancer, the retrospectively comparative studies strongly suggest that the dosimetric advantage of IMRT over three-dimensional conformal radiotherapy can translate into improved clinical outcomes, despite the lack of prospective randomized evidence. As a novel form of conventional IMRT technique, volumetric modulated arc therapy can produce equivalent or superior dosimetric quality with significantly higher treatment efficiency in esophageal cancer. Compared with photon therapy, proton therapy has the potential to achieve further clinical improvement due to their physical properties; however, prospective clinical data, long-term results, and cost-effectiveness are needed.

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

PubMed

Burt, Bryan M; Groth, Shawn S; Sada, Yvonne H; Farjah, Farhood; Cornwell, Lorraine; Sugarbaker, David J; Massarweh, Nader N

2017-08-01

To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

A versatile nanoplatform for synergistic combination therapy to treat human esophageal cancer.

PubMed

Wang, Xin-Shuai; Kong, De-Jiu; Lin, Tzu-Yin; Li, Xiao-Cen; Izumiya, Yoshihiro; Ding, Xue-Zhen; Zhang, Li; Hu, Xiao-Chen; Yang, Jun-Qiang; Gao, She-Gan; Lam, Kit S; Li, Yuan-Pei

2017-06-01

One of the major goals of precision oncology is to promote combination therapy to improve efficacy and reduce side effects of anti-cancer drugs based on their molecular mechanisms. In this study, we aimed to develop and validate new nanoformulations of docetaxel (DTX) and bortezomib (BTZ) for targeted combination therapy to treat human esophageal cancer. By leveraging our versatile disulfide cross-linked micelles (DCMs) platform, we developed nanoformulations of DTX and BTZ (named DTX-DCMs and BTZ-DCMs). Their physical properties were characterized; their anti-cancer efficacies and mechanisms of action were investigated in a human esophageal cancer cell line in vitro. Furthermore, the in vitro anti-tumor activities of combination therapies (concurrent drug treatment, sequential drug treatment, and treatment using different ratios of the drugs) were examined in comparison with the single drug treatment and free drug strategies. These drug-loaded nanoparticles were spherical in shape and relatively small in size of approximately 20-22 nm. The entrapment efficiencies of DTX and BTZ into nanoparticles were 82.4% and 84.1%, respectively. The drug release rates of DTX-DCMs and BTZ-DCMs were sustained, and greatly increased in the presence of GSH. These nanodrugs were effectively internalized by KYSE30 esophageal cancer cells, and dose-dependently induced cell apoptosis. We further revealed a strong synergistic effect between DTX-DCMs and BTZ-DCMs against KYSE30 esophageal cancer cells. Sequential combination therapy with DTX-DCMs followed by BTZ-DCMs exhibited the best anti-tumor efficacy in vitro. This study demonstrates that DTX and BTZ could be successfully nanoformulated into disulfide cross-linked micelles. The nanoformulations of DTX and BTZ demonstrate an immense potential for synergistic combination therapy to treat human esophageal cancer.

A "TNM" classification system for cancer pain: the Edmonton Classification System for Cancer Pain (ECS-CP).

PubMed

Fainsinger, Robin L; Nekolaichuk, Cheryl L

2008-06-01

The purpose of this paper is to provide an overview of the development of a "TNM" cancer pain classification system for advanced cancer patients, the Edmonton Classification System for Cancer Pain (ECS-CP). Until we have a common international language to discuss cancer pain, understanding differences in clinical and research experience in opioid rotation and use remains problematic. The complexity of the cancer pain experience presents unique challenges for the classification of pain. To date, no universally accepted pain classification measure can accurately predict the complexity of pain management, particularly for patients with cancer pain that is difficult to treat. In response to this gap in clinical assessment, the Edmonton Staging System (ESS), a classification system for cancer pain, was developed. Difficulties in definitions and interpretation of some aspects of the ESS restricted acceptance and widespread use. Construct, inter-rater reliability, and predictive validity evidence have contributed to the development of the ECS-CP. The five features of the ECS-CP--Pain Mechanism, Incident Pain, Psychological Distress, Addictive Behavior and Cognitive Function--have demonstrated value in predicting pain management complexity. The development of a standardized classification system that is comprehensive, prognostic and simple to use could provide a common language for clinical management and research of cancer pain. An international study to assess the inter-rater reliability and predictive value of the ECS-CP is currently in progress.

Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer.

PubMed

Cui, Zhen; Tian, Ye; He, Bin; Li, Hongwei; Li, Duojie; Liu, Jingjing; Cai, Hanfei; Lou, Jianjun; Jiang, Hao; Shen, Xueming; Peng, Kaigui

2015-01-01

Radiation pneumonitis is one of the most severe complications of esophageal cancer. To explore the factors correlated to radiation pneumonitis induced by precise radiotherapy for elderly patients with esophageal cancer. The retrospective analysis was used to collect clinical data from 186 elderly patients with esophageal cancer. The incidence of radiation pneumonitis was observed, followed by statistical analysis through ANVON or multiple regression analysis. 27 in 186 cases of esophageal cancer suffered from radiation pneumonitis, with incidence of 14.52%. The single factor analysis showed that, Karnofsky performance status (KPS) score, chronic obstructive pulmonary disease, concurrent chemoradiotherapy, gross tumor volume (GTV) dose, lung V20, mean lung dose (MLD) and planning target volume (PTV) were associated with radiation pneumonitis. The logistic regression analysis indicated that, concurrent chemoradiotherapy, GTV dose, lung V20 and PTV were the independent factors of radiation pneumonitis. The concurrent chemoradiotherapy, GTV dose, lung V20, MLD and PTV are the major risk factors of radiation pneumonitis for elderly patients with esophageal cancer.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Advances in esophageal cancer: A new perspective on pathogenesis associated with long non-coding RNAs.

PubMed

Huang, Xiaomei; Zhou, Xi; Hu, Qing; Sun, Binyu; Deng, Mingming; Qi, Xiaolong; Lü, Muhan

2018-01-28

Esophageal cancer is a malignant digestive tract cancer with high mortality. Although studies have found that esophageal cancer is involved in a complex and important gene regulation network, the pathogenesis remains unclear. The recently described long non-coding RNAs (lncRNAs) are one effective part of the gene regulation network. However, in past decades, lncRNAs were thought to be "transcript noise" or "pseudogenes" and were thus ignored. Early studies indicated that lncRNAs play pivotal roles during evolution. However, in recent years, increasing research has revealed that many lncRNAs are associated with tumorigenesis. In particular, lncRNAs may act as important elements for epigenetic regulation, transcription, post-transcriptional regulation and post-translational modification of proteins. Additionally, they may be novel biomarkers for tumors and therapeutic targets in cancer. Here, we summarize the functions of lncRNAs in esophageal cancer, with an emphasis on lncRNA-mediated regulatory mechanisms that affect the biological characteristics of esophageal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Fokas, Emmanouil; Rödel, Claus

2015-10-01

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. 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. 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. Altogether, CRT constitutes an important tool in the treatment armamentarium for esophageal cancer. Further optimization of CRT using modern technology and imaging, targeted therapies, and newer chemotherapeutic agents is a major

Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer.

PubMed

Leszczynska, Katarzyna B; Dobrynin, Greg; Leslie, Rhea E; Ient, Jonathan; Boumelha, Adam J; Senra, Joana M; Hawkins, Maria A; Maughan, Tim; Mukherjee, Somnath; Hammond, Ester M

2016-11-01

Esophageal cancer has a persistently low 5-year survival rate and has recently been classified as a cancer of unmet need by Cancer Research UK. Consequently, new approaches to therapy are urgently required. Here, we tested the hypothesis that an ATR inhibitor, VX-970, used in combination with standard therapies for esophageal cancer could improve treatment outcome. Using esophageal cancer cell lines we evaluated the efficacy of combining VX-970 with cisplatin and carboplatin in vitro and with radiation in vitro and in vivo. Radiation experiments were also carried out in hypoxic conditions to mimic the tumor microenvironment. Combining VX-970 with cisplatin, carboplatin and radiation increased tumor cell kill in vitro. A significant tumor growth delay was observed when VX-970 was combined with radiotherapy in vivo. VX-970 is an effective chemo/radiosensitizer which could be readily integrated in the current treatment paradigm to improve the treatment response in esophageal cancer and we plan to test it prospectively in the forthcoming phase I dose escalation safety study combining the ATR inhibitor VX-970 with chemoradiotherapy in esophageal cancer (EudraCT number: 2015-003965-27). Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial.

PubMed

van Vulpen, Jonna K; Siersema, Peter D; van Hillegersberg, Richard; Nieuwenhuijzen, Grard A P; Kouwenhoven, Ewout A; Groenendijk, Richard P R; van der Peet, Donald L; Hazebroek, Eric J; Rosman, Camiel; Schippers, Carlo C G; Steenhagen, Elles; Peeters, Petra H M; May, Anne M

2017-08-18

Following esophagectomy, esophageal cancer patients experience a clinically relevant deterioration of health-related quality of life, both on the short- and long-term. With the currently growing number of esophageal cancer survivors, the burden of disease- and treatment-related complaints and symptoms becomes more relevant. This emphasizes the need for interventions aimed at improving quality of life. Beneficial effects of post-operative physical exercise have been reported in several cancer types, but so far comparable evidence in esophageal cancer patients is lacking. The aim of this study is to investigate effects of physical exercise on health-related quality of life in esophageal cancer patients following surgery. The Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study is a multicenter randomized controlled trial including 150 esophageal cancer patients after surgery with curative intent. Patients are randomly allocated to an exercise group or usual care group. The exercise group participates in a 12-week combined aerobic and resistance exercise program, supervised by a physiotherapist near the patient's home-address. In addition, participants in the exercise group are requested to be physically active for at least 30 min per day, every day of the week. Participants allocated to the usual care group are asked to maintain their habitual physical activity pattern. The primary outcome is health-related quality of life (EORTC-QLQ-C30). Secondary outcomes include esophageal cancer specific quality of life, fatigue, anxiety and depression, sleep quality, work-related factors, cardiorespiratory fitness (VO 2peak ), muscle strength, physical activity, malnutrition risk, anthropometry, blood markers, recurrence of disease and survival. All questionnaire outcomes, diaries and accelerometers are assessed at baseline, post-intervention (12 weeks post-baseline) and 24 weeks post-baseline. Physical fitness, anthropometry and blood markers are assessed

Meat consumption and risk of esophageal and gastric cancer in a large prospective study.

PubMed

Cross, Amanda J; Freedman, Neal D; Ren, Jiansong; Ward, Mary H; Hollenbeck, Albert R; Schatzkin, Arthur; Sinha, Rashmi; Abnet, Christian C

2011-03-01

Red and processed meats could increase cancer risk through several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During ∼10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas. Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile=1.79, 95% CI: 1.07-3.01, P for trend=0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR=1.44, 95% CI: 1.01-2.07, P for trend=0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR=1.35, 95% CI: 0.97-1.89, P for trend=0.022; HR=1.45, 95% CI: 0.99-2.12, P for trend=0.463; or HR=1.47, 95% CI: 0.99-2.20, P for trend=0.063, respectively). Benzo[a]pyrene, nitrate, and nitrite were not associated with esophageal or gastric cancer. We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer.

Cord blood-derived cytokine-induced killer cellular therapy plus radiation therapy for esophageal cancer: a case report.

PubMed

Wang, Liming; Huang, Shigao; Dang, Yazheng; Li, Ming; Bai, Wen; Zhong, Zhanqiang; Zhao, Hongliang; Li, Yang; Liu, Yongjun; Wu, Mingyuan

2014-12-01

Esophageal cancer is a serious malignancy with regards to mortality and prognosis. Current treatment options include multimodality therapy mainstays of current treatment including surgery, radiation, and chemotherapy. Cell therapy for esophageal cancer is an advancing area of research. We report a case of esophageal cancer following cord blood-derived cytokine-induced killer cell infusion and adjuvant radiotherapy. Initially, she presented with poor spirit, full liquid diets, and upper abdominal pain. Through cell therapy plus adjuvant radiotherapy, the patient remitted and was self-reliant. Recognition of this curative effect of sequent therapy for esophageal cancer is important to enable appropriate treatment. This case highlights cord blood-derived cytokine-induced killer cell therapy significantly alleviates the adverse reaction of radiation and improves the curative effect. Cell therapy plus adjuvant radiotherapy can be a safe and effective treatment for esophageal cancer.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J; Kligerman, S; Lu, W

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 changesmore » 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

Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA Microarray

PubMed Central

Wang, Hai-Tao; Kong, Jian-Ping; Ding, Fang; Wang, Xiu-Qin; Wang, Ming-Rong; Liu, Lian-Xin; Wu, Min; Liu, Zhi-Hua

2003-01-01

AIM: To obtain human esophageal cancer cell EC9706 stably expressed epithelial membrane protein-1 (EMP-1) with integrated eukaryotic plasmid harboring the open reading frame (ORF) of human EMP-1, and then to study the mechanism by which EMP-1 exerts its diverse cellular action on cell proliferation and altered gene profile by exploring the effect of EMP-1. METHODS: The authors first constructed pcDNA3.1/myc-his expression vector harboring the ORF of EMP-1 and then transfected it into human esophageal carcinoma cell line EC9706. The positive clones were analyzed by Western blot and RT-PCR. Moreover, the cell growth curve was observed and the cell cycle was checked by FACS technique. Using cDNA microarray technology, the authors compared the gene expression pattern in positive clones with control. To confirm the gene expression profile, semi-quantitative RT-PCR was carried out for 4 of the randomly picked differentially expressed genes. For those differentially expressed genes, classification was performed according to their function and cellular component. RESULTS: Human EMP-1 gene can be stably expressed in EC9706 cell line transfected with human EMP-1. The authors found the cell growth decreased, among which S phase was arrested and G1 phase was prolonged in the transfected positive clones. By cDNA microarray analysis, 35 genes showed an over 2.0 fold change in expression level after transfection, with 28 genes being consistently up-regulated and 7 genes being down-regulated. Among the classified genes, almost half of the induced genes (13 out of 28 genes) were related to cell signaling, cell communication and particularly to adhesion. CONCLUSION: Overexpression of human EMP-1 gene can inhibit the proliferation of EC9706 cell with S phase arrested and G1 phase prolonged. The cDNA microarray analysis suggested that EMP-1 may be one of regulators involved in cell signaling, cell communication and adhesion regulators. PMID:12632483

Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA Microarray.

PubMed

Wang, Hai-Tao; Kong, Jian-Ping; Ding, Fang; Wang, Xiu-Qin; Wang, Ming-Rong; Liu, Lian-Xin; Wu, Min; Liu, Zhi-Hua

2003-03-01

To obtain human esophageal cancer cell EC9706 stably expressed epithelial membrane protein-1 (EMP-1) with integrated eukaryotic plasmid harboring the open reading frame (ORF) of human EMP-1, and then to study the mechanism by which EMP-1 exerts its diverse cellular action on cell proliferation and altered gene profile by exploring the effect of EMP-1. The authors first constructed pcDNA3.1/myc-his expression vector harboring the ORF of EMP-1 and then transfected it into human esophageal carcinoma cell line EC9706. The positive clones were analyzed by Western blot and RT-PCR. Moreover, the cell growth curve was observed and the cell cycle was checked by FACS technique. Using cDNA microarray technology, the authors compared the gene expression pattern in positive clones with control. To confirm the gene expression profile, semi-quantitative RT-PCR was carried out for 4 of the randomly picked differentially expressed genes. For those differentially expressed genes, classification was performed according to their function and cellular component. Human EMP-1 gene can be stably expressed in EC9706 cell line transfected with human EMP-1. The authors found the cell growth decreased, among which S phase was arrested and G1 phase was prolonged in the transfected positive clones. By cDNA microarray analysis, 35 genes showed an over 2.0 fold change in expression level after transfection, with 28 genes being consistently up-regulated and 7 genes being down-regulated. Among the classified genes, almost half of the induced genes (13 out of 28 genes) were related to cell signaling, cell communication and particularly to adhesion. Overexpression of human EMP-1 gene can inhibit the proliferation of EC9706 cell with S phase arrested and G1 phase prolonged. The cDNA microarray analysis suggested that EMP-1 may be one of regulators involved in cell signaling, cell communication and adhesion regulators.

Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

PubMed

Cao, Yin; Xiang, JianBo; Qian, Nong; Sun, SuPing; Hu, LiJun; Yuan, YongGui

2015-01-01

To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

PubMed

Dipetrillo, Thomas; Suntharalingam, Mohan; Ng, Thomas; Fontaine, Jacques; Horiba, Naomi; Oldenburg, Nicklas; Perez, Kimberly; Birnbaum, Ari; Battafarano, Richard; Burrows, Whitney; Safran, Howard

2012-02-01

To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer. Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Forty patients were enrolled, 37 patients with adenocarcinoma and 3 patients with squamous cell cancer. The treatment-related grade 3 nonhematologic toxicities included esophagitis (7%), nausea (7%), and fatigue (5%). Three patients with clinical endoscopic CR (2 with squamous cell cancer) refused surgery. Twelve of the remaining 37 patients (32%) had a pathologic CR. The 12 patients with pathologic CR all had adenocarcinoma. PPX, cisplatin, and concurrent radiation are well tolerated, easily administered regimen for esophageal cancer with a low incidence of significant esophagitis and a high pathologic CR rate consistent with the preclinical data of PPX and radiation.

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.

Esophageal Cancer Treatment Is Underutilized Among Elderly Patients in the USA.

PubMed

Molena, Daniela; Stem, Miloslawa; Blackford, Amanda L; Lidor, Anne O

2017-01-01

Large numbers of elderly patients in the USA receive no treatment for esophageal cancer, despite evidence that multimodality treatment can increase survival. Our goal is to identify factors that may contribute to lack of treatment. Using Surveillance Epidemiology and End Results (SEER)-Medicare Linked Database (2001-2009), we identified regional esophageal cancer patients ≥65 years old. Treatment was defined as receiving any medical or surgical therapy for esophageal cancer. Logistic regression analysis was performed to identify factors associated with failure to receive treatment. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox proportional hazard model. There were 5072 patients (median age, 75 years; interquartile range (IQR), 71-81 years). Majority were treated with definitive chemoradiation (48.49 %). Factors associated with lack of treatment included West geographic region and ≥80 years old. Patients who received therapy had better OS (log-rank, p < 0.001). Compared with treated patients, non-treated patients had worse adjusted OS (HR, 1.43; 95 % confidence interval (CI), 1.33-1.55; p < 0.001). Elderly patients with locally advanced esophageal cancer who received treatment had improved 5-year survival compared with patients without treatment. Disparities in utilization of treatment are associated with regional and socioeconomic factors, not presence of comorbidities.

Radiation therapy and esophageal cancer.

PubMed

Shridhar, Ravi; Almhanna, Khaldoun; Meredith, Kenneth L; Biagioli, Matthew C; Chuong, Michael D; Cruz, Alex; Hoffe, Sarah E

2013-04-01

Squamous cell carcinoma and adenocarcinoma account for more than 90% of all esophageal cancer cases. Although the incidence of squamous cell carcinoma has declined, the incidence of adenocarcinoma has risen due to increases in obesity and gastroesophageal reflux disease. The authors examine the role of radiation therapy alone (external beam and brachytherapy) for the management of esophageal cancer or combined with other modalities. The impact on staging and appropriate stratification of patients referred for curative vs palliative intent with modalities is reviewed. The authors also explore the role of emerging radiation technologies. Current data show that neoadjuvant chemoradiotherapy followed by surgical resection is the accepted standard of care, with 3-year overall survival rates ranging from 30% to 60%. The benefit of adjuvant radiation therapy is limited to patients with node-positive cancer. The survival benefit of surgical resection after chemoradiotherapy remains controversial. External beam radiation therapy alone results in few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. Brachytherapy can provide better long-term palliation of dysphagia than metal stent placement. Although three-dimensional conformal treatment planning is the accepted standard, the roles of IMRT and proton therapy are evolving and potentially reduce adverse events due to better sparing of normal tissue. Future directions will evaluate the benefit of induction chemotherapy followed by chemoradiotherapy, the role of surgery in locally advanced disease, and the identification of responders prior to treatment based on microarray analysis.

[Remission of acquired hemophilia A following radiation therapy for esophageal cancer].

PubMed

Yanagisawa, Kunio; Ogawa, Yoshiyuki; Mitsui, Takeki; Noguchi, Hiroyuki; Shimizu, Hiroaki; Ishizaki, Takuma; Handa, Hiroshi; Ieko, Masahiro; Ichinose, Akitada; Nojima, Yoshihisa

2016-04-01

Although acquired hemophilia A (AHA) often develops in patients with neoplasms, there are few reports on the efficacy of radiation therapy during the bleeding phase of AHA in the prior literature. We herein present a case of AHA experiencing remission soon after radiation therapy for esophageal cancer. A man in his seventies, who had a history of radical nephrectomy for left renal cell carcinoma, received a diagnosis of esophageal cancer. Three months later, he noticed a right thigh hematoma, and was transferred to our hospital. Laboratory data revealed a marked reduction of coagulation factor VIII (FVIII) activity at 0.9% and the inhibitor to FVIII was detected in his serum at 21.8 BU/ml. Under a diagnosis of AHA, the patient received high-dose oral prednisolone, which failed to achieve disease remission. He then underwent radiation therapy to eradicate the underlying esophageal cancer. Despite tapering of the prednisolone dosage, FVIII inhibitor declined to undetectable levels. In this case, radiation therapy for the underlying cancer was associated with achieving complete remission of AHA.

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis.

PubMed

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity.

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takeda, Ken; Nemoto, Kenji; Saito, Haruo

2005-07-01

Purpose: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. Methods and Materials: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. Amore » median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. Results: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage

Medical expenditure for esophageal cancer in China: a 10-year multicenter retrospective survey (2002-2011).

PubMed

Guo, Lan-Wei; Huang, Hui-Yao; Shi, Ju-Fang; Lv, Li-Hong; Bai, Ya-Na; Mao, A-Yan; Liao, Xian-Zhen; Liu, Guo-Xiang; Ren, Jian-Song; Sun, Xiao-Jie; Zhu, Xin-Yu; Zhou, Jin-Yi; Gong, Ji-Yong; Zhou, Qi; Zhu, Lin; Liu, Yu-Qin; Song, Bing-Bing; Du, Ling-Bin; Xing, Xiao-Jing; Lou, Pei-An; Sun, Xiao-Hua; Qi, Xiao; Wu, Shou-Ling; Cao, Rong; Lan, Li; Ren, Ying; Zhang, Kai; He, Jie; Zhang, Jian-Gong; Dai, Min

2017-09-07

Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02% of the overall expenditure. These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Study on chemotherapeutic sensitizing effect of nimotuzumab on different human esophageal squamous carcinoma cells.

PubMed

Yang, Xiaoyu; Ji, Yinghua; Kang, Xiaochun; Chen, Meiling; Kou, Weizheng; Jin, Cailing; Lu, Ping

2016-02-01

Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5-fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P<0.05), but not statistically significant for EC9706 (P>0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P<0.05), but not on in the EC1 chemotherapy group (P>0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1

Hepatic radiation injury mimicking metastasis in distal esophageal cancer.

PubMed

Demey, Karel; Van Veer, Hans; Nafteux, Philippe; Deroose, Christophe M; Haustermans, Karin; Coolen, Johan; Vandecaveye, Vincent; Coosemans, Willy; Van Cutsem, Eric

2017-08-01

A new hypermetabolic lesion on 18 FDG-PET/CT after neo-adjuvant chemoradiotherapy for distal esophageal cancer can be a hepatic metastasis and should be examined carefully before esophagectomy. We present a case of acute and nodular radiation-induced injury of the left liver after neo-adjuvant chemoradiotherapy for distal esophageal cancer, which resembles a hepatic metastasis on 18 FDG-PET/CT. Acute and nodular radiation hepatitis (RH) can be a potential cause of false-positive findings of malignancy and therefore exclude patients who could benefit from esophagectomy. 18 FDG-PET/CT images should therefore carefully be interpreted and compared with the radiation beams, dose distribution and eventually clarified by DW-MR imaging.

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis

PubMed Central

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity. PMID:28442917

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis.

PubMed

Xu, Wei-Yu; Yang, Xiao-Bo; Wang, Wen-Qin; Bai, Yi; Long, Jun-Yu; Lin, Jian-Zhen; Xiong, Jian-Ping; Zheng, Yong-Chang; He, Xiao-Dong; Zhao, Hai-Tao; Sang, Xin-Ting

2018-05-21

To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC). We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English. A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400 (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, P = 0.000). Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.

Fatal hemoptysis in patients with advanced esophageal cancer treated with apatinib

PubMed Central

Wang, Wei; Zhang, Lin; Xie, Yan; Zhen, Tianchang; Su, Gongzhang; Zang, Qi

2018-01-01

Targeted therapy is commonly used for treating advanced malignant tumors. Compared with cytotoxic drugs, targeted drugs have the characteristics of good curative results, less adverse effects, and convenient oral administration. Hence, they are especially suitable for patients with cancer who are not able to tolerate chemotherapy. Anti-angiogenic therapy can achieve the objective by inhibiting the formation of new blood vessels in tumors. Apatinib is a novel tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2. It has been proven to be effective and safe in treating patients with gastric carcinoma and gastroesophageal junction carcinoma. So far, no reports are available on the treatment of esophageal cancer with apatinib. Two patients with advanced esophageal cancer were treated with oral apatinib because of their poor physical condition. After treatment, the dyspnea symptoms disappeared and quality of life significantly improved. Chest computed tomography showed massive necrosis of tumor tissues in each patient. The tumors significantly reduced and a cavity was formed locally in each patient. However, both patients died of massive hemoptysis, probably due to the rupture of the bronchial artery eroded by tumors. The results indicated that apatinib was effective in treating some patients with advanced esophageal cancer, and adverse effects were controllable. However, doctors should choose appropriate candidates according to apatinib’s indications. In addition, the use of apatinib should be carefully controlled for patients with esophageal cancer, especially in those with large vessels and trachea or bronchus eroded by tumor, so as to avoid or reduce the occurrence of fatal hemorrhage. PMID:29765235

Fatal hemoptysis in patients with advanced esophageal cancer treated with apatinib.

PubMed

Wang, Wei; Zhang, Lin; Xie, Yan; Zhen, Tianchang; Su, Gongzhang; Zang, Qi

2018-01-01

Targeted therapy is commonly used for treating advanced malignant tumors. Compared with cytotoxic drugs, targeted drugs have the characteristics of good curative results, less adverse effects, and convenient oral administration. Hence, they are especially suitable for patients with cancer who are not able to tolerate chemotherapy. Anti-angiogenic therapy can achieve the objective by inhibiting the formation of new blood vessels in tumors. Apatinib is a novel tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2. It has been proven to be effective and safe in treating patients with gastric carcinoma and gastroesophageal junction carcinoma. So far, no reports are available on the treatment of esophageal cancer with apatinib. Two patients with advanced esophageal cancer were treated with oral apatinib because of their poor physical condition. After treatment, the dyspnea symptoms disappeared and quality of life significantly improved. Chest computed tomography showed massive necrosis of tumor tissues in each patient. The tumors significantly reduced and a cavity was formed locally in each patient. However, both patients died of massive hemoptysis, probably due to the rupture of the bronchial artery eroded by tumors. The results indicated that apatinib was effective in treating some patients with advanced esophageal cancer, and adverse effects were controllable. However, doctors should choose appropriate candidates according to apatinib's indications. In addition, the use of apatinib should be carefully controlled for patients with esophageal cancer, especially in those with large vessels and trachea or bronchus eroded by tumor, so as to avoid or reduce the occurrence of fatal hemorrhage.

Apigenin induced apoptosis in esophageal carcinoma cells by destruction membrane structures.

PubMed

Zhu, Haiyan; Jin, Hua; Pi, Jiang; Bai, Haihua; Yang, Fen; Wu, Chaomin; Jiang, Jinhuan; Cai, Jiye

2016-07-01

Apigenin has shown to have killing effects on some kinds of solid tumor cells. However, the changes in cell membrane induced by apigenin on subcellular- or nanometer-level were still unclear. In this work, human esophageal cancer cells (EC9706 and KYSE150 cells) were employed as cell model to detect the cytotoxicity of apigenin, including cell growth inhibition, apoptosis induction, membrane toxicity, etc. MTT assay showed that apigenin could remarkably inhibit the growth and proliferation in both types of cells. Annexin V/PI-based flow cytometry analysis showed that the cytotoxic effects of apigenin in KYSE150 cells were mainly through early apoptosis induction, while in EC9706 cells, necrosis, and apoptosis were both involved in cell death. The morphological and ultrastructural properties induced by apigenin were investigated at single cellular- or nanometer-level using atomic force microscopy (AFM). Additionally, lactate dehydrogenase (LDH) leakage was measured to assess the changes in membrane permeability. The results indicated that apigenin increased the membrane permeability and caused leakage of LDH, which was consistent with damages on membrane ultrastructure detected by AFM. Therefore, membrane toxicity, including membrane ultrastructure damages and enhanced membrane permeability, played vital roles in apigenin induced human esophageal cancer cell apoptosis. SCANNING 38:322-328, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

PubMed

Nakamura, Kenichi; Yoshida, Naoya; Baba, Yoshifumi; Kosumi, Keisuke; Uchihara, Tomoyuki; Kiyozumi, Yuki; Ohuchi, Mayuko; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Sakamoto, Yasuo; Watanabe, Masayuki; Baba, Hideo

2017-06-01

The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

Optoacoustic imaging of tissue blanching during photodynamic therapy of esophageal cancer

NASA Astrophysics Data System (ADS)

Jacques, Steven L.; Viator, John A.; Paltauf, Guenther

2000-05-01

Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

Comparing treatment plan in all locations of esophageal cancer: volumetric modulated arc therapy versus intensity-modulated radiotherapy.

PubMed

Lin, Jang-Chun; Tsai, Jo-Ting; Chang, Chih-Chieh; Jen, Yee-Min; Li, Ming-Hsien; Liu, Wei-Hsiu

2015-05-01

The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations.This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume.In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques.IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted.

The outcomes of esophageal and gastric cancer treatments in a retrospective study, single center experience.

PubMed

Alimoghaddam, Kamran; Jalali, Arash; Aliabadi, Leyla Sharifi; Ghaffari, Fatemeh; Maheri, Roghieh; Eini, Ezzat; Mashhadireza, Maryam; Mousavi, Seied Asadollah; Bahar, Babak; Jahani, Mohammad; Ghavamzadeh, Ardeshir

2014-01-01

Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients. In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011. The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 - 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 - 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 - 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 - 67.3%), 32.8% (95% CI: 22.1 - 48.7%), and 56.7% (95% CI: 50.1 - 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 - 69.8%), 39.5% (95 CI: 28.1 - 55.5%), and 68.2% (95% CI: 61.8 - 75.3%), respectively (p < 0.001). Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease. Cancer of the GEJ has a poor prognosis compared to

Combined antegrade and retrograde esophageal dilation for head and neck cancer-related complete esophageal stenosis.

PubMed

Goguen, Laura A; Norris, Charles M; Jaklitsch, Michael T; Sullivan, Christopher A; Posner, Marshall R; Haddad, Robert I; Tishler, Roy B; Burke, Elaine; Annino, Donald J

2010-02-01

Assess the safety and efficacy of combined antegrade and retrograde esophageal dilation (CARD) for complete esophageal stenosis following head and neck cancer (HNC) treatment. Review HNC dysphagia management. Retrospective review of all patients undergoing CARD following HNC treatment between May 2001 and September 2008. Forty-five patients were identified for review. Parameters assessed included: ability to obtain intraoperative esophageal patency, complications, number of dilations required, diet, and gastric tube (GT) status. Factors associated with dilation failure were analyzed. Intraoperative esophageal patency was obtained in 91% of patients. Median number of all dilations per patient was three. Median number of CARDs per patient was one. Resumption of oral intake occurred in 36/45 (80%). Diet results included: regular or soft diet 32/45 (71%), GT removal 27/45 (60%), and GT dependence with nothing by mouth 9/45 (20%). Laryngeal and pharyngeal stenosis, radionecrosis, tracheotomy dependence, and elongated stenosis were associated with dilation failure. Complications occurred in 18/63 (29%) CARD procedures: eight pneumomediastinum, seven GT site problems, two esophageal perforations, and one pharyngeal infection. All complications resolved spontaneously or with minimal interventions. CARD was safe and effective. Intraoperative patency was achieved in 91% of patients. Eighty percent resumed oral intake. The majority of patients had their GTs removed and resumed a soft or regular diet. Dilation failure was associated with laryngeal, pharyngeal, and excessively long esophageal stenosis, often resulting from radionecrosis. Complications were minor. CARD should be considered before relegating patients with complete esophageal stenosis to chronic GT dependence or subjecting them to laryngopharyngo esophagectomy.

In silico dissection of miRNA targetome polymorphisms and their role in regulating miRNA-mediated gene expression in esophageal cancer.

PubMed

Nariman-Saleh-Fam, Ziba; Bastami, Milad; Somi, Mohammad Hossein; Samadi, Naser; Abbaszadegan, Mohammad Reza; Behjati, Farkhondeh; Ghaedi, Hamid; Tavakkoly-Bazzaz, Javad; Masotti, Andrea

2016-12-01

Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribution of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer.

Baseline measure of health-related quality of life (Functional Assessment of Cancer Therapy-Esophagus) is associated with overall survival in patients with esophageal cancer.

PubMed

Kidane, Biniam; Sulman, Joanne; Xu, Wei; Kong, Qin Quinn; Wong, Rebecca; Knox, Jennifer J; Darling, Gail E

2016-06-01

Functional Assessment of Cancer Therapy-Esophagus is a health-related quality of life instrument validated in patients with esophageal cancer. It is composed of a general component and an esophageal cancer subscale. Our objective was to determine whether the baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores are associated with survival in patients with stage II and III cancer of the gastroesophageal junction or thoracic esophagus. Data from 4 prospective studies in Canadian academic hospitals were combined. These included consecutive patients with stage II and III esophageal cancer who received neoadjuvant therapy followed by surgery or chemoradiation/radiation alone. All patients completed baseline Functional Assessment of Cancer Therapy-Esophagus. Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores were dichotomized on the basis of median scores. Cox regression analyses were performed. There were 207 patients treated between 1996 and 2014. Mean age was 61 ± 10.6 years. Approximately 69.6% of patients (n = 144) had adenocarcinoma. All patients had more than 9 months of follow-up. In patients with stage II and III, 93 deaths were observed. When treated as continuous variables, baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were associated with survival with hazard ratios of 0.89 (95% confidence interval [CI], 0.81-0.96; P = .005) and 0.68 (95% CI, 0.56-0.82; P < .001), respectively. When dichotomized, they were also associated with survival with a hazard ratio of 0.58 (95% CI, 0.38-0.89; P = .01) and 0.43 (95% CI, 0.28-0.67; P < .001), respectively. In patients with stage II and III esophageal cancer being considered for therapy, higher baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were independently associated with longer survival, even after adjusting for age, stage, histology, and

Challenges to "Classic" Esophageal Candidiasis: Looks Are Usually Deceiving.

PubMed

Alsomali, Mohammed I; Arnold, Michael A; Frankel, Wendy L; Graham, Rondell P; Hart, Phil A; Lam-Himlin, Dora M; Naini, Bita V; Voltaggio, Lysandra; Arnold, Christina A

2017-01-01

We undertook the first case control study of histologically confirmed esophageal candidiasis (EC). A computer search from July 2012 through February 2015 identified 1,011 esophageal specimens, including 40 cases of EC and 20 controls. The EC incidence was 5.2%; it was associated with immunosuppression and endoscopic white plaques and breaks. Smoking was a predisposing factor, and alcohol was protective. EC had no unique symptoms, and 54% of endoscopic reports did not suspect EC. Important histologic clues included superficial and detached fragments of desquamated and hyper-pink parakeratosis, acute inflammation, intraepithelial lymphocytosis, dead keratinocytes, and bacterial overgrowth. Thirty percent had no neutrophilic infiltrate. Pseudohyphae were seen on H&E in 92.5% (n = 37/40). "Upfront" periodic acid-Schiff with diastase (PAS/D) on all esophageal specimens would have generated $68,333.49 in patient charges. Our targeted PAS/D strategy resulted in $13,044.87 in patient charges (cost saving = 80.9%, $55,288.62). We describe the typical morphology of EC and recommend limiting PAS/D to cases where the organisms are not readily identifiable on H&E and with at least one of the following: (1) ulcer, (2) suspicious morphology, and/or (3) clinical impression of EC. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Prognostic and clinicopathological significance of platelet to lymphocyte ratio in esophageal cancer: a meta-analysis.

PubMed

Deng, Juhong; Zhang, Peng; Sun, Yue; Peng, Ping; Huang, Yu

2018-03-01

The prognostic and clinicopathological significance of the platelet to lymphocyte ratio (PLR) has been studied in various cancers. However, studies examining the role of PLR in esophageal cancer have not yielded consistent results. The purpose of this meta-analysis was to study the prognostic and clinicopathological significance of PLR in esophageal cancer patients. We performed a literature search in three major databases: PubMed, Web of Science and Embase (up until May 1, 2017). The clinicopathologic significance of PLR and its prognostic significance were analyzed. Our meta-analysis consisted of 13 studies with 4,621 patients. The pooled hazard ratios (HRs) showed that a high PLR was associated with poor survival of esophageal cancer [HR =1.283; 95% confidence interval (CI): 1.173-1.404; P<0.001]. Subgroup analysis revealed that elevated PLR was associated with poor survival in esophageal squamous cell carcinoma (HR =1.281; 95% CI: 1.098-1.493; P=0.002). The pooled odds ratio (OR) indicated that high PLR was also associated with the depth of tumor invasion (OR =1.543, 95% CI: 1.269-1.876, P<0.001), lymph node metastasis (OR =1.427, 95% CI: 1.195-1.705, P<0.001), tumor length (OR =1.81, 95% CI: 1.331-2.461, P<0.001), and Tumor stage (OR =1.459, 95% CI: 1.235-1.724, P<0.001). Our results demonstrate that elevated PLR was significantly associated with poor prognosis of esophageal cancer. Furthermore, the high PLR might predict worse clinicopathological features of esophageal cancer patients.

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.

Clinical significance of preoperative and postoperative cytokeratin 19 messenger RNA level in peripheral blood of esophageal cancer patients.

PubMed

Qiao, Y-F; Chen, C-G; Yue, J; Ma, Z; Yu, Z-T

2016-11-01

The purpose of this study is to analyze the correlation between preoperative/postoperative Cytokeratin 19 (CK19) messenger RNA (mRNA) level in peripheral blood (PB) and the clinical significance in esophageal cancer patients with different clinicopathological factors. We detected the preoperative and postoperative CK19 mRNA level in the PB of 139 esophageal cancer patients who underwent complete resection and evaluated its clinical significance. We found that both the preoperative and postoperative CK19 mRNA level increased in the esophageal cancer patients with lymph node metastasis, relapse or distant metastasis compared with that in cancers without lymph node metastasis, relapse or distant metastasis. High postoperative CK19 mRNA levels indicate a short disease-free survival (DFS) for the whole cohort esophageal cancer patients, whereas the high preoperative CK19 mRNA levels only indicate a short DFS for the esophageal cancer patients with squamous cell carcinoma, TNM III stage, and lymph node metastasis. The dynamic change of CK19 mRNA levels could indicate the prognosis of esophageal cancer patients. The patients with decreasing CK19 mRNA level after surgery had good prognosis, and the patients with changeless CK19 mRNA level had poor prognosis. Taken together, CK19 mRNA levels could be a promising marker in assessing prognosis or assigning treatment for the esophageal cancer patients according to different clinicopathological factors. © 2015 International Society for Diseases of the Esophagus.

[Neoadjuvant therapy for esophageal cancer - indication and efficacy].

PubMed

Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

2007-10-01

Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-FU/CDDP improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called "trimodality therapy" has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried.

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

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