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Cancer of the Esophagus

The esophagus (UK spelling: oesophagus) is a long hollow muscular tube which connects the throat to the stomach. Esophageal cancer is a disease where malignant (cancerous) cells arise in the tissues of the esophagus. The most common symptom is difficulty in swallowing. It can also be associated with weight loss and sometimes pain or discomfort behind the breast bone or in the back - these symptoms should be checked by a doctor but not are sure signs of cancer. There are two main types of esophageal cancer (depending on how the cells appear under the microscope); approximately half are classed as "squamous cell carcinomas" and half as "adenocarcinomas". People with frequent gastric reflux leading to Barrett's Esophagus have an increased risk of developing esophageal cancer.

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Information for Patients and the Public
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Latest Research Publications
Molecular biology of Esophageal Cancer

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  • PubMed search for publications about Esophageal Cancer - Limit search to: [Reviews]

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    MeSH term: Esophageal Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Fukuoka E, Yamashita K, Tanaka T, et al.
Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8
Anticancer Res. 2019; 39(8):4539-4548 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP).
PATIENTS AND METHODS: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8
RESULTS: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8
CONCLUSION: NAC-FP induced PD-L1 expression on ICs and CD8

Tanaka Y, Ueno T, Yoshida N, et al.
Is Oral Mucositis Occurring During Chemotherapy for Esophageal Cancer Patients Correctly Judged? EPOC Observational Cohort Study.
Anticancer Res. 2019; 39(8):4441-4448 [PubMed] Related Publications
BACKGROUND/AIM: Oral mucositis (OM) is one of the frequent adverse events experienced by patients receiving chemotherapy. Most diagnoses of OM are based on complaints from patients. The aim of this study was to develop a tool to diagnose OM accurately.
MATERIALS AND METHODS: A central review system (CRS) was created to allow judgment when the patient background is completely unknown. The primary endpoint was the rate of grade 2 or higher OM, and the secondary endpoint was the difference in grade between each institution's clinician judgement and that of the CRS.
RESULTS: In total, 53 patients were registered from four institutions. CRS successfully detected grade 2 or higher OM in 16 (30.2%) of the 53 patients. The detection rate of all grades of OM was 41.5% (22 of 53 patients) by each institution's clinician judgement and 84.9% (45 of 53 patients) by CRS judgement (p<0.0001).
CONCLUSION: OM during chemotherapy may be underestimated.

Ohsawa M, Hamai Y, Ibuki Y, et al.
Long-term Esophageal Cancer Survivor Treated by Bypass for Esophagobronchial Fistula After Chemoradiotherapy: A Case Report.
Anticancer Res. 2019; 39(8):4399-4403 [PubMed] Related Publications
BACKGROUND: An esophagorespiratory fistula (ERF) is a fatal complication for patients with tracheobronchial invasion by esophageal cancer. We report the case of a long-term esophageal cancer survivor treated by esophageal bypass operation for ERF after chemoradiotherapy (CRT).
CASE REPORT: A 44-year-old man was treated with definitive CRT (i.e. 66 Gy radiotherapy, chemotherapy with cisplatin, and 5-fluorouracil) for unresectable locally advanced esophageal cancer with massive invasion of the left main bronchus. Although a complete clinical response was obtained, the patient developed pneumonia due to an ERF. Esophageal bypass operation was performed for symptomatic relief. The patient's symptoms improved and oral ingestion became possible. No recurrence has been seen for 12 years.
CONCLUSION: Esophageal bypass surgery can help in relieving symptoms and might be associated with long-term survival for esophageal cancer patients with ERF after good response to CRT. Thus, bypass surgery is a useful option in the treatment for esophageal cancer with ERF.

Sdralis EK, Davakis S, Syllaios A, et al.
Prognostic Value of Subcarinal Lymph Nodes in Minimally Invasive Esophagectomy for Cancer.
Anticancer Res. 2019; 39(8):4291-4295 [PubMed] Related Publications
BACKGROUND/AIM: Surgical resection for esophageal cancer has remained the gold-standard therapy provided worldwide. Subcarinal lymph-nodes are classified as peri-esophageal nodes and their dissection may be performed during a 2- or 3-stage esophagectomy. The necessity and prognostic value of subcarinal lymphadenectomy is still debatable. The purpose of this study was to investigate the rate of invaded subcarinal lymph-nodes out of the total lymph-nodes resected. Detection of invaded nodes was correlated with clinical staging and tumor differentiation.
PATIENTS AND METHODS: This is a retrospective analysis of consecutive esophagectomies for cancer, performed in a UK tertiary center. The study was conducted over a 3-year period.
RESULTS: The rate of subcarinal lymph-node invasion was extremely low according to the results of our analysis.
CONCLUSION: Lymphadenectomy is not devoid of clinical impact on patients and therefore, the decision should actually be the outcome of a dynamic balance between complications and survival benefit.

Jingu K, Takahashi N, Murakami Y, et al.
Is Concurrent Chemotherapy With Radiotherapy for Esophageal Cancer Beneficial in Patients Aged 80 Years or Older?
Anticancer Res. 2019; 39(8):4279-4283 [PubMed] Related Publications
BACKGROUND/AIM: To determine whether concurrent chemotherapy with radiotherapy should be performed in elderly patients with esophageal cancer.
PATIENTS AND METHODS: A total of 185 patients aged 80 years or older who were treated with definitive radiotherapy alone or combined with chemoradiotherapy for esophageal cancer at seven institutions were enrolled. In order to compare survival rates of patients treated with chemoradiotherapy with those of patients treated with radiotherapy alone, propensity score matching was performed to homogenize the two populations.
RESULTS: For the whole patient cohort, the 3-year overall survival (OS) rate was 52.6% and the median survival was 42.5 months. After propensity score matching, the 3-year OS rate for the chemoradiotherapy group was not significantly better than that for the group treated with radiotherapy alone (53.7% vs. 59.9%, p=0.876).
CONCLUSION: Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older did not have significant OS benefit over radiotherapy alone.

Matsumoto A, Yuda M, Tanaka Y, et al.
Efficacy of Percutaneous Endoscopic Gastrostomy for Patients With Esophageal Cancer During Preoperative Therapy.
Anticancer Res. 2019; 39(8):4243-4248 [PubMed] Related Publications
BACKGROUND/AIM: This study aimed to clarify the benefits and disadvantages of percutaneous endoscopic gastrostomy (PEG) for patients with esophageal cancer (EC) during preoperative therapy.
MATERIALS AND METHODS: We retrospectively reviewed 92 patients who underwent esophagectomy for EC after preoperative therapy. Patients were divided into the PEG group (n=14) and the control group (n=78) and compared regarding patient characteristics, nutritional status, operative variables, and postoperative complications.
RESULTS: In the PEG group first nutritional status and tumor stage were significantly worse, but changes of nutritional status from first visit to operation were significantly better. According to the intraoperative thermal imaging, there was no patient with blood flow disturbance in the gastric conduit due to PEG. Short-term surgical outcomes did not significantly differ.
CONCLUSION: PEG has less adverse effects on gastric tube production in esophagectomy and may be considered in highly selective patients during preoperative therapy.

Xie K, Sun H, Gao L, et al.
A study on the correlation between radiation field size and gamma index passing rate for MatriXX.
Medicine (Baltimore). 2019; 98(30):e16536 [PubMed] Related Publications
This study aimed to analyze the influence of the radiation field size on the passing rate of the treatment planning system using MatriXX if the field irradiated the circuit.Two sets of static fields which were 10 cm and 30 cm in the left-right direction (X), and was 31 cm to 40 cm in gun-target direction (Y) were designed. In these fields, the gantry was 0 and the monitor units were 200 MU. Two plans from an esophagus carcinoma patient with a planning target volume of 86.4 cm and a cervical carcinoma patient with a planning target volume (PTV) of 2094.1 cm were chosen. The passing rates of these plans were gained without and with protecting the circuit area from lead alloys. The gamma analysis was used and the standard was set to 3%/3 mm.The verification passing rate decreased from 95.0% to 69.2% when X was 10 cm while Y increased from 31 cm to 40 cm. With the protection from low melting point lead alloys, the passing rate was from 96.2% to 89.6%. The results of the second set of plans without lead alloys were similar but the passing rate decreased more sharply. The passing rates of the 2 patients were 99.5% and 57.1%. With the protection of the lead alloys, their passing rates were 99.8% and 72.1%, respectively.The results showed that with the increase of the radiation field size in the Y direction, more areas were irradiated in the circuit, and the passing rate gradually decreases and dropped sharply at a certain threshold. After putting lead alloys above the circuit, the passing rate was much better in the static field but was still less than 90% in the second patient volumetric modulated arc therapy (VMAT) because the circuit was irradiate in other directions. In daily QA, we should pay attention to these patients with long size tumor.

Cho JH
Massive esophageal bleeding in long-standing achalasia complicated by esophageal carcinoma and aspirin-induced stasis ulcer: Case report.
Medicine (Baltimore). 2019; 98(30):e16519 [PubMed] Related Publications
RATIONALE: Esophageal hemorrhage may occasionally develop subsequent to esophagitis and stasis ulcer, but potentially fatal esophageal bleeding is very uncommon in primary achalasia.
PATIENT CONCERNS: We describe a case of a 64-year-old man with long-standing achalasia and megaesophagus who presented acute episodes of life-threatening upper gastrointestinal bleeding.
DIAGNOSES AND INTERVENTIONS: Five esophagogastroduodenoscopies (EGD) were conducted and during each large amount of static food, bloody material, and clots should be removed from the esophagus because of impaired esophageal transit. Eventually, diffuse multiple irregular ulcers were observed in the middle and lower portions of the esophagus that were presumed to have been caused by aspirin stasis based on considerations of previous drug use. EGD also revealed a 2.0 × 2.5 cm flat nodular lesion with central ulceration at the mid-to-lower esophagus and adherent blood clots suggestive of bleeding stigma. The biopsy specimen demonstrated esophageal cancer. Accordingly, a diagnosis of massive esophageal hemorrhage in long-standing achalasia complicated by squamous cell carcinoma, possibly triggered by acute mucosal irritation and ulcer caused by aspirin stasis, was made. The patient then successfully underwent the Ivor-Lewis operation. Resultantly, the tumor was diagnosed as moderately differentiated squamous cell carcinoma stage IIA (T2N0M0).
OUTCOMES: The patient's postoperative course was uneventful, and no evidence of tumor recurrence or metastasis has been found during the 6 months of follow-up examination. He was tolerating normal food with only minimal reflux symptoms.
LESSONS: Although, fortunately in the described case, esophageal cancer was diagnosed at a relatively early stage because it is the acute presentation of life-threatening upper gastrointestinal bleeding, this report cautions that when symptoms of dysphagia are aggravated, taking drugs capable of acting as local irritants, such as aspirin, could cause fatal esophageal hemorrhage in achalasia.

Deng HY, Lan X, Zheng X, et al.
The association between statin use and survival of esophageal cancer patients: A systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(29):e16480 [PubMed] Related Publications
Whether statin use has any impact on survival of esophageal cancer patients remains controversial. Therefore, we conducted a meta-analysis focusing on current topic for the first time.We systematically searched the following databases for relevant studies comparing survival between statin users and non-users among esophageal cancer patients up to March 16, 2019: Pubmed, Embase, and Web of Science. We extracted data of hazard ratio (HR) with 95%confidence interval (CI) of all-cause and cancer-specific mortality for analysis. We used the STATA 12.0 software to perform this meta-analysis.We finally included a total of 4 cohort studies involving a total of 20,435 esophageal cancer patients (5319 statin users and 15116 non-users). Our meta-analysis found that statin use after diagnosis of esophageal cancer was significantly correlated to decreased all-cause (random effects: HR = 0.81, 95%CI: 0.75-0.89, P < .001; I = 68.1%) and cancer-specific mortality (fixed effects: HR = 0.84, 95%CI: 0.78-0.89, P < .001; I = 46.6%) in esophageal cancer patients. When stratified by pathological subtypes, the protective effect of statin use after diagnosis of esophageal cancer was observed in both esophageal adenocarcinoma patients and esophageal squamous cell carcinoma patients. Moreover, statin use before diagnosis of esophageal cancer was also confirmed to have favorable survival benefit for esophageal cancer patients.Statin use was significantly correlated to lower mortality risk of esophageal cancer patients regardless of the time when statins were taken and pathological subtypes of esophageal cancer. Statins may serve as promising adjunctive anticancer agents for treating esophageal cancer.

Liu Y, Lu Q, Wu XL, et al.
Ultrasonographic imaging of calcifying fibrous tumor of cervical esophagus: A case report.
Medicine (Baltimore). 2019; 98(28):e16425 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor characterized by cytologically benign fibroblasts that produce abundant collagen with scattered lymphocytes, plasma cells, and psammomatous or dystrophic calcifications.
PATIENT CONCERNS: A 37 years old women was initially diagnosed thyroid nodule in local hospital. She was referred to receive microwave ablation of the nodule in our hospital. The patient was in good health with occasional foreign body sensation in the neck. Routine laboratory examination was normal.
DIAGNOSIS: The lesion was suspected benign and originating from the esophagus rather than the thyroid gland by conventional ultrasound and contrast-enhanced ultrasound in our hospital and was finally proved to be CFT by pathology.
INTERVENTIONS: The lesion was surgically removed.
OUTCOMES: The patient recovered well and was followed up for 2 years without recurrence.
LESSONS: Although imaging diagnosis of CFT is difficult, the findings of clear border, coarse calcification on conventional ultrasound and peripheral hypoenhancement without central enhancement on contrast-enhanced ultrasound (CEUS), together with real-time evaluation of the relationship between the tumor and esophagus help to distinguish CFT of cervical esophagus from other lesions in the neck.

Chai L, Yang G
MiR-216a-5p targets TCTN1 to inhibit cell proliferation and induce apoptosis in esophageal squamous cell carcinoma.
Cell Mol Biol Lett. 2019; 24:46 [PubMed] Free Access to Full Article Related Publications
Background: MiR-216a-5p has been reported to be associated with several tumors, including prostate cancer and melanoma. However, its expression level and potential role in esophageal squamous cell carcinoma (ESCC) remain uncertain.
Results: Here, we found that miR-216a-5p expression was significantly down-regulated in clinical ESCC tissues and cells. Functional assays were performed to evaluate the biological effects of miR-216a-5p on cell proliferation and cell apoptosis by CCK-8 assay and flow cytometry in ESCC cell lines, EC9706 and TE-9. The results showed that miR-216a-5p overexpression repressed cell proliferation and induced cell apoptosis. Through bioinformatics prediction and luciferase reporter assay, we revealed that miR-216a-5p could directly target tectonic family member 1 (TCTN1). Moreover, TCTN1 was obviously suppressed by miR-216a-5p overexpression. In addition, TCTN1 expression was significantly increased and inversely correlated with the levels of miR-216a-5p in ESCC tissues. More importantly, down-regulation of TCTN1 imitated, while restoration of TCTN reversed the effects of miR-216a-5p on cell proliferation and apoptosis. At the molecular level, we further found that TCTN1 overexpression reversed the effects of miR-216a-5p transfection on the expression of PCNA, Bcl-2 and Bad.
Conclusions: Our results demonstrate that miR-216a-5p might serve as a tumor suppressor in ESCC cells through negatively regulating TCTN1 expression, indicating the possibility that miR-216a-5p and TCTN1 might be attractive targets for ESCC therapeutic intervention.

Zhong X, Huang G, Ma Q, et al.
Identification of crucial miRNAs and genes in esophageal squamous cell carcinoma by miRNA-mRNA integrated analysis.
Medicine (Baltimore). 2019; 98(27):e16269 [PubMed] Free Access to Full Article Related Publications
Esophageal squamous cell carcinoma (ESCC) is a malignancy that severely threatens human health and carries a high incidence rate and a low 5-year survival rate. MicroRNAs (miRNAs) are commonly accepted as a key regulatory function in human cancer, but the potential regulatory mechanisms of miRNA-mRNA related to ESCC remain poorly understood.The GSE55857, GSE43732, and GSE6188 miRNA microarray datasets and the gene expression microarray datasets GSE70409, GSE29001, and GSE20347 were downloaded from Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network and functional modules were established using the STRING database and were visualized by Cytoscape. Kaplan-Meier analysis was constructed based on The Cancer Genome Atlas (TCGA) database.In total, 26 DEMs and 280 DEGs that consisted of 96 upregulated and 184 downregulated genes were screened out. A functional enrichment analysis showed that the DEGs were mainly enriched in the ECM-receptor interaction and cytochrome P450 metabolic pathways. In addition, MMP9, PCNA, TOP2A, MMP1, AURKA, MCM2, IVL, CYP2E1, SPRR3, FOS, FLG, TGM1, and CYP2C9 were considered to be hub genes owing to high degrees in the PPI network. MiR-183-5p was with the highest connectivity target genes in hub genes. FOS was predicted to be a common target gene of the significant DEMs. Hsa-miR-9-3p, hsa-miR-34c-3p and FOS were related to patient prognosis and higher expression of the transcripts were associated with a poor OS in patients with ESCC.Our study revealed the miRNA-mediated hub genes regulatory network as a model for predicting the molecular mechanism of ESCC. This may provide novel insights for unraveling the pathogenesis of ESCC.

Ito T, Honma Y, Hirano H, et al.
S-1 Monotherapy After Failure of Platinum Plus 5-Fluorouracil Chemotherapy in Recurrent or Metastatic Esophageal Carcinoma.
Anticancer Res. 2019; 39(7):3931-3936 [PubMed] Related Publications
BACKGROUND/AIM: Platinum plus 5-fluorouracil (FP) is a first-line regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (RM-ESCC). In this retrospective study, we evaluated the efficacy and safety of S-1 monotherapy as a salvage line treatment for RM-ESCC, focusing on the reasons for discontinuation of prior FP.
MATERIALS AND METHODS: The subjects of this study had RM-ESCC and received S-1 after failure of FP.
RESULTS: Eleven patients were enrolled. Nine patients were refractory and two were intolerant to prior FP. The median progression-free survival and overall survival time were 3.0 and 11.7 months, respectively. Overall response rate was 22.2% and disease control rate of the 11 patients was 36.4%. Median relative dose intensity of 5-FU was 100% (range=85-100%).
CONCLUSION: S-1 efficacy in RM-ESCC when given after FP was modest. Favorable OS may be attributed to good local control rather than to the efficacy of S-1 monotherapy.

Li J, Zhao Z, Du G, et al.
Safety and efficacy of pulsed low-dose rate radiotherapy for local recurrent esophageal squamous cell carcinoma after radiotherapy: Study protocol for a prospective multi-center phase II trial.
Medicine (Baltimore). 2019; 98(26):e16176 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Re-irradiation after radiotherapy is a common treatment for locally recurrent esophageal cancer. However, the side effects of re-irradiation are serious. The most serious adverse reactions of re-irradiation include esophageal perforation and hemorrhage caused by esophageal perforation. Studies have shown that pulsed low-dose rate radiotherapy (PLDR) induces a hypersensitivity effect on tumor tissue and a hyper-repair effect on normal tissue, which can simultaneously reduce damage on the normal tissue and increase the therapeutic effect on the tumor. The objective of this study is to explore whether PLDR can reduce rate of esophageal perforation and improve efficacy in patients with recurrent esophageal squamous cell carcinoma (ESCC) after radiotherapy.
METHODS AND ANALYSIS: This study is a prospective, multi-center, open, single-arm clinical trial designed to enroll 27 patients with locally recurrent ESCC after radiotherapy with or without chemotherapy. Re-irradiation will be performed using intensity modulated radiation therapy in 50 Gy/25 fractions. The strategy of PLDR includes dividing 2 Gy into 10 fractions, and administering each irradiating dose of 20 cGy at an interval of 3 minutes before the next low-dose irradiation. The actual dose rate of administration each time will be 16.67 cGy /minute. The primary endpoint in this study is the rate of esophageal perforation. The secondary endpoints are the objective remission rate, the palliative effect on quality of life and pain, and the time of disease progression. The observation time is 2 years after the end of the study.
TRIAL REGISTRATION: Clinical trial number: ChiCTR1900020609.

Zhang Y, Chen H, Zhu H, Sun X
CBX8 promotes tumorigenesis and confers radioresistance in esophageal squamous cell carcinoma cells through targeting APAF1.
Gene. 2019; 711:143949 [PubMed] Related Publications
As a transcriptional repressor, Chromobox 8 (CBX8) overexpression is found to be associated with tumorigenesis in several cancers. However, its role in radiotherapy resistance remains poorly characterized. Our study is the first to explore the correlation between CBX8 and radioresistance. We report here that CBX8 is upregulated in Esophageal Squamous Cell Carcinoma (ESCC) tissues and cells and serves as an indicator of poor prognosis for ESCC patients. CBX8 knockdown inhibits cell proliferation, colony formation capability, DNA repair and promotes cell apoptosis. Moreover, the transcriptome sequencing analysis demonstrates that CBX8 downregulates the expression of Apoptotic protease activating factor 1 (APAF1), which is the core protein that mediates mitochondrial apoptotic pathways. APAF1 depletion could abrogate apoptosis induced by CBX8 knockdown in irradiated ESCC cells. Our results provide novel insight into CBX8 as a therapeutic target to improve the radiosensitivity of ESCC.

Lee JY, Kim YH, Park YJ, et al.
Improved detection of metastatic lymph nodes in oesophageal squamous cell carcinoma by combined interpretation of fluorine-18-fluorodeoxyglucose positron-emission tomography/computed tomography.
Cancer Imaging. 2019; 19(1):40 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: We sought to evaluate the diagnostic performance of fluorine-18-fluorodeoxyglucose positron-emission tomography/computed tomography (
METHODS: Two hundred three patients with oesophageal squamous cell carcinoma underwent
RESULTS: A total of 1099 nodal stations were dissected and 949 nodal stations were proven to demonstrate metastasis. SUV
CONCLUSIONS: The diagnostic accuracy of PET/CT for nodal metastasis in oesophageal squamous cell carcinoma was improved by the combined interpretation of

Bakheet N, Park JH, Hu HT, et al.
Fully covered self-expandable esophageal metallic stents in patients with inoperable malignant disease who survived for more than 6 months after stent placement.
Br J Radiol. 2019; 92(1100):20190321 [PubMed] Related Publications
OBJECTIVES: To investigate the clinical outcomes of fully covered self-expanding metal stent (FCSEMS) placement in patients with malignant esophageal obstruction who survived longer than 6 months.
METHODS: From January 2002 to January 2018, 88 FCSEMS were placed in 64 patients (mean age 62.9 ± 11.6 years; 58 males) with inoperable malignant esophageal obstruction with or without esophago-respiratory fistula. Only patients who survived more than 6 months with FCSEMS in place were included. Data regarding technical and clinical success, complications, reinterventions, stent patency, and patient survival were obtained from a prospectively maintained hospital database.
RESULTS: The technical and clinical success rates were 100 % (64/64). During follow-up, the median dysphagia score significantly improved (3.09 ± 0.68 to 1.05 ± 0.60,
CONCLUSIONS: Our data suggest that esophageal FCSEMS placement is an effective option for patients with malignant dysphagia when survival longer than 6 months is expected. The rate of complications increases with time, and SEMS development is needed to keep up with the advancement in oncological treatment.
ADVANCES IN KNOWLEDGE: Fully covered esophageal self-expandable stent placement is effective in patients surviving more than 6 months, however, the rate of complications also increases. SEMS development is needed to cope with the advancement in oncological treatment.

Bachmann K, Bockhorn M, Mann O, et al.
Aberrant expression of Sec61α in esophageal cancers.
J Cancer Res Clin Oncol. 2019; 145(8):2039-2044 [PubMed] Related Publications
INTRODUCTION: The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients.
MATERIALS AND METHODS: Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry.
RESULTS: Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751).
CONCLUSIONS: Thus, Sec61α measurement has not an additional prognostic benefit for the patients.

Lorenzi B, Davakis S, Syllaios A, et al.
Minimally Invasive Circumferential Hiatal Dissection for the Treatment of Adenocarcinoma of the Distal Esophagus and Esophago-gastric Junction: Technical Considerations Combined With Histopathological Outcomes.
Anticancer Res. 2019; 39(6):3219-3225 [PubMed] Related Publications
BACKGROUND/AIM: Circumferential resection margin involvement is an independent prognostic factor in patients with adenocarcinoma of the distal esophagus and esophago-gastric junction. However, there is currently no consensus on the extent and the technique of hiatal dissection. We describe a minimally invasive technique of circumferential hiatal dissection for adenocarcinoma of the distal esophagus and esophago-gastric junction with its related histopathological results.
PATIENTS AND METHODS: A prospective study of 40 consecutive patients undergoing hybrid (laparoscopic/thoracotomic) or totally minimally invasive Ivor-Lewis esophagogastrectomy over a period of 21 months was conducted. Dissection of the hiatus included peri-esophageal surrounding tissues in a cylindrical fashion maximizing the distance from the oesophageal wall. Crural muscle fibers and pleura bilaterally, pericardial fat anteriorly and pre-aortic tissue posteriorly were excised en bloc. Histopathological results particularly focused on involvement of the circumferential resection margin. Neoadjuvant chemotherapy was given to 24 (60%) patients.
RESULTS: Complete histological clearance (R0) was achieved in 92.5% (n=37) according to the criteria of the College of American Pathologists and in 87.5% (n=35) according to those of the Royal College of Pathologists. In pT3 tumors (n=22), the circumferential resection margin was negative in 20 patients (91%) according to the College of American Pathologists, and in 17 (77%) according to the Royal College of Pathologists.
CONCLUSION: Adoption of this safe and reproducible technique might reduce the incidence of circumferential resection margin involvement and improve pathological outcomes. In addition, there may be positive implications for training and quality control.

Goto M, Okitsu H, Yuasa Y, et al.
Thoracoscopic Oesophagectomy Using Prone Positioning for Oesophageal Cancer With Right Aortic Arch: A Case Report.
Anticancer Res. 2019; 39(6):3207-3211 [PubMed] Related Publications
BACKGROUND/AIM: Right aortic arch (RAA) is a rare abnormality of the aortic arch that forms a vascular ring. Oesophageal cancer (EC) accompanied with RAA is even rarer, and in such cases, it is very important to understand the anatomical structure in the upper mediastinum in order to perform a safe and curative operation.
PATIENTS AND METHODS: A 67-year-old man who presented with pharyngeal discomfort was admitted to our hospital. Further examinations revealed advanced thoracic EC accompanied with RAA and aortic diverticulum.
RESULTS: After neoadjuvant chemotherapy, we successfully and safely performed thoracoscopic oesophagectomy and lymphadenectomy using the prone positioning.
CONCLUSION: There exist only a few reports of thoracoscopic oesophagectomy for EC with RAA. Sufficient preoperative preparation and sharing an adequate strategy for the surgical approach with the surgical team are definitely necessary. Although the thoracoscopic approach for EC with RAA is useful, more considerations are needed for some issues.

Kitagawa H, Iwabu J, Yokota K, et al.
Intraoperative Neurological Monitoring During Neck Dissection for Esophageal Cancer With Aberrant Subclavian Artery.
Anticancer Res. 2019; 39(6):3203-3205 [PubMed] Related Publications
We report a case of esophageal cancer with a non-recurrent inferior laryngeal nerve associated with aberrant right subclavian artery that was treated by neck dissection using intraoperative neurological monitoring followed by thoracoscopic esophagectomy. A 76-year-old man had dysphagia. Endoscopy revealed thoracic esophageal cancer, and computed tomography revealed the presence of an aberrant right subclavian artery between the esophagus and vertebrae. We performed neck dissection followed by thoracoscopic esophagectomy. During the neck dissection, we confirmed a non-recurrent inferior laryngeal nerve through intraoperative neurological monitoring. No postoperative complications were observed, and the patient was discharged 19 days after surgery. We recommend using intraoperative neurological monitoring to avoid injury to the non-recurrent inferior laryngeal nerve associated with the aberrant right subclavian artery.

Sohda M, Miyazaki T, Sakai M, et al.
Multidisciplinary Therapy for Locally Advanced Oesophageal Cancer With Special Reference to Surgical Conversion and Salvage.
Anticancer Res. 2019; 39(6):3167-3175 [PubMed] Related Publications
BACKGROUND/AIM: Unresectable oesophageal cancer with surrounding invasion carries a particularly poor prognosis. The chemoradiotherapy treatment for locally-unresectable oesophageal cancer aims to initially control local invasion before proceeding to the next treatment, and is ideally used with curative intent. The aim of this study was to investigate patient treatment course and survival to determine the best treatment and evaluate surgical intervention for these advanced cancers.
PATIENTS AND METHODS: A total of 147 patients who were diagnosed with clinical T4b oesophageal cancer were included in this study.
RESULTS: Forty-three patients had undergone curative resection of the tumour and surrounding invasion at midterm evaluation, 104 patients continued with definitive chemoradiotherapy, and salvage surgery was performed in 21 patients. Multivariate analysis of disease-specific survival showed that response at the midterm evaluation and surgical intervention (conversion surgery + salvage surgery) were significant prognostic factors.
CONCLUSION: Surgical intervention was an independent prognostic factor, and operation should be performed in eligible patients after considering the risks and proper timing.

Toyokawa T, Tamura T, Sakurai K, et al.
Postoperative Inflammation Is an Independent Prognostic Factor in Patients With Thoracic Esophageal Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(6):2777-2784 [PubMed] Related Publications
BACKGROUND: The aim of this study was to elucidate the impact of postoperative inflammatory response on prognosis in patients with stage I thoracic esophageal squamous cell carcinoma (ESCC).
MATERIALS AND METHODS: Seventy-five consecutive patients who underwent subtotal esophagectomy for clinical stage I thoracic ESCC were reviewed retrospectively. Maximum serum CRP level (CRP
RESULTS: Optimal cut-off values were 10.7 mg/dl for CRP

Wang Y, Zhang X, Jiang Y, et al.
Comparison of hand-sewn versus mechanical esophagogastric anastomosis in esophageal cancer: Protocol for a systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(23):e15676 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Many studies have been conducted to compare the hand-sewn and mechanical staples in esophageal cancer (EC) patients who received esophagogastric anastomosis. However, the results remain controversial. Hence, the purpose of the meta-analysis is to evaluate the impact of different anastomosis methods on the early and long-term outcomes.
METHODS: We will perform a systematic electronic search of the PubMed, Embase, Cochrane Library, Web of Science for relevant articles published in English language. Pooled odds ratios will be calculated for the effect on discrete variables including anastomotic leakage, anastomotic strictures, 30-day mortality, quality of life, cardiac and pulmonary complications. The weighted mean difference was calculated for the effect size on continuous variables such as operative time and bleeding amount. We will use the software Review Manager 5.3 and STATA 14.0 to perform the meta-analysis to calculate the data synthesis.
RESULTS: The review will provide a high-quality synthesis of current evidence of the impact of different anastomosis methods on postoperative course in ECs after esophagectomy. The results will be published in a peer-reviewed journal.
CONCLUSION: This systematic review and meta-analysis will compare the different anastomosis methods in EC patients. The results will better offer some specific suggestions for esophagogastric anastomosis.
PROSPERO REGISTRATION NUMBER: This systematic review protocol has been registered in the PROSPERO network (No. CRD 42019109523).

Yan Q, Chen T, Yang H, et al.
The Effect of FERMT1 Regulated by miR-24 on the Growth and Radiation Resistance of Esophageal Cancer.
J Biomed Nanotechnol. 2019; 15(3):621-631 [PubMed] Related Publications
The present study addresses the role and underlying mechanism of FERMT1 in the development of esophageal cancer (EC). High level of FERMT1 expression was found in human EC tissues and was significantly correlated with poor overall survival. Overexpression of FERMT1 by a lentiviral vector markedly promoted EC cell proliferation and radiation resistance

Ardalan Khales S, Abbaszadegan MR, Majd A, Forghanifard MM
Linkage between EMT and stemness state through molecular association between TWIST1 and NY-ESO1 in esophageal squamous cell carcinoma.
Biochimie. 2019; 163:84-93 [PubMed] Related Publications
Aberrant expression of cancer testis antigens (CTAs) is reported in tumors, especially those with stemness properties. A number of CTAs can induce epithelial mesenchymal transition (EMT) process and promote cancer stem cells (CSCs) characteristics. We aimed in this study to analyze the correlation between NY-ESO1 and TWIST1 in esophageal squamous cell carcinoma (ESCC), as well as their impact on EMT process. Gene expression profiling of NY-ESO1 and TWIST1 was performed in 43 esophageal tumors compared to their margin normal tissues of using qRT-PCR, and their correlation with clinicopathological variables of the patients was evaluated. In silico analysis of the NY-ESO1, epithelial and mesenchymal cell markers and also their promoter sequences was executed. ESCC cell lines KYSE-30 and YM-1 were transduced to ectopically express TWIST1 using a retroviral system, followed by qRT-PCR mRNA expression analysis to reveal the probable correlation among TWIST1, NY-ESO1 and EMT markers gene expression. Scratch assay was performed to estimate migration of TWIST1-induced cells. Overexpression of TWIST1 and NY-ESO1 mRNA was observed in 42% and 39.5% (P ˂ 0.05) of tumors, respectively. Expression of the genes was significantly correlated with each other (p = 0.005). TWIST1 and NY-ESO1 overexpression was significantly associated with stage of progression and size of tumors, respectively. A direct association between TWIST1 and NY-ESO1 mRNA expression was confirmed by induced ectopic expression of TWIST1 in ESCC cell lines KYSE-30 and YM-1. TWIST1-induced cells led to increase migration in ESCC cell line. Furthermore, significant up-regulation of EMT markers was observed following ectopic expression of TWIST1 in these cells. Based on our findings, it may be proposed that a vital association is exist between the EMT and the acquisition of cancer stemness state in tumor cells through the TWIST1/NY-ESO1 axis and it can be a critical hallmark in ESCC tumorigenesis.

Wu Y, Yang Y, Xian YS
HCRP1 inhibits cell proliferation and invasion and promotes chemosensitivity in esophageal squamous cell carcinoma.
Chem Biol Interact. 2019; 308:357-363 [PubMed] Related Publications
Hepatocellular carcinoma related protein 1 (HCRP1), which is essential for internalization and degradation of ubiquitinated membrane receptors, was reported to play crucial roles in cancer pathogenesis and progression. However, the functional roles of HCRP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we investigated the effects of HCRP1 on ESCC cells and the underlying mechanism. Our results demonstrated that HCRP1 was lowly expressed in ESCC tissues and cell lines. Overexpression of HCRP1 significantly suppressed ESCC cell proliferation and invasion as well as the epithelial-mesenchymal transition (EMT) process. Furthermore, HCRP1 increased the sensitivity of ESCC cells towards cisplatin/fluorouracil. Mechanistically, HCRP1 inhibited the activity of Wnt/β-catenin signaling pathway in ESCC cells. In conclusion, these findings indicated that HCRP1 suppressed ESCC cell proliferation and invasion through regulation of the Wnt/β-catenin pathway. Therefore, HCRP1 may function as a tumor suppressor in ESCC progression.

Washington K, Watkins JR, Jay J, Jeyarajah DR
Oncologic Resection in Laparoscopic Versus Robotic Transhiatal Esophagectomy.
JSLS. 2019 Apr-Jun; 23(2) [PubMed] Free Access to Full Article Related Publications
Background and Objectives: As the use of robotic surgery continues to increase, little is known about robotic oncologic outcomes compared with traditional methods in esophagectomy. The aim of this study was to examine the perioperative oncologic outcomes of patients undergoing laparoscopic versus robot-assisted transhiatal esophagectomy (THE).
Methods: Thirty-six consecutive patients who underwent laparoscopic and robot-assisted THE for malignant disease over a 3-year period were identified in a retrospective database. Eighteen patients underwent robotic-assisted THE with cervical anastomosis, and 18 patients underwent laparoscopic THE. All procedures were performed by a single foregut and thoracic surgeon.
Results: Patient demographics were similar between the 2 groups with no significant differences. Lymph node yields for both laparoscopic and robot-assisted THE were similar at 13.9 and 14.3, respectively (
Conclusions: Laparoscopic and robot-assisted THEs yield similar perioperative oncologic results including lymph node yield and margin status. In the transition from laparoscopic surgery, robotic surgery should be considered oncologically noninferior compared with laparoscopy.

Li P, Wang X, Lai Y, et al.
The prognostic value of pre-treatment prognostic nutritional index in esophageal squamous cell carcinoma: A meta-analysis.
Medicine (Baltimore). 2019; 98(22):e15280 [PubMed] Related Publications
BACKGROUND: Prognostic nutritional index (PNI) is an easily obtained index inflecting both one's nutritional and inflammatory status. Its clinical role in esophageal squamous cell carcinoma (ESCC) remains still in debate. The aim of this meta-analysis was to assess the prognostic value and the clinical-pathological features of pre-treatment PNI in ESCC patients.
METHODS: A comprehensive search of online databases (PubMed, Embase, Web of Science) was performed. Studies explored the relationship between pre-treatment PNI and long-term survival of ESCC patients were regarded eligible for this meta-analysis. Outcomes were extracted and synthesized. Hazard ratio (HR) and relative ratio (RR) with 95% confidence interval (CI) were used to evaluate the prognostic value of PNI on long-term survival and association with clinical-pathological features, respectively. The heterogeneity levels and publication bias between studies were also estimated.
RESULTS: Nine observational studies involving 2276 patients were considered eligible for this meta-analysis. The pooled results showed that low PNI score was significantly correlated with poorer overall survival (OS) of esophageal cancer (pooled HR = 1.418 95%CI: 1.200-1.676, P = .000), poorer recurrence free survival (HR = 1.880 95%CI: 1.207-2.929, P = .005) but not cancer specific survival (CSS) (HR = 1.948 95%CI: 0.544-6.977, P = .306). The PNI value was not related with patient age, sex, depth of tumor invasion, nodular metastasis, and differential grade but the TNM stage (III/IV vs 0/I/II, RR = 1.276, 95% CI 1.146-1.420).
CONCLUSIONS: Low pre-treatment PNI was significantly related with OS and recurrence free survival but not CSS for ESCC. PNI was a reliable prognostic factor of ESCC, and higher stage ESCC have higher incidence of low PNI.

Piñerúa-Gonsálvez JF, Zambrano-Infantino RDC, Benítez S
Arq Gastroenterol. 2019 Jan-Mar; 56(1):41-44 [PubMed] Related Publications
BACKGROUND: Esophageal cancer is the eighth most common cancer. The prognosis is bleak in patients with advanced stages. Patients with early disease have a better prognosis than those with advanced stage. There are several techniques for the screening of premalignant and superficial lesions including chromoendoscopy.
OBJECTIVE: This article aimed to determine the effectiveness of chromoendoscopy with toluidine blue combined with Lugol's solution for diagnosis of esophageal premalignant and superficial neoplastic lesions in high risk patients.
METHODS: Routine white light upper endoscopy was performed. Toluidine blue was sprayed from the gastroesophageal junction to 20 cm of the dental arch. Then the uptake dye areas were characterized. Later Lugol's solution was sprayed. Areas with less-intense staining were characterized. Biopsy of the toluidine blue capturing areas and areas with less-intense staining of Lugol's solution were taken. In the cases where lesions were not evidenced after application of dyes, biopsies four quadrants of the esophageal mucosa were taken. The samples were evaluated by a digestive pathologist.
RESULTS: Barrett's esophagus was the most common premalignant lesion and the early neoplastic lesion was adenocarcinoma with a sensitivity of 100%, specificity 85.7%, positive predictive value 30%, negative predictive value 100%, positive likelihood ratio 7 negative likelihood ratio 0.
CONCLUSION: Chromoendoscopy with toluidine blue combined with Lugol's solution is a useful tool in the screening of esophageal premalignant lesions and superficial neoplasms.

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