Histological Type Of Esophageal Cancer Research Articles

Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era

Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.

Improving esophageal cancer screening across the globe: Translating knowledge into action.

Esophageal cancer (EC) is a pressing global health concern, ranking as the eighth most common cancer and the sixth leading cause for cancer-related deaths worldwide. Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are the two major histological types of esophageal cancer associated with distinct risk factors and geographical distributions. Unfortunately, the outcomes for both types of EC remain discouraging, with a five-year survival rate of less than 20% when diagnosed at advanced stages. Advanced endoscopic techniques have the potential to vastly enhance patient outcomes and impede the progression of pre-malignant lesions to cancer. However, low screening rates with endoscopy due to its invasive nature and high cost hinder its effectiveness. Despite extensive research on risk predictors, a significant number of cases still go undiagnosed, highlighting the need for improved screening techniques that can be implemented at the population level. To increase uptake, a shift towards minimally invasive, well-tolerated and cost-effective non-endoscopic technologies is crucial. The implementation of such devices in primary care settings, specifically targeting high-risk populations, can be a promising strategy. With early detection and enrollment in surveillance programs, there is hope for substantial improvement in morbidity and mortality rates through modern minimally invasive endoscopic and surgical techniques.

The analysis of periodontal diseases and squamous cell esophageal cancer: A retrospective study

AimThe potential links between periodontal disease and various cancers have drawn more and more attention in recent years. The objective of the current study was to investigate any potential associations between parameters of periodontal disease, the number of teeth lost, and the risk of developing squamous cell esophageal cancer in a representative adult sample. Materials and MethodsThe study sample included 178 healthy individuals with matched age and socioeconomic status as controls and 60 patients with the primary histological type of esophageal cancer, Squamous Cell Esophageal Cancer. Data were collected from cases and controls on epidemiological factors like age, gender, smoking status, alcohol intake, socio-economic status, level of education, and prior medical/dental history. The clinical data on periodontal health status was obtained through a clinical examination. This data concerned Probing Pocket Depth (PPD), Clinical Attachment Loss (CAL), the number of teeth lost, and the common risk factors for Squamous Cell Esophageal Carcinoma. Additionally, univariate, and logistic regression models that were modified for potential confounders were used to estimate unadjacent and adjacent odds ratios (ORs) and 95% confidence intervals (CIs). ResultsLower socioeconomic status (p = 0.048) (OR = 1.882, 95% CI = 0.987–3.591), smoking (p = 0.052) (OR = 1.768, 95% CI = 0.931–3.359), moderate and heavy alcohol abuse (p = 0.035) (OR = 1.880, 95% CI = 0.987 3.579), and irregular tooth brushing frequency (p = 0.001) (OR = 0.326, 95% CI = 0.171–0.619) were indeed discovered to be significantly linked. ConclusionIndividuals with lower socio-economic status, smoking, moderate and heavy alcohol consumption, and irregular tooth brushing frequency were significantly associated with Periodontal diseases and Squamous Cell Esophageal Cancer.

Genetic alteration and ctDNA mutation profiling of esophageal cancer in Chinese patients.

e16046 Background: Esophageal cancer is the sixth most common cause of cancer-related mortality. There are two distinct histological types of esophageal cancer: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). In China, ESCC is the major subtype. Higher incidence of EAC is observed in western countries. Liquid biopsy detecting circulating tumor DNA is a non-invasive, real-time and highly sensitive approach that is able to identify and monitor the genetic mutations in tumor. Methods: In this study, we collected 490 Chinese esophageal cancer patients from 2018-2022 and characterized the mutational landscape of esophageal tumor tissue and circulating tumor DNA by whole exome sequencing or deep sequencing of targeted gene panel. The consistency of genetic alteration between tumor and ctDNA was also explored. Results: A total of 176 patients with plasma and 345 patients with cancer tissue were analyzed, among them, 31 patients had both ctDNA and tissue biopsy data. 277 genes with 1257 mutations were identified from plasma samples of 176 patients. The top frequently mutated genes were TP53 (89.1%), KMT2D (24.0%), SYNE1 (14.9%), NOTCH1 (14.3%), EP300 (13.7%), LRP1B (13.7%) and ZNF750 (10.3%). The mutation rates of these genes between ctDNA and tissue biopsy (N = 31 patients) were in concordance by Fisher's exact test (P > 0.05). Most frequent mutations were found in TP53 gene, which account for 89.1% of total plasma samples and 90.4% of tumor tissues. KMT2D gene mutations were detected in 24% of patients which encode histone methyltransferase that methylates the Lys-4 position of histone H3 and regulates transcriptional activation, indicating epigenetic regulation might be involved in the pathogenesis of esophageal cancer. Functional enrichment analysis was performed including Gene Ontology (GO) and KEGG analysis across all the three domains, Biological process, Molecular Function, and Cellular component. The KEGG terms with the highest enrichment score were PI3K−Akt signaling pathway, which is a key driver in carcinogenesis. In addition, we didn’t observe the mutually exclusive mutation or co-occurrence pattern of any gene pairs in our cohort. Conclusions: We demonstrated the utility of liquid biopsy to draw a ctDNA mutation profiling of esophageal cancer in Chinese patients. Genetic mutations identified from ctDNA showed consistency with mutations from tumor tissue.

Construction of the Interaction Network of Hub Genes in the Progression of Barrett's Esophagus to Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is one of the histologic types of esophageal cancer with a poor prognosis. The majority of EAC originate from Barrett's esophagus (BE). There are few studies focusing on the dynamic progression of BE to EAC. R software was used to analyze differentially expressed genes (DEGs) based on RNA-seq data of 94 normal esophageal squamous epithelial (NE) tissues, 113 BE tissues and 147 EAC tissues. The overlapping genes of DEGs between BE and EAC were analyzed by Venn diagram tool. The hub genes were selected by Cytoscape software based on the protein-protein interaction network of the overlapping genes using STRING database. The functional analysis of hub genes was performed by R software and the protein expression was identified by immunohistochemistry. In the present study, we found a large degree of genetic similarity between BE and EAC, and further identified seven hub genes (including COL1A1, TGFBI, MMP1, COL4A1, NID2, MMP12, CXCL1) which were all progressively upregulated in the progression of NE-BE-EAC. We have preliminarily uncovered the probable molecular mechanisms of these hub genes in disease development and constructed the ceRNA regulatory network of hub genes. More importantly, we explored the possibility of hub genes as biomarkers in the disease progression of NE-BE-EAC. For example, TGFBI can be used as biomarkers to predict the prognosis of EAC patients. COL1A1, NID2 and COL4A1 can be used as biomarkers to predict the response to immune checkpoint blockade (ICB) therapy. We also constructed a disease progression risk model for NE-BE-EAC based on CXCL1, MMP1 and TGFBI. Finally, the results of drug sensitivity analysis based on hub genes showed that drugs such as PI3K inhibitor TGX221, bleomycin, PKC inhibitor Midostaurin, Bcr-Abl inhibitor Dasatinib, HSP90 inhibitor 17-AAG, and Docetaxel may be potential candidates to inhibit the progression of BE to EAC. This study is based on a large number of clinical samples with high credibility, which is useful for revealing the probable carcinogenic mechanism of BE to EAC and developing new clinical treatment strategies.

The Effect of the Appropriate Timing of Radiotherapy on Survival Benefit in Patients with Metastatic Esophageal Cancer Who Have Undergone Resection of Primary Site: A SEER Database Analysis.

Background Metastatic esophageal cancer (MEC) is an advanced stage of esophageal cancer. However, still, resection of primary site and radiotherapy are considered treatment modalities to treat patients with MEC. Hence, this study is aimed at exploring the effect of the appropriate timing of radiotherapy on the survival benefit of these patients by comparing cancer-specific survival (CSS). Method The patient information was obtained from the National Surveillance Epidemiology and End Results (SEER) database between the years 2004 and 2017. We used the SEER∗ STAT (V8.3.9.2) software to search and download data. Patients treated with pre- and postoperative radiotherapy were divided into two groups. The propensity score matching (PSM) analysis was performed to increase the comparability of data within two groups. We used the Kaplan-Meier method to analyze and compare the CSS between the two groups. The Cox risk model was used to analyze variables affecting patient survival. Results A total of 599 patients with MEC who experienced resection of the primary site and radiotherapy were recruited. 144 pairings formed through PSM. The 5-year CSS was 23.0% and 11.7% for patients who have undergone pre- and postoperative radiotherapy, respectively. Patients who have undergone preoperative radiotherapy showed better CSS than those who received postoperative radiotherapy (P < 0.001). The multivariate Cox analysis of the entire cohort showed that age > 60 years at the time of diagnosis (HR = 1.481, 95% CI: 1.1341-1.934, and P = 0.04) and other histological types of esophageal cancer (HR = 1.581, 95% CI: 1.067-2.341, and P = 0.022) increased the risk of cancer-related death. Inversely, marriage (HR = 0.696, 95% CI: 0.514-0.942, and P = 0.019) and preoperative radiotherapy (HR = 0.664, 95% CI: 0.517-0.853, and P < 0.001) reduced the risk of death from cancer. Conclusions For patients with MEC, preoperative radiotherapy might have a significant effect on the survival benefit over those who receive postoperative radiotherapy.

Identification of prognostic biomarkers associated with tumor microenvironment in ceRNA network for esophageal squamous cell carcinoma: a bioinformatics study based on TCGA database

BackgroundEsophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in the world with high incidence rate and poor prognosis. Infiltrated immune and stromal cells are vital components of tumor microenvironment (TME) and have a significant impact on the progression of ESCC. The competitive endogenous RNA (ceRNA) hypothesis has been proved important in the molecular biological mechanisms of tumor development. However, there are few studies on the relationship between ceRNA and ESCC TME.MethodsThe proportion of tumor-infiltrating immune cells and the amount of stromal and immune cells in ESCC cases were calculated from The Cancer Genome Atlas database using the CIBERSORT and ESTIMATE calculation methods. After stratified identification of differentially expressed genes, WGCNA and miRNA prediction system were applied to construct ceRNA network. Finally, PPI network and survival analysis were selected to discriminate prognostic signature. And the results were verified in two independent groups from Gene Expression Omnibus and Lanzhou, China.ResultsWe found that high Stromal and ESTIMATE scores were significantly associated with poor overall survival. Three TME-related key prognostic genes were screened, namely, LCP2, CD86, SLA. And the expression of them was significantly correlated with infiltrated immunocytes. It is also found that ESTIMATE Score and the expression of CD86 were both related to TNM system of ESCC.ConclusionsWe identified three novel TME-related prognostic markers and their lncRNA-miRNA-mRNA pathway in ESCC patients, which may provide new strategies for the targeted therapy.

Long non‑coding RNA BANCR promotes proliferation, invasion and migration in esophageal squamous cell carcinoma cells via the Raf/MEK/ERK signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a major histological type of esophageal cancer, identified as a leading cause of tumor-associated death worldwide. In addition, long non-coding RNA (lncRNA) BRAF-activated non-coding RNA (BANCR) expression is increased in the plasma of patients with ESCC, which can be reversed by tumor resection. Thus, the aim of the present study was to investigate the underlying mechanism of BANCR in ESCC progression. The relative mRNA expression of BANCR was determined via reverse transcription-quantitative PCR. The cell behaviors of Eca-109 cells were detected using Cell Counting Kit-8, colony formation, wound healing and Transwell chamber assays. Finally, the expression levels of proteins involved in the Raf/MEK/ERK signaling pathway and cell metastasis were analyzed with western blotting. The results revealed that lncRNA BANCR was highly expressed in ESCC cells compared with in normal esophageal cells. BANCR overexpression enhanced proliferation, migration and invasion of ESCC cells, and BANCR silencing exerted opposite effects. Moreover, BANCR overexpression induced activation of the Raf/MEK/ERK signaling pathway in ESCC cells. Notably, U0126, a specific MEK inhibitor, decreased MEK and ERK expression, and blocked the promotive effects of BANCR overexpression on the proliferation, migration and invasion of ESCC cells. Overall, lncRNA BANCR facilitated the proliferation, migration and invasion of ESCC cells via the Raf/MEK/ERK signaling pathway. Thus, lncRNA BANCR may be a promising target for inhibiting ESCC growth and metastasis.

Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China and has an extremely poor prognosis. Circulating free DNA (cfDNA) and plasma heat shock protein 90alpha (Hsp90a) are two novel noninvasive biomarkers for diagnosis and prognostic prediction of several types of cancer. However, to the best of our knowledge, the roles of the two biomarkers in ESCC are still unknown.MethodsHere, we recruited 93 primary ESCC patients and detected plasma concentrations of the two markers at different time points, including 1–3 days pre-chemotherapy, 1–7 days pre-surgery and 7–14 days post-surgery. Baseline concentrations of the two markers were associated with main characteristics of ESCC patients which were collected at first diagnosis. Correlation between the two markers and traditional serum biomarkers at baseline was also examined. Furthermore, dynamic changes of the cfDNA and Hsp90α concentrations among different time points and the potential clinical significance were assessed.ResultsConsequently, there was no significant association between baseline concentrations of the two markers and clinical features. Especially, cfDNA demonstrated stronger correlation with other circulating biomarkers than Hsp90α at baseline level. Importantly, both cfDNA and Hsp90α concentrations were significantly increased after surgery. Kaplan–Meier survival analysis showed that a change in concentration of cfDNA (ΔcfDNA) but not Hsp90α (ΔHSP90ɑ) between pre-surgery and post-surgery had significant effect on the overall survival of surgical patients with ESCC.ConclusionThus, ΔcfDNA evaluation could be a promising prognostic marker for surgical ESCC patients. Our findings may improve the understanding of the function of cfDNA and Hsp90α in ESCC.

Epidemiology, Risk Factors, Clinical-Imaging Features And Priorities For The Prevention Of Esophageal Cancer In The Fergana Valley Of Uzbekistan

Cancer of the digestive system is the most common cause of death among malignant neoplasms (Table 1). According to the International Agency for Research on Cancer (IARC) for 2008, the incidence of cancer of the digestive system was 49.2 people per 100 thousand people per year, the mortality rate was 34.3 people per 100 thousand. At a relatively low incidence rate, esophageal cancer is the seventh most common cause of death from malignant tumors, giving way to lung, breast, stomach, liver, prostate, and colon cancers. This is due to the extremely malignant nature of the course, early metastasis, and late diagnosis of esophageal cancer. The aggressiveness index, calculated as the ratio of deaths to new cases, is extremely high in esophageal cancer and is about 95%. The absolute number of deaths from esophageal cancer in 2008 in the world was 406 thousand people. In developing countries, morbidity and mortality from esophageal cancer are significantly higher than in developed countries (Table 2). The most common two histological types of esophageal cancer are squamous cell carcinoma and esophageal adenocarcinoma. Despite the similarity of the clinical picture, diagnostic and therapeutic tactics, an extremely unfavorable prognosis for both forms of esophageal cancer, these malignant neoplasms have different risk factors, socio-geographic and ethnic characteristics, knowledge of which is necessary for the timely establishment of the diagnosis and preventive measures. Squamous cell carcinoma of the esophagus (Fig. 1) is an extremely aggressive epithelial malignant tumor of stratified squamous epithelium, in most cases localized between the middle and lower third of the esophagus, the tumor is rare in the cervical esophagus

The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma.

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer, and accounts for 90% of all cancer cases. Despite the progress made in surgery, chemotherapy, and radiotherapy, the mortality rate from esophageal cancer remains high, and the overall 5-year survival rate is less than 20%, even in developed countries. The C-X-C motif chemokine ligand 12 (CXCL12) is a member of the CXC chemokine subgroup, which is widely expressed in a variety of tissues and cells. CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor, C-X-C motif chemokine receptor type 4 (CXCR4), where it causes embryonic development, immune response, and angiogenesis. In addition, increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells. Studies have shown that CXCL12 and its receptor, CXCR4, are highly expressed in ESCC. This abnormal expression contributes to tumor proliferation, lymph node and distant metastases, and worsening prognosis. At present, antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors. This article summarizes the structure, function, and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC. Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.

Extracellular miRNAs for the Management of Barrett's Esophagus and Esophageal Adenocarcinoma: A Systematic Review.

Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett’s esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.

Identification of the Prognostic Value of Tumor Microenvironment-Related Genes in Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological type of esophageal cancer, but there is a lack of definite prognostic markers for this cancer.Methods: We used the ESTIMATE algorithm to access the tumor microenvironment (TME) of ESCC cases deposited in the TCGA database, and identified TME-related prognostic genes using Cox regression analysis. A least absolute shrinkage and selector operation or LASSO algorithm was used to identify key prognostic genes. Risk scores were calculated, and a clinical predictive model was constructed to evaluate the prognostic value of TME-related genes.Results: We found that high immune and stromal scores were significantly associated with poor overall survival (p < 0.05). We identified a total of 1,151 TME-related differently expression genes, among which 67 were prognosis-related genes. Through the LASSO method, 13 key prognostic genes were selected, namely, ADAMTS16, LOC51089, CH25H, CORO2B, DLGAP1, GYS2, HAL, MXRA8, NPTX1, OTX1, RET, SLC24A2, and SPI1, and a 13-gene risk score was constructed. A higher score was indicative of a poorer prognosis than a lower risk score (hazard ratio = 8.21, 95% confidence interval: 2.56–26.31; P < 0.001). The risk score was significantly correlated with immune/stromal scores and various types of infiltrating immune cells, including CD8 cells, regulatory T cells, and resting macrophages.Conclusion: We characterized the tumor microenvironment in ESCC, and identified the key prognosis genes. The risk score based on the expression profiles of these genes is proposed as an indicator of TME status and is instrumental in predicting patient prognosis.

Robot-assisted minimally invasive esophagectomy for esophageal cancer: Meticulous surgery minimizing postoperative complications.

Minimally invasive esophagectomy (MIE) has been reported to reduce postoperative complications especially pulmonary complications and have equivalent long‐term survival outcomes as compared to open esophagectomy. Robot‐assisted minimally invasive esophagectomy (RAMIE) using da Vinci surgical system (Intuitive Surgical, Sunnyvale, USA) is rapidly gaining attention because it helps surgeons to perform meticulous surgical procedures. McKeown RAMIE has been preferably performed in East Asia where squamous cell carcinoma which lies in more proximal esophagus than adenocarcinoma is a predominant histological type of esophageal cancer. On the other hand, Ivor Lewis RAMIE has been preferably performed in the Western countries where adenocarcinoma including Barrett esophageal cancer is the most frequent histology. Average rates of postoperative complications have been reported to be lower in Ivor Lewis RAMIE than those in McKeown RAMIE. Ivor Lewis RAMIE may get more attention for thoracic esophageal cancer. The studies comparing RAMIE and MIE where recurrent nerve lymphadenectomy was thoroughly performed reported that the rate of recurrent nerve injury is lower in RAMIE than in MIE. Recurrent nerve injury leads to serious complications such as aspiration pneumonia. It seems highly probable that RAMIE is beneficial in performing recurrent nerve lymphadenectomy. Surgery for esophageal cancer will probably be more centralized in hospitals with surgical robots, which enable accurate lymph node dissection with less complications, leading to improved outcomes for patients with esophageal cancer. RAMIE might occupy an important position in surgery for esophageal cancer.

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

Picropodophyllotoxin, an Epimer of Podophyllotoxin, Causes Apoptosis of Human Esophageal Squamous Cell Carcinoma Cells Through ROS-Mediated JNK/P38 MAPK Pathways.

Esophageal squamous cell carcinoma (ESCC), a major histologic type of esophageal cancer, is one of the frequent causes of cancer-related death worldwide. Picropodophyllotoxin (PPT) is the main component of Podophyllum hexandrum root with antitumor activity via apoptosis-mediated mechanisms in several cancer cells. However, the underlying mechanism of the PPT effects in apoptosis induction in cancer remains ambiguous. Hence, in this study, we evaluate the anti-cancer effects of PPT in apoptotic signaling pathway-related mechanisms in ESCC cells. First, to verify the effect of PPT on ESCC cell viability, we employed an MTT assay. PPT inhibited the viability of ESCC cells in time- and dose-dependent manners. PPT induced G2/M phase cell cycle arrest and annexin V-stained cell apoptosis through the activation of the c-Jun N-terminal kinase (JNK)/p38 pathways. Furthermore, the treatment of KYSE 30 and KYSE 450 ESCC cells with PPT induced apoptosis involving the regulation of endoplasmic reticulum stress- and apoptosis-related proteins by reactive oxygen species (ROS) generation, the loss of mitochondrial membrane potential, and multi-caspase activation. In conclusion, our results indicate that the apoptotic effect of PPT on ESCC cells has the potential to become a new anti-cancer drug by increasing ROS levels and inducing the JNK/p38 signaling pathways.

Chemoradiotherapy for Esophageal Cancer

Esophageal cancer is a highly lethal malignancy. Squamous cell cancer (SCC) and adenocarcinoma are two major histologic types of esophageal cancer. The therapeutic approaches for both histologic types tend to be similar. Endoscopic therapy is considered in patients with Tis and T1a, and surgery alone is recommended in patients with T1N0 esophageal SCC or adenocarcinoma. Definitive chemoradiotherapy is a reasonable option for patients unable to withstand surgery. Esophagectomy is considered as the initial treatment for patients with clinical T2N0 esophageal SCC and those with adenocarcinoma with low lymph node metastasis risk. Combined modality therapy is recommended for patients with T3N0, T4aN0, and clinically node-positive thoracic esophageal cancer, regardless of histology. Definitive concurrent chemoradiotherapy is the most appropriate treatment approach for patients with esophageal SCC who are not surgical candidates. Definitive concurrent chemoradiotherapy is also considered for esophageal SCC patients who are potential surgical candidates with an endoscopically documented complete response after neoadjuvant chemoradiotherapy. For chemoradiotherapy non-responders, surgery is recommended for those who remain operable after chemoradiotherapy. Esophagectomy is also recommended for patients with esophageal adenocarcinoma after neoadjuvant chemoradiotherapy. Definitive concurrent chemoradiotherapy is preferred over surgery in patients with cervical esophageal cancer because its survival rate is similar to that of surgery and major morbidity can be avoided. Concurrent chemoradiotherapy rather than radiation therapy alone is recommended for patients who can tolerate this approach for non-metastatic, inoperable, or unresectable esophageal SCC or adenocarcinoma. Key words: Chemoradiotherapy; Drug therapy; Esophageal neoplasms; Therapeutics

In silico evidence of high frequency of miRNA-related SNPs in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer significantly reported in developing nations. There is an increasing evidence suggesting that single nucleotide polymorphisms (SNPs) in the untranslated regions of genes (3'-UTRs) targeted by microRNAs (miRNAs) can change the target gene's expression and thereby affect the individual's cancer risk. Thus, in support ofthe role of SNPs occurring in miRNA target sites (miR-TS-SNPs) in the cancer, we analyzed the next generation sequencing data of 10 ESCC patients. In each patient, about 3,000 SNPs in 3'-UTRs were obtained in their whole-exome sequencing profiles. We applied two separate methods, manual and computational in silico approaches, to predict the miR-TS-SNPs with more effects on the miRNA-target interactions. dbSNP, 1000G, ExAC, Iranome, miRandb, miRCancer, TargetScan, Human, miRNASNP2 and miRBase databases were used for positive selection of miR-TS-SNPs and DIANA-miRPath v3.0 for pathway analysis. We identified six rare germline miR-TS-SNPs and two other ones with unknown miR-TS-SNPs. We interestingly observed all of these variants in only one patient, whichcan be evidence of the relationship between miR-TS-SNPs and cancer incidence. The study of cancer genetics including miR-TS-SNPs reveals miRNAs and their related pathways, whichwill be greatly useful in cancer researchfrom noninvasive biomarkers to new treatments.

Decreased risk of esophageal squamous cell carcinoma among metformin users in a population-based cohort study.

e15507 Background: Metformin, mainly used in the treatment of diabetes, may prevent various types of cancer, but no study has specifically examined its potential influence on the risk of esophageal squamous cell carcinoma, the major histological type of esophageal cancer. The aim of this study was to determine the association between metformin use and esophageal squamous cell carcinoma. Methods: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified from the Swedish Prescribed Drug Registry, 411,603 (5%) were users of metformin. The metformin users were compared with 10 times as many frequency-matched non-users of metformin (n = 4,116,030) by age and sex. Multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, calendar year, place of residence, tobacco smoking, alcohol overconsumption, and use of non-steroidal anti-inflammatory drugs or statins. Results: The incidence rates of esophageal squamous cell carcinoma were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the non-users. Metformin users overall were at a decreased risk of esophageal squamous cell carcinoma compared with non-users (adjusted HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users who were 56 years old when they started their metformin therapy (HR 0.44, 95% CI 0.30-0.65). Conclusions: Metformin therapy may decrease the risk of developing esophageal squamous cell carcinoma.

Differential Diagnosis in Esophageal Cancer. Review on literature

Esophageal cancer represents a neoplasm that is thought to have both an increased incidence and prevalence in the following years. Although much progress has been made in the detection and the early treatment of esophageal cancer, the prognosis is still limited, and mortality remains very high. The most common histological types of esophageal cancer are squamous cell carcinoma, and, respectively, adenocarcinoma. Lately, there has been an accelerated increase in the incidence of adenocarcinoma, in the context of increased prevalence of gastro-esophageal reflux disease and obesity, but also of the current alimentary diet, especially in developed countries. The esophagus has its anatomical features. Moreover, it is located topographicallyin a complex cervico-thoraco-abdominal area, unique for a viscus. From the clinical point of view, the onset of symptoms of esophageal cancer is insidious. For these reasons, special attention should be pain in the early detection and differentiation of this neoplasm from other pathologies. These pathologies are very varied and may comprise other esophageal diseases, neighborhood pathologies such as cervical, thoracic, abdominal, systemic pathologies (immunologic, infectious) or other pathologies such as the oro-maxillo-facial, oculo-orbital, vascular, muscular, and cutaneous ones. Keywords: esophagus, cancer, differential diagnosis