Primary Esophageal Cancer Research Articles

Outcomes of curative esophageal cancer surgery in elderly: A meta-analysis.

BACKGROUNDAn increasing number of older patients is undergoing curative, surgical treatment of esophageal cancer. Previous meta-analyses have shown that older patients suffered from more postoperative morbidity and mortality compared to younger patients, which may lead to patient selection based on age. However, only studies including patients that underwent open esophagectomy were included. Therefore, it remains unknown whether there is an association between age and outcome in patients undergoing minimally invasive esophagectomy.AIMTo perform a systematic review on age and postoperative outcome in esophageal cancer patients undergoing esophagectomy.METHODSStudies comparing older with younger patients with primary esophageal cancer undergoing curative esophagectomy were included. Meta-analysis of studies using a 75-year age threshold are presented in the manuscript, studies using other age thresholds in the Supplementary material. MEDLINE, Embase and the Cochrane Library were searched for articles published between 1995 and 2020. Risk of bias was assessed with the Newcastle-Ottawa Scale. Primary outcomes were anastomotic leak, pulmonary and cardiac complications, delirium, 30- and 90-d, and in-hospital mortality. Secondary outcomes included pneumonia and 5-year overall survival.RESULTSSeven studies (4847 patients) using an age threshold of 75 years were included for meta-analysis with 755 older and 4092 younger patients. Older patients (9.05%) had higher rates of 90-d mortality compared with younger patients (3.92%), (confidence interval = 1.10-5.56). In addition, older patients (9.45%) had higher rates of in-hospital mortality compared with younger patients (3.68%), (confidence interval = 1.01-5.91). In the subgroup of 2 studies with minimally invasive esophagectomy, older and younger patients had comparable 30-d, 90-d and in-hospital mortality rates. CONCLUSIONOlder patients undergoing curative esophagectomy for esophageal cancer have a higher postoperative mortality risk. Minimally invasive esophagectomy may be important for minimizing mortality in older patients.

Survival benefit of perioperative chemotherapy for T1-3N0M0 stage esophageal cancer: a SEER database analysis.

BackgroundThe effect of perioperative chemotherapy on patients with lymph node-negative esophageal cancer (EC) is controversial. This study explored which EC patients, staged under the T1-3N0M0, would benefit from perioperative chemotherapy.MethodsData on patients with diagnosed primary EC were retrieved from Surveillance, Epidemiology and End Results (SEER) database. Propensity score-matched (PSM) method was performed to balance baseline covariates. Multivariate Cox regression analysis and Kaplan-Meier curve were used to assess potential survival difference between patients undergoing surgery plus perioperative chemotherapy (SA + CT) and those undergoing surgery alone (SA).ResultsIn a total of 2,711 EC patients (T1–3N0M0), 166 patients underwent SA + CT and 2,545 patients received SA. In the multivariable analysis, T stage was significantly related to prognosis of EC patients before and after matching. Subgroup analysis showed that perioperative chemotherapy was associated with poor cancer-specific survival (CSS) for stage T1 patients. There was no effect of perioperative chemotherapy on overall survival (OS) or CSS for T2 patients, whereas a remarkable improvement in OS and CSS was observed for T3 patients. Survival analysis showed that T3 stage EC patients obtained survival benefit from SA + CT. Prognosis in the SA group was significantly better than in the SA + CT group for T1 patients. However, T2 patients showed no significant increase in survival after undergoing SA + CT compared with SA.ConclusionsT3 patients benefit more from SA + CT. However, perioperative chemotherapy does not present survival benefit to T1–2 patients, and it is an adverse prognostic factor for T1 patients.

Risk Factors and Genetic Biomarkers of Multiple Primary Cancers in Esophageal Cancer Patients.

Esophageal cancer (EC) is a deadly cancer that frequently develops multiple primary cancers (MPCs). However, the risk biomarkers of MPC in EC have hardly been investigated. We retrospectively enrolled 920 subjects with primary EC and analyzed the possible risk factors as well as MPC single-nucleotide polymorphisms (SNPs) from blood DNA. A total of 184 subjects (20.0%) were confirmed to have MPC, 59 (32.8%) had synchronous MPC, and 128 (69.6%) had head and neck cancer. Elderly EC patients have an increased risk of having gastrointestinal cancer (Odds ratio, OR[95% CI]=6.70 [1.49–30.19], p=0.013) and a reduced risk of developing HNC (OR[95% CI]=0.44 [0.24–0.81], p=0.008). MPC risk was also associated with betel nut chewing (OR[95% CI]=1.63, 1.14–2.32], p=0.008), the A allele of ALDH2:rs671 (p=0.074 and 0.030 for GA and AA, respectively), the CC genotype in CISH:rs2239751 (OR[95% CI]=1.99 [1.2–3.32], p=0.008), and the G allele of ERCC5:rs17655 (p=0.001 and 0.090 for GC and CC, respectively). ADH1B:rs1229984 also correlated with MPC risk (p=0.117). Patients carrying four risk SNPs had a 40-fold risk of MPC (OR[95% CI]=40.25 [6.77–239.50], p<0.001) and a 12.57-fold risk of developing second primary cancer after EC (OR[95% CI]=12.57 [1.14–138.8], p=0.039) compared to those without any risk SNPs. In conclusion, hereditary variations in ALDH2, CISH, ERCC5, and ADH1B have great potential in predicting the incidence of MPC in EC patients. An extensive cancer screening program during clinical follow-up would be beneficial for patients with high MPC susceptibility.

Multiple Primary Synchronous Gastric, Esophageal, and Rectal Cancer and Isolated Esophageal Metastasis from Rectal Cancer: Case Report

Multiple Primary Synchronous Gastric, Esophageal, and Rectal Cancer and Isolated Esophageal Metastasis from Rectal Cancer: Case Report

Downregulation of miR-375 contributes to ERBB2-mediated VEGFA overexpression in esophageal cancer.

Esophageal cancer (EC) is a lethal cancer with an extremely aggressive nature and poor survival rate. However, the molecular mechanisms driving the occurrence and progression of EC are not well understood. MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of protein-coding genes. miRNA-mediated gene regulation plays an important role in EC. By cross-referencing studies from NCBI, we found that microRNA-375 (miR-375) is one of the most frequently downregulated miRNAs in EC. We assessed expression of miR-375 in EC cell lines and primary EC tissues and their matched normal tissues. We found significant downregulation of miR-375 in both cell lines and EC tissues. Forced expression of miR-375 attenuated EC cell proliferation and invasion. Human epidermal growth factor receptor 2 (HER2, ERBB2), a known proto-oncogene, was identified here as one of the potential target genes of miR-375. Ectopic expression of miR-375 significantly suppressed the expression of ERBB2 and subsequently downregulated one of its target genes, vascular endothelial growth factor A (VEGFA), which is related to cancer invasion and metastasis. These findings suggest that miR-375 acts as a tumor suppressor by blocking the ERBB2/VEGFA pathway with the potential to modulate the occurrence and/ or progression of EC.

The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study

BackgroundThe epidemiology of esophageal cancer has changed dramatically over the past 4 decades in many Western populations. We aimed to understand the Hungarian epidemiologic trends of esophageal squamous cell cancer (SCC) and adenocarcinoma (AC).MethodsWe performed a cross-sectional study using data from esophageal cancer patients diagnosed between 1992 and 2018 at eight tertiary referral centers in four major cities of Hungary. We retrospectively identified cases in the electronic databases of each center and collected data on gender, age at diagnosis, year of diagnosis, specialty of the origin center, histological type, and localization of the tumor. Patients were grouped based on the two main histological types: AC or SCC. For statistical analysis, we used linear regression models, chi-square tests, and independent sample t tests.ResultsWe extracted data on 3,283 patients with esophageal cancer. Of these, 2,632 were diagnosed with either of the two main histological types; 737 had AC and 1,895 SCC. There was no significant difference in the gender ratio of the patients between AC and SCC (80.1 vs 81.8% males, respectively; p = 0.261). The relative incidence of AC increased over the years (p < 0.001, b = 1.19 CI: 0.84–1.54). AC patients were older at diagnosis than SCC patients (64.37 ± 11.59 vs 60.30 ± 10.07 years, p < 0.001). The age of patients at the diagnosis of primary esophageal cancer increased over time (p < 0.001, R = 0.119).ConclusionsThe rapid increase in the relative incidence of AC and simultaneous decrease of the relative incidence of SCC suggest that this well-established Western phenomenon is also present in Hungary.

Long-term Survival After Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Nationwide Propensity-score Matched Analysis.

This study aimed to compare long-term survival following MIE versus OE for esophageal cancer using a nationwide propensity-score matched cohort. MIE provides lower postoperative morbidity and mortality, and similar short-term oncological quality compared to OE. Data was acquired from the Dutch Upper Gastrointestinal Cancer Audit. Patients undergoing minimally invasive or open, transthoracic or transhiatal esophagectomy for primary esophageal cancer between 2011 and 2015 were included. A propensity-score matching analysis for MIE versus OE was performed separately for transthoracic and transhiatal esoph-agectomies. A total of 1036 transthoracic MIE and OE patients, and 582 transhiatal MIE and OE patients were matched. Long-term survival was comparable for MIE and OE for both transthoracic and transhiatal procedures (5-year overall survival: transthoracic MIE 49.2% vs OE 51.1%, P 0.695; transhiatal MIE 48.4% vs OE 50.7%, P 0.832). For both procedures, MIE yielded more lymph nodes (transthoracic median 21 vs 18, P < 0.001; transhiatal 15 vs 13, P 0.007). Postoperative morbidity was comparable after transthoracic MIE and OE (60.8% vs 64.9%, P 0.177), with a reduced length of stay after transthoracic MIE (median 12 vs 15 days, P < 0.001). After transhiatal MIE, more postoperative complications (64.9% vs 56.4%, P 0.034) were observed, without subsequent difference in length of stay. Long-term survival after MIE was equivalent to open in both propensity-score matched cohorts of patients undergoing transthoracic or transhiatal esophageal resections. Transhiatal MIE was accompanied withmore postoperative morbidity. Both transthoracic and transhiatal MIE resulted in a more extended lymphadenectomy.

Stenting of the esophagus in the course of the malignant dysphagia in elderly patients

Esophageal cancer is a disease with difficult clinical management, and palliative therapy is the only predominant treatment. This retrospective study analyses the results of clinical management of elderly patients (&gt;75 years of age) who were treated with esophageal stenting for malignant dysphagia due to primary esophageal cancer, including squamous cell carcinoma (SCC), esophageal adenocarcinoma (EAC), as well as secondary esophageal malignant strictures due to non-small cell lung cancer (NSCLC). Patients with esophago-respiratory fistula (ERF) were also included in the study. This study included 166 patients aged 75–88 (mean age, 78) years. Nine (5.4%) patients had upper malignant esophageal stenosis, 48 (28.1%) had the middle, 43 (25.9%) in the lower part of the esophagus, 49 (29.5%) patients had EAC-related stenosis, and 17 (10.2%) patients reported lung cancer-related esophageal stenosis. Dysphagia was rated at 2.8 (range, 2–3) before stenting and at 1.2 (range, 1–2) after the stenting procedure. Seven (4%) patients experienced stenting migration, 12 (7.2%) had granulation tissue overgrowth and prosthesis obstruction, two (1.2%) developed respiratory failure, and one (0.6%) patient died. Twelve (7.2%) patients were treated for ERF with double-stenting, and three (1.8%) patients developed a secondary fistula after the stent implantation. The mean survival of patients with esophageal cancer and ERF was 101.8 days and 62.5 days, respectively. Esophageal stenting has proven a safe procedure in patients over 75 years of age. It has a low rate of stenting obstruction and migration. Patients with ERF are a particularly difficult group to treat, show very poor outcomes and short survival rates.

The clinical and financial cost of mental disorders among elderly patients with gastrointestinal malignancies.

The clinical and financial effects of mental disorders are largely unknown among gastrointestinal (GI) cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database, we identified patients whose first cancer was a primary colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer as well as those with coexisting depression, anxiety, psychotic, or bipolar disorder. Survival, chemotherapy use, total healthcare expenditures, and patient out‐of‐pocket expenditures were estimated and compared based on the presence of a mental disorder. We identified 112,283 patients, 23,726 (21%) of whom had a coexisting mental disorder. Median survival for patients without a mental disorder was 52 months (95% CI 50–53 months) and for patients with a mental disorder was 43 months (95% CI 42–44 months) (p < 0.001). Subgroup analysis identified patients with colorectal, gastric, or anal cancer to have a significant association between survival and presence of a mental disorder. Chemotherapy use was lower among patients with a mental disorder within regional colorectal cancer (43% vs. 41%, p = 0.01) or distant colorectal cancer subgroups (71% vs. 63%, p < 0.0001). The mean total healthcare expenditures were higher for patients with a mental disorder in first year following the cancer diagnosis (increase of $16,823, 95% CI $15,777‐$18,173), and mean patient out‐of‐pocket expenses were also higher (increase of $1,926, 95% CI $1753–$2091). There are a substantial number of GI cancer patients who have a coexisting mental disorder, which is associated with inferior survival, higher healthcare expenditures, and greater personal financial burden.

330 Poster - Exposure of the oesophagus in breast cancer radiotherapy: A systematic review of oesophageal doses published 2013–2018

Background: Breast cancer radiotherapy has been shown to increase the risk of subsequent primary oesophageal cancer. It is unclear if avoidance of the oesophagus is being considered routinely during radiotherapy treatment planning. This study aims to describe exposure of the oesophagus from modern breast cancer regimens.

Clinical outcomes of endoscopic piecemeal mucosal resection for superficial esophageal carcinoma and precancerous lesions

Objective: To explore the short and long-term outcomes of endoscopic piecemeal mucosal resection including endoscopic mucosal resection (EMR) and multiband mucosectomy (MBM) for superficial esophageal carcinoma and precancerous lesions, and analyze the risk factors for prognosis. Methods: From March 1 2001 to May 31 2017, 371 patients with 416 lesions who were diagnosed as superficial esophageal carcinoma or high-grade intraepithelial neoplasm and underwent EMR or MBM were retrospectively enrolled in this study. Long-term recurrence free survival (RFS) rate and the risk factors, including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, for the long-term outcome were also analyzed. Results: The incidence of complication was 17.1% in the EMR group and 17.4% in the MBM group, without significant difference (P=1.000). The median follow-up period was 70.6 months. The 5-years RFS was 93.9% and 10-years RFS was 87.8%, respectively. Local recurrence was found in 2 cases in each group and they were curatively treated by endoscopic submucosal dissection. Heterogeneous multiple primary esophageal cancer was diagnosed in 5 and 3 cases for the EMR and MBM group, of whom 5 cases were curatively treated with endoscopic resection. Other 3 cases were diagnosed with advanced esophageal cancer, of whom 2 patients died. Lymph node metastasis (LNM) was found in 5 cases in the EMR group and 4 cases in the MBM group, of whom 6 patients died. Distant metastasis was found in 5 cases in the EMR group and 3 cases in the MBM group, of whom 5 patients died. There were 83 patients combined with risk factors including submucosal invasion, poorly differentiation, vascular invasion and positive vertical margin, of whom 8 patients were diagnosed as LNM and 8 patients as distant metastasis. The 5-years RFS of patients with 1, 2, and 3 risk factors were 93.6%, 82.2%, and 25.0%, and the difference was statistically significant (P<0.001). Conclusions: EMR and MBM are both safe and feasible procedures for superficial esophageal carcinoma and precancerous lesions. Additional treatments should be selected according to the variety of risk factors to acquire better long-term outcome and life quality.

Chinese expert consensus on multiple primary cancers of hypopharynx and esophagus

Hypopharyngeal cancer and esophageal cancer often occur synchronously or metachronously. Timely screening, diagnosis and individual treatment are important to improve the prognosis of patients. At present, there is no clinical guideline or consensus in this cross-cutting area in China, and there is a need of consistent diagnosis and treatment recommendation for these patients. Under the sponsorship of the Committee of Esophageal Cancer in China Anti-Cancer Association, the Chinese Working Group on Cooperative Diagnosis and Treatment of Hypopharyngeal and Esophageal Cancer was established by domestic experts in the fields of otolaryngology head and neck surgery, radiation oncology, and gastrointestinal endoscopy. This consensus document on multiple primary cancers (simultaneous or metachronous) of the hypopharynx and esophagus was developed through literature review, collective experience and expert discussions. The goals of the consensus include: (1) raising concern for this cross-cutting field; (2) establishing a preliminary clinical diagnosis and treatment recommendation; (3) preparing for the establishment of future high-level guidelines through standardized clinical practice.

Safety and feasibility of minimally invasive surgical interventions for esophageal and gastric cancer in the acute setting: a nationwide cohort study

BackgroundMinimally invasive esophagectomy and gastrectomy are increasingly performed and might be superior to their open equivalents in an elective setting. The aim of this study was to evaluate whether minimally invasive approaches can be safely applied in the acute setting as well.MethodsAll patients who underwent an acute surgical intervention for primary esophageal or gastric cancer between 2011 and 2017 were identified from the nationwide database of the Dutch Upper GI Cancer Audit (DUCA). Conversion rates, postoperative complications, re-interventions, postoperative mortality, hospital stay and oncological outcomes (radical resection rates and median lymph node yield) were evaluated.ResultsBetween 2011 and 2017, surgery for esophagogastric cancer was performed in an acute setting in 2% (190/8861) in The Netherlands. A total of 14 acute resections for esophageal cancer were performed, which included 7 minimally invasive esophagectomies and 7 open esophagectomies. As these numbers were very low, no comparison between minimally invasive and open esophagectomies was made. A total of 122 acute resections for gastric cancer were performed, which included 39 minimally invasive gastrectomies and 83 open gastrectomies. Conversion occurred in 9 patients (23%). Minimally invasive gastrectomy was at least comparable to open gastrectomy regarding postoperative complications (36% versus 51%), median hospital stay (9 days [IQR: 7–16 days] versus 11 days [IQR: 7–17 days]), readmissions (8% versus 11%) and oncological outcomes (radical resection rate: 87% versus 66%, median lymph node yield: 21 [IQR: 15–32 days] versus 16 [IQR: 11–24 days]).ConclusionsMinimally invasive surgery for gastric cancer is safe and feasible in the acute setting, with at least comparable postoperative clinical and short-term oncological outcomes compared to open surgery but a relatively high conversion rate.

Complications Related to Esophageal Stent (Boston Scientific Wallflex vs. Merit Medical Endotek) Use in Benign and Malignant Conditions

BackgroundIn our institutions, there are two types of stents used: the Boston Scientific Wallflex (Marlborough, Massachusetts) and Merit Medical Endotek (South Jordan, Utah). So we performed this retrospective study to compare complication rates in various esophageal disorders to improve our quality of care.MethodsCharts were reviewed to capture gender, indications of stent placement, stent length/diameter, age of the patient at the time of stent placement, length of hospital stay, physicians performing a procedure, and complications within 90 days of stent placement.ResultsA total of 67 patients (71.6% male) underwent stent placement (WallFlex 49.3% and Merit 50.8%) for malignant (68.7%) mainly esophageal obstruction by primary esophageal cancer (89.1%) and benign causes (31.3%) mainly esophageal leak (66.7%). Merit and WallFlex used in malignant conditions were 82.4% and 54.6%, respectively, and in benign conditions, they were 17.7% and 45.5%, respectively. The mean age at which endoscopy was performed was 64. Complications post Merit and WallFlex placement were 79.4% and 60.6%, respectively. Complications with malignant and benign conditions were 73.9% and 61.9%, respectively. Complications with 19, 18, and 23 mm diameters were 75.0%, 66.7%, and 69.4%, respectively. Complications with 120, 150, 100, 15, 12, 10 mm stent lengths were 84.6%, 58.3%, 58.8%, 80.0%, 75.0%, and 33.3%, respectively.ConclusionOur study showed that the Merit stent was mainly used, and the major indication of stent placement was a malignant condition. Major complications were seen when the reason for stent placement was a malignant condition, the diameter was 19 mm, the length was 120 mm, and the use of the Merit stent.

Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation.

Long non-coding RNAs (lncRNAs) are transcribed pervasively in the genome and act to regulate chromatin remodeling and gene expression. Dysregulated lncRNA expression has been reported in many cancers, but the role of lncRNAs in esophageal cancer (EC) has so far remained poorly understood. In this study, we aimed to understand the effect of lncRNA LINC01234 on EC development through competitively binding to microRNA-193a-5p (miR-193a-5p). The Gene Expression Omnibus (GEO) database was used for microarray-based EC expression profiling. Gain- and loss-of-function analyses were carried out in human EC-derived Eca-109 and EC9706 cells. Expression analyses of miR-193a-5p, LINC01234, CCNE1, caspase-3, p21, Bax, cyclinD1 and Bcl-2 were performed using RT-qPCR and Western blotting. Cell proliferation, colony formation and apoptosis analyses were carried out using MTT, Hoechst 33258 and flow cytometry assays. A xenograft EC model in nude mice was used to evaluate in vivo tumor growth and CCNE1 expression. Microarray-based analyses revealed that LINC01234 expression was increased in primary EC samples, whereas that of miR-193a-5p was decreased. We found that CCNE1 was a target of miR-193a-5p and that LINC01234, in turn, sponges miR-193a-5p. After treatment with si-LINC01234 or miR-193a-5p mimic, EC cells (Eca-109 and EC9706) exhibited cyclinD1 and Bcl-2 downregulation, and caspase-3, p21, Bax and cleaved caspase-3 upregulation. LINC01234 silencing or miR-193a-5p upregulation resulted in decreased proliferation and colony formation, and increased apoptosis of EC cells. In addition, LINC01234 silencing or miR-193a-5p upregulation resulted in reduced in vivo EC tumor growth and CCNE1 expression in nude mice. We found that silencing of LINC01234 suppresses EC development by inhibiting CCNE1 through competitively binding to miR-193a-5p, which suggests that LINC01234 may represent a novel target for EC therapy.

Epigenetic therapy inhibits metastases by disrupting premetastatic niches.

Cancer recurrence after surgery remains an unresolved clinical problem1-3. Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4-6. There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7. Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy.

Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling

BackgroundThere are seven insulin-like growth factor binding proteins (IGFBPs) that bind insulin-like growth factors (IGFs). IGFBP like protein1 (IGFBPL1) is a new member of this family. The function and mechanism of IGFBPL1 in esophageal cancer remains to be elucidated.MethodsEight esophageal cancer cell lines, 114 cases of esophageal dysplasia, and 501 cases of primary esophageal cancer samples were examined in this study. Methylation-specific polymerase chain reaction (MSP), immunohistochemistry, Western blot, flow cytometry, RNA interference assay, and xenograft mouse models were employed.ResultsThe expression of IGFBPL1was lost and complete methylation was found in KYSE150 and KYSE410 cells. Reduced expression and partial methylation of IGFBPL1 was found in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells. High expression and unmethylation was detected in KYSE510 cells. Restoration of IGFBPL1 expression was found in KYSE150 and KYSE410 cells and the expression of IGFBPL1 was increased in Bic1, KYSE140, KYSE450, KYSE520, and COLO680N cells, after 5-AZA-2′-deoxycytidine treatment. IGFBPL1 was methylated in 47.3% (53/114) of esophageal dysplasia and 49.1% (246/501) of human primary esophageal squamous cell carcinoma (ESCC). Methylation of IGFBPL1 was significantly associated with TNM stage (p = 0.012), and tumor size (p = 0.009). IGFBPL1 inhibited esophageal cancer cell clonal formation and proliferation and induced cell apoptosis and G1/S phase arrest. Further study found that IGFBPL1 is involved in PI3K-AKT signaling and IGFBPL1 suppressed human ESCC xenografts growth in mice.ConclusionIGFBPL1 suppresses esophageal cancer cell growth by inhibiting PI3K-AKT signaling in vitro and in vivo. IGFBPL1 is a novel tumor suppressor in human esophageal cancer.

Clinicopathological features and prognosis of patients with esophageal cancer as the second primary cancer: a large population-based analysis using the SEER program [2000-2015

BackgroundThis study used the Surveillance, Epidemiology, and End Results (SEER) data to investigate clinicopathological characteristics and prognoses of patients with esophageal cancer as a second primary cancer from 2000 to 2015.MethodsEsophageal cancer as the second primary cancer (SEPC) patient information collected from the SEER database were extracted, evaluated, and compared with only primary esophageal cancer (OPEC) patient data. Overall survival (OS) was evaluated by the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) by the Cox proportional hazards regression identified risk factors that predicted OS and the results were used to construct a nomogram to predict OS in SEPC patients.ResultsA total of 7,161 esophageal cancer patients were identified from the SEER registry, which included 813 patients (11.4%) with SEPC in the patient history. The most common cancer for the first primary cancer prior to esophageal cancer (FPC) was genital system cancer (43.5%). The median OS was 7 (95% CI: 6.69–11.31) months and was not significantly different from that of patients with OPEC. The patients with SEPC appeared with unique clinical pathological features compared with OPEC, including older age, more squamous cell carcinoma, and early stage esophageal cancer, and less lower third of esophageal cancer (P<0.001). UVA and MVA identified M stage, surgery, and chemotherapy as independent risk factors. The nomogram had a calibration index of 0.682.ConclusionsSEPC had unique clinicopathological characteristics. M stage, surgery, and chemotherapy were independently associated with OS. The nomogram accurately predicted OS.

Superiority of NBI endoscopy to PET/CT scan in detecting esophageal cancer among head and neck cancer patients: a retrospective cohort analysis

BackgroundSecond primary cancer of the esophagus is frequent in head and neck patients, especially in high-risk populations, and has a great impact on the prognosis. Although Positron emission tomography (PET)/computed tomography (CT) scan is commonly conducted in head and neck patients, its ability to detect early esophageal cancer is limited. Narrow-band imaging endoscopy is an accurate and convenient technique for esophageal examination. We aimed to compare PET/CT scan and narrow-band imaging endoscopy for the detection of esophageal cancer in head and neck cancer patients.MethodsFrom November 2015 to November 2018, all head and neck cancer patients who underwent both PET/CT scan and narrow-band imaging endoscopy at Changhua Christian Hospital were retrospectively enrolled. Descriptive statistics, receiver operating characteristic curve analysis, logistic regression analysis, independent Student’s t-test, and Kaplan–Meier survival analysis were conducted with MedCalc Statistical Software.ResultsA total of 147 subjects were included in the analysis; suspicious esophageal lesions were identified by PET/CT scan in 8 (5.44%) and by narrow-band imaging in 35 (23.81%). The final pathologic diagnoses were esophageal squamous cell carcinoma in 10 and high-grade dysplasia in 5. The respective sensitivity, specificity, and area under the curve for detecting suspicious esophageal lesions were 33.33, 97.73%, and 0.655 for PET/CT scan, and 100.0, 84.85%, and 0.924 for narrow-band imaging endoscopy. Hypopharyngeal or laryngeal location of the primary head and neck cancer was the only risk factor for developing second primary esophageal cancer.ConclusionsPET/CT scan was inferior to narrow-band imaging endoscopy in detecting second primary esophageal cancer in head and neck cancer patients. In addition to PET/CT scan, narrow-band imaging endoscopy should be considered in head and neck patients at high risk for developing second primary esophageal cancer.

Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer.

Background:Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown.Methods:Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS).Results:Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways.Conclusions:When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.