Survival In Esophageal Carcinoma Research Articles

18F]FDG PET/CT beyond staging: Prognostic significance of sarcopenia and adipose tissue metabolism in esophageal carcinomas.

This study aimed to investigate the relationship between PET and CT parameters and sarcopenia, adipose tissue, and tumor metabolism in esophageal carcinoma (EC) and its impact on survival in EC. Our study included 122 EC patients who underwent PET/CT for staging. Muscle and adipose tissue characteristics were evaluated, including lumbar (L3) and cervical (C3) muscle areas, psoas major (PM) and sternocleidomastoid muscle (SCM) parameters, and PET parameters for visceral and subcutaneous adipose tissue (SAT). Sarcopenia was determined using CT images, with a threshold for muscle tissue at the L3 vertebral level, and its impact on overall survival (OS) was investigated. Sarcopenia was detected in 48 patients. SULmax in the primary tumor (PT) was significantly higher in sarcopenic patients (SP). The frequency of distant metastasis was higher in SP and OS was significantly lower. In the locally advanced stage, sarcopenia status decreased survival. L3, PM, C3, and SCM muscle areas were highly correlated. Subcutaneous adipose tissue SUVmax was significantly increased in SP and those with distant metastasis. Univariate analysis identified PT SULmax, PT SUVmean, PT TLG, lymph node and distant metastasis, SAT SUVmax, and sarcopenia as poor prognostic factors, while multivariate analysis confirmed BMI, distant metastasis, PT SUVmean, PT TLG as independent predictors of OS. This study demonstrated that sarcopenia, linked to reduced survival, correlates with primary tumor SULmax, distant metastasis, and subcutaneous tissue PET parameters, exerting a notable impact on survival, particularly in locally advanced stages. Attenuation-corrected CT can be used instead of diagnostic CT, and sarcopenia can be diagnosed using not only L3 but also C3 slices.

18Fluorodeoxyglucose positron emission tomography (18F-FDG PET)–derived tumoral and peritumoral radiomic parameters can predict pathological subtype and survival in esophageal carcinoma

The aim of this study is to investigate the importance of the quantitative parameters of the tumoral and peritumoral regions in prediction of pathological subtypes and 1-year survival in patients with esophageal carcinoma. A total of 103 patients with esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC) and in whom 18fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) was performed were included in the study. One-year progression-free survival (PFS) and overall survival times of all patients were noted. Primary tumor and peritumoral area were drawn with manual segmentation on the 18F-FDG PET images. Seventy-three quantitative parameters were extracted from tumoral and peritumoral volumes of interest by using software. The differences of parameters of tumoral and peritumoral regions were determined statistically between pathological subtypes and between 1-year survivors and non-survivors. Diagnostic models were created with the statistically significant parameters. The model that consists of a tumoral and a peritumoral parameter could classify the pathological subtypes in 61% of the patients correctly (area under the curve [AUC]: 0.706, 61.2% accuracy, 53.7% sensitivity, and 75% specificity). The model that was created with 2 tumoral parameters could classify the 1-year survival in 66% of the patients correctly (AUC: 0.695, 66% accuracy, 73.6% sensitivity, and 56.1% specificity). The model consisting of a tumoral and a peritumoral parameter detected 1-year PFS in 66% of the patients accurately (AUC: 0.687, 66% accuracy, 72.4% sensitivity, and 55.6% specificity). The quantitative parameters obtained from tumoral and peritumoral regions can provide information about pathological subtypes and 1-year survival in esophageal carcinoma.

Impacts of heavy smoking on non-coding RNA expression for patients with esophageal carcinoma

BackgroundSmoking is a well-recognized risk factor for esophageal carcinoma, but the underlying molecular mechanism remains unclear. Previous studies have demonstrated the predictive value of non-coding RNA (ncRNA) for the prognosis of esophageal carcinoma; however, the expression of smoking-related ncRNAs has not been systematically characterized. Herein, we comprehensively assessed the hazard of heavy smoking and its impact on ncRNA expression patterns in patients with esophageal carcinoma.MethodsTranscriptome and clinical features of patients with esophageal carcinoma were acquired from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was employed to calculate the hazard ratio (HR) of smoking behavior. Differential expression analysis was conducted with the “edgeR” package. The smoking-related RNA regulatory network was based on lncRNA‒miRNA and miRNA‒mRNA pairs and visualized by Cytoscape 3.7.1. We applied Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for functional annotation. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used for model construction. We applied Kaplan‒Meier analysis with a log-rank test for survival analysis, with group comparison by the Wilcoxon signed ranked test.ResultsHeavy smoking contributed to the poor overall survival of esophageal carcinoma, with an HR of 3.167 (95% CI: 1.077–9.312). A total of 195 lncRNAs and 73 miRNAs were differentially expressed between patients with or without smoking behavior. We constructed smoking-related RNA regulatory networks, and functional annotation enriched a series of cancer-related pathways. We generated a smoking-related prognostic risk score and found that patients with a high score had a poor prognosis. Fourteen out of 23 immune cell types differentially infiltrated into a distinct risk group, while no correlation was observed between the risk score and immune cells.ConclusionAltogether, we profiled smoking-related ncRNA expression patterns and constructed an RNA regulatory network, providing a landscape of smoking-related molecular mechanisms of esophageal carcinoma. The smoking-related risk score, which was related to prognosis, revealed that tobacco smoking could suppress tumor immunity via the ncRNA mechanism.

Radiation Dose-Effect Relation in Patients with Esophageal Squamous Cell Carcinoma: A National Cancer Center Data and Literature-Based Analysis.

Introduction Despite receiving definitive chemoradiotherapy (dCRT) with radiation dose (RTD) of 50.4 Gy, survival of esophageal carcinoma was dismal. The effect of RTD in cancer control and radiotoxicity, and the extent to which local-regional control (LRC) influenced survival remain vague. This study aimed at evaluating RTD-effect relationship in esophageal squamous cell carcinoma (ESCC). Methods 1440 dRT/CRT-treated ESCC patients were enrolled. Restricted cubic spline regression model was applied to reveal nonlinear relationship between RTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRC and overall survival (OS) or progression-free survival (PFS). Results For 1440 dRT/CRT-treated ESCC patients, with RTD escalating, hazard ratios (HRs) of OS, PFS, LRC declined until RTD exceeded 60 Gy, then increased. HR of treatment-related mortality was stable until RTD exceeded 60 Gy, then increased. HR of LRC was lower for majority of patients treated with RTD≥60 Gy, except for those with KPS<80, T1-2 lesion, or without lymph node metastasis. LRA revealed strong correlations between LRC and OS/PFS. 45.5% and 44.9% of OS and PFS improvements were owing to improved LRC. Conclusions RTD of 60 Gy was well tolerated, with favorable survival resulted of LRC improvement in local-advanced ESCC. Further stratification analyses based on radiation sensitivity will be helpful to determine potential beneficiaries of RTD escalation.

Is Tumor Regression Grade Sufficient to Predict Survival in Esophageal Cancer with Trimodal Therapy?

Background This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT). Methods Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan–Meier method and log–rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods. Results From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264–5.566, P < 0.001) and disease-free survival (HR: 2.801, 95% CI: 1.874–4.187, P < 0.001). The modified TRG system combining tumor regression with nodal status stratified patients survival with good discrimination. Conclusions Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.

Effect of perioperative flurbiprofen axetil on long-term survival of patients with esophageal carcinoma who underwent thoracoscopic esophagectomy: A retrospective study.

Background and ObjectivesNonsteroidal anti‐inflammatory drugs (NSAIDs) have an anti‐inflammatory response, but it remains unclear whether the perioperative use of flurbiprofen axetil can influence postoperative tumor recurrence and survival in esophageal carcinoma. We aimed to explore the effect of perioperative intravenous flurbiprofen axetil on recurrence‐free survival (RFS) and overall survival (OS) in patients with esophageal carcinoma who underwent thoracoscopic esophagectomy.MethodsThis retrospective study included patients who underwent surgery for esophageal carcinoma between December 2009 and May 2015 at the Department of Thoracic Surgery, Anhui Provincial Hospital. Patients were categorized into a non‐NSAIDs group (did not receive flurbiprofen axetil), single‐dose NSAIDs group (received a single dose of flurbiprofen axetil intravenously), and multiple‐dose NSAIDs group (received multiple doses of flurbiprofen).ResultsA total of 847 eligible patients were enrolled. Univariable and multivariable analyses revealed that the intraoperative use of flurbiprofen was associated with long‐term RFS (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.42–0.76, p = .001) and prolonged OS (HR: 0.49, 95% CI: 0.38–0.63, p = .001).ConclusionsPerioperative flurbiprofen axetil therapy may be associated with prolonged RFS and OS in patients with esophageal carcinoma undergoing thoracoscopic esophagectomy.

Expression of CDC20, TOP2A in Esophageal Phosphorus Carcinoma and Its Relationship with Survival of Esophageal Carcinoma

Objective: To study the expression of CDC20, TOP2A in esophageal squamous cell carcinoma and its relationship with survival of esophageal carcinoma. Methods: 65 patients with esophageal squamous cell carcinoma from January 2016 to June 2018 were selected by computer random selection. All patients were treated with radical operation. The CDC20, TOP2A expression of the patients was examined. At the same time, the relationship between 3-year survival rate and CDC20, TOP2A was analyzed by follow-up investigation. Results: the CDC20, TOP2A expression level of cancer tissue group was higher than that of adjacent tissue group and normal tissue group (P &lt;0.05), and the CDC20, TOP2A expression level of adjacent tissue group was higher than that of normal tissue group (P &lt;0.05). There was no significant difference in sex, age, tumor size, tumor location and CDC20, TOP2A expression level in patients with esophageal squamous cell carcinoma, P &gt;0.05; there were differences between groups (P P &gt;0.05) and positive proportion in TNM stage, lymphatic metastasis, invasion factor and CDC20, TOP2A expression level; there were differences in tumor differentiation, 5-year survival rate and CDC20, TOP2A expression level (P P &gt;0.05), and showed inverse proportion relationship. Conclusion: metastasis, recurrence and prognosis of esophageal squamous cell carcinoma are related to the level of CDC20,TOP2A expression. These two indexes can effectively evaluate the pathological situation of esophageal cancer and provide an important reference for the prognosis of esophageal squamous cell carcinoma patients.

The Academic Facility Is Associated with Higher Utilization of Esophagectomy and Improved Overall Survival for Esophageal Carcinoma

BackgroundOperable esophageal carcinoma is potentially curable with surgical resection. The short-term outcomes and overall survival rate for operable esophageal carcinoma may be impacted by the healthcare facility type where patients receive care. MethodsA total of 37, 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Data Base at over 12,721 facilities were analyzed. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazard models were used to evaluate differences in overall survival between facility types, which accounted for facility esophageal cancer volume. Propensity score methodology with inverse probability of treatment weighting was used to adjust for patient related baseline differences between facility types. ResultsPatients with clinical stage I–III esophageal carcinoma who underwent esophagectomy at academic healthcare facilities had a significantly better overall survival compared with patients who underwent esophagectomy at community healthcare facilities [HR = 0.89: CI [0.84–0.95] (p = 0.0005)]. The rate of esophagectomy was significantly higher at the academic facilities (49.0% versus 26.5%; p < 0.0001). The 30-day and 90-day mortality rates for esophagectomy were significantly better for patients who underwent esophagectomy for esophageal cancer at the academic facility types. ConclusionPatients with clinical stage I–III esophageal carcinoma who received care at academic facility types had significantly better overall survival compared with community facility types. The utilization of esophagectomy was significantly higher and the short-term surgical outcomes were better for patients treated at academic facility types.

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma.

Objective We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results With cut-off criteria of P < 0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

Reduced miR-203 predicts metastasis and poor survival in esophageal carcinoma.

We analyzed data from two non-coding RNA profiling arrays made available by the Gene Expression Omnibus (GEO) and found 17 miRNAs with remarkable differential expression between malignant and normal esophageal tissue. Correlation analysis between expression of these 17 miRNAs and patients’ clinicopathological characteristics showed that miR-203 was down-regulated in esophageal carcinoma (EC) tissues and was significantly associated with lymph node metastasis and poor overall survival. Overexpression of miR-203 significantly attenuated cellular proliferation, migration and invasion by EC cells in culture. Additionally, gene expression profiles and bioinformatics analysis revealed KIF5C to be a direct target of miR-203, and KIF5C overexpression partially counteracted the tumor inhibitory effects of miR-203 on EC cells. We also observed that miR-203, reduced KIFC5 protein levels, promoted cytoplasmic accumulation of Axin2, and reversed the invasive phenotype of EC cells. Taken together, these data demonstrate that miR-203 is a tumor suppressor in EC cells and its expression level could potentially be used as a prognostic indicator for EC patient outcomes.

Systemic inflammatory dynamics during chemoradiotherapy predict response, relapse, metastasis, and survival in esophageal carcinoma.

Lymphopenia associated with chemoradiotherapy predicts prognosis in esophageal carcinoma. The purpose of our study was to evaluate alterations in hematologic measures of inflammation during chemoradiation. We performed an observational study evaluating adults treated with chemoradiation in the neoadjuvant or definitive setting for stage II-III esophageal carcinoma. Multivariable logistic regression evaluated predictors of pathologic response. Survival was analyzed by time-varying multivariable Cox proportional hazards regressions. A total of 94 patients were included with median follow-up of 1.6 years. Elevated neutrophil:lymphocyte ratio (NLR) was predictive of incomplete pathologic response to neoadjuvant chemoradiation (OR, 1.07; P = .0030) as well as shorter distant metastasis-free survival (HR, 1.01; P = .0369) and reduced overall survival (HR, 1.01; P = .0448). An NLR > 5.55 in week two of chemoradiation predicted shorter overall survival (P = .0070). Upon adjusted analysis, NLR was independently associated with reduced probability of complete pathologic response (OR, 0.80; P = .0291), as well as poor histologic response to neoadjuvant chemoradiation (OR, 1.05; P = .0303), shorter disease-free survival (HR, 1.02; P = .0077), and reduced overall survival (HR, 1.02; P = .0070). Dynamic time-dependent changes in NLR during chemoradiation predict response, relapse, metastasis, and survival in esophageal carcinoma. Prospective validation is warranted.

Prognostic Value of MicroRNAs in Esophageal Carcinoma: A Meta-Analysis.

BackgroundNumerous articles have reported that abnormal expression levels of microRNAs (miRNAs) are related to the survival times of esophageal carcinoma (EC) patients, which contains esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Nevertheless, there has not been a comprehensive meta-analysis to assess the accurate prognostic value of miRNAs in EC.MethodsStudies published in English up to April 12, 2018 that evaluated the correlation of the expression levels of miRNAs with overall survival (OS) in EC were identified by online searches in PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews performed by two independent authors. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the correlation between OS and miRNA expression. HR ≥ 2 was considered cutoff for considering the miRNA as prognostic candidate.ResultsForty-four pertinent articles with 22 miRNAs and 4310 EC patients were ultimately included. EC patients with tissue expression levels of high miR-21 or low miR-133a (HR = 2.48, 95% CI = 1.50–4.12), miR-133b (HR = 2.15, 95% CI = 1.27–3.62), miR-138 (HR = 2.27, 95% CI = 1.68–3.08), miR-203 (HR = 2.83, 95% CI = 1.35–5.95), miR-375 and miR-655 (HR = 2.66, 95% CI = 1.16–6.12) had significantly poorer OS (P < 0.05). In addition, EC patients with blood expression levels of high miR-21 (HR = 2.19, 95% CI = 1.31–3.68) and miR-223 had significantly shorter OS (P < 0.05).ConclusionsIn conclusion, tissue expression levels of miR-21, miR-133a, miR-133b, miR-138, miR-203, miR-375, and miR-655 and blood expression levels of miR-21 and miR-223 demonstrate significant prognostic value. Among them, the expression levels of miR-133a, miR-133b, miR-138, miR-203, and miR-655 in tissue and the expression level of miR-21 in blood are potential prognostic candidates for predicting OS in EC.

PS02.043: OVEREXPRESSION OF HSP27 AND HSP70 ARE ASSOCIATED WITH DECREASED SURVIVAL AMONG PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

Abstract Background Heat shock protein (HSP) 27 and 70 overexpression is associated with several malignancies but reports of their incidence and association with survival among patients with esophageal carcinoma (EC) are scarce. COX-2 expression is induced by inflammation, and it has been linked to a Barrett's esophagus and a wide variety of cancers. High COX-2 expression has been linked to poor survival in EC but results regarding association to clinicopathological factors are conflicting. Methods Immunohistochemical analysis for HSP27, HSP70 and COX-2 was performed on 97 cancer cases, 19 Barrett cases and 5 controls treated between 1990 - 2007. Data was gathered from patient records and survival data was acquired in December 2015. Results Higher tumor stage was significantly associated with poorer survival (P &lt; 0001), which was independent of HSP27, HSP70 and COX-2 immunostaining. HSP27 was moderately or strongly positive in 61,8% of the cancer cases, which was significantly associated to poorer survival (25,6 and 19 months versus 65,1 in weakly positive samples) (P = 0,01). Similar results were seen for HSP70, for which 30,4% of the cases were stained moderately or strong positive, and survival was 15 and 17,3 months compared to 41,7 months in weakly stained cases. COX-2 was negative in 83,3% of the cancer cases, and none of the samples had strong COX-2 immunostaining. COX-2 did not correlate with survival. Conclusion Moderate or high HSP27 and HSP70 staining intensities were associated with poor survival among patients with esophageal adenocarcinoma, which is now reported for the first time. According to previous studies opposite conclusions for esophageal squamous cell carcinoma was found. COX-2 did not impact survival in our study even though it's been found to be a negative prognostic factor in several previous studies. Disclosure All authors have declared no conflicts of interest.

Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

Objective:We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer.Methods:We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positron-emission tomography (PET)/computed tomography (CT). All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated.Results:One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively). Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001).Conclusion:Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study.

Impact of comorbidities and use of common medications on cancer and non-cancer specific survival in esophageal carcinoma.

BackgroundChronic comorbidities and some of the commonly-used medications are thought to affect cancer patients’ outcomes, but their relative impact on esophageal carcinoma (EC) has not been well studied. The purpose of the study was to identify the chronic comorbidities and/or commonly-used medications that impact EC patient survival.MethodsA total of 1174 EC patients treated with chemoradiotherapy (CRT) with or without surgery in one institution from 1998 to 2012 were retrospectively included. Seven kinds of frequently occurring chronic comorbidities and 18 types of regularly-taken medications were obtained from medical records. Since it is expected prognostic factors have different effects between surgery patients and non-surgery patients, the impact value of all variables and the corresponding interactions with surgery on survival were evaluated in Cox proportional hazards regression model. Overall mortality, EC-specific mortality and non EC-specific mortality were endpoints.ResultsWe found that atrial fibrillation was the only comorbidity that showed a significant impact on non-EC specific survival for all patients (HR 1.72, P = 0.03), whereas hypothyroidism was the only comorbidity that was evaluated as an independent predictive factor for overall survival (OS) (HR 0.59, P = 0.02) and EC-specific survival (HR 0.62, P = 0.05), but this association was seen only in the non-surgical patients. No other medications were found to have a significant impact for OS, EC-specific survival or non-EC specific survival in multivariable analysis.ConclusionsOur data indicate that certain comorbidities rather than medication use affect EC-specific survival or non EC-specific survival in EC patients treated with CRT with or without surgery. Comorbidity information may better guide individual treatment in EC.

Impact of alcohol consumption on survival in patients with esophageal carcinoma: a large cohort with long-term follow-up.

Alcohol is a well-established cause of esophageal carcinoma, but its effect on survival is little known and contradictory. To clarify whether drinking is an independent predictor of survival in esophageal carcinoma, 2151 Chinese patients, receiving surgical resection from January 1997 to December 2008, were followed until March 2014. Cox proportional hazards analysis was applied to evaluate the prognostic effect of alcohol consumption. The median follow-up was 64 months. The median overall survival (OS; 42 months) and disease-free survival (DFS; 33 months) for never-drinkers were significantly higher than ever-drinkers (27 and 22 months, respectively). In the multivariate Cox model that was adjusted for age, weight loss, stage according to criteria set by the American Joint Committee on Cancer, radicality of surgery, adjuvant treatment, smoking status, and gender, the hazard ratios of ever-drinking were 1.22 (1.06–1.41, P = 0.005) on OS, and 1.16 (1.01–1.34, P = 0.037) on DFS. The hazardous effect on OS and DFS of drinking grew statistically significantly in a dose-dependent manner with increasing amount of alcohol consumption per day (both P-value for trend < 0.05). The predictive effect of drinking on OS (P = 0.596) or DFS (P = 0.207) was not significant in the subgroup with esophageal adenocarcinoma (n = 195). The current study revealed that the survival is shortened, of those patients who consume alcohol before diagnosis of esophageal squamous cell carcinoma, which are not attributable to differences in stage, smoking status, and gender. Alcohol control should be emphasized to reduce mortality of esophageal carcinoma, and further outcome studies should include alcohol as a potential prognosticator.

Clinical significance of preoperative serum tumor markers in esophageal squamous cell carcinoma.

Serum tumor markers (TMs) were seldom reported in esophageal carcinoma (ESCC), and the results were still unsatisfactory. We retrospectively analyzed carcinoembryonic antigen, CA125, CA199, CA724 and CA242 in ESCC patients. The preliminary relations between serum TMs and clinicopathological factors or prognosis were analyzed by Fisher's exact test and Kaplan-Meier method firstly. Then, the cut-off values of these serum TMs were delimited according to lymph node metastasis, hematogenic metastasis and 2-year survival or 5-year survival of ESCC by receiver operating characteristic curve. Based on these cut-off values, the relations between the serum TMs and clinicopathological factors or prognosis were analyzed again. Univariate and multivariate analyses of Cox regression proportional hazard model were performed to evaluate the prognostic parameters for survival. We chose 13.65 U/mL, 9.945 U/mL and 6.25 U/mL as new cut-off values of CA125, CA199 and CA724, respectively, and chose 25.35 U/mL as the cut-off value of CA125 for ESCC hematogenous metastasis. with these optimal cut-off values, CA199, CA125 and CA724 were associated with ESCC hematogenous metastasis, and CA199 and CA125 were associated with ESCC lymph node metastasis, but not associated with other clinicopathological factors. The prognosis was better in patients with CA125 ≤ 13.65 U/mL than those with CA125 > 13.65U/mL. Vascular tumor thrombus, grading, T grade, lymph node metastasis and CA125 were independent prognostic factors. CA125 could predict lymph node metastasis, hematogenic metastasis and prognosis with the cut-off value 13.65 U/mL.

Study of metabonomic profiles of human esophageal carcinoma by use of high-resolution magic-angle spinning 1H NMR spectroscopy and multivariate data analysis

Esophageal carcinoma (EC) is one of the most common malignant tumors. EC survival has remained disappointingly low because of the high malignancy of esophageal cancer and the lack of obvious clinical symptoms at an early stage. Early diagnosis is often difficult because the small tumor nodules are frequently missed. Metabonomics based on high-resolution magic-angle spinning (HRMAS) NMR has been popular for tumor detection because it is highly sensitive, provides rich biochemical information and requires no sample pretreatment. (1)H HRMAS spectra of non-involved adjacent esophageal tissues and of well differentiated and moderately differentiated esophageal carcinoma tumors were recorded and analyzed by use of multivariate and statistical analysis techniques. Moderately differentiated EC tumors were found to have increased total choline, alanine, and glutamate and reduced creatine, myo-inositol, and taurine compared with non-involved adjacent tissues. Moreover, clear differences between the metabonomic profiles of EC tissues enabled tumor differentiation. Furthermore, the integral Gly/MI ratio for samples of different tissue types were statistically significantly different; this was sufficient both for distinguishing non-involved tissues from esophageal carcinoma and for classification of well differentiated and moderately differentiated EC tumors.

Involvement of CXCR4 Chemokine Receptor in Metastastic HER2-Positive Esophageal Cancer

A functional linkage of the structurally unrelated receptors HER2 and CXCR4 has been suggested for breast cancer but has not been evaluated for esophageal carcinoma. The inhibition of HER2 leads to a reduction of primary tumor growth and metastases in an orthotopic model of esophageal carcinoma. The chemokine receptor CXCR4 has been implicated in metastatic dissemination of various tumors and correlates with poor survival in esophageal carcinoma. The aim of this study was to investigate a correlation between the expression levels of HER2 and CXCR4 and to evaluate the involvemnent of CXCR4-expression in HER2-positive esophageal carcinoma. The effects of HER2-inhibition with trastuzumab and of CXCR4-inhibition with AMD3100 on primary tumor growth, metastatic homing, and receptor expression were evaluated in vitro and in an orthotopic model of metastatic esophageal carcinoma using MRI for imaging. The clinical relevance of HER2- and CXCR4-expression was examined in esophageal carcinoma patients. A significant correlation of HER2- and CXCR4-expression in primary tumor and metastases exists in the orthotopic model. Trastuzumab and AMD3100 treatment led to a significant reduction of primary tumor growth, metastases and micrometastases. HER2-expression was significantly elevated under AMD3100 treatment in the primary tumor and particularly in the metastases. The positive correlation between HER2- and CXCR4-expression was validated in esophageal cancer patients. The correlation of CXCR4- and HER2-expression and the elevation of HER2-expression and reduction of metastases through CXCR4-inhibition suggest a possible functional linkage and a role in tumor dissemination in HER2-positive esophageal carcinoma.

Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy

BackgroundP53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma.MethodsSerum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted.ResultsTwenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT.ConclusionsAnti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.