• Korean Journal of Bronchoesophagology
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• v.17 no.1
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• pp.23-28
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• 2011

Diagnosis of early esophageal cancer has become more frequent as a result of improved endoscopic technology, surveillance programmes, and increasing experience and awareness on the part of endoscopists. In early esophageal cancer, squamous cell carcinoma and early adenocarcinoma must be managed differently because they have different origins, pathogenesis. and clinical characteristics. The current treatment options vary widely, from extended resection with lymphadenectomy to endoscopic mucosal resection (EMR) or ablation. None of these treatment options can be recommended universally. Instead, an individualized strategy should be based on the depth of tumor infiltration into the mucosa or submucosa, the presence or absence of lymph node metastases, the multicentricity of tumor growth, the length of the segment of intestinal metaplasia, and comorbidities of the patient. EMR has become increasingly important, both as a diagnostic tool for the staging of esophageal carcinomas and as a method of carrying out definitive treatment when the cancer meets certain criteria in which the risk of lymph-node metastasis is negligible. EMR may be sufficient in a subset of patients who have m1 or m2 squamous cell carcinoma and in patients who have isolated foci of high-grade intraepithelial neoplasia or mucosal cancer.

• Journal of Chest Surgery
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• v.40 no.12
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• pp.843-850
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• 2007

Background: The Ivor-Lewis operation has been widely applied for treating thoracic esophageal cancer, but more acceptable results from three-field lymph node dissection have recently been reported. In this study the efficacy of the Ivor-Lewis operation was evaluated. Material and Method: Among the 273 patients, who underwent operation for esophageal cancer between September 1994 and August 2004, we retrospectively studied 172 patients with esophageal squamous cell carcinoma and who had no other primary cancer and who underwent complete resection with an Ivor-Lewis operation. The postoperative complications, the short and long-term survival and the recurrence patterns were analyzed. Result: The postoperative staging was as follows: stage I in 40 cases, IIA in 48 cases, IIB in 18 cases, III in 55 cases, IVA in 5 cases and IVB in 6 cases. The operative mortality rate was 4% (7 of 172 pts). Postoperative complication occurred in 32 patients (18%) and tumor recurred in 55 patients (32%). The overall 5-year survival rate was 48%; it was 85.6% in stage I patients, 47.6% in IIA patients, 65% in IIB patients, 22.8% in III patients and 0% for those in IV (p<0.05). The 5-year survival rate according to the location of esophageal cancer was 26.5% for patients with tumor in the upper 1/3 of the esophagus and 52.4% for patients with tumor in the mid and lower 1/3 (p>0.05). Conclusion: The Ivor-Lewis operation is an acceptable surgical procedure for thoracic esophageal squamous cell carcinoma. Yet it is necessary to consider other surgical procedures, and especially three-field lymph node dissection for treating upper 1/3 esophageal cancer.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3491-3497
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• 2013

Background: Gastric and esophageal cancers are among the most lethal human malignancies worldwide. Of all malignancies estimated in Iran (47,100), gastric and esophageal cancers were responsible for 7,800 and 3,500 deaths in 2008 respectively. The present study aimed to provide an image of patho-epidemiological characteristics with their trends during two past decades with emphasis on topographic, morphologic, and some demographic features. Materials and Methods: In a hospital-based retrospective study in 2009, all pathological reports from esophageal endoscopies and gastric biopsies through a 20 years period (1989-2008) were collected and analyzed in four interval periods(five years each). Also, all eligible samples in hospital archives were enrolled for further testing. Besides, demography, topography and morphology of all samples were determined and analyzed by statistical software. Results: No significant statistical difference was seen in frequency of espohageal and gastric tumors throughout the study. Esophageal cancer cases were older than gastric. Sex ratio was 2.33/1 and men had a higher rate of both esophageal and gastric tumors. Stomach cancer included 64.3% of all cases. Inferior third and end of esophagus were common locations for esophageal tumors whereas proximal stomach was common for gastric tumors. Squamous cell carcinoma and adenocarcinoma were common morphological types of tumors in esophagus and stomach respectively. Conclusions: Morphological trends showed an increase of esophageal adenocarcinoma and diffuse/intestinal ratio in stomach cancers. Trends in incidence from gastric cancer decreased based on topographic studies but we could not find a topographical trend toward cadia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3921-3925
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• 2014

RASSF1A has been reported to be a candidate tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the association between RASSF1A promoter methylation and ESCC remains unclear. Eligible studies were identified through searching PubMed, Medline, Web of Science, and the China National Knowledge Infrastucture database. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Twelve studies involving 859 cases and 675 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and ESCC overall (OR = 11.7, 95% CI: 6.59-20.9, z=8.36, P<0.00001). Subgroup analysis showed that the OR for heterogeneous tissues was 5.35 (95% CI = 2.95-9.71) while for autologous tissues it was 16.0 (8.31-30.96). For patient sample size, the OR for the <50 subgroup was 9.92 (95% CI = 2.88-34.2) and for the 50 case group was 13.1 (95% CI = 6.59-25.91). The OR for a relationship between RASSF1A methylation and TNM stages was 0.27 (95% CI=0.10-0.77), whereas there were no significant differences in RASSF1A methylation in relation to gender and differentiation among ESCC cases. This meta-analysis suggests a significant association between RASSF1A methylation and ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7161-7165
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• 2015

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. Materials and Methods: p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. Results: p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. Conclusions: Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2245-2250
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• 2015

Background: The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to evaluate whether preoperative the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) could predict the prognosis of ESCC patients undergoing esophagectomy. Materials and Methods: Records from 218 patients with histologically diagnosed ESCC who underwent attempted curative surgery from January 2007 to December 2008 were retrospectively reviewed. Besides clinicopathological prognostic factors, we evaluated the prognostic value of the LMR, the NLR, and the PLR using Kaplan-Meier curves and Cox regression models. Results: The median follow-up was 38.6 months (range 3-71 months). The cut-off values of 2.57 for the LMR, 2.60 for the NLR and 244 for the PLR were chosen as optimal to discriminate between survival and death by applying receiver operating curve (ROC) analysis. Kaplan-Meier survival analysis of patients with low preoperative LMR demonstrated a significant worse prognosis for DFS (p=0.004) and OS (p=0.002) than those with high preoperative LMR. The high NLR cohort had lower DFS (p=0.004) and OS (p=0.011). Marginally reduced DFS (p=0.068) and lower OS (p=0.039) were found in the high PLR cohort. On multivariate analysis, only preoperative LMR was an independent prognostic factor for both DFS (p=0.009, HR=1.639, 95% CI 1.129-2.381) and OS (p=0.004, HR=1.759, 95% CI 1.201-2.576) in ESCC patients. Conclusions: Preoperative LMR better predicts cancer survival compared with the cellular components of systemic inflammation in patients with ESCC undergoing esophagectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7221-7227
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• 2013

Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

• Journal of Chest Surgery
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• v.51 no.3
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• pp.187-194
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• 2018

Background: Death domain-associated protein (DAXX), originally identified as a pro-apoptotic protein, is now understood to be either a pro-apoptotic or an anti-apoptotic factor with a chromatin remodeler, depending on the cell type and context. This study evaluated DAXX expression and its clinical implications in squamous cell carcinoma of the esophagus. Methods: Paraffin-embedded tissues from 60 cases of esophageal squamous carcinoma were analyzed immunohistochemically. An immune reaction with more than 10% of tumor cells was interpreted as positive. Positive reactions were sorted into 2 groups: reactions in 11%-50% of tumor cells and reactions in more than 51% of tumor cells, and the correlations between expression and survival and clinical prognosticators were analyzed. Results: Forty-three of the 60 cases (71.7%) showed strong nuclear DAXX expression, among which 19 cases showed a positive reaction (31.7%) in 11%-50% of tumor cells, and 24 cases (40.0%) showed a positive reaction in more than 51% of tumor cells. A negative reaction was found in 17 cases (28.3%). These patterns of immunostaining were significantly associated with the N stage (p=0.005) and American Joint Committee on Cancer stage (p=0.001), but overall survival showed no significant difference. There were no correlations of DAXX expression with age, gender, or T stage. However, in stage IIB (p=0.046) and stage IV (p=0.014) disease, DAXX expression was significantly correlated with survival. Conclusion: This investigation found upregulation of DAXX in esophageal cancer, with a 71.7% expression rate. DAXX immunostaining could be used in clinical practice to predict aggressive tumors with lymph node metastasis in advanced-stage disease, especially in stages IIB and IV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5445-5451
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• 2015

Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.