• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3075-3079
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• 2014

Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI< $24.00kg/m^2$ and $BMI{\geq}24.00kg/m^2$). Results: There were 41 patients in the low/normal BMI group (BMI< $24.00kg/m^2$) and 19 in the high BMI group ($BMI{\geq}24.00kg/m^2$). No significant differences were observed in patient characteristics between these. We found no difference in 2-year OS and DFS associated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysis revealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymph node status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic. There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708) between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFS associated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking, tumor location, the status of lymph node metastases and BMI. Conclusions: BMI was not associated with survival in patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factor for patients undergoing CRT for ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.767-773
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• 2012

The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Understanding molecular changes in ESCC should improve identification of risk factors with different molecular subtypes and provide potential targets for early detection and therapy. Our study aimed to obtain a molecular signature of ESCC through the regulation network based on differentially expressed genes (DEGs). We used the GSE23400 series to identify potential genes related to ESCC. Based on bioinformatics we constructed a regulation network. From the results, we could establish that many transcription factors and pathways closely related with ESCC were linked by our method. STAT1 also arose as a hub node in our transcriptome network, along with some transcription factors like CCNB1, TAP1, RARG and IFITM1 proven to be related with ESCC by previous studies. In conclusion, our regulation network provided information on important genes which might be useful in investigating the complex interacting mechanisms underlying the disease.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5437-5442
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• 2014

Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase $C{\varepsilon}$ gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigat the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.797-802
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• 2015

Background: The purpose of this study was to prospectively evaluate the predictive value of perfusion computed tomography (CT) for response of local advanced esophageal carcinoma to radiotherapy and chemotherapy. Materials and Methods: Before any treatment, forty-three local advanced esophageal squamous cell carcinomas were prospectively evaluated by perfusion scan with 16-row CT from June 2009 to January 2012. Perfusion parameters, including perfusion (BF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Seventeen cases received definitive radiotherapy and 26 received concurrent chemo-radiotherapy. The response was evaluated by CT scan and esophagography. Differences in perfusion parameters between responders and non-responders were analyzed, and ROCs were used to assess predictive value of the baseline parameters for treatment response. Results: There were 25 responders (R) and 18 non-responders (NR). Responders showed significantly higher BF (R:34.1 ml/100g/min vs NR: 25.0 ml/100g/min, p=0.001), BV (23.2 ml/100g vs 18.3 ml/100g, p=0.009) and PED (32.5 HU vs 28.32HU, P=0.003) than non-responders. But the baseline TTP (R: 38.2s vs NR: 44.10s, p=0.172) had no difference in the two groups. For baseline BF, a threshold of 36.1 ml/100g/min achieved a sensitivity of 56%, and a specificity of 94.4% for detection of clinical responders from non-responders. Conclusions: The results suggest that the perfusion CT can provide some helpful information for identifying tumors that may respond to radio-chemotherapy.

• Journal of Chest Surgery
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• v.21 no.5
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• pp.856-862
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• 1988

The survival rate after resectional operation for carcinoma of the esophagus is still very low and many factors contribute to these poor results. We analyze the clinical results of 56 operated patients among 62 esophageal cancer patients between March, 1974 and July, 1988. Among the 62 patients, 52 patients were squamous cell carcinoma and 8 were adenocarcinoma, one was leiomyosarcoma and one was adenosquamous cell carcinoma. The classification of esophageal cancer was based on TNM classification of American Joint Committee on cancer". Among the operated patients, stage I was 5[9.6%], stage II was 13[25%], stage III was 26[50%], stage IV was 8[15.4%]. And its one year survival rate was 80%, 69%, 11.5%, 0% for each stages. The rate of resectability was 30.3% and resection of esophagus with esophagogastrostomy and extended lymph node dissection was performed on 17 patients without distant metastasis or adjacent organ invasion. Substernal esophago-colono-gastrostomy, Celestine tube insertion and feeding gastrostomy was performed on remained 39 patients. The analysis of postoperative survival duration revealed the superiority of esophagectomy with extended lymph node dissection over other palliative operation. [1 year survival rate: 79% versus 21%] We concluded that the survival rate of esophageal resection with lymph node dissection group was superior to nonresective palliative operation group. And transthoracic approach was superior to extrathoracic approach in involved lymph node dissection and esophageal resection in locally invaded cases.ases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2309-2312
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• 2014

Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.

• 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.

• 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.14 no.1
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• pp.21-25
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• 2013

Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.