Development and validation of nomograms to intraoperatively predict metastatic patterns in regional lymph nodes in patients diagnosed with esophageal cancer.

BACKGROUND: An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict patterns of regional lymph node (LN) metastasis in patients with esophageal cancer. METHODS: The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017. RESULTS: Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort. CONCLUSION: This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.

Comparison Between Size and Stage of Preoperative Tumor Defined by Preoperative Magnetic Resonance Imaging and Postoperative Specimens After Radical Resection of Esophageal Cancer.

BACKGROUND: Our objective is to explore the accuracy of magnetic resonance imaging in determining the preoperative T and N staging, pathological stage, and the length of esophageal tumor in patients with esophageal cancer. METHODS: This retrospective analysis included 57 patients admitted to the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University between January 2015 and December 2016. Postoperative pathological results were used as the reference to verify the accuracy of magnetic resonance imaging in evaluating tumor T and N staging, pathological stage, and tumor length. The correlation between tumor lengths-measured using magnetic resonance imaging and the surgical specimen measurements-was evaluated. RESULTS: The mean age of the patients was 64.6 ± 7.2 years, with a range of 47 to 77 years. The overall accuracy rate of magnetic resonance imaging in T staging of esophageal cancer was 63.2%; magnetic resonance imaging was generally consistent in the N staging of esophageal cancer. Magnetic resonance imaging and surgical evaluation of tumor length were in excellent agreement (κ = .82, P < .001), while that of gastroscopy and postoperative pathology was moderate (κ = .63, P < .001). CONCLUSION: Magnetic resonance imaging is highly accurate in determining the preoperative T and N staging, pathologic stage, and tumor length in patients with esophageal cancer, which is important in deciding the choice of preoperative treatment and the surgical approach.

Concurrent liposomal paclitaxel and cisplatin chemotherapy improved outcomes for locally advanced esophageal squamous cell carcinoma treated with intensity-modulated radiotherapy.

BACKGROUND: To ascertain whether concurrent chemotherapy using liposomal paclitaxel and cisplatin could improve the outcomes of patients with locally advanced esophageal squamous cell carcinoma receiving intensity-modulated radiotherapy (IMRT). METHODS: A total of 72 patients with locally advanced esophageal squamous cell carcinoma, which were admitted to our hospital from October 2011 to December 2013, were retrospectively analyzed in this study. RESULTS: Thirty-six patients (50%) were treated with IMRT alone, while the other 36 patients (50%) were treated by IMRT combined with chemotherapy containing liposomal paclitaxel and cisplatin. Patients treated with chemoradiotherapy showed significantly superior overall survival (OS) and progression-free survival (PFS) compared to patients treated with IMRT alone (median OS: respectively, 29.7 vs. 12.9 months, P=0.0287; median PFS: respectively, 14.0 vs. 6.5 months, P=0.0186). Multivariate Cox analysis confirmed the inclusion of chemotherapy as an independent predictor of favorable OS and PFS. Both chemoradiotherapy and IMRT were well-tolerated in our cohort. CONCLUSIONS: Chemotherapy improved the prognosis of locally advanced esophageal squamous cell carcinoma treated with IMRT. Large prospective studies are needed to confirm the therapeutic value of IMRT combined with chemotherapy in locally advanced esophageal squamous cell carcinoma.

Systematic cancer-testis gene expression analysis identified CDCA5 as a potential therapeutic target in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with poor prognosis. Cancer-testis genes (CTGs) have been vigorously pursued as targets for cancer immunotherapy, but the expressive patterns and functional roles of CTGs remain unclear in ESCC. METHODS: A systematic screening strategy was adopted to screen CTGs in ESCC by integrating multiple public databases and RNA expression microarray data from 119 ESCC subjects. For the newly identified ESCC prognosis-associated CTGs, an independent cohort of 118 patients with ESCC was recruited to validate the relationship via immunohistochemistry. Furthermore, functional assays were performed to determine the underlying mechanisms. FINDINGS: 21 genes were recognized as CTGs, in particular, CDCA5 was aberrantly upregulated in ESCC tissues and significantly associated with poor prognosis (HR = 1.85, 95%CI: 1.14-3.01, P = .013). Immunohistochemical staining confirmed that positive CDCA5 expression was associated with advanced TNM staging and a shorter overall survival rate (45.59% vs 28.00% for CDCA5-/+ subjects, P = 1.86 × 10-3). H3K27 acetylation in CDCA5 promoter might lead to the activation of CDCA5 during ESCC tumorigenesis. Functionally, in vitro assay of gain- and loss-of-function of CDCA5 suggested that CDCA5 could promote ESCC cells proliferation, invasion, migration, apoptosis resistance and reduce chemosensitivity to cisplatin. Moreover, in vivo assay showed that silenced CDCA5 could inhibit tumor growth. Mechanistically, CDCA5 knockdown led to an arrest in G2/M phase and changes in the expression of factors that played fundamental roles in the cell cycle pathway. INTERPRETATION: CDCA5 contributed to ESCC progression and might serve as an attractive target for ESCC immunotherapy. FUND: This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20181083 and BK20181496), Jiangsu Top Expert Program in Six Professions (No. WSW-003 and WSW-007), Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2016790 and BE2018746), Jiangsu Medical Young Talent Project (No. QNRC2016566), the Program of Jiangsu Medical Innovation Team (No. CXTDA2017006), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1487) and Jiangsu Province 333 Talents Project (No. BRA2017545).

Identification of Germline Mismatch Repair Gene Mutations in Lung Cancer Patients With Paired Tumor-Normal Next Generation Sequencing: A Retrospective Study.

Background: Paired tumor-normal targeted next-generation sequencing (NGS) is primarily used to identify actionable somatic mutations, but can also detect germline variants including pathogenic germline mutations in DNA mismatch repair (MMR) genes that underlie Lynch syndrome. In the present study we examined paired NGS data from lung cancer patients to identify germline mutations in MMR genes. As lung cancer is not one of the recognized Lynch syndrome-associated neoplasms, we also investigated whether these lung cancer cases are due to Lynch syndrome or are instead sporadic cancers occurring in Lynch syndrome patients. Methods: A retrospective study of 1,179 lung cancer patients with available paired NGS data was performed to identify germline mutations in the MMR genes MLH1, MSH2, MSH6, and PMS2, and evaluate tumor mutation burden (TMB). Microsatellite instability (MSI) testing was done on select cases with MMR gene mutations by either NGS or PCR/capillary electrophoresis approach. Immunohistochemistry (IHC) for MMR proteins was performed in select patients. Results: Pathogenic or likely-pathogenic germline mutations in PMS2, MSH2, or MSH6 were detected in 0.5% (6/1,179) of lung cancer patients; three of the patients had a family history of colon or gastric cancer. The median age at diagnosis of these cases was 68.5 years old. None of these six patients exhibited MSI or loss of MMR protein expression. Among them, no second hit somatic mutations in MMR genes (including single-nucleotide variants, small insertions or deletions and copy number alterations) were detected, and the median TMB was 4.5 muts/MB. Subsequent genetic testing of family members identified new Lynch syndrome cases in two first-degree relatives. Conclusion: These data imply that lung cancers in Lynch syndrome patients are unrelated to the underlying Lynch syndrome diagnosis and occur spontaneously. Nonetheless, paired tumor-normal NGS can identify germline mutations to help reveal Lynch syndrome in cancer patients. This has important implications for cancer screening and risk reduction in these patients and their families.

Comprehensive Analysis of lncRNA-miRNA- mRNA Network Ascertains Prognostic Factors in Patients with Colon Cancer.

BACKGROUND: Non-coding RNAs are competing endogenous RNAs in the occurrence and development of tumorigenesis; numerous microRNAs are aberrantly expressed in colon cancer tissues and play significant roles in oncogenesis development and metastasis. However, large clinical and RNA data are lacking to further confirm the exact role of these RNAs in tumors. This study aimed to ascertain differential RNA expression between colon cancer and normal colon tissues. MATERIALS AND METHODS: RNA sequencing and clinical data of patients with colon cancer were procured from The Cancer Genome Atlas database; differentially expressed long non-coding RNA, differentially expressed messenger RNAs, and differentially expressed microRNAs were achieved using the limma package in edgeR to generate competing endogenous RNAs networks. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with ggplot2 package, the Kaplan-Meier survival method was used to predict survival in patients with colon cancer. RESULTS: In total, 1174 differentially expressed long non-coding RNAs, 2068 differentially expressed messenger RNAs, and 239 differentially expressed microRNAs were generated between 480 colon cancer and 41 normal colon tissue samples. Three competing endogenous RNA networks were established. Gene Ontology analysis indicated that the genes of the up-regulated microRNA network were involved in negative regulation of transcription, DNA-template, and those of down-regulated microRNA network were involved in transforming growth factor ß receptor signaling pathways, response to hypoxia, cell migration, while Kyoto Encyclopedia of Genes and Genomes analyses of these networks turned out to be negative. Three long non-coding RNAs (AP004609.1, ARHGEF26-AS1, and LINC00491), 3 microRNAs (miRNA-141, miRNA-216a, and miRNA-193b) and 3 RNAs (ULBP2, PHLPP2, and TPM2) were detected to be associated with prognosis by the Kaplan-Meier survival analysis. Additionally, univariate and multivariate Cox regression analyses showed that the microRNA-216a of the competing endogenous RNA might be an independent prognostic factor in colon cancer. CONCLUSIONS: This study constructed the non-coding RNA-related competing endogenous RNA networks in colon cancer and sheds lights on underlying biomarkers for colon cancer cohorts.

Genome-wide copy number variation analysis identified ANO1 as a novel oncogene and prognostic biomarker in esophageal squamous cell cancer.

Copy number variations (CNVs) represent one of the most common genomic alterations. This study aimed to evaluate the roles of genes within highly aberrant genome regions in the prognosis of esophageal squamous cell cancer (ESCC). Exome sequencing data from 81 paired ESCC tissues were used to screen aberrant genomic regions. The associations between CNVs and gene expression were evaluated using gene expression data from the same individuals. Then, an RNA expression array profile from 119 ESCC samples was adopted for differential gene expression and prognostic analyses. Two independent ESCC cohorts with 315 subjects were further recruited to validate the prognostic value using immunohistochemistry tests. Finally, we explored the potential mechanism of our identified novel oncogene in ESCC. In total, 2003 genes with CNVs were observed, of which 76 genes showed recurrent CNVs in more than three samples. Among them, 32 genes were aberrantly expressed in ESCC tumor tissues and statistically correlated with CNVs. Strikingly, 4 (CTTN, SHANK2, INPPL1 and ANO1) of the 32 genes were significantly associated with the prognosis of ESCC patients. Patients with a positive expression of ANO1 had a poorer prognosis than ANO1 negative patients (overall survival rate: 42.91% versus 26.22% for ANO1-/+ samples, P < 0.001). Functionally, ANO1 promoted ESCC cell proliferation, migration and invasion by activating transforming growth factor-ß pathway. Knockdown of ANO1 significantly inhibited tumor progression in vitro and in vivo. In conclusion, ANO1 is a novel oncogene in ESCC and may serve as a prognostic biomarker for ESCC.

Clinicopathologic predictors of metastasis of different regional lymph nodes in patients intraoperatively diagnosed with stage-I non-small cell lung cancer.

BACKGROUND: Selection of the best lymph node for dissection is a controversial topic in clinical stage-I non-small cell lung cancer (NSCLC). Here, we sought to identify the clinicopathologic predictors of regional lymph node metastasis in patients intraoperatively diagnosed with stage-I NSCLC. METHODS: A retrospective review of 595 patients intraoperatively diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with complete lymph node dissection was performed. Univariate and multivariable logistic regression analysis was performed to determine the independent predictors of regional lymph node metastasis. RESULTS: Univariate logistic regression and multivariable analysis revealed three independent predictors of the presence of metastatic hilar lymph nodes, five independent predictors for lobe specific mediastinal lymph nodes, two independent predictors for lobe nonspecific mediastinal lymph nodes and two independent predictors for skipping mediastinal lymph nodes. CONCLUSIONS: A complete mediastinal lymph node dissection may be considered for patients suspected of nerve invasion and albumin (> 43.1 g/L) or nerve and vascular invasions. Lobe-specific lymph node dissection should probably be performed for patients suspected of pulmonary membrane invasion, vascular invasion, CEA (> 2.21 ng/mL), and tumor (> 1.6 cm) in the right lower lobe or mixed lobes. Hilar lymph node dissection should probably be performed for patients suspected of having bronchial mucosa and cartilage invasion, vascular invasion, and CEA (> 2.21 ng/mL).

LINC00665 Induces Acquired Resistance to Gefitinib through Recruiting EZH2 and Activating PI3K/AKT Pathway in NSCLC.

Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor, has been used as the first choice of treatment for advanced non-small-cell lung cancer. However, during the course of treatment, cancer cells often develop resistance to gefitinib without fully understood mechanisms. In this study, we aimed to elucidate an important role of long intergenic non-coding RNA 00665 in developing resistance to gefitinib in non-small-cell lung cancer. We showed that long intergenic non-coding RNA 00665 expression was significantly upregulated in lung cancer tissues and cells with acquired gefitinib resistance. Long intergenic non-coding RNA 00665 knockdown restored gefitinib sensitivity both in vitro and in vivo by suppressing cell proliferation and inducing apoptosis. Moreover, knockdown of long intergenic non-coding RNA 00665 markedly reduced activation of EGFR and its downstream event protein kinase B (AKT). Moreover, LINC00665 could interact with EZH2 and regulate the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Thus, our study suggests that long intergenic non-coding RNA 00665 is important for non-small-cell lung cancer to develop drug resistance and might be a potential biomarker for drug resistance and a therapeutic target for non-small-cell lung cancer.

iTRAQ-Based Quantitative Proteomic Analyses of High Grade Esophageal Squamous Intraepithelial Neoplasia.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and is the fourth most lethal cancer in China. Little is known about the proteome of high grade esophageal squamous intraepithelial neoplasia (HGN), which is a premalignant lesion of ESCC. A quantitative proteomic analysis using an isobaric tag for relative and absolute quantification (iTRAQ) approach is used to characterize the protein expression profiles in HGN. Among the 3156 identified proteins, a total of 236 proteins are discovered to be differentially expressed. Compared with paired normal esophageal epithelial tissues, 138 proteins are upregulated and 98 proteins are downregulated in HGN. Bioinformatics analyses are performed according to gene ontology, clusters of orthologous groups, and kyoto encyclopedia of genes and genomes enrichment analyses. Six differentially expressed proteins are chosen and validated by Western blotting. The results of the study increase our understanding of early tumorigenesis during ESCC, and provide insights into the proteome at the initial stages of the disease that can be used to identify potential biomarkers for early diagnosis and for therapeutic targets.

Efficacy and safety of chemoradiation therapy compared with chemotherapy for esophageal carcinoma: An updated meta-analysis of randomized controlled trials.

BACKGROUND: The role of the chemoradiation therapy (CRT) and chemotherapy (CT) in the treatment of esophageal carcinoma (EC) remains controversial. Therefore, we conducted this meta-analysis to compare the efficacy and safety of CRT with CT in the treatment of EC patients. METHODS: PubMed, Embase, Web of Science, and The Cochrane library were systematically reviewed for randomized controlled trials (RCTs) that compared CRT with CT. Outcomes included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection, recurrence rate, mortality rate, and adverse events. Pooled estimates were expressed with hazard ratio (HR) with 95% confidence intervals (95% CIs) and risk ratio (RR) with 95% CIs. RESULTS: Eight RCTs involving 1274 patients were included in this meta-analysis. Compared with CT, CRT was not associated with significantly improved OS (HR = 0.91, 95% CI: 0.82, 1.01; P = .072) and PFS (RR = 3.62, 95% CI: 1.10, 11.95; P = .035). The pCR rate and R0 resection rate were significant higher in the CRT group than that in the CT group (RR = 3.62, 95% CI: 1.10, 11.95, P = .035; RR = 1.18, 95% CI: 1.09, 1.27, P < .001; respectively). EC patients who received CRT had a higher mortality rate (RR = 2.50, 95% CI: 1.14, 5.48; P = .022) than those treated with CT, and the incidence of grade 3 or 4 adverse events was similar between the 2 groups (RR = 0.91, 95% CI: 0.62, 1.32; P = .612). CONCLUSION: On the basis of the current evidence, our results suggested that CRT seemed to have benefit in the radical resection, but no effect in the survival benefits. Further large-scale, well-conducted RCTs are needed to verify our findings.

Apparent diffusion coefficient values detected by diffusion-weighted imaging in the prognosis of patients with locally advanced esophageal squamous cell carcinoma receiving chemoradiation.

PURPOSE: Previous studies have demonstrated that apparent diffusion coefficient (ADC) values measured by magnetic resonance imaging have prognostic value in patients with esophageal squamous cell carcinoma (ESCC). However, the role of ADC needs to be validated in a cohort of Chinese ESCC patients. This study assessed the role of ADC in predicting the outcome of patients with ESCC treated only by chemoradiation in the People's Republic of China. PATIENTS AND METHODS: Seventy-three patients with local advanced ESCC were retrospectively analyzed in this study; none of the patients underwent surgery before or after chemoradiation. The ADC values of the primary tumors were determined by magnetic resonance imaging. The ADC values were then correlated with clinicopathological and other radiological parameters. Survival analysis was carried out to determine if ADC had an impact on survival of these patients. RESULTS: The median ADC value of the esophageal cancer tissue was 1.256*10-3 mm2/sec (range: 0.657-2.354*10-3 mm2/sec, interquartile range 0.606*10-3 mm2/sec). No clinicopathological or radiological parameters were associated with the ADC values except the sites of tumor tissues. ADC <1.076*10-3 mm2/sec predicted significantly worse survival in patients with ESCC (12.9 months vs undefined, P=0.0108). CONCLUSION: The ADC value is a potent prognostic factor which can be used to predict the outcome of patients with ESCC treated only by chemoradiation.

[Study on the association of gastric conduit width and postoperative early delayed gastric emptying in middle-lower esophageal cancer patients undergoing Ivor-Lewis procedure].

OBJECTIVE: To examine the relationship between gastric conduit width and postoperative early delayed gastric emptying (DGE) in patients with middle-lower esophageal carcinoma who underwent Ivor-Lewis operation. METHODS: Clinical data of 282 consecutive patients with middle-lower esophageal cancer who underwent the Ivor-Lewis operation by same surgical team in our department from January 2013 to June 2015 were retrospectively analyzed. Patients were divided into three groups according to the width of gastric conduit: width > 5.0 cm as broad group (n=93); width 3.0-5.0 cm as moderate group (n=70); width < 3.0 cm as narrow group (n=119). The gastric conduits of patients in narrow group were completely positioned the esophageal bed and fixed to the pericardium posterior wall. None of patients received pyloroplasty or pylorotomy. Perioperative data, operation-associated complications, and postoperative upper gastrointestinal radiographic results(1 week and 4 weeks after operation) were compared among groups. RESULTS: The baseline data among these groups were comparable in terms of age, gender, tumor TNM staging, pathological types, serum albumin level, and the rate of receiving neoadjuvant therapy(all P>0.05). There were no significant differences in operative time, blood loss, and postoperative hospital stay among groups(all P>0.05). No patients died during perioperative peried. Anastomotic leakage occurred in 2 cases, one from broad group and another from narrow group. The incidences of arrhythmia and postoperative pulmonary complications, including infection, atelectasis, pneumothorax, and pleural effusion were similar among groups (all P>0.05). The average amount of gastric juice drainage in narrow group was (98±57) ml/day, which was markedly lower than that in broad group [(157±62) ml/day, P=0.000] and in moderate group [(123±68) ml/day, P=0.008]. One week after operation, the overall incidence of DGE was 10.6%(30/282), the incidence of DGE in broad, moderate, narrow groups was 17.2%(16/93), 14.3%(10/70), and 3.4%(4/119) respectively, and broad and moderate groups had higher incidence as compared to narrow group (P=0.001 and P=0.006). CONCLUSION: During the Ivor-Lewis operation, application of a narrow gastric conduit (width < 3.0 cm), which completely position the esophageal bed with fixation to the pericardium posterior wall, can significantly reduce the incidence of postoperative early DGE.

Long-term clinical outcome of intensity-modulated radiation therapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: This study evaluated the effectiveness and safety of intensity-modulated radiation therapy (IMRT) for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Between August 2009 and December 2011, 112 patients with pathologically confirmed ESCC treated with IMRT at Jiangsu Province People's Hospital and Nantong Tumor Hospital were included in a retrospective analysis. Patients received either IMRT alone (group A) or concurrent chemoradiotherapy (CRT) (group B). A radiation dose of 60-66 Gy administered in 30-33 fractions was delivered to the tumor. The patients in group B simultaneously received 2 cycles of cisplatin-based doublets with either 5-fluorouracil or taxotere. The Kaplan-Meier method was used to compute the survival time. Early and late toxicities were scored according to CTCAE v.3.0. RESULTS: The response rate of group B (91.07%) was not significantly greater than that of group A (89.29%) (χ2 = 0.10, p = 0.75). The 1- and 3-year survival rates of group B (87.5% and 57.14%, respectively) were greater than those of group A (69.64% and 37.50%, respectively). The difference in overall survival was statistically significant between groups A and B (χ2 = 5.30, p = 0.02; χ2 = 4.33, p = 0.04). Hematological toxicity, gastrointestinal toxicity, and treatment-related esophagitis were significantly higher in group B than group A (16.07% vs. 33.93%, p = 0.04; 10.71% vs. 26.79%, p = 0.03; 19.64% vs. 44.64%, p = 0.01). However, intergroup differences in terms of late toxicity were not significant. CONCLUSIONS: IMRT was a practical and feasible technique to treat ESCC. Concurrent CRT could increase local tumor control and long-term survival. The CRT regimen was associated with a higher incidence of acute gastrointestinal and hematological toxicity.

Ginsenoside Rg3 enhances radiosensitization of hypoxic oesophageal cancer cell lines through vascular endothelial growth factor and hypoxia inducible factor 1α.

OBJECTIVE: To determine if the pretreatment of hypoxic human oesophageal carcinoma cell lines (EC109, TE1 and KYSE170) with ginsenoside Rg3 (Rg3) increases their radiosensitivity to X-rays. METHODS: The growth inhibitory effect of different Rg3 concentrations was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Radiation sensitivity was measured using a clone formation assay and flow cytometry was used to measure the effects of Rg3 on radiation-induced apoptosis. Western blot analysis was used to measure the effects of Rg3 on the levels of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). RESULTS: Rg3 inhibited EC109, TE1 and KYSE170 cell growth in a dose- and time-dependent manner. Pretreatment with 10 µmol/ml Rg3 increased EC109, TE1 and KYSE170 radiosensitivity. Rg3 plus radiation significantly increased the apoptosis rate compared with radiation alone. Rg3 also decreased VEGF and HIF-1α protein levels in EC109 cells in a dose-dependent manner. The combination of Rg3 and radiation increased the fragmentation of double-stranded DNA. CONCLUSION: Rg3 enhanced the radiosensitivity of human oesophageal carcinoma cell lines cultured under hypoxic conditions possibly by downregulating VEGF and HIF-1α protein levels.

[Comparative analysis on the classic and modified Ivor-Lewis procedure in the treatment of mid-low thoracic esophageal carcinoma].

OBJECTIVE: To retrospectively evaluate the efficacy of classic and modified Ivor-Lewis surgical procedure in the treatment of mid-low thoracic esophageal cancer. METHODS: Clinical data of 140 patients with middle-lower thoracic esophageal cancer undergoing modified Ivor-Lewis esophagectomy from March 2009 to April 2010 (modified group) and 112 patients with same disease undergoing classic Ivor-Lewis esophagectomy from April 2010 to April 2011 in our department were collected. Operative time, surgical complications, total number of harvested lymph node, distribution of lymph nodes, lymph node metastasis rate, as well as postoperative pathological stage were compared between two groups. RESULTS: There were no significant differences between two groups in general informations, operative time and surgical complications (P>0.05). The number of harvested superior mediastinum lymph nodes in classic Ivor-Lewis group was significantly more than that in modified group (8.0±2.1 vs. 3.1±0.6, P<0.05). Ratio of postoperative positive lymph node metastasis was significantly higher in classic Ivor-Lewis group as compared to modified group[41.1% (46/112) vs. 27.9% (39/140), P<0.05]. CONCLUSION: As compared to modified Ivor-Lewis procedure, classic Ivor-Lewis procedure is better in the resection of superior mediastinum lymph node and the evaluation of postoperative pathological stage, therefore it conforms better to the principle of cancer treatment of esophageal carcinoma.