Preliminary evaluation of postoperative radiotherapy with small T-shaped field in thoracic esophageal squamous cell carcinoma

BackgroundThe optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the primary outcome of postoperative radiotherapy with small T-shaped field encompassing the tumor bed, positive lymph node areas, bilateral supraclavicular areas, and upper and middle mediastinal areas.MethodsA total of 96 thoracic ESCC patients were enrolled, with 49 and 47 cases in the small T-shaped field group and tumor bed field group, respectively. All of the patients received intensity-modulated radiotherapy (IMRT), and chemotherapy was administrated concurrently or sequentially. The median time of follow-up was 25 (range, 7–47) months.ResultsAt the end of the follow-up period, in the small T-shaped field group, 8 (16.3%) patients had locoregional recurrence (LRR) and 12 (24.5%) had distant metastasis (DM), while in the tumor bed field group, 15 (31.9%) patients had LRR and 11 (23.4%) had DM. Although the rates of LRR and DM were not statistically different, LRR incidence in the mediastinal lymph nodes of the small T-shaped field group was strikingly lower than that of the tumor bed field group. The overall survival (OS) of the small T-shaped field group was higher than that of the tumor bed field group, but the difference was not statistically significance. In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups; all of these side effects were tolerable and controllable, and none of the patients experienced ≥ grade 3 pneumonitis, esophagitis, esophageal stricture, or life-threatening hemorrhage.ConclusionsIn conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.     

Interleukin 13 participates in terminal differentiation of esophageal squamous cell carcinoma cells

BackgroundIn China, esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of all esophageal cancer cases. Interleukin 13 (IL-13) was widely reported to play a key role in tumor progression. Our previous study reported that IL-13 was a favorable predictive marker for the overall survival of esophageal squamous cell carcinoma (ESCC) patients, but how IL-13 contributes to ESCC progression remains unknown. This study aims to explore the role of IL-13 and its underlying downstream molecular mechanisms in ESCC progression.MethodsTissue microarrays including 262 primary ESCC tumor tissues were collected and analyzed. The expression of IL-13 in ESCC tumor tissue was detected with immunohistochemistry staining (IHC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to qualify the expressions of KRT13, KRT4 and 15-lipoxygenase-1 (15-LOX-1) in cultured ESCC cell lines with recombinant IL-13 treatment.ResultsIL-13 was expressed in the esophageal epithelium cells and ESCC tumor cells. High IL-13 expression in ESCC tumor cells predicted a good prognosis for patients. Recombinant human IL-13 raised KRT13 and 15-LOX-1 mRNA levels, but lowered KRT4 mRNA level 15-LOX-1 in ESCC cells in vitro.ConclusionsIn summary, our study suggests that IL-13 might improve the prognosis of ESCC by promoting the terminal differentiation of ESCC cells. This may offer potential new therapeutic target for early treatment of ESCC.     

Larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction: A promising treatment for selected cervical esophageal squamous cell carcinoma

Background/AimsThere is no consensus on treatment for cervical esophageal squamous cell carcinoma (ESCC). Our aim is to evaluate the feasibility and outcome of larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction for the treatment of cervical ESCC without tumor involvement of the larynx and hypopharynx.Materials and MethodsRetrospective analysis of patients with cervical ESCC who underwent R0 surgical resection from 2006 to 2011 in our center was performed. Kaplan-Meier method was used to calculate the survival time for patients.ResultsIn total, 74 cervical ESCC patients were enrolled in the study. The mortality rate in 30 days was 8.1%, the total complication rate (at least one) was 47.3%, anastomosis leakage occurrence was 37.8%, mechanical ventilation ratewas12.2%, the rate of normal oral diet within 15 days was 71.6%, and the anastomosis recurrence rate in follow-up was 8.1%. Detailed analysis showed that the anastomosis leakage, pulmonary infection, laryngeal recurrent nerve injury, and chylothorax were the most common complications in surgical patients. Finally, the survival data showed that the median survival time was 31.83 months (95% CI=12.39–51.28 months) and the 3-year and 5-year survival rates were 49.1% and 35.5%, respectively.ConclusionLarynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction might be a feasible and effective surgical alternative for the cervical ESCC patients whose tumor does not involve the larynx and hypopharynx.     

Comparison of clinicopathologic features and survival between eastern and western population with esophageal squamous cell carcinoma

Background

Esophageal squamous cell carcinoma (ESCC) is the major histologic subtype of esophageal cancer, characterized by a high mortality rate and geographic differences in incidences. It is unknown whether there is difference between “eastern” ESCC and “western” ESCC. This study is attempted to demonstrate the hypothesis by comparing ESCC between Chinese residents and Caucasians living in the US.

Methods

The data sources of this study are from United States SEER limited-use database and Shanghai Cancer Registries by Shanghai Municipal Center for Disease Control (SMCDC). Consecutive, non-selected patients with pathologically diagnosed ESCC, between January 1, 2002 and December 31, 2006, were included in this analysis. 1-year, 3-year and 5-year survival estimates were computed and compared between two populations. A Cox proportional hazards model was used to determine factors affecting survival differences.

Results

A total of 1,718 Chinese, 1,624 Caucasians ESCC patients with individual American Joint Commission on Cancer (AJCC) staging information were included in this study. The Caucasian group had a significantly higher proportion of female patients than Chinese (38.24% vs. 18.68% P<0.01). ESCC was diagnosed in Chinese patients at an earlier age and stage than Caucasians. Generally, Chinese patients had similar overall survival rate with Caucasian by both univariate and multivariate analysis. Overall survival was significantly worse only in male Caucasians compared to Chinese patients (median survival time, 12.4 vs. 14.5 months, P<0.01, respectively).

Conclusions

ESCC from eastern and western countries might have some different features. These differences need to be taken into account for the management of ESCC patients in different ethnic groups.     

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. The 11q13 region is amplified in ∼15% of breast cancers. Whether ANO1 is amplified in breast tumors, the extent to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained unknown. We have found that ANO1 is amplified and highly expressed in breast cancer cell lines and primary tumors. Amplification of ANO1 correlated with disease grade and poor prognosis. Knockdown of ANO1 in ANO1-amplified breast cancer cell lines and other cancers bearing 11q13 amplification inhibited proliferation, induced apoptosis, and reduced tumor growth in established cancer xenografts. Moreover, ANO1 chloride channel activity was important for cell viability. Mechanistically, ANO1 knockdown or pharmacological inhibition of its chloride-channel activity reduced EGF receptor (EGFR) and calmodulin-dependent protein kinase II (CAMKII) signaling, which subsequently attenuated AKT, v-src sarcoma viral oncogene homolog (SRC), and extracellular signal-regulated kinase (ERK) activation in vitro and in vivo. Our results highlight the involvement of the ANO1 chloride channel in tumor progression and provide insights into oncogenic signaling in human cancers with 11q13 amplification, thereby establishing ANO1 as a promising target for therapy in these highly prevalent tumor types.     

Amplification of the telomerase RNA component gene as a new genetic marker for disease progression and prognosis in esophageal squamous cell carcinoma

Amplification of the human telomerase RNA component (TERC) gene was found in esophageal squamous cell carcinoma (ESCC). However, its roles in the progression and prognosis of ESCC have not been well understood. The amplification of TERC in normal mucosa, low‐grade and high‐grade intraepithelial neoplasia, and invasive ESCC samples were evaluated using a fluorescence in situ hybridization assay. The amplification of TERC invariably occurred in high‐grade intraepithelial neoplasia and invasive ESCC, partially occurred in low‐grade intraepithelial neoplasia specimens, and seldom occurred in normal mucosa. The average signal ratio of TERC to chromosome 3 centromere‐specific probe (TERC/CSP3) was 1.00 ± 0.01 (average ± standard deviation) in normal mucosas, 1.01 ± 0.08 in low‐grade intraepithelial neoplasias, 1.39 ± 0.26 in high‐grade intraepithelial neoplasias, and 1.56 ± 0.41 in invasive ESCC. High TERC/CSP3 ratio was positively associated with lymph node metastasis (P = 0.005) and advanced tumor stage (P = 0.045). Patients with high amplification of TERC had poor survival (P = 0.01). The amplification of TERC could be used as a new genomic marker for disease progression and prognosis of ESCC. The amplified TERC gene may be a potential therapeutic target for ESCC.     

老年营养风险指数与接受根治性放化疗的老年食管癌患者的预后关系研究

目的 研究老年营养风险指数（GNRI）与接受根治性放疗或放化疗的老年食管癌患者预后间的关系。方法 回顾性分析河北医科大学第四医院2007年1月至2013年12月197例接受根治性放疗或放化疗且年龄≥75岁的食管鳞癌患者的临床资料,计算患者放疗前后老年营养风险指数（GNRI）、体质量指数（BMI）并进行分组。Kaplan-Meier法对生存时间行单因素预后分析,Cox回归模型行多因素预后分析。结果 放疗前GNRI评分正常组139例,异常组58例,两组5年生存率及无进展生存率分别为11.08%、9.82%和8.73%、6.18%（P>0.05）。放疗后GNRI评分正常组68例,异常组129例,5年生存率及无进展生存率分别为17.04%、7.42%和16.17%、3.65%（χ²=12.316、14.617,P<0.05）。单因素分析显示,T分期、N分期、TNM分期、大体肿瘤体积（GTV）、放疗前中性粒细胞与淋巴细胞比值（NLR）及放疗后BMI、放疗后血红蛋白水平、放疗后GNRI与总生存时间（OS）相关（χ²=6.569~22.434,P<0.05）;T分期、GTV、放疗前NLR及放疗后的BMI、放疗后血红蛋白水平、放疗后GNRI与无进展生存时间（PFS）相关（χ²=4.579~18.990,P<0.05）。多因素分析显示,T分期、N分期、放疗前NLR、放疗后血红蛋白水平、放疗后GNRI为患者OS的独立影响因素（P<0.05）。放疗前NLR、放疗后血红蛋白水平、放疗后GNRI为患者PFS的独立影响因素（P<0.05）。多因素分析显示,T分期、放疗后的血红蛋白水平、GNRI均为影响患者近期疗效的独立相关因素（χ²=4.716、13.083、4.519,P<0.05）。结论 营养指标GNRI可作为老年食管鳞癌患者的有效预后指标。临床工作中对GNRI评分风险较高的老年患者可积极行营养干预以改善患者预后。