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Objective: To investigate the effects of nimotuzumab on radiosensitivity of ECA-109 and TE-13 esophageal carcinoma cell lines and explore its possible mechanism. Methods: The ECA-109 and TE-13 cells were divided into control group, irradiation group, medicine group, and combined group (irradiation + medicine). In the combined group, ECA-109 and TE-13 cells were treated with nimotuzumab for 24 h before irradiation, and the cells were collected 2 h after irradiation. The radiosensitizing effects of nimotuzumab on ECA-109 and TE-13 cells were evaluated by clone formation assay. Cell apoptosis was detected by flow cytometry. Western blotting was used to evaluate the expression of EGFR, p-EGFR, DNA-PKcs, p-DNA-PKcs and γH2AX. Results: The values of D q (quasithreshold dose), D 0 (mean lethal dose)and SF 2 (surviving fraction at 2 Gy) of ECA-109 and TE-13 cells in the combined group were significantly lower than those of the radiation group (for ECA-109 cells, 1.11 vs. 1.72, 1.40 vs. 2.14, 0.42 vs. 0.66, respectively; for TE-13 cells, 0.41 vs. 0.46, 0.43 vs. 0.65, 0.40 vs. 0.71, respectively (all P <0.05). The sensitivity enhancement ratio (SER) of ECA-109 and TE-13 cells were 1.35 and 1.43, respectively. Flow cytometry showed that the apoptosis rate of ECA-109 and TE-13 cells in the combined group were significantly higher than those of the radiation group [for ECA-109 cells, (41.31±1.52)% vs. (9.54±0.52)%; for TE-13 cells, (46.28±0.28)% vs. (11.32±0.31)%, both P <0.01]. Western blotting showed that the expression levels of EGFR and DNA-PKcs were not significantly different in all groups (all P >0.05). Compared with those of the control group, p-EGFR and p-DNA-PKcs of the radiation group were significantly higher in both cell lines ( P <0.05), and the γH2AX levels in the radiation group and medicine group were significantly higher than that of the control group ( P <0.05). Compared with those of the radiation group and medicine group, p-EGFR and p-DNA-PKcs protein expression in the combined group were decreased significantly ( P <0.05), while γH2AX protein expression was significantly increased ( P <0.05). Conclusions: Nimotuzumab can enhance the radiosensitivity of esophageal cancer ECA-109 and TE-13 cells. The potential mechanism may be related to the inhibition of EGFR phosphorylation and down-regulation of DNA damage repair proteins. The radiosensitizing effect of nimotuzumab is greater on poorly differentiated esophageal cancer cells.

Objective: To explore the patterns and influencing factors of lymph node metastasis of adenocarcinoma of the esophagogastric junction (AEG)., Methods: Clinicopathological data of 393 AEG patients who underwent radical resection and lymphadenectomy in the thoracic or abdominal cavity were collected. We analyzed the metastatic patterns of 5 119 excised lymph nodes with an average of 13 nodes per patient according to Siewert classification, and the associations between lymphatic metastasis and clinicopathological factors, such as tumor invasion, differentiation, maximum diameter, or pathological type were analyzed., Results: The lymph node metastasis rate and ratio (LNR) were 70.0% (275/393) and 29.1% (1 492/5 119), respectively. All the Siewert subtypes of AEG mainly metastasize downwards to the abdominal lymph nodes, while also spread upwards to the mediastinal lymph nodes. Among them, the lymph node metastasis rate was highest in Siewert type Ⅰ and lowest in Siewert type Ⅲ AEG. The lymph node metastasis rate and ratio in T1, T2, T3, T4 AEGs were 0%, 29.4%, 75.0%, 74.6% and 0%, 10.1%, 14.2%, 32.0%, respectively (χ(2)=35.305, P<0.001 and χ(2)=134.034, P<0.001). The lymph node metastasis rate and ratio of the poorly differentiated adenocarcinoma were 36.0% and 79.3%, respectively, significantly higher than 22.1% and 61.7% of the well-differentiated adenocarcinoma (χ(2)=14.468, P<0.001 and χ(2)=120.009, P<0.001). The lymph node metastasis rate and ratio of patients with a tumor in maximum diameter ≥4 cm were 73.1% and 30.9%, significantly higher than 46.8% and 14.6%, respectively, in the patients with a tumor in maximum diameter of <4 cm (χ(2)=13.636, P<0.001 and χ(2)=64.767, P<0.001). The group of vascular tumor thrombus showed significantly higher lymph node metastasis rate and ratio than those in the group with no vascular tumor thrombus (84.6% versus 67.1%, χ(2)=7.946, P=0.005; and 45.0% versus 26.0%, χ(2)=112.723, P<0.001). The lymph node metastasis ratio of mucinous and signet ring cell adenocarcinoma was 34.9%, significantly higher than 28.5% of the adenocarcinoma (χ(2)=8.710, P<0.001) The depth of tumor invasion and degree of tumor differentiation were independent factors affecting lymph node metastasis (P=0.001 and P<0.001)., Conclusions: The lymph node metastasis rate and ratio of AEG are high and influenced by many clinicopathological factors. The patterns of lymph node metastasis are different among different Siewert subtype AEGs.The depth of tumor invasion and differentiation degree are independent factors affecting lymphatic metastasis.

Objective: To investigate the clinicopathological characteristics, patterns of lymph node metastasis and the influencing factors in esophageal adenocarcinoma., Methods: A total of 201 cases of esophageal adenocarcinoma were selected for this study, including 89 cases of pure adenocarcinoma, 57 cases of adenoacanthoma cell carcinoma, 33 cases of mucoepidermoid carcinoma and 22 cases of adenoid cystic carcinoma. A total of 2026 lymph nodes were dissected with an average of 10 lymph nodes. The rule of lymph node metastasis in patients with esophageal adenocarcinoma was analyzed, and the risk factors for lymph node metastasis were identified., Results: Esophageal adenocarcinoma in the middle thoracic esophagus accounted for 50.7% of all patients, and 43.8% in the lower thoracic esophagus. Ninety out of 201 cases (44.8%) had lymph node metastasis. 322 lymph nodes were positive for metastatic adenocarcioma with a metastatic ratio of 15.9% (322/2026). Among the patients with upper-thoracic esophageal carcinoma, 9.1% (1/11) of the cases had lymph node metastasis in the superior mediastinum but no lymph node metastasis was found in the middle mediastinum, lower mediastinal and abdominal lymph nodes. The middle-thoracic esophageal adenocarcinoma showed more extensive lymph node metastasis. Lower mediastinal and abdominal lymph node metastases were common in lower-thoracic esophageal cancer. Multivariate analysis showed that gender, length of lesion, depth of invasion and vascular invasion were independent risk factors for lymph node metastasis in esophageal adenocarcinoma (P=0.010, P=0.006, P=0.000, P=0.019, respectively). Male patients had more lymph node metastasis than female patients (49.1% vs 26.3%,P=0.011). The rates of lymph node metastasis in the tumor length ≤3 cm group, 3.1-5 cm group and >5 cm group were 20.4%, 42.9% and 65.7%, respectively. Lymphatic metastasis rates in the T1, T2, T3, T4 stage cancers were 7.1%, 36.8%, 38.1% and 69.4%, respectively, (P<0.001). Patients with vascular invasion had a higher rate of lymph node metastasis (73.9%) than the patients without vascular invasion (41.0%) (P=0.003)., Conclusions: Most of the esophageal adenocarcinoma are distributed in the middle thoracic esophagus, followed by that in the lower thoracic segment. The lymph node metastasis rate, lymph node metastasis ratio and pattern of lymph node metastasis are similar to those of esophageal squamous cell carcinoma. Male, tumor length, depth of invasion and vascular invasion are risk factors of lymph node metastasis for patients with esophageal adenocarcinoma.