Apoptosis disorders have an important function in the development of gastrointestinal cancer. BNIP3 is a member of the BH3-only subfamily of the bcl-2 family, which contains a BH3 domain and a transmembrane domain, and belongs to the mitochon-drial pro-apoptotic proteins. BNIP3 induces cell death via the caspase-independent mitochondrial apoptotic pathway and mediates au-tophagic cell death. BNIP3 expression is regulated by hypoxia and other factors. BNIP3 expression in tumors exhibits tissue specificity;BNIP3 is highly expressed in some tumors, including breast, lung, and cervical tumors. In pancreatic, gastric, and colorectal cancers, BNIP3 is epigenetically silenced. The absence of BNIP3 in the tumors can cause tumor cells to tolerate hypoxia and may be associated with chemotherapy and radiotherapy resistance. A comprehensive understanding of the spectrum of BNIP3 expression in a various tu-mors is necessary to use BNIP3 as a marker in clinical applications to treat tumors and as a new target in tumor prognosis.

Objective To investigate the correlation between different clinicopathological factors and the recurrence and metastasis of advanced adenocarcinoma of the esophagogastric junction after curative resection,and to analyze the effects of the factors on the prognosis of these patients.Methods The clinical data of 385 patients with advanced adenocarcinoma of the esophagogastric junction who received curative resection at the Affiliated Hospital of Tianjin Medical University from January 2000 to January 2007 were retrospectively analyzed.There were 228 patients did not have tumor recurrence and metastasis (non-recurrence and metastasis group) and 157 patients had tumor recurrence and metastasis (recurrence and metastasis group).Risk factors which might influence postoperative recurrence and metastasis were analyzed using univariate analysis (chi-square test) and multivariate analysis (Logistic regression model).All patients were followed up via out-patient examination or phone call.The survival curve was drawn by Kaplan-Meier method,and the survival analysis was done by Log-rank test.Results The median time for follow-up was 36 months (range,3-108 months).A total of 157 patients had postoperative tumor recurrence and metastasis,and the mean time of tumor recurrence was 17.9 mouths.The results of univariate analysis showed that tumor type,differentiation degree,invasion depth,number of positive and negative lymph nodes,TNM staging were risk factors for the postoperative recurrence and metastasis of adenocarcinoma of the esophagogastric junction after curative resection (x2=5.248,13.493,12.319,18.315,9.704,10.281,P ＜ 0.05).The results of multivariate analysis showed that differentiation degree,invasion depth,number of positive and negative lymph nodes were the independent risk factors influencing the recurrence and metastasis of adenocarcinoma of the esophagogastric junction after curative resection (OR =1.805,1.809,1.520,0.763,P ＜0.05).The numbers of positive lymph nodes in the non-recurrence and metastasis group and the recurrence and metastasis group were 3.86 ± 0.28 and 6.89 ± 0.58,with a significant difference (t =5.118,P ＜ 0.05).The number of negative lymph nodes in the non-recurrence and metastasis group and the recurrence and metastasis group were 14.04 ±0.54 and 10.53 ±0.56,with a significant difference between the 2 groups (t =4.386,P ＜0.05).The 5-year survival rates of patients with the numbers of positive lymph nodes of 0,1-2,3-6 and more than 7 were 46.4％,43.8％,27.1％ and 7.2％,respectively,and the corresponding median survival time were 53,47,35 and 26 months.There was a significant difference in the 5-year survival rate among patients with different numbers of positive lymph nodes (x2 =54.783,P ＜ 0.05).The 5-year survival rates of patients with the number of negative lymph nodes under 9,between 10 and 15 and more than 16 were 22.1％,21.5％ and 45.5％,respectively,and the corresponding median survival time were 28,34,47 months.There was a significant difference in the 5-year survival rate among patients with different numbers of negative lymph nodes (x2=22.814,P ＜ 0.05).Conclusions Tumor type,invasion depth,number of positive and negative lymph nodes are independent risk factors of postoperative recurrence and metastasis of adenocarcinoma of the esophagogastric junction,and the number of positive and negative lymph nodes are important for the prognosis of patients with adenocarcinoma of the esophagogastric junction.

Objective To investigate the expression of Krüppel-like factor 4 (KLF4) protein in esophageal squamous cell carcinoma (ESCC) tissues and to explore its correlation with clinical pathological features as well as prognosis.Methods The expression of KLF4 protein in cancer tissues and normal esophageal tissues from surgical paraffin specimens of 98 thoracic ESCC cases with complete clinical,pathological and follow-up date were detected by immunohistochemistry.The expression of KLF4 at protein level in 20 freshly surgical esophageal cancer tissues and normal esophageal mucous tissues were examined by Western blot.The relation between the expression of KLF4 protein,clinicopathological characteristics and prognosis was analyzed,t-test was used for measurement data analysis.Chi-square test was performed to analyze the correlation between KLF4 protein expression and clinicopathological features.Survival analysis was analyzed by the Kaplan-Meier method.The comparisons of survival rates were analyzed by Log-rank test.Results The positive rate of KLF4 protein expression in normal esophageal tissues and ESCC tissues was 82.7％ (81/98) and 43.9％ (43/98),respectively,the difference was statistically significant (x2=31.701,P＜0.01).The expression of KLF4 at protein level in 20 cases of fresh esophageal cancer tissues and normal esophageal mucosa tissues was 0.576±0.050 and 0.684 ± 0.095,respectively,the difference was statistically significant (t =4.932,P＜0.01).The expression of KLF4 at protein level was correlated with lymph node metastasis and TNM stage (x2 =10.871 and 6.482,P=0.001 and 0.039),however not correlated with gender,age,location,tumor size,degree of differentiation and the depth of invasion (x2=0.214,3.442,5.748,0.891,0.013 and 1.479,P=0.644,0.064,0.056,0.345,0.911 and 0.477).In 98 patients,the 5-year survival rate of cases with KLF4 protein positive expression and negative expression was 48.8％ and 25.5％ and the median survival period was 55 months and 26 months,the differences were statistically significant (x2 =5.747 and 4.493,P=0.017 and 0.034).Conclusion KLF4 as a tumor suppressor gene may play an important role in the genesis,development and metastasis of ESCC,and may become a biological indicator of the severity and prognosis in ESCC.

Objective The purification methods of the exosomes derived form T cells were established in order to get high quan-tity exosomes .Methods Exosomes from T cells culture supernatants were purified by ExoQuick Precipitation ,ultrafiltration and sucrose gradient centrifugation ,differential ultracentrifugation ,and confirmed via using transmission electron microscopy .The pro-tein expression of the exosomes were analyzed by SDS-PAGE electrophoresis .Western blotting was used to test the expression of IL-2 .Results The protein concentration of the exosomes purified through ExoQuick Precipitation ,ultrafiltration and sucrose gradi-ent centrifugation were higher than through differential ultracentrifugation (P<0 .05) .SDS-PAGE displayed the difference among the exosome purified by three methods .Three kinds of exosomes all expressed IL-2 .Conclusion ExoQuick Precipitation ,ultrafiltra-tion and sucrose gradient centrifugation technique can obtain high purity and complete exosome sample .

Esophagectomy and lymph node dissection are the cornerstones for the treatment of esophageal cancer. Upper mediastinal lymph node dissection is of great value for accurate staging and improving the prognosis of patients. Lymph node dissection along the left recurrent laryngeal nerve is the most challenging procedures in esophageal surgery, and there has been no relevant consensus on the scope and boundary of lymph node dissection. In recent years, with the application of endoscopic technology, especially robotic surgery system in esophagectomy, and the introduction of the concept of superior mediastinal microdissection, the authors have proposed the border of lymph node dissection along the left recurrent laryngeal nerve, so as to achieve precise, radical and standardized dissection. Combined with their own experiences, the authors elaborate on the anatomic boundary, extent and technique of lymph node dissection along the left recurrent laryngeal nerve.

Breast cancer is one of the most common malignant tumors in women, and its incidence has increased year by year, which is one of the most important causes of death among women, especially young women. Studying related cell signal transduction that affects the development and progression of breast cancer can help prevent the occurrence of breast cancer, slow down the cancer progression and improve the prognosis of patients. nitric oxide (NO) is a kind of signaling molecule. Many studies have shown that the production and expression of NO are closely related to breast cancer. NO-related cell signal transduction significantly affects the occurrence and development of breast cancer. However, the understanding of the relationship between NO and breast cancer associated cell signal transduction needs to be further improved. In this paper, the related studies on NO-related cellular signal transduction in breast cancer were reviewed with a view to improving the understanding of the development and progression of breast cancer.

OBJECTIVETo investigate the pattern of early lymph node metastasis of thoracic esophageal squamous cell carcinoma and its prognostic value.

METHODSClinical and follow-up data of 126 patients with pathological stage pN1 of esophageal squamous cell carcinoma undergoing radical esophagectomy in our department from January 2005 to December 2008 were analyzed retrospectively. Impact of lymph node metastasis pattern on prognosis was investigated.

RESULTSThe relatively common sites of lymph node metastasis were upper mediastinum(53.8%), middle and lower thoracic paraesophageal(38.3%), right and left cardiac(34.4%) and the left gastric artery(36.8%). Univariate analysis showed that the lymph node metastasis of subcarinal, middle and lower thoracic paraesophageal and the left gastric artery was associated with 5-year survival rate. Multivariate analysis revealed that the presence of subcarinal and middle and lower thoracic paraesophagea lymph node metastasis was an independent risk factor of survival.

CONCLUSIONSUpper mediastinal, middle and lower thoracic paraesophageal, right and left cardiac and the left gastric artery are the earliest lymph node metastasis sites of esophageal squamous cell carcinoma. The presence of subcarinal and middle and lower thoracic paraesophagea lymph node metastasis is an independent risk factor of survival. Patient prognosis should be analyzed with lymph node metastasis pattern based on the 7th edition UICC-AJCC TNM classification system.

Carcinoma, Squamous Cell ; pathology ; surgery ; Esophageal Neoplasms ; pathology ; surgery ; Esophagectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate

OBJECTIVETo investigate the log odds of positive lymph nodes(LODDS) on the prognosis of patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy.

METHODSClinical data of 136 patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy from January 2005 to January 2009 were retrospectively analyzed. LODDS was estimated using the calculation: log(pnod+0.5)/(tnod-pnod+0.5), in which pnod indicates the number of positive lymph nodes and tnod indicates the total number of lymph nodes retrieved. The best cut-off value for LODDS was identified by using the receiver operating characteristic (ROC) curve. Drawing of survival curves was employed with the Kaplan-Meier estimator, and survival rate was analyzed using Log-rank test. The Cox proportional hazard model was used to identify independent factors associated with prognosis.

RESULTSA total of 136 patients, including 112 males and 24 females, seventy-nine patients were 65 years or older(range 27-92 years), and were included in the present study. Among them, the most cancer site was the middle third of the thoracic esophagus(115 cases), followed by the lower third(13 cases), and the upper third(8 cases). There were 70 patients with tumor diameter ≤3.5 cm and 66 patients with tumor diameter >3.5 cm. There were 32 patients with stage pT1-2, and 104 with stage pT3-4. The number of patients in TNM classification I, II and III was 14, 85 and 37, respectively. All the patients received radical esophagectomy with primary tumor resection and lymph node dissection. The median follow-up time was 44.2 months(range, 4.4-98.4 months). Five-year overall survival rate was 43.2%, and the median total survival time was 48 months. ROC analysis showed that the appropriate cut-off value of LODDS was -1.2. There were 99 patients with LODDS≤-1.2(LODDS1 stage), 37 patients with LODDS >-1.2(LODDS2 stage), the median survival time and 5-year survival rate were 56.5 months and 48.3% in patients with LODDS1 stage and 30.0 months and 29.7% in patients with LODDS 2 stage, respectively, with significant difference(χ(2)=4.980, P=0.026). Multivariate analyses showed that recurrence(HR=0.627, 95% CI:0.395 to 0.996; P=0.048) and LODDS >-1.2(HR=1.853; 95% CI:1.155 to 2.974; P=0.011) were the independent factors affecting the prognosis of patients.

CONCLUSIONSFor patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy, LODDS stage has a unique prediction for prognosis, and patients with LODDS less than -1.2 (cut-off value) have a better prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; diagnosis ; surgery ; Esophageal Neoplasms ; diagnosis ; surgery ; Esophagectomy ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate

Objective: To compare and evaluate the prognostic value of the 7^th and 8^th edition of The AJCC Esophageal Cancer Staging System for patients with stage Ⅱ and Ⅲ esophageal squamous cell carcinoma. Methods: The clinical data of 328 esophageal cancer patients who received operation at Department of Esophageal Cancer, Tianjin Tumour Hospital from January 2006 to December 2010 were restrospectively analyzed. There were 63 female and 265 male patients. The mean age was 65 (range: 33 to 87) years. Univariate and multivariate analysis were performed to identify the prognosis factors. Results: The five years overall survival rates among patients with stage Ⅱ and Ⅲ were both significantly different (χ²=87.035, 84.730, all P=0.000) according to the 7^th and 8^th editions of the TNM staging systems. The five years overall survival rate among patients with stage ⅡB and ⅢA were significantly different (39.6% vs 23.4%, P=0.001) according to the 7^th edition of the esophageal cancer staging systems.According to the 8^th edition of the esophageal cancer staging system, the 5 years survival rate of patients with stage ⅡA and ⅡB, ⅢB and Ⅳ was statistically significant (58.5% vs. 35.5%, P=0.040; 18.9% vs. 0, P=0.000). In multivariate analysis, tumor size, T staging, N staging and tumor differentiation (HR=1.592, 95%CI: 1.185 to 2.139, P=0.002; HR=1.519, 95% CI: 1.236 to 1.867, P=0.000; HR=1.647, 95% CI: 1.448 to 1.874, P=0.000; HR=1.404, 95% CI: 1.059 to 1.861, P=0.018) were the main independent prognosis factors affecting the prognosis of esophageal squamous cell carcinoma patients. Conclusions Both the 7^th and the 8^th editions of TNM staging systems are able to reflect the clinical prognosis of patients receiving radical resection of esophageal cancer, and the factors of tumor size, differentiaton, invasion depth and lymph node metastases are the independent predictors of prognosis. The 8^th edition provides a more detailed and more reasonable for the staging of stage Ⅱ and Ⅲ for esophageal cancer patients than the 7^th edition, and it is more accurate for the prognosis of patients with esophageal cancer after surgery.

Objective:To investigate the clinical efficacy of Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 404 patients with esophageal cancer who underwent Da Vinci robot-assisted esophagectomy in Tianjin Medical University Cancer Hospital and Institute from June 2017 to June 2022 were collected. There were 349 males and 55 females, aged (62±8)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) comparison of clinical features in patients who were admitted in different time periods. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the one way ANOVA. Measurement data with skewed distribution were represented as M(IQR), and comparison among multiple groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Intraoperative conditions. The operation time, volume of intraoperative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, left recurrent laryngeal nerve lymph node metastasis rate, right recurrent laryngeal nerve lymph node dissection rate, the number of right recurrent laryngeal nerve lymph node dissected, right recurrent laryngeal nerve lymph node metastasis rate were (306±56)minutes,200(100)mL, 29.9±13.1, 18.5±9.7, 78.47%(317/404), 4.0(3.0), 17.35%(55/317), 94.55%(382/404), 3.0(2.0), 21.20%(81/382). (2) Postoperative conditions. The tumor histopathological type (squamous cell carcinoma, neuroendocrine carcinoma, adenocarcinoma, carcinosarcoma, adenosquamous carcinoma, malignant melanoma), incidence rate of overall complications, cases with recurrent laryngeal nerve paralysis, cases with pulmonary complications, cases with anastomotic fistula, cases with incision infection, cases with chylothorax, cases with arrhythmia, cases with deep vein thrombosis, cases with other complications, incidence of re-admission to the intensive care unit, duration of postoperative hospital stay, 90-day mortality were 377, 11, 7, 5, 3, 1, 27.48%(111/404), 8.91%(36/404), 10.64%(43/404), 6.93%(28/404), 0.99%(4/404), 2.48%(10/404), 1.73%(7/404), 0.50%(2/404), 1.98%(8/404), 6.93%(28/404), 16(11)days, 0.50%(2/404). (3) Comparison of clinical features in patients who were admi-tted in different time periods. The number of patients who were admitted from June 2017 to May 2018, from June 2018 to May 2019, from June 2019 to May 2020, from June 2020 to May 2021, from June 2021 to June 2022 was 40, 56, 57, 116, 135, respectively. There were significant differences in age, tumor histopathological type, pT staging, neoadjuvant therapy, operation time, volume of intra-operative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, the number of right recurrent laryngeal nerve lymph node dissected, incidence rate of overall complications among patients who were admitted in different time periods ( P<0.05). Conclusion:The Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve is safe and feasible, which can achieve good short-term efficacy.