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 tumor diameter on the prognosis of patients with advanced esophageal squamous cell carcinoma(ESCC) after Ivor-Lewis surgical resection.Methods The clinical data of 254 patients with advanced ESCC who received Ivor-Lewis surgical resection at the Affiliated Hospital of Tianjin Medical University from January 2005 to December 2008 were retrospectively analyzed.All the patients were followed up via outpatient examination,telephone interview and correspondence till December 2013.Survival curve was drawn by the Kaplan-Meier method,and survival rate was analyzed using the Log-rank test.Receiver-operating-characteristic (ROC) curve analysis was used to determine the appropriate cutoff value of tumor size.Univariate and multivariate analysis were done using the chi-square test and COX regression model.Results Of 254 patients,223 patients were followed up for a median time of 30 months (range,3-108 months) with a follow-up rate of 87.80％ (223/254).The median total survival time was 27 months,and the 1,3,5-year overall survival rates were 72.7％,42.2％ and 31.3％,respectively.ROC analysis showed that the appropriate cutoff value of tumor diameter was 3.5 cm.The median survival time and 5-year survival rate were 36 months and 39.3％ in patients with tumor diameter ≤ 3.5 cm and 18 months and 25.4％ in patients with tumor diameter ＞ 3.5 cm,respectively,with a significant difference (x2 =9.494,P ＜ 0.05).The results of univariate analysis showed that the age,tumor diameter,depth of tumor invasion,lymph node metastasis and postoperative adjuvant therapy were related factors affecting the prognosis of patients with advanced ESCC after Ivor-Lewis surgical resection (x2=4.459,9.494,6.993,10.382,5.507,P ＜ 0.05).The results of multivariate analysis showed that tumor diameter ＞ 3.5 cm,lymph node metastasis and no postoperative adjuvant therapy were the independent factors affecting the prognosis of patients with advanced ESCC after Ivor-Lewis surgical resection (HR =1.631,1.681,0.677,95％ confidence interval:1.151-2.312,1.198-2.358,0.487-0.942,P ＜ 0.05).Of 159 patients without postoperative lymph node metastasis,median survival time and 5-year accumulated survival rate were 49 months and 46.4％ in patients with tumor diameter ≤ 3.5 cm and 23 months and 32.0％ in patients with tumor diameter ＞ 3.5 cm,respectively,with a significant difference (x2 =6.412,P ＜ 0.05).Conclusions The tumor diameter ＞ 3.5 cm,lymph node metastasis and no postoperative adjuvant therapy are the independent factors affecting the prognosis of patients with advanced ESCC after Ivor-Lewis surgical resection,meanwhile there is an assessed value of tumor diameter on the prognosis of patients without lymph node metastasis.

To explore the model of the standardized training for health management talents by referring to the standardized training for resident-doctors.This article analyzed the necessities of the model of the standardized training for health management talents from two aspects.After that,it elaborated on the significance of standardized training.At last,it proposed some ideas about constructing the standardized training for health management talents.

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 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 evaluate the prognostic value of the preoperative Geriatric Nutritional Risk Index (GNRI) in patients with esophageal squamous cell carcinoma after radical resection. Methods: Clinicopathological and laboratory data of 315 elderly patients with esophageal squamous cell carcinoma who were older than 60 years and underwent radical resection in Tianjin Medical University Cancer Institute and Hospital from January 2008 to December 2012 were retrospectively analyzed. The GNRI formula was as follows:1.489×serum albumin (g/L)+41.7×(current body weight/ideal body weight). According to the GNRI, patients were divided into the normal and abnormal GNRI groups. The χ2 test was used to analyze the relationship between the GNRI and the clinicopathological char-acteristics of patients. The Kaplan-Meier method was used to analyze the survival rate, and survival analysis was conducted using the Log-rank test. Multivariate survival analysis was conducted using the Cox proportional risk regression model. Results: There were 259 patients in the normal GNRI group (GNRI>98) and 56 patients in the abnormal GNRI group (GNRI≤98). The GNRI was closely correlated with age, tumor location, tumor diameter, serum albumin level, body mass index (BMI), and lymph node metastasis (all P<0.05). The 5-year survival rates in the normal and abnormal GNRI groups were 41.2% and 27.0%, respectively, with statistical significance (P=0.002). Univariate analysis showed that age, tumor diameter, serum albumin level, BMI, GNRI, platelet-lymphocyte ratio, tumor invasion depth, and lymph node metastasis were risk factors for the prognosis of patients with esophageal squamous cell carcinoma (all P<0.05). Multivariate analysis showed that the preoperative GNRI (hazard ratio=0.687, 95% confidence interval: 0.487-0.968, P=0.032) was an independent factor affecting the prognosis of patients with esophageal squamous cell carcinoma. Subgroup analysis showed that the survival rates in the normal GNRI group were significantly higher than those in the abnormal GNRI group (P=0.036 and 0.010, respectively), regardless of lymph node metastasis. Conclusions: The preoperative GNRI is associated with malignant biological behav-ior in elderly patients with esophageal squamous cell carcinoma and can be used as a useful indicator for predicting survival after radi-cal resection.

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 investigate the pattern of lymph node metastasis and analyze prognostic factors of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective case-control study was conducted.The clinicopathological data of 368 patients with Siewert type Ⅱ AEG who were admitted to Tianjin Medical University Cancer Institute and Hospital from June 2010 and November 2015 were collected.There were 323 males and 45 females,aged from 35 to 80 years,with an average age of 64 years.Of 368 patients,209 underwent left transthoracic surgery,1 12 underwent thoracoabdominal surgery,and 47 underwent Ivor-Lewis surgery.Observation indicators:(1) total lymph node metastasis and metastasis of various lymph node stations;(2) follow-up and survival;(3) prognostic factors analysis;(4) influencing factors affecting thoracic lymph node metastasis.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to November 2018.Measurement data with skewed distribution were represented as M (range).Count data were represented as absolute number or percentage.The survival time and rate were calculated using the Kaplan-Meier method.The univariate and multivariate analyses were done by the COX proportional hazard model.Results (1) Total lymph node metastasis and metastasis of various lymph node stations:the total lymph node metastasis rate was 66.58％ (245/368) in 368 patients.The metastasis rates of abdominal lymph nodes,thoracic lymph nodes,lower mediastinal lymph nodes,and upper mediastinal lymph nodes were 65.49％ (241/368),12.77％ (47/368),12.23％ (45/368),and 1.09％ (4/368),respectively.The order of metastasis rate of various lymph node stations from high to low was 51.99％(170/237) of No.7 left gastric artery,34.23％(89/260) of No.1 right paracardial region,33.88％ (83/245) of No.2 left paracardial region,28.91％ (85/294) of No.3 lesser curvature,27.10％(29/107) of No.1 1 splenic artery,19.75％(16/81) of No.9 celiac trunk,15.25％(36/236) of No.E8Lo lower paraesophageal region,11.94％ (16/134) of No.4 greater curvature,11.76％ (6/51) of No.E8M middle paraesophageal region,11.1 1％(10/90) of No.8 common hepatic artery,4.65％(4/86) of No.E9L left inferior pulmonary ligament and 3.39％ (2/59) of No.E7 subcarinal region.(2) Follow-up and survival:of the 368 patients,309 were followed up for 1-103 months,with a median follow-up time of 38 months.The survival time of 309 patients was 0.7-101.9 months,and the median survival time was 35.9 months.During the followup,the postoperative l-,2-,3-year overall survival rates were 85.9％,68.6％,and 58.7％,respectively.(3) Prognostic factors analysis.Results of univariate analysis showed that tumor differentiation degree,presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,tumor diameter,and length of esophageal invasion were associated factors affecting prognosis of patients (x2 =8.776,26.582,46.057,18.679,22.460,9.158,P＜0.05).Results of multivariate analysis showed that presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter were independent influencing factors for prognosis of patients [odds ratio (OR) =1.699,1.271,1.422,1.238,95％ confidence interval:1.102-2.621,1.019-1.481,1.090-1.856,0.971-1.481,P＜0.05].(4) Influencing factors affecting thoracic lymph node metastasis:results of univariate analysis showed that tumor diameter,length of esophageal invasion,number of lymph lodes harvested in thorax were related factors for thoracic lymph node metastasis (x2 =5.129,43.140,10.605,P＜0.05).Results of multivariate analysis showed that length of esophageal invasion ≥2 cm,number of lymph lodes harvested in thorax ≥ 4 were independent risk factors for thoracic lymph node metastasis (OR =6.321,1.097,95％ confidence interval:2.982-13.398,1.026-1.173,P＜0.05).Conclusion Lymph node metastasis of Siewert type Ⅱ AEG spreads two regions,mainly at abdominal lymph nodes,followed by the thoracic lymph nodes.Presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter are independent influencing factors for prognosis of patients.Presence of thoracic lymph node metastasis indicates poor prognosis of patients.Length of esophageal invasion ≥ 2 cm and number of lymph lodes harvested in thorax ≥4 are independent risk factors for thoracic lymph node metastasis.

Objective To investigate the clinical efficacy of minimally invasive esophagectomy and open triple-incision esophagectomy for esophageal cancer (EC).Methods The retrospective cohort study was conducted.The clinicopathological data of 454 EC patients who were admitted to the Tianjin Medical University Cancer Institute and Hospital from January 2012 to September 2016 were collected.Of 454 patients,229 undergoing thoracoscopic esophagectomy (194) or combined thoracoscopic + laparoscopic esophagectomy (35) were allocated into the minimally invasive group,and 225 undergoing open triple-incision esophagectomy in the left cervical,right chest and epigastric regions were allocated into the open group.Observation indicators:(1) intraoperative situations;(2) postoperative recovery situations;(3) stratified analysis;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect the postoperative survival up to October 2017.Measurement data with normal distribution were represented as-x±s,and t test was used for comparison between groups.Measurement data with skewed distribution were described as M (range),non-parametric test was used for comparison between groups.Count data were expressed as percentage,and the chi-square test or fisher exact probability method were used to test comparison between groups.KaplanMeier method was used to calculate survival rate and draw survival curve.Log-rank test was used for survival analysis.Results (1) Intraoperative situations:operation time,numbers of upper mediastina lymph node dissected and right laryngeal nerve lymph node dissected in stage 0-Ⅱ of TNM staging and numbers of neck lymph nodes dissected in stage Ⅲ of TNM staging were respectively (307±70)minutes,4 (range,0-18),2 (range,0-10),0 (range,0-24) in the minimally invasive group and (267±49)minutes,3 (range,0-15),1 (range,0-7),0 (range,0-46) in the open group,with statistically significant differences between groups (t =7.071,Z=-2.207,-2.717,-1.969,P＜0.05).(2) Postoperative recovery situations:thoracic drainage-tube removal time and volume of drainage fluid were respectively 5 days (range,2-88 days),280 mL (range,0-7 792 mL)in the minimally invasive group and 8 days (range,1-72 days),1 650 mL (range,225-7 970 mL),with statistically significant differences between groups (Z =-9.618,-15.443,P ＜ 0.05).The cases with total postoperative complications,arrhythmia and recurrent laryngeal nerve paralysis were 72,20,35 in the minimally invasive group and 100,36,56 in the open group,with statistically significant differences between groups (x2=8.155,5.542,6.533,P＜0.05).Patients may be combined with multiple complications.Two patients died within 30 days postoperatively,including 1 with respiratory failure and 1 with pulmonary embolism.Patients with other complications were improved after symptomatic and supportive treatments.(3) Stratified analysis:of 229 patients in the minimally invasive group,93 underwent surgery within the physician's learning curve and 136 underwent surgery after physician's learning curve.Operation time,volume of intraoperative blood loss,dissected numbers of upper mediastina lymph node,right laryngeal nerve lymph node,left laryngeal nerve lymph node,middle mediastinal lymph node and lower mediastinal lymph node,cases with pneumonia,recurrent laryngeal nerve paralysis,chylothorax,anastomotic stenosis,anastomotic fistula,respiratory failure and pulmonary embolism in 93 patients were respectively (306±68)minutes,(217± 178)mL,3 (range,0-20),2 (range,0-8),0 (range,0-10),6(range,0-17),1 (range,0-6),5,16,1,5,3,2,2 in the minimally invasive group and (308±72)minutes,(200±112)mL,4 (range,0-37),2 (range,0-10),0 (range,0-8),7 (range,0-20),1 (range,0-10),4,19,3,3,4,4,0 in the open group,with a statistically significant difference in number of upper mediastina lymph node dissected between groups (Z=-2.472,P＜0.05) and no statistically significant difference in other indicators between groups (t =-0.160,0.917,Z =-0.113,-1.698,-0.950,-0.510,x2 =0.342,0.446,P＞0.05).(4) Follow-up and survival situations:of 454 patients,415 were followed up for 1-62 months,with a median time of 28 months.Among the 415 patients,operation time ≥ 3 years was detected in 162 patients,(77 in the minimally invasive group and 85 in the open group),and 3-year cumulative survival rates of the minimally invasive and open groups were 68.1％ and 53.8％,showing no statistically significant difference between groups (x2=3.293,P＞0.05).Further subgroup analysis showed that postoperative 3-year cumulative survival rates of patients with the stage Ⅰ-Ⅱ and Ⅲ of TNM staging were respectively 82.1％,53.7％ in the minimally invasive group and 62.6％,48.6％ in the open group,showing no statistically significant difference between groups (x2=2.664,0.382,P＞ 0.05).Conclusion Minimally invasive esophagectomy has some characteristics of less surgical trauma postoperative complications,and its resection effect is comparable to open esophagectomy.