Value of number of negative lymph nodes in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model / 中华消化外科杂志

Objective:To investigate the value of number of negative lymph nodes (NLNs) in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 924 patients with esophageal cancer after neoadjuvant therapy uploaded to the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute from 2004 to 2015 were collected. There were 1 624 males and 300 females, aged 63 (range, 23?85)years. All 1 924 patients were randomly divided into the training dataset of 1 348 cases and the validation dataset of 576 cases with a ratio of 7:3 based on random number method in the R software (3.6.2 version). The training dataset was used to constructed the nomogram predic-tion model, and the validation dataset was used to validate the performance of the nomogrram prediction model. The optimal cutoff values of number of NLNs and number of examined lymph nodes (ELNs) were 8, 14 and 10, 14, respectively, determined by the X-tile software (3.6.1 version), and then data of NLNs and ELNs were converted into classification variables. Observation indicators: (1) clinicopathological characteristics of patients in the training dataset and the validation dataset; (2) survival of patients in the training dataset and the validation dataset; (3) prognostic factors analysis of patients in the training dataset; (4) survival of patients in subgroup of the training dataset; (5) prognostic factors analysis in subgroup of the training dataset; (6) construction of nomogram prediction model and calibration curve. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction efficacy of nomogram prediction model was evaluated using the area under curve (AUC) of the receiver operating characteristic curve and the Harrell′s c index. Errors of the nomogram prediction model in predicting survival of patients for the training dataset and the validation dataset were evaluated using the calibration curve. Results:(1) Clinicopathological characteristics of patients in the training dataset and the validation dataset. There was no significant difference in clinicopatholo-gical characteristics between the 1 348 patients of the training dataset and the 576 patients of the validation dataset ( P>0.05). (2) Survival of patients in the training dataset and the validation dataset. All 1 924 patients were followed up for 50(range, 3?140)months, with 3-year and 5-year cumulative survival rate as 59.4% and 49.5%, respectively. The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the training dataset was 46.7%, 62.0% and 66.0%, respectively, and the 5-year cumulative survival rate was 38.1%, 52.1% and 59.7%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=33.70, P<0.05). The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the validation dataset was 51.1%, 54.9% and 71.2%, respectively, and the 5-year cumulative survival rate was 39.3%, 42.5% and 55.7%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=14.49, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the training dataset was 53.9%, 60.0% and 62.7%, respectively, and the 5-year cumulative survival rate was 44.7%, 49.1% and 56.9%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=9.88, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the validation dataset was 56.2%, 47.9% and 69.3%, respectively, and the 5-year cumula-tive survival rate was 44.9%, 38.4% and 51.9%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=9.30, P<0.05). (3) Prognostic factors analysis of patients in the training dataset. Results of multivariate analysis showed that gender, neoadjuvant pathological (yp) T staging, ypN staging (stage N1, stage N2, stage N3) and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=0.65, 1.44, 1.96, 2.41, 4.12, 0.69, 0.56, 95% confidence interval as 0.49?0.87, 1.17?1.78, 1.59?2.42, 1.84?3.14, 2.89?5.88, 0.56?0.86, 0.45?0.70, P<0.05). (4) Survival of patients in subgroup of the training dataset. Of the patients with NLNs in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 61.1%, 71.6% and 76.8%, respectively, and the 5-year cumulative survival rate was 50.7%, 59.9% and 70.1%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=12.66, P<0.05). Of the patients with positive lymph nodes in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 26.1%, 42.9% and 44.7%, respectively, and the 5-year cumulative survival rate was 20.0%, 36.5% and 39.3%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=20.39, P<0.05). (5) Prognostic factors analysis in subgroup of the training dataset. Results of multivariate analysis in patients with NLNs in the training dataset showed that gender, ypT staging and number of NLNs (>14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadju-vant therapy ( hazard ratio=0.67, 1.44, 0.56, 95% confidence interval as 0.47?0.96, 1.09?1.90, 0.41?0.77, P<0.05). Results of multi-variate analysis in patients with positive lymph nodes in the training dataset showed that race as others, histological grade as G2, ypN staging as stage N3 and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=2.73, 0.70, 2.08, 0.63, 0.59, 95% confidence interval as 1.43?5.21, 0.54?0.91, 1.44?3.02, 0.46?0.87, 0.44?0.78, P<0.05). (6) Construction of nomogram prediction model and calibration curve. Based on the multivariate analysis of prognosis in patients of the training dataset ,the nomogram prediction model for the prognosis of patients with esophageal cancer after neoadju-vant treatment was constructed based on the indicators of gender, ypT staging, ypN staging and number of NLNs. The AUC of nomogram prediction model in predicting the 3-, 5-year cumulative survival rate of patients in the training dataset and the validation dataset was 0.70, 0. 70 and 0.71, 0.71, respectively. The Harrell′s c index of nomogram prediction model of patients in the training dataset and the validation dataset was 0.66 and 0.63, respectively. Results of calibration curve showed that the predicted value of the nomogram prediction model of patients in the training dataset and the validation dataset was in good agreement with the actual observed value. Conclusion:The number of NLNs is an independent influencing factor for the prognosis of esophageal cancer patients after neoadjuvant therapy, and the nomogram prediction model based on number of NLNs can predict the prognosis of esophageal cancer patients after neoadjuvant therapy.

Effect of the preoperative Geriatric Nutritional Risk Index on the prognosis of patients with esophageal squamous cell carcinoma after radical resection / 中国肿瘤临床

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.

The pattern of lymph node metastasis and prognostic factors analysis of Siewert type Ⅱ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

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.

Impact of the number of lymph node examined on the prognosis of esophageal squamous cell carcinoma / 中华消化外科杂志

Objective To investigate the effect of the number of lymph nodes examined (NLNE) on the prognosis of esophageal squamous cell carcinoma (ESCC).Methods The retrospective case-control study was conducted.The clinicopathological date of 628 ESCC patients who underwent radical resection in the Tianjin Medical University Cancer Institute and Hospital from January 2005 to March 2013 was collected.Patients underwent radical resection of ESCC through right thorax.Observation indicators:(1) surgical and postoperative pathological examinations;(2) follow-up and survival situations;(3) effect of NLNE on the prognosis of ESCC;(4) factors analysis affecting prognosis of ESCC patients;(5) subgroup analysis.Follow-up using outpatient examination,telephone interview and mail was performed to detect postoperative survival up to February 2018.Measurement data with skewed distribution were described as M (range).Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate cut-off of the NLNE.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the survival analysis was done by the log-rank test.Multivariate analysis was done by the Cox proportional hazard model.Results (1) Surgical and postoperative pathological examinations:472 and 156 patients underwent respectively Ivor-Lewis and Mckeown operations.There were 284 patients with tumor diameter ≤ 3.5 cm and 344 patients with tumor diameter ＞ 3.5 cm.The total NLNE was 11 139 for all of the 628 patients,with an average NLNE of 18 per case(range,2-78 per case) and a median NLNE of 16 per case.Of 628 patients,high-,moderate-and low-differentiated tumors were respectively detected in 48,469 and 111 patients;staging T0-1,T2,T3 and T4a of depth of tumor invasion in 30,119,260 and 219 patients;N0,N1,N2 and N3 of degree of lymph node metastasis in 349,173,69 and 37 patients;rN0,rN1,rN2 and rN3 of rate of lymph node metastasis in 349,184,54 and 41 patients.(2) Follow-up and survival situations:all the 628 patients were followed up for 3-144 months,with a median time of 36 months.The 1-,3-and 5-year survival rates were 82.4％,53.7％ and 41.3％,respectively.(3)Effect of NLNE on the prognosis of ESCC:ROC curve showed that the appropriate cut-off value of the NLNE was 16.Using NLNE =16 as a cut-off value,5-year survival rate was respectively 36.7％ in patients with NLNE ＜ 16 and 45.1％ in patients with NLNE ≥ 16,with a statistically significant difference in survival (x2 =9.527,P＜0.05).According to a median NLNE of 23,the patients with NLNE ≥ 16 were further divided into patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23.Results showed that 5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 36.7％,41.2％ and 50.3％,with a statistically significant difference in survival among them (x2 =10.588,P＜0.05),between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =4.419,P＜0.05).There was no statistically significant difference between patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23 (x2 =1.413,P＞0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞23 was respectively 38.6％ and 50.3％,with a statisctically significant difference (x2 =5.885,P＜0.05).(4)Factors analysis affecting prognosis of ESCC patients:results of univariate analysis showed that age,smoking history,BMI,tumor diameter,NLNE,depth of tumor invasion,degree and rate of lymph node metastasis were related factors affecting the prognosis of ESCC patients (x2 =5.454,4.875,7.669,10.691,10.588,30.612,59.780,76.565,P＜0.05).Results of muhivariate analysis showed that age,tumor diameter,NLNE,depth of tumor invasion and rate of lymph node metastasis were independent factors affecting the prognosis of ESCC patients [HR=1.268,1.300,0.762,1.354,1.357,95％ confidence interval (CI):1.034-1.556,1.038-1.629,0.662-0.878,1.183-1.549,1.089-1.692,P＜0.05].(5) Subgroup analysis:among 279 patients with lymph node metastasis,5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 23.7％,19.4％ and 39.5％,with a statistically significant difference among them (x2 =8.397,P＜0.05),between patients with 16≤ NLNE ≤ 23 and NLNE ＞ 23 (x2=5.425,P＜0.05).There was no statistically significant difference between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =0.389,P＞ 0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞ 23 was respectively 21.9％ and 39.5％,with a statisctically significant difference (x2=7.942,P＜ 0.05).Among 349 patients without lymph node metastasis,5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 45.6％,60.3％ and 59.2％,with a statistically significant difference among them (x2 =9.755,P＜0.05) and between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =8.208,P＜0.05).There was no statistically significant difference between patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23 (x2 =0.284,P＞0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞ 23 was respectively 51.1％ and 59.2％,with no statisctically significant difference (x2 =1.147,P＞ 0.05).Conclusions The NLNE is an independent factor affecting the prognosis of ESCC patients,and at least 16 to 23 lymph nodes should be dissected.For patients with lymph node metastasis,and more than 23 lymph nodes should be dissected.For patients without lymph node metastasis,more than 23 lymph nodes dissection cannot obviously improve the prognosis of patients.

Analysis of therapeutic effects between minimally invasive esophagectomy and open triple-incision esophagectomy / 中华消化外科杂志

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.

Predictive value of log odds of positive lymph nodes for the prognosis of patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Clinical 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.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSIONS</b>For 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.</p>

Effects of tumor diameter on the prognosis of patients with advanced esophageal squamous cell carcinoma after Ivor-Lewis surgical resection / 中华消化外科杂志

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.

Expression of leptin and adiponectin in esophageal squamous cell carcinoma and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To preliminarily investigate the expression and clinical significance of leptin and adiponectin in esophageal squamous cell carcinoma (ESCC).</p><p><b>METHODS</b>The expression of leptin and adiponectin in ESCC and normal esophageal mucosal tissue was detected by immunohistochemical staining with tissue microarray. The correlation between leptin, adiponectin and clinicalpathological features was statistically analyzed.</p><p><b>RESULTS</b>The expression of leptin was significantly upregulated in the ESCC than in the normal esophageal mucosa tissue [65.6% (80/122) versus 27.5% (11/40), P < 0.001]. Expression of leptin was significantly correlated with lymph node involvement and advanced tumor stage (P = 0.009 and P = 0.043, respectively). Expression of adiponectin was significantly down-regulated in ESCC compared with that in normal esophageal mucosal tissue [22.1% (27/122) versus 47.5% (19/40), P = 0.002]. Expression of adiponectin was significantly correlated with lymph node involvement (P = 0.020). Correlation analysis showed a positive correlation between the expression of leptin and lymph node metastasis and TNM stage (r = 0.235 and r = 0.183, respectively), and a negative correlation between the expression of adiponectin and lymph node metastasis (r = -0.229). There was no significant correlation between the expressions of leptin and adiponectin (P > 0.05), and between the body mass index and the expression of leptin and adiponectin, and lymph node metastasis (P > 0.05 for all).</p><p><b>CONCLUSIONS</b>An imbalanced expression of adipocytokines exits in ESCC. The expression of leptin and adiponectin is correlated with lymph node metastasis and/or tumor stage. Therefore, imbalanced expression of leptin and adiponectin may have a potential role in the carcinogenesis and disease progression of ESCC.</p>

Effect of number of metastatic lymph nodes and metastatic lymph node ratio on the prognosis in patients with adenocarcinoma of the esophagogastric junction after curative resection / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the effects of number of positive lymph nodes and metastatic lymph node ratio (LNR) in evaluation of recurrence risk and overall survival in patients with adenocarcinoma of the esophagogastric junction (AEG) after curative resection.</p><p><b>METHODS</b>Clinical data of 337 AEG patients who underwent curative resection in our hospital were retrospectively reviewed. The pN stage was categorized based on the number of metastatic lymph nodes and LNR stage, and was determined by the best cutoff approach at log-rank test. Univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model were used to analyze the effects of pN and LNR on recurrence-free survival and overall survival of these patients. Receiver operating characteristic (ROC) curves were plotted to compare the accuracy of prognosis prediction with pN and LNR.</p><p><b>RESULTS</b>The 5-year recurrence-free survival rate and overall survival rate for all patients were 25.5% and 29.9%, respectively. The 5-year recurrence-free survival rates were 47.6%, 23.2%, 17.1% and 5.7% for pN0, pN1, pN2, and pN3, respectively, (P < 0.001) and the 5-year overall survival rates were 53.3%, 28.9%, 18.9% and 7.3%, respectively (P < 0.001). The 5-year recurrence-free survival rates were 47.6%, 24.3%, 11.4% and 2.0% for LNR0, LNR1, LNR2, and LNR3, respectively (P < 0.001), and the 5-year overall survival rates were 53.3%, 28.5%, 15.0%, 2.6%, respectively (P < 0.001). Univariate analysis showed that tumor size, macroscopic type, degree of differentiation, pT, pN, LNR and TNM stage were significantly associated with RFS and OS (P < 0.05). Cox multivariate analysis showed that either pN or LNR was independent risk factor for RFS and OS (P < 0.001). When pN and LNR were entered into the Cox hazard ratio model as covariates at the same time, LNR remained as an independent prognosis factor for RFS and OS (P < 0.001), but pN was not (P > 0.05). ROC curves showed that the area under the curve of LNR stage was larger than that of pN stage in prediction of both RFS and OS, however the differences were not statistically significant (P > 0.05).</p><p><b>CONCLUSIONS</b>LNR is an independent risk factor associated with the prognosis of AEG patients. The value of LNR in prediction of recurrence hazard and overall survival was better than that of pN stage. It offers some helpful suggestions for AEG patients risk classification, allowing clinicians to develop a reasonable treatment.</p>

Analysis of early lymph node metastasis pattern and prognosis in thoracic esophageal squamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the pattern of early lymph node metastasis of thoracic esophageal squamous cell carcinoma and its prognostic value.</p><p><b>METHODS</b>Clinical 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>Upper 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.</p>

Relative factors of recurrence and metastasis of advanced adenocarcinoma of the esophagogastric junction after curative resection / 中华消化外科杂志

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.

Research advancement on BNIP3 in gastrointestinal cancer / 中国肿瘤临床

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.

Expression of Krüppel-like factor 4 protein in esophageal squamous cell carcinoma and its clinical significance / 中华消化杂志

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.