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.

Lymph node dissection for Siewert Ⅱ esophagogastric junction adenocarcinoma: a retrospective study of three surgical procedures / 中华胸心血管外科杂志

Objective The surgical approaches and extent of lymph node dissection for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction(AEG) are controversial.The present study was aimed to investigate the application of right thansthoracic Ivor-Lewis(IL),left transthoracic(LTT),and left thoracoabdominal(LTA) approach in Siewert type Ⅱ AEG.Methods The data of 196 patients with Siewert type Ⅱ AEG received surgical resection in our cancer center between January 2014 and April 2016 was retrospectively analyzed.Finally,136 patients met the inclusion criteria were enrolled in the study and divided into the IL(47 cases),LTT(51 cases),and LTA group(38 cases).Clinical and short-term treatment effects were compared among the three groups.Results The patients with weight loss,diabetes,and heart disease increased in the LTT group (P =0.054,P =0.075,and P =0.063,respectively).Operation time was significantly longest in the IL group (P =0.000),but the amount of bleeding and tumor size did not significantly differ among the three groups (P =0.176 and P =0.228,respectively).The IL group had the significantly longest proximal surgical margin (P =0.000) and most number of total (P =0.000) and thoracic lymph nodes(P =0.000) dissected.Both the IL and LTA groups had more abdominal lymph nodes dissected than the LTT group(P =0.000).In general,the IL and LTT group had the highest dissection rates of every station of thoracic (P ＜ 0.05) and lower mediastinal lymph nodes (P ＜ 0.05),respectively.The dissection rate of the paracardial,left gastric artery,and gastric lesser curvature lymph nodes did not differ significantly among the three groups(P ＞ 0.05),but the dissection rate of the hepatic artery,splenic artery,and celiac trunk lymph nodes was significantly highest in the IL group (P ＜0.05).Postoperative hospital stay,perioperative complications,and mortality did not differ significantly among the three groups(P ＞ 0.05).Conclusion Compared with the traditional left transthoracic approach,the Ivor-Lewis approach did not increase the perioperative mortality and complication rates in Siewert type Ⅱ AEG,but obtained satisfactory length of the proximal surgical margin,and was better than left transthoracic approach in thoracic and abdominal lymph node dissection.However,the advantages of Ivor-Lewis procedure requires further follow-up and validation through prospective randomized controlled trials.

Progress on the molecular targeted therapy in esophageal cancer / 国际生物医学工程杂志

Esophageal cancer is the eighth most common cancer worldwide and one of the most common malignant tumors in China.Despite the continuous improvement in the methods of comprehensive treatment such as surgery,radiotherapy and chemotherapy,the prognosis and five-year survival rate of patients with esophageal cancer remain poor.Targeted therapy for esophageal cancer inhibits the proliferation and migration of esophageal cancer cells and promotes apoptosis by regulating related signaling pathways.Up to now,a variety of molecular targets and related regulatory mechanisms of esophageal cancer have been discovered,and a variety of targeted therapeutic drugs have been designed,some of which have achieved certain effects in clinical trials.At present,targeted molecular therapeutic targets such as HER-2,VEGFR,EGFR and other targeted therapeutic drugs (monoclonal antibodies and tyrosinase inhibitors) have achieved clinical effects in esophageal cancer treatments.Preliminary progress have been made in the study of some key kinases,such as such as mTOR,AXL,C-MET,AURKA,etc,in various signaling pathways,and the development of the relevant targeted therapeutic agents for esophageal cancer.Meanwhile,esophageal cancer immunotherapy targeting PD-1 shows good prospects,and the immunotherapy drugs,such as Pembrolizumab,have achieved good therapeutic effects.Additionally,new targets for esophageal cancer,such as MMP-9 and COX-2,have been found to be potential targets for esophageal cancer treatments.

Lymph node metastasis and prognostic factors for T1 esophageal cancer / 中华外科杂志

Objective@#To evaluate the lymph node metastasis (LNM) pattern and related prognostic factors for T1 esophageal cancer.@*Methods@#Clinical data of 143 cases of pT1 esophageal cancer patients (120 male and 23 female patients with median age of 60 years) who underwent esophagectomy and lymph node resection during January 2011 and July 2016 at the Department of Esophageal Cancer of Tianjin Medical University Cancer Institute and Hospital were reviewed, including 50 cases of T1a patients and 93 cases of T1b patients. The LNM pattern was analyzed and the prognostic factors related to LNM were assessed by χ2 test and Logistic regression analysis.@*Results@#Of 143 patients, 25 patients had LNM. The LNM rates were 17.5% for pT1 tumors, 16.0%(8/50) for pT1a tumors, and 22.6%(21/93) for T1b tumors. Of 25 patients with LNM, one patient had cervical metastasis, 15 patients with thoracic metastasis, and 17 patients with abdominal metastasis. The relatively highest LNM sites were laryngeal recurrent nerve (8 cases), left gastric artery (8 cases), right and left cardiac (6 cases) and thoracic paraesophageal (5 cases). Logistic regression analysis showed that the depth of tumor infiltration (OR=4.641, 95%CI: 1.279 to 16.836, P=0.020), tumor size (OR=5.301, 95%CI: 1.779 to 15.792, P=0.003), tumor location (OR=3.238, 95% CI: 1.248 to 8.401, P=0.016), and tumor differentiation (OR=5.301, 95%CI: 1.719 to 16.347, P=0.004) were independent prognostic factors related to LNM for T1 esophageal cancer. Tumor size (OR=4.117, 95% CI: 1.228 to 13.806, P=0.022) was an independent risk factor related to thoracic LNM, and the vessel invasion (OR=6.058, 95% CI: 1.228 to 29.876, P=0.027) and tumor location (OR=8.113, 95% CI: 1.785-36.872, P=0.007) were independent prognostic factors related to abdominal LNM.@*Conclusions@#T1 esophageal cancer has a relatively high LNM rate, and the depth of tumor infiltration, tumor size, tumor location and tumor differentiation are correlated with LNM. The LNM risk and extent must be considered comprehensively in decision-making of a better surgical treatment and lymph node resection strategy.

Comparison of the effect of lymph node dissection performed by Ivor-Lewis or left-sided thoracic esophagogastrectomy for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction / 中华肿瘤杂志

Objective@#To compare the extent of lymphadenectomy and postoperative complications between Ivor-Lewis procedure and left sided thoracotomy in patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction (AEG).@*Methods@#The clinical data of 101 patients with Siewert type Ⅱ EG who received surgical treatment between January 2014 and September 2015 in the Department of Esophageal Cancer, Tianjin Medical University Cancer Hospital were analyzed retrospectively. These patients were divided into Ivor-Lewis group (IL, n=38) and left- sided thoracotomy group (LT, n=63) according to the operation mode. The number and extent of dissected lymph nodes and postoperative complications were compared between the two groups.@*Results@#The surgical blood loss, length of postoperative stay, anastomotic leakage, pulmonary infection, respiratory failure and complications of incision of the two groups showed no significant differences (P>0.05 of all). The operation time of IL group was 200 min, significantly longer than the LT group (120 min, P<0.05). The number of resected lymph nodes in the IL and LT groups were (20±9) and (13±7), respectively, with a statistically significant difference (P<0.001). Significantly more thoracic lymph nodes (7±5) were harvested in the IL group than in the LT group (2±2, P<0.001), and the number of resected abdominal lymph nodes in the IL and LT groups were (13±8) and (11±7), with a non-significant difference (P=0.157). As regarding the lymph node dissection rate, the IL approach was obviously better than the LT approach in the following lymph node stations: superior mediastinal nodes, subcarinal nodes, left hilar nodes, right hilar nodes, middle thoracic paraesophageal nodes, lower thoracic paraesophageal nodes, lymph nodes along the common hepatic artery, and lymph nodes along the splenic artery(P<0.05 for all).@*Conclusions@#The Ivor-Lewis procedure achieves better thoracic and abdominal lymph node dissection, and does not cause more postoperative complications than the left-sided thoracotomy in patients with Siewert type Ⅱ AEG. However, these findings need to be confirmed by large-scale randomized clinical trial in the future.

Comparative study between thoracoscopic and open esophagectomy on perioperative complications and stress response / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the perioperative complications and the stress response between thoracoscopic esophagectomy and open esophagectomy in patients with esophageal cancer.</p><p><b>METHODS</b>Clinicopathologic data of 154 patients with esophageal cancer undergoing thoracoscopic esophagectomy (thoracoscope group) and 113 undergoing open procedure(open group) in the Tianjin Medical University Cancer Institute and Hospital from October 2012 to September 2014 were analyzed retrospectively. The incidence of perioperative complications and the change of stress response index in patients without complications were compared between two groups.</p><p><b>RESULTS</b>The total complication rate in thoracoscope and open group was 33.8% and 38.1%(P = 0.470) respectively. Compared with open group, incidence of ligation of thoracic duct(2.6% vs. 14.2%), recurrent laryngeal nerve paralysis (16.9% vs. 28.3%), chylothorax (0 vs. 4.4%), atelectasis (1.3% vs. 7.1%), pleural effusion (0.6% vs. 6.2%) and acute respiratory distress(0.6% vs. 6.2%) were obviously decreased in thoracoscope group(all P<0.05). No significant differences were observed in other complications (all P>0.05). Thirty-two cases and 24 cases without complication and with complete test data in thoracoscope and open group were selected for the detection of stress response index. There were no significant differences in white blood cell count, and the levels of cortisol, thyroxine (FT3 and FT4) and C-reactive protein between two groups at the same time points (before operation, 1, 3 and 6 days after operation) (all P>0.05).</p><p><b>CONCLUSION</b>Thoracoscopic esophagectomy has some obvious advantages associated with less pulmonary complications, lower morbidity of injury in thoracic duct and recurrent laryngeal nerve, while no significant difference of stress response is found in patients without complication between thoracoscope group and open group.</p>

Retrospective comparative study of preoperative complications and lymphadenectomy between thoracoscopic esophagectomy and open procedure / 中华胸心血管外科杂志

Objective To analyze the differences in paraoperative morbidity and lymph node dissection between thoracoscopic esophagectomy and open procedure.Methods From October 2012 to April 2014,207 patients with esophageal cancer underwent surgery.125 patients underwent video-assisted esophagectomy,and 82 underwent open procedure.In the minimally invasive group,there were 109 thoracoscopic cases and 16 thoracolaparoscopic cases.Results There were significant differences between the thoracoscope group and the open group in atelectasis(0.8％ vs.7.3％,P ＜ 0.05),pleural effusion (0 vs.4.9％,P ＜ 0.05),acute respiratory distress (0 vs.6.1％,P ＜ 0.05),ligation of thoracic duct (3.2％ vs.15.9 ％,P ＜ 0.05),recurrent laryngeal nerve paralysis (19.2％ vs.32.9％,P ＜ 0.05),c hylothorax (0 vs.4.9％,P ＜ 0.05),number of lymphonode along the right recurrent laryngeal nerve lymphatic chains[1.91 ± 0.73 vs.1.12 ± 0.81,P ＜ 0.05)] and achievement ratio(97.6％ vs.89.0％,P ＜0.05) and number of lymphonode along the left recurrent laryngeal nerve lymphatic chains (0.93 ± 0.71 vs.1.76 ± 0.84,P ＜ 0.05) and achievement ratio(52％ vs.76.8％,P ＜ 0.05).No significant differences were observed in pneumonia,anastomotic leak,thoracic abscess,esophago-tracheal fistula,re-laparotomy,re-thoracotomy,wound infection,arrhythmia,cardia failure,renal failure,hepatic inadequacy,cerbral infarction,and mortality(P ＞ 0.05).There were also no significant differences in number of lymphonode and achievement ratio of periesophagel lymph nodes,subcarinal lymph nodes and hilar lymph nodes (all P ＞ 0.05).Conclusion The thoracoscopic esophagectomy has some obvious advantage associated with less pulmonary complications,lower injury of thoracic duct and recurrent laryngeal nerve,more lymphonode and higher achievement ratio along the right recurrent laryngeal nerve lymphatic chains.But it has still a larger space for improvement of lymphadenectomy along the left recurrent laryngeal nerve lymphatic chains.

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>