Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer / 中华胃肠外科杂志

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Clinical controversy and research thoughts on lymphadenectomy of gastric cancer / 中华胃肠外科杂志

Lymphadenectomy, as one of the controversial foci in clinic, is an extremely important part of radical surgery for gastric cancer. So far, the preliminary consensus has been reached on the scope and number of lymph node dissection, based on the etiological mechanism, disease progression, diagnosis and treatment prognosis of gastric cancer. At present, some clinical issues of lymphadenectomy in curative gastrectomy are still need to be addressed. Firstly, standardized procedure in lymph node dissection for gastric cancer is a prerequisite to decrease the incidence of postoperative complications and to improve the prognosis of gastric cancer patients. Furthermore, the plausible treatment strategy in perioperative phase is also deemed as the other key method to offer a benefit of survival rate for advanced stage patients after lymphadenectomy. Last but not least, the technologies for enhancement the prediction accuracy of lymph node metastasis preoperatively or intraoperatively should be worthy in-depth study.

The value of negative lymph node count in prediction of prognosis of advanced gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of negative lymph node count (NLNC) in prediction of prognosis of advanced gastric cancer after radical resection.</p><p><b>METHODS</b>The 544 cases of radical gastrectomy patients with complete clinical and follow-up data between January 2011 and July 2007 were collected. Survival was determined by the Kaplan-Merier method and univariate analysis was done by Log-rank test, Multivariate analysis was performed using the Cox proportional hazard regression model.</p><p><b>RESULTS</b>Univariate analysis showed age (χ(2) = 4.449), T stage (χ(2) = 30.482), N stage (χ(2) = 205.452), location of tumor (χ(2) = 16.649), tumor size (χ(2) = 35.117), macroscopic type (χ(2) = 4.750), histological grade (χ(2) = 6.130), NLNC stage (χ(2) = 150.369) and type of gastrectomy (χ(2) = 25.605) were related to survival. Among them, T stage, N stage, tumor size and NLNC stage were independent risk factors for survival (P < 0.05). The prognostic factors of patients were performed subgroup analysis, NLNC > 15 group can prolong the survival than NLNC ≤ 15 group in the T2 stage (HR = 0.315), T4 stage (HR = 0.401), the same classification of location of tumor (HR = 0.286-0.493), tumor size (HR = 0.336, 0.465), macroscopic type (HR = 0.306, 0.418), histological grade (HR = 0.411, 0.365) and type of gastrectomy (HR = 0.444, 0.358 and 0.356, all P < 0.05). More NLNC can prolong Disease-Free Survival for patient of early recurrence (χ(2) = 8.648, P = 0.003).</p><p><b>CONCLUSIONS</b>Sufficient negative lymph node count can prolong the survival and decrease the risk of early recurrence.</p>

The prognostic analysis of tumor size in T4a stage gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of tumor size in the prognosis of T4a stage gastric cancer.</p><p><b>METHODS</b>The best cut-off point depending on tumor size was selected by Kaplan-Meier. Compare cliniclópathological characteristics between small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate analysis was done by Log-rank test and multivariate analysis was performed using the Cox proportional hazard regression model. The independent prognostic factors of patients were performed subgroup analysis.</p><p><b>RESULTS</b>Eight centimetre was the optimal cut-off of tumor size for T4a stage gastric cancer. There were significantly differences between SSG and LSG in tumor location (χ² = 15.695), histological grade (χ² = 4.393), macroscopic type (χ² = 5.629) and early recurrence (χ² = 4.292). Univariate analysis showed age (χ² = 4.463), tumor size (χ² = 9.057), macroscopic type (χ² = 6.679), histological grade (χ² = 5.122), location of tumor (χ² = 8.707) and N stage (χ² = 132.954) are related to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192) were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR = 1.876) was independent risk factor for survival (P = 0.000). Further stratified analysis indicated that the 5-year survival rate of LSG is significantly lower than that of SSG in T4a stage patients of gastric cancer without lymph nodes metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01).</p><p><b>CONCLUSIONS</b>Tumor size is an independent prognostic factor in patients of T4a stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant impact on the prognosis of T4a stage gastric cancer without lymph nodes metastasis or poorly differentiated.</p>

The significance of No.13 lymph node dissection in D2 gastrectomy for lower-third advanced gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and necessity of No.13 lymph node dissection in D2 radical gastrectomy for lower-third advanced gastric cancer (AGC).</p><p><b>METHODS</b>Data of 379 cases who were diagnosed as TNM II-III stage AGC were collected from January 2001 to June 2007. One hundred cases who undergone No.13 lymph node dissection during D2 gastrectomy for lower-third AGC were selected as study group. Other 279 cases (control group) received only D2 gastrectomy. The differences in clinicopathologic and intraoperative and postoperative parameters and 5-years survival rate were compared using the SPSS 17.0 software.</p><p><b>RESULTS</b>There were no significant differences between the two groups in patients' gender, age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth, lymph node metastasis, TNM classification, operative time, blood loss and the incidence of postoperative complications (P > 0.05). In the study group, there were 9 patients with positive No. 13 lymph node, and its 5-year survival rate (46.0%) was higher than the control group (36.5%, χ² = 4.452, P < 0.05). The Univariate analysis showed that age (χ² = 7.539), No.13 lymph node dissection (χ² = 4.452), tumor size (χ² = 7.100), duodenum invasion (χ² = 9.106), tumor depth (χ² = 7.428), lymph node metastasis (χ² = 45.046), TNM classification (χ² = 57.008) are associated with prognosis of lower-third AGC (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 - 0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR = 5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 - 3.394) as independent prognostic factors (P < 0.05).</p><p><b>CONCLUSION</b>No. 13 lymph node dissection for TNM II-III stage lower-third advanced gastric cancer is feasible and necessary.</p>

Prognostic value of metastatic lymph node ratio for gastric cancer patients with less than 15 lymph nodes dissection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of metastatic lymph node ratio (MLR) for gastric cancer patients with less than 15 lymph nodes dissected.</p><p><b>METHODS</b>Clinical data of 610 gastric cancer patients undergoing operation in Tianjin Cancer Hospictal from January 2003 to July 2007 were analyzed retrospectively. Patients were divided into two groups: <15 lymph nodes dissected group (n=320) and ≥ 15 lymph nodes dissected group (n=290). MLR was classified based on the following intervals: rN1 ≤ 10%, rN2 10%-30%, rN3 30%-60% and rN4 >60%. Survival was determined by Kaplan-Meier method and difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. Survival rates were compared between two groups in pN and rN stages respectively.</p><p><b>RESULTS</b>In <15 nodes group, all the survival differences among various rN stages were not significant (all P>0.05), while in same rN stage, all the survival differences among various pN stages were not significant (all P>0.05). Significant differences of 5-year cumulative survival rates were found between the two groups in pN2 and pN3a stage patients (both P<0.05) while no significant differences were found among different rN stages (all P>0.05). Multivariate analysis demonstrated rN stage was an independent prognostic factor for gastric cancer patients with <15 lymph nodes dissected (P=0.012, RR=1.617, 95%CI:1.111-2.354).</p><p><b>CONCLUSION</b>The rN staging system based on MLR can predict the prognosis of gastric cancer patients with less than 15 lymph nodes dissected.</p>

Analysis of clinicopathologic characteristics and prognosis on mixed histology type of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinicopathologic characteristics and prognosis of mixed histological type (MHT) gastric cancer.</p><p><b>METHODS</b>Clinical and follow-up data of 1108 gastric cancer patients undergoing radical operation in Tianjin Cancer Hospital between 2003 and 2006 were analyzed retrospectively. Clinicopathologic characteristics of MHT gastric cancer were summarized and the prognosis was analyzed by Kaplan-Meier analysis and COX regression.</p><p><b>RESULTS</b>Among the 1108 patients, 144 (13.0%) had mixed histology type of gastric cancer. Compared to the unitary histological type (UHT), MHT gastric cancer had bigger tumor size, higher proportion of T4 tumor, and was easier for lymph node and distant metastasis (all P<0.05). The 3- and 5-year survival rates of patients with MHT were 26.5% and 10.8% respectively, which were lower than those with UHT (58.8% and 35.0%, P<0.01). Univariate and multivariate analyses showed TNM classification was an independent prognostic factor (P<0.01).</p><p><b>CONCLUSIONS</b>MHT gastric cancer shows worse prognosis than UHT gastric cancer. There is no difference in prognosis among various combination of MHT gastric cancer. TNM classification is an independent prognostic factor of MHT gastric cancer.</p>

Clinicopathological characteristics and prognostic analysis of bone metastasis in gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors of bone metastasis in gastric cancer patients.</p><p><b>METHODS</b>Clinicopathological data of 66 gastric cancer patients with bone metastasis, who were treated at the Tianjin Medical University Cancer Institute and Hospital from October 1997 to September 2011, were analyzed retrospectively. The clinicopathological characteristics of the primary cancer and bone metastasis were summarized and the prognosis was analyzed.</p><p><b>RESULTS</b>Of 66 patients, 4 underwent operation, 28 chemotherapy, 32 inhibitors of bone resorption,8 local treatment and 23 symptomatic treatment alone. The median survival time of these 66 patients was 5 months (95%CI:3.3-6.7 months). The 1-, 2- and 3-year survival rates were 9.1%, 3.0% and 1.5%, respectively. Univariate Log-rank test indicated that gender, bone metastasis combined with other distant metastasis and chemotherapy were significant prognostic factors (all P<0.05). Multivariate analysis revealed bone metastasis combined with other distant metastasis was an independent prognostic factor (P=0.011, RR=2.067, 95%CI:1.178-3.626).</p><p><b>CONCLUSIONS</b>Prognosis of patients with bone metastasis from gastric cancer is poor. Chemotherapy-based comprehensive treatment may improve the prognosis of these patients.</p>

Prognostic analysis of 280 patients with T4a gastric cancer who underwent curative resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the predicators of survival and recurrence after curative resection for gastric cancer patients with serosal invasion.</p><p><b>METHODS</b>Clinical and follow-up data of 280 patients with T4a gastric cancer(according to the 7th UICC TNM Classification for gastric cancer) who underwent curative resection for gastric cancer between January 1997 and December 2003 were analyzed retrospectively.</p><p><b>RESULTS</b>Five-year survival rate of these 280 patients was 50.0% and 158 patients (56.4%) presented with recurrence after surgery. The 3-year disease-free survival rate was 57.5%. The number of lymph node metastasis and metastatic lymph node ratio(MLR) were identified as the independent predicators for overall survival(P<0.05). The extent of lymph node metastasis was identified as the independent predicators for disease free survival (P<0.05). The extent of lymph node metastasis, the number of lymph node metastasis, and MLR were identified as the independent predicators for recurrence after surgery(P<0.05).</p><p><b>CONCLUSIONS</b>The number of lymph node metastases, extent of lymph node metastasis and MLR are independent predictors of overall survival and recurrence in T4a gastric cancer patients after curative resection.</p>

Analysis of clinicopathological characteristics and prognosis of patients with gastric cancer in different locations after radical resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the differences among gastric cancers in different locations (upper, middle, and lower) in the clinicopathological characteristics and prognosis of gastric cancer.</p><p><b>METHOD</b>Clinicopathological data of 146 patients with gastric cancer undergone radical gastrectomy from January 2001 to December 2003 were analyzed retrospectively. These patients were divided into three groups:tumors in the upper third of the stomach (group U), middle third (group M) and lower third (group L).</p><p><b>RESULTS</b>There were significant differences in the the Borrmann types among three groups and between every two groups (P<0.01). Compared with group M and group L, cases in group U were older (P=0.034), had a larger tumor size (P=0.001) and limited extent of lymph node dissection (P=0.009). Compared with group M and group U, cases in group L had earlier nodal status P=0.007) and TNM stage (P=0.020), and the recurrence rate was lower (P=0.006). Survival time of group M and group U was significantly shorter than that of group L (P=0.007, P=0.001).</p><p><b>CONCLUSIONS</b>Tumors in the upper third and the lower third of stomach are associated with distinct clinicopathological characteristics whereas tumor in the middle third shares some characteristics of both entities. The prognosis differs significantly among tumor locations.</p>

Prognostic analysis of liver metastasis in gastric cancer patients with radical gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To elucidate the prognostic factors of liver metastasis in gastric cancer patients with radical gastrectomy.</p><p><b>METHODS</b>Clinicopathological data of 87 liver metastasis patients, undergone radical gastrectomy for gastric cancer from 1996 to 2001, were retrospectively analyzed.</p><p><b>RESULTS</b>Of these 87 patients, the 1-, 3- and 5-year survival rates were 28.8%, 3.6% and 0 respectively and the average survival time after gastrectomy was (11.3+/-1.1) months. By univariate analysis, tumor location, tumor size, histologic differentiation, invasive depth, Lauren classification, metastasis of lymph nodes from lymphadenectomy, vascular invasion, nervous invasion, peritoneal metastasis, number of liver metastasis, liver metastatic distribution and resection of liver metastasis were found to be significant factors associated with the prognosis of liver metastatic patients after radical gastrectomy. By multivariate analysis, location, the Lauren classification, liver metastatic distribution and resection of liver metastasis were found to be independent factors associated with hepatic metastasis after radical gastrectomy.</p><p><b>CONCLUSION</b>Location of gastric cancer, Lauren classification, liver metastatic distribution and resection of liver metastasis are important factors to evaluate the prognosis of liver metastasis in gastric cancer patients with radical gastrectomy.</p>

Number of lymph node metastases: a significant prognostic factor for patients with radical resection of carcinoma of the ampulla of Vater / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To identify prognostic factors predicting survival after radical resection of ampullary carcinoma.</p><p><b>METHODS</b>Clinical data of sixty- five patients with cancer of the ampulla of Vater underwent pancreaticoduodenectomy and regional lymphadenectomy were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 1380 lymph nodes dissected from the resected specimens was examined to detect the presence of metastasis. The median follow- up period was 83 months. Univariate analysis revealed that factors associated with poor survival included the number and the location of positive nodes. Thirty- three of the 65 patients had a total of 116 positive lymph nodes, of whom 20 had 1- 3 positive regional nodes lymph and 13 had > or = 4 positive regional lymph nodes. Multivariate analysis revealed that the number of positive nodes lymph was an independent prognostic factor (P=0.007), while the locations of lymph nodes failed to remain as an independent variable. The survival rate in patients with > or = 4 positive lymph nodes was significantly lower than that in those with 1- 3 positive lymph nodes. The median survival time was 49 months with a 5- year survival rate of 43% in patients with 1- 3 positive lymph nodes, whereas all patients with > or = 4 positive nodes died of the disease within 23 months after resection (P=0.0001).</p><p><b>CONCLUSION</b>The number of positive regional lymph nodes is an independent prognostic factor in patients with ampullary carcinoma after resection.</p>

Tropism of adult liver stem cells toward hepatocellular carcinoma cells in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the biological behavior of adult liver stem cells in a co-cultured system of them with hepatocellular carcinoma (HCC) cells without direct contact between the two kinds of cells.</p><p><b>METHODS</b>WB-F344, a kind of rat adult liver stem cell, and rat embryonic fibroblasts (REF) from a primary culture were engineered to express enhanced green fluorescent protein (EGFP) by recombinant adenoviral-mediated methods. Two kinds of cells marked with EGFP were established, namely WB-EGFP and REF-EGFP. After the HCC cells grew to 40%-60% confluence in the culture dish with a 10-mm cell-free area, a similar number of WB-EGFP and REF-EGFP were placed in the blank areas respectively. Then, we constantly studied the movement behavior of WB-EGFP in the co-culture system with HCC cells.</p><p><b>RESULTS</b>The results showed that WB-EGFP cells migrated to the area of HCC cells slowly. Their appearance was found not only when WB-EGFP cells were seeded into the cell-free area at the center of the dish, but also when seeded into the blank area at the extreme edge of the plate. This trait was not observed in the co-cultured system of REF-EGFP and HCC cells, and most REF-EGFP were still localized in their initial area after 72 hours of incubation.</p><p><b>CONCLUSIONS</b>The results mean that adult liver stem cells have a biological behavior of selective tropism toward HCC cells in vitro, and suggest a possibility of using migratory liver stem cells as a delivery vehicle for gene therapy for HCC.</p>