Ru peng Zhang

Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer

AIM To investigate the impact of prognostic nutritional index (PNI) on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy. METHODS The data for 386 patients with gastric cancer were extracted and analyzed between January 2003 and December 2008 in our center. The patients were divided into two groups according to the cutoff value of the PNI: those with a PNI ≥ 46 and those with a PNI < 46. Clinicopathological features were compared between the two groups and potential prognostic factors were analyzed. The relationship between postoperative complications and PNI was analyzed by logistic regression. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. RESULTS The optimal cutoff value of the PNI was set at 46, and patients with a PNI ≥ 46 and those with a PNI < 46 were classified into PNI-high and PNI-low groups, respectively. Patients in the PNI-low group were more likely to have advanced tumor (T), node (N), and TNM stages than patients in the PNI-high group. The low PNI is an independent risk factor for the incidence of postoperative complications (OR = 2.223). The 5-year overall survival (OS) rates were 54.1% and 21.1% for patients with a PNI ≥ 46 and those with a PNI < 46, respectively. The OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stages II (P = 0.001) and III (P < 0.001) disease. CONCLUSION The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications, but also to predict long-term survival after total gastrectomy. The PNI should be included in the routine assessment of advanced gastric cancer patients.

Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren’s classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

Prognostic value of number of examined lymph nodes in patients with node-negative gastric cancer

AIM To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery. METHODS A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study. Patients were divided into 4 groups according to eLNs through cut-point analysis. Clinicopathological features were compared between ≤ 15 eLNs group and > 15 eLNs group and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage. Overall survival was also compared among the four groups. Finally, we explored the recurrent sites associated with eLNs. RESULTS Patients with eLNs > 15 had a better survival compared with those with eLNs ≤ 15 for the entire cohort. By the multivariate survival analysis, we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival (OS) of patients with node-negative gastric cancer. According to the cut-point analysis, T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs. Patients with ≤ 15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with > 15 eLNs. CONCLUSION Number of eLNs could predict the prognosis of node-negative gastric cancer, and dissection of > 15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

Prognostic value of the lymph node ratio in stage III gastric cancer patients undergoing radical resection

Objective The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer. Methods A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan–Meier survival curves and log-rank tests were used for the survival analysis. Results By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearsons correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging. Conclusions The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system.

Validity and Necessity of Sub-classification of N3 in the 7 th UICC TNM Stage of Gastric Cancer

BACKGROUND The 7th TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous. METHODS Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed. RESULTS Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors. CONCLUSIONS The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.

Evaluating the clinical feasibility: the direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer

OBJECTIVE To elucidate the clinical significance of the methylated status of CpG site count of PCDH10 promoter in the survival prediction in gastric cancer (GC). METHODS In the previous study, we demonstrated that the methylated CpG site count was significantly associated with the overall survival (OS) of GC patients by using the bisulfite genomic sequencing (BGS) with no less than five clones per sample. It was so complex and expensive for patients to undergo the BGS clones. In this study, we detected the different CpG site counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC samples of 471 patients by directly bisulfite genomic sequencing (D-BGS) without any clone. Furthermore, we evaluated the relationships between the methylated status of PCDH10 promoter and OS. RESULTS Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to present with PCDH10 promoter methylation by D-BGS. Patients who presented with 5 or more methylated CpG site counts of PCDH10 promoter had significantly poorer prognosis than patients who with less than 5 methylated CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival analysis, we demonstrated that T stage, N stage and the hypermethylated CpG site counts of PCDH10 DNA promoter were the independent predictors of OS of GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA promoter had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other two independent predictors of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA promoter as the best prognostic predictor of GC. CONCLUSIONS Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS.

Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer

AIM To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis. METHODS Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to December 2006, were analyzed retrospectively. Patients with pT4 stage or distant metastasis were excluded. We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features, such as age, tumor size, tumor location and depth of invasion. At the same time, the relationship between postoperative chemotherapy and the 5-year survival rate among different subgroups were also analyzed. RESULTS The overall 5-year survival rate of the entire cohort was 63.7%. The 5-year survival rate was poor in those patients who were: (1) more than 65 years old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper portion of the stomach; and (4) with pT3 tumor. The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor (P = 0.019), but not in other subgroups. Moreover, there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups (P > 0.05). CONCLUSION For gastric cancer patients without lymph node metastasis, extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor. However, there was no evidence of a survival benefit from postoperative chemotherapy alone.