Jing Yu Deng

Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.

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.

The role of preoperative neutrophil–lymphocyte and platelet–lymphocyte ratio in patients after radical resection for gastric cancer

Abstract The objective of this study was to investigate the impact of neutrophil–lymphocyte ratio (NLR) and the platelet–lymphocyte ratio (PLR) on the postoperative complication and long-term outcomes in patients with resectable gastric cancer (GC). A total of 377 patients who underwent curative resection for GC were enrolled. In logistic analysis, PLR (p = 0.09) was independently associated with the incidence of postoperative complication. The results of multivariate survival analysis showed the NLR and PLR were introduced as prognostic factors for operable GC, the NLR may represent a useful prognostic index for the prediction of overall survival (OS) in advanced GC (p = 0.021).

The most appropriate category of metastatic lymph nodes to evaluate overall survival of gastric cancer following curative resection.

The purpose of this study was to provide a nodal grouping category based on metastatic lymph nodes to evaluate overall survival in gastric cancer patients following curative resection (R0).

Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years

AIM To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients. METHODS We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2007 in our center. Patients were categorized into three groups: younger group (age < 50 years), middle-aged group (50-69 years), and elderly group (≥ 70 years). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The log-rank test was used to assess statistical differences between curves. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of age on survival at each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. We analyzed the potential prognostic factors for patients aged ≥ 70 years. Finally, the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated. RESULTS In the elderly group, there was a male predominance. At the same time, cancers of the upper third of the stomach, differentiated type, and less-invasive surgery were more common than in the younger or middle-aged groups. Elderly patients were more likely to have advanced tumor-node-metastasis (TNM) stage and larger tumors, but less likely to have distant metastasis. Although 5-year overall survival (OS) rate specific to gastric cancer was not significantly different among the three groups, elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients (elderly vs middle-aged vs younger patients = 22.0% vs 36.6% vs 38.0%, respectively). In the TNM-stratified analysis, the differences in OS were only observed in patients with II and III tumors. In multivariate analysis, only surgical margin status, pT4, lymph node metastasis, M1 and sex were independent prognostic factors for elderly patients. The 5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection, and these patients benefited little from chemotherapy. CONCLUSION Age ≥ 70 years was an independent prognostic factor for gastric cancer after gastrectomy. D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.

Impact of intraoperative blood loss on survival after curative resection for gastric cancer

AIM To elucidate the potential impact of intraoperative blood loss (IBL) on long-term survival of gastric cancer patients after curative surgery. METHODS A total of 845 stage I-III gastric cancer patients who underwent curative gastrectomy between January 2003 and December 2007 in our center were enrolled in this study. Patients were divided into 3 groups according to the amount of IBL: group 1 (< 200 mL), group 2 (200-400 mL) and group 3 (> 400 mL). Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified by the Cox proportional hazards regression model. Stratified analysis was used to investigate the impact of IBL on survival in each stage. Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer. Finally, we explored the possible factors associated with IBL and identified the independent risk factors for IBL ≥ 200 mL. RESULTS Overall survival was significantly influenced by the amount of IBL. The 5-year overall survival rates were 51.2%, 39.4% and 23.4% for IBL less than 200 mL, 200 to 400 mL and more than 400 mL, respectively (< 200 mL vs 200-400 mL, P < 0.001; 200-400 mL vs > 400 mL, P = 0.003). Age, tumor size, Borrmann type, extranodal metastasis, tumour-node-metastasis (TNM) stage, chemotherapy, extent of lymphadenectomy, IBL and postoperative complications were found to be independent prognostic factors in multivariable analysis. Following stratified analysis, patients staged TNM I-II and those with IBL less than 200 mL tended to have better survival than those with IBL not less than 200 mL, while patients staged TNM III, whose IBL was less than 400 mL had better survival. Tumor location, tumor size, TNM stage, type of gastrectomy, combined organ resection, extent of lymphadenectomy and year of surgery were found to be factors associated with the amount of IBL, while tumor location, type of gastrectomy, combined organ resection and year of surgery were independently associated with IBL ≥ 200 mL. CONCLUSION IBL is an independent prognostic factor for gastric cancer after curative resection. Reducing IBL can improve the long-term outcome of gastric cancer patients following curative gastrectomy.

Effect of complication grade on survival following curative gastrectomy for carcinoma

AIM To elucidate the potential impact of the grade of complications on long-term survival of gastric cancer patients after curative surgery. METHODS A total of 751 gastric cancer patients who underwent curative gastrectomy between January 2002 and December 2006 in our center were enrolled in this study. Patients were divided into four groups: no complications, Grade I, Grade II and Grade III complications, according to the following classification systems: T92 (Toronto 1992 or Clavien), Accordion Classification, and Revised Accordion Classification. Clinicopathological features were compared among the four groups 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 used to investigate the impact of complications of each grade on survival. RESULTS Significant differences were found among the four groups in age, sex, other diseases (including hypertension, diabetes and chronic obstructive pulmonary disease), body mass index (BMI), intraoperative blood loss, tumor location, extranodal metastasis, lymph node metastasis, tumor-node-metastasis (TNM) stage, and chemotherapy. Overall survival (OS) was significantly influenced by the complication grade. The 5-year OS rates were 43.0%, 42.5%, 25.5% and 9.6% for no complications, and Grade I, Grade II and Grade III complications, respectively (P < 0.001). Age, tumor size, intraoperative blood loss, lymph node metastasis, TNM stage and complication grade were independent prognostic factors in multivariate analysis. With stratified analysis, lymph node metastasis, tumor size, and intraoperative blood loss were independent prognostic factors for Grade I complications (P < 0.001, P = 0.031, P = 0.030). Age and lymph node metastasis were found to be independent prognostic factors for OS of gastric cancer patients with Grade II complications (P = 0.034, P = 0.001). Intraoperative blood loss, TNM stage, and chemotherapy were independent prognostic factors for OS of gastric cancer patients with Grade III complications (P = 0.003, P = 0.005, P < 0.001). There were significant differences among patients with Grade I, Grade II and Grade III complications in TNM stage II and III cancer (P < 0.001, P = 0.001). CONCLUSION Complication grade may be an independent prognostic factor for gastric cancer following curative resection. Treatment of complications can improve the long-term outcome of gastric cancer patients.

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.

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.

Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to predict the survival of gastric cancer.

BACKGROUND E3 ubiquitin ligase Ring finger protein 180 (RNF180) has been identified as a novel tumor suppressor in gastric cancer and the methylated CpG site count of RNF180 DNA promoter can predict the prognosis for gastric cancer patients. OBJECTIVE In the previous study, we demonstrated that methylated CpG site count of RNF180 DNA promoter was significantly associated with the survival of patients with gastric cancer using the bisulfite genomic sequencing (BGS) in the gastric cancer tissue with five clones per sample. It was so complicate for each patient underwent the BGS detection with clones. It is important to explore a simple, rapid and accurate method to detect methylated CpG site count to predicting the prognosis for gastric cancer patients. METHODS At present study, we detected hypermethylated and hypomethylated CpG site count of RNF180 DNA promoter in samples of 480 gastric cancer patients by direct bisulfite sequencing. RESULTS We found that patients who possessed seven or less hypermethylated CpG sites of RNF180 DNA promoter had much better survival (p= 0.008), which was similar to our previous research results by using the BGS with clones. With the multivariate survival analysis, we found that T stage, N stage and hypermethylated CpG site count of RNF180 DNA promoter were the independent predictors of prognosis for gastric cancer patients. CONCLUSIONS hypermethylated CpG site count of RNF180 DNA promoter for evaluating the prognosis of gastric cancer was reasonable by using the direct bisulfite sequencing.