Xiao-Long Chen

Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer

AbstractImmune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear.We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8+, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions.We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome. Multivariate analysis indicated that tumor size, longitudinal tumor location, N stage, TCD68+/SCD68+ ratio, TCD8+/TFoxp3+ ratio, density of TFoxp3+ cells, and TCD66b+/SCD66b+ ratio were independent prognostic factors, which were all selected into the nomogram. The calibration curve for likelihood of survival demonstrated favorable consistency between predictive value of the nomogram and actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for predicting prognosis was significantly higher than that of TNM staging system (0.70).Collectively, high TCD68+/SCD68+ ratio and TCD8+/TFoxp3+ ratio were associated with improved overall survival, whereas high density of TFoxp3+ cells and TCD66b+/SCD66b+ ratio demonstrated poor overall survival, which are promising independent predictors for overall survival in gastric cancer.

Total vs. proximal gastrectomy for proximal gastric cancer: a systematic review and meta-analysis.

BACKGROUND/AIMS To compare effectiveness between total gastrectomy (TG) and proximal gastrectomy (PG) for proximal gastric cancer. METHODOLOGY PubMed, Embase, Cochrane library and Chinese CNKI databases were searched to select eligible studies comparing TG to PG for proximal gastric cancer. Outcome measures included overall survival, recurrence, mortality and morbidity rates, as well as nutritional states. Meta-analyses were performed by RevMan 5.0. RESULTS One randomized controlled trial and 7 retrospective studies involving 1077 patients were included. Meta-analysis showed no significant difference of 5-year overall survival rate (OR=0.89, p=0.53). However, TG achieved a lower recurrence rate (Peto OR=0.53, p=0.004). PG experienced higher morbidity risk (OR=0.11, p<0.00001), concerning higher risks of reflux esophagitis (OR=0.04, p<0.00001) and anastomotic stenosis (OR=0.14, p<0.00001) in a short period. TG performed longer operation time (p=0.002) and more blood loss (p<0.00001). Operative mortality and nutritional states were comparable without significant differences. CONCLUSIONS Based on current retrospective evidences, TG and PG had similar overall survival outcome for proximal gastric cancer, but TG showed lower recurrence rate. PG with gastroesophagostomy had higher incidence of reflux esophagitis and anastomotic stenosis. TG can be recommendation for proximal gastric cancer, although more high-quality trials are still expected.

Docetaxel, Cisplatin and Fluorouracil (DCF) Regimen Compared with Non-Taxane-Containing Palliative Chemotherapy for Gastric Carcinoma: A Systematic Review and Meta-Analysis

Background Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC. Methods PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities. Results Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences. Conclusion DCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent.

The Impact of Body Mass Index on the Surgical Outcomes of Patients With Gastric Cancer: A 10-Year, Single-Institution Cohort Study.

Abstract This study aimed to investigate the impact of body mass index (BMI) on the short-term and long-term results of a large cohort of gastric cancer (GC) patients undergoing gastrectomy. Recently, the “obesity paradox” has been proposed, referring to the paradoxically “better” outcomes of overweight and obese patients compared with nonoverweight patients. The associations between BMI and surgical outcomes among patients with GC remain controversial. A single-institution cohort of 1249 GC patients undergoing gastrectomy between 2000 and 2010 were categorized to low-BMI (<18.49 kg/m2), normal-BMI (18.50–24.99 kg/m2), and high-BMI (≥25.00 kg/m2) groups. The postoperative complications were classified according to the Clavien-Dindo system, and their severity was assessed by using the Comprehensive Complication Index (CCI). The impact of BMI on the postoperative complications and overall survival was analyzed. There were 908, 158, and 182 patients in the normal-BMI, low-BMI, and high-BMI groups, respectively. The overall morbidity in the high-BMI group (24.7%) was higher than that in either the low-BMI or the normal-BMI group (20.9% and 15.5%, respectively; P = 0.006), but the mean CCI in the low-BMI group was significantly higher (8.32 ± 19.97) than the mean CCI in the normal-BMI and high-BMI groups (3.76 ± 11.98 and 5.58 ± 13.07, respectively; P < 0.001). The Kaplan–Meier curve and the log-rank test demonstrated that the low-BMI group exhibited the worst survival outcomes compared with the normal-BMI group, whereas the high-BMI group exhibited the best survival outcomes (P < 0.001). In multivariate analysis, BMI was identified as an independent prognostic factor. In the stage-specific subgroup analysis, a low BMI was associated with poorer survival in the cases of stage III–IV diseases. Low BMI was associated with more severe postoperative complications and poorer prognosis. Despite a higher risk of mild postoperative complications, the high-BMI patients exhibited paradoxically “superior” survival outcomes compared with the normal-BMI patients. These findings confirm the “obesity paradox” in GC patients undergoing gastrectomy.

Comparison on Clinicopathological Features and Prognosis Between Esophagogastric Junctional Adenocarcinoma (Siewert II/III Types) and Distal Gastric Adenocarcinoma: Retrospective Cohort Study, a Single Institution, High Volume Experience in China

AbstractThe incidence of the EGJA is rapidly increasing. The clinicopathological features have not yet been elucidated. The aim of this study was to analyze the differences in clinicopathological features and prognosis between patients with esophagogastric junctional adenocarcinoma (EGJA) and distal gastric adenocarcinoma (DGA).In this retrospective study, 1230 patients who underwent gastrectomy between January 2006 and December 2010 in West China Hospital were enrolled. Patients were divided into 2 groups based on tumor location. Clinicopathological characteristics, postoperative complications, and survival outcomes were compared. Univariate and multivariate analysis were also used to evaluate the prognostic factors of DGA and EGJA.Patients with gastric adenocarcinoma were divided into 2 study groups according to tumor location: 321 EGJA (26.1%) and 909 DGA (73.9%). Tumors with larger diameter, more advanced pT and pN stage were more common in EGJA. Significant differences were revealed in 3-year overall survival rate (3-YS) between 2 groups: EGJA (57.5%) and DGA (65.5%) (P = 0.001), and further analysis indicate that there was also significant difference on 3-YS between EGJA (76.9%) and DGA (84.2%) (P = 0.012) in stage II. From our multivariate analysis, we found that there were different independent prognostic indicators for DGA and EGJA.The clinicopathological features of EGJA were strikingly different from DGA and patients with EGJA showed a worse prognosis when compared with DGA. The pT stage, pN stage, pM stage, tumor size, age, and radical degree were determined to be independent factors of prognosis for DGA, while only combined organ resection, pN stage, and pM stage were independent prognostic factors for EGJA.

Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients.

The Value of Palliative Gastrectomy for Gastric Cancer Patients With Intraoperatively Proven Peritoneal Seeding.

AbstractThe aim of this study was to evaluate the survival benefit of palliative gastrectomy for gastric cancer patients with peritoneal seeding proven intraoperatively and to identify positive predictive factors for improving survival.The value of palliative resection for gastric cancer patients with peritoneal metastasis is controversial.From 2006 to 2013, 267 gastric cancer patients with intraoperatively identified peritoneal dissemination were retrospectively analyzed. Patients were divided into resection group and nonresection group according to whether a palliative gastrectomy was performed. Clinicopathologic variables and survival were compared. Subgroup analyses stratified by clinicopathologic factors and multivariable analysis for overall survival were also performed.There were 114 patients in the resection group and 153 in nonresection group. The morbidities in the resection and nonresection groups were 14.91% and 5.88%, respectively (P = 0.014). There, however, was no difference in mortality between the 2 groups. The median survival time of patients in the resection group was longer than in nonresection group (14.00 versus 8.57 months, P = 0.000). The median survivals among the patients with different classifications of peritoneal metastasis were statistically significant (P = 0.000). Patients undergoing resection followed by chemotherapy had a significantly longer median survival, compared with that of patients who had chemotherapy alone, those who had resection alone, or those who had not received chemotherapy or resection (P = 0.000). Results of subgroup analyses showed that except for P3 patients and patients with multisite distant metastases, overall survival was significantly better in patients with palliative gastrectomy, compared with the nonresection group. In multivariate analysis, P3 disease (P = 0.000), absence of resection (P = 0.000), and lack of chemotherapy (P = 0.000) were identified as independently associated with poor survival.Palliative gastrectomy might be beneficial to the survival of gastric cancer patients with intraoperatively proven P1/P2 alone, rather than P3. Postoperative palliative chemotherapy could improve survival regardless of operation and should be recommended.

Survival benefit and safety of no. 10 lymphadenectomy for gastric cancer patients with total gastrectomy.

Abstract This study was aimed to evaluate the survival benefit and safety of No. 10 lymphadenectomy for gastric cancer patients with total gastrectomy. Splenic hilar lymph nodes (LNs) are required to be dissected in total gastrectomy with D2 lymphadenectomy. However, there has still not been a consensus in aspects of survival and safety on No. 10 LN resection. From January 2006 to December 2011, 453 patients undergoing total gastrectomy for gastric cancer were retrospectively analyzed. Patients were grouped according to No. 10 lymphadenectomy (10D+/10D−). Clinicopathologic characteristics were compared between the 2 groups. These patients had undergone a follow-up until January 2014. The overall survival, morbidity, and mortality rate were analyzed. Subgroup analyses which were stratified by the sex, age, tumor location, lymphadenectomy extent, curative degree, differentiation, tumor size, and TNM staging (ie, stages of tumor) were performed. There were 220 patients in 10D+ group, whereas 233 in 10D− group. In terms of prognosis, the baseline features between the 2 groups were almost comparable. The incidence of No. 10 LN metastasis was 11.82%. There was no difference in morbidity and mortality between the 2 groups. Significantly more LNs were harvested from patients in 10D+ group (P = 0.000). The estimated overall 5-year survival rates were 46.44% and 37.43% in 10D+ group and 10D− group respectively, which is not statistically significant (P = 0.3288). Although no statistical significance was found in the estimated 5-year survival rate, these data were obviously higher in patients with age >60 years, Siewert II/ III tumors, N1 status, or IIIa/IIIc stages when No. 10 lymphadenectomies were performed. Although the differences were obvious, the 5-year survival rates between the 2 groups did not reach statistical significances, which was probably caused by too small patient samples. High-quality studies with larger sample sizes are needed before stronger statement can be done. Until then, the No. 10 LNs’ resection might be recommended in total gastrectomy with D2 lymphadenectomy with an acceptable incidence of complications.

Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma

The prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma (GC) has been widely reported and is still under debate. Here, we evaluated the prognostic significance of preoperative serum CA125, CA19-9 and CEA in patients with GC. 1692 patients with GC who underwent gastrectomy were divided into the training (from January 2005 to December 2011, n = 1024) and the validation (from January 2012 to December 2013, n = 668) cohorts. Positive groups of CA125 (> 13.72 U/ml), CA19-9 (> 23.36 U/ml) and CEA (> 4.28 ng/ml) were significantly associated with more advanced clinicopathological traits and worse outcomes than that of negative groups (all P < 0.01). In Cox regression analysis, tumor size (P < 0.001, P = 0.005), pTNM stage (P < 0.001, P < 0.001) and CA125 (P = 0.026, P = 0.005) were independent prognostic factors both in two cohorts. Nomograms of these two cohorts based on the number of positive serum tumor markers (NPTM) were more accurate in prognostic prediction than TNM stage alone. Our findings suggested that elevated preoperative serum CA125, CA19-9 and CEA were associated with more advanced clinicopathological traits and less favorable outcomes. In addition, CA125 as an independent prognostic factor should be further investigated. Nomogram based on NPTM could accurately predict the prognosis of GC patients.

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.