Zhi-Xin Chen

Prognostic value of cancer stem cell marker CD133 expression in gastric cancer: a systematic review.

Objective To investigate the correlation between CD133-positive gastric cancer and clinicopathological features and its impact on survival. Methods A search in the Medline and Chinese CNKI (up to 1 Dec 2011) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1 etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Results A total of 773 gastric cancer patients from 7 studies were included. The median rate of CD133 expression by immunohistochemistry (IHC) was 44.8% (15.2%–57.4%) from 5 studies, and that by reverse transcription polymerase chain reaction (RT-PCR) was 91.3% (66.7%–100%) from 4 studies. The accumulative 5-year overall survival rates of CD133-positive and CD133-negative patients were 21.4% and 55.7%, respectively. Meta-analysis showed that CD133-positive patients had a significant worse 5-year overall survival compared to the negative ones (OR = 0.20, 95% CI 0.14–0.29, P<0.00001). With respect to clinicopathological features, CD133 overexpression by IHC method was closely correlated with tumor size, N stage, lymphatic/vascular infiltration, as well as TNM stage. Conclusion CD133-positive gastric cancer patients had worse prognosis, and was associated with common clinicopathological poor prognostic factors.

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.

D2 plus para-aortic lymphadenectomy versus standardized D2 lymphadenectomy in gastric cancer surgery

PurposeTo evaluate the survival benefits and safety of D2 plus para-aortic lymphadenectomy (D2 + PALD) for gastric carcinoma.MethodsPatients with gastric carcinoma, who agreed to undergo D2 + PALD between February 2001 and December 2003, were allocated to the D2 + PALD group, and compared with a control group who underwent D2 lymphadenectomy. Patients were followed up until August 2007.ResultsSixty-two patients were allocated to the D2 + PALD group, and a concurrent 55 patients were allocated to the D2 group. The mean follow-up period was 57.6 (range 43.0—77.6) months, with 11.1% lost to follow-up. The morbidity and mortality rates were 24.2% and 0% in the D2 + PALD group, and 27.3% and 1.8% in the D2 group, respectively. The overall 3- and 5-year survival rates were 77.5% and 65.8% in the D2 + PALD group, and 73.2% and 66.1% in the D2 group, respectively, without a significant difference. The frequency of metastasis to the para-aortic lymph nodes (PALN) was 8.1%. The logistic regression revealed that PALN metastasis was correlated to metastasis of No. 8a and No. 9 lymph nodes (P = 0.021 and P = 0.030, respectively).ConclusionAlthough D2 + PALD can be performed safely with an acceptable incidence of complications when performed by well-trained gastrointestinal surgeons, its survival benefits are not significantly greater than those of D2 lymphadenectomy. Therefore, routine D2 + PALD should not be recommended.

Is CD133 a biomarker for cancer stem cells of colorectal cancer and brain tumors? A meta-analysis

Background CD133 has been used to identify normal and cancer stem cells from several different tissues. Nowadays some researchers have reported that CD133 expression was not restricted to cancer stem cells (CSCs) of colorectal cancer and brain tumors, and CD133-negative subsets could also initiate tumors. We therefore performed a meta-analysis to assess the value of CD133 as a biomarker of CSCs for colorectal cancer and brain tumors. Methods A Medline search was performed to identify relevant studies for the analysis. The meta-analysis was done using RevMan 5.0 software. Outcome measures were colony formation rate and xenotransplanted tumor formation rate. Results Fifteen identified studies were available for analysis. For in vitro tests, there were no significant differences in the colony formation rates between CD133-positive and CD133-negative cells for colorectal cancer and brain tumors. For in vivo tests, the xenotransplanted tumor formation rate showed a significant difference between CD133-positive cells and CD133-negative cells in colorectal cancer only, corresponding to a risk difference of 0.40 (95%CI: 0.07, 0.73). Samples (cell lines versus tissues), applied biomarkers (combined versus single), and injection site were included as factors in sensitivity analyses, but the results were very inconsistent. Conclusions CD133 may not be suitable as a universe biomarker in identifying CSCs of colorectal cancer and brain tumors. Additional studies are necessary to further delineate its role.

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.

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.

Transthoracic Resection versus Non-Transthoracic Resection for Gastroesophageal Junction Cancer: A Meta-Analysis

Background The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic resection with those of patients who were not undergoing transthoracic resection. Method Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation related events. Results Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis, with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic resection and group without transthoracic resection (P>0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD =  −0.03, 95% CI −0.06- 0.00 and RD = 0.00, 95% CI −0.05- 0.05) of RCTs and non-RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic resection (WMD =  −5.80, 95% CI −10.38- −1.23) but did not seem to differ in number of harvested lymph nodes, operation time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were similar to the primary analyses. Conclusions There were no significant differences of survival rate and postoperative morbidity and mortality between transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of included studies were suboptimal.