Baogui Wang

Expression of Rac1, HIF-1α, and VEGF in Gastric Carcinoma: Correlation with Angiogenesis and Prognosis

Background: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma. Material and Methods: The expression of Rac1, HIF-1α, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens. Results: The proportion of specimens expressing Rac1, HIF-1α, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1α, and VEGF expression were significantly correlated with Laurens classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1α, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1α, and VEGF expression and MVD ≥ 26.3 were significantly shorter than those with negative Rac1, HIF-1α, and VEGF expression and MVD < 26.3. Conclusion: Rac1, HIF-1α, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1α, and VEGF may be a useful index for treatment and prognosis.

Lymph node metastasis is mediated by suppressor of cytokine signaling-3 in gastric cancer

Suppressor of cytokine signaling-3 (SOCS-3), a multifunctional cytokine, is able to inhibit cell growth and migration by blocking the Janus kinase signal transducers and activators of transcription signaling (JAK/STAT) activation in oncogenesis. Although the STAT-3 expression was associated with lymph node metastasis from gastric cancer (GC), the implication of SOCS-3 expression in GC is not clearly elucidated. In this study, SOCS-3, STAT-3, and pSTAT-3 were evaluated in GC tissues and adjacent non-tumor tissues of 107 patients who underwent curative surgery by immunohistochemistry. Further, SOCS-3 and STAT-3 mRNA levels were also detected simultaneously. In addition, survival analysis was performed between clinicopathologic variables and prognosis of GC patients. Finally, correlative analysis was adopted for demonstration the best predicator of the survival independent factor. From the results, we demonstrated that only the lymph node metastasis was the independent predictor of the overall survival (OS) of GC patients, although SOCS-3, STAT-3, and other variables were significantly relative to OS. With multivariate logistical regression analysis, SOCS-3, STAT-3, and the status of extragastric nodal metastasis were identified to be the independent factors of the lymph node metastasis from GC. Ultimately, the SOCS-3 was the best predicator of lymph node metastasis from GC identified with the nominal regression analysis. Therefore, SOCS-3 should be considered as a potential indicator for prediction the lymph node metastasis from GC.

Outcome in relation to numbers of nodes harvested in lymph node-positive gastric cancer

AIMS We conducted a retrospective case-control study to compare the prognostic differences of lymph node-positive gastric cancer patients between dissected lymph nodes (DLNs) <15 group and DLNs > or =15 group. METHODS A retrospective study of 323 lymph node-positive gastric patients who underwent potentially curative resection for gastric cancer was analyzed to identify the prognostic differences between DLNs <15 group and DLNs > or =15 group. Of these patients, 49 patients with <15 DLNs were matched with 147 patients with > or =15 DLNs according to gender, age, location of primary tumor, and type of gastrectomy. RESULTS Patients with n1 lymph node metastasis (according to JCGC), serosal involvement, ratio of positive lymph nodes less than 25%, or without adjuvant chemotherapy in > or =15 DLN group had comparatively longer median survival than patients with homologous clinicopathologic variables in <15 DLN group, respectively. Patients with n1 stage lymph node metastasis, serosal involvement, non-intestinal Lauren classification, or without adjuvant chemotherapy in <15 DLN group had higher recurrence rate than patients with homologous clinicopathologic variables in > or =15 DLN group, respectively. In addition, we demonstrated that patients with more than n1 stage lymph node metastasis in <15 DLN group had higher rate of peritoneal dissemination than those with more than n1 lymph node metastasis in > or =15 DLN group. CONCLUSIONS DNL > or =15 was an important factor to improve the prognosis of lymph node-positive gastric cancer patients after potential curative resection.

N stages of the seventh edition of TNM Classification are the most intensive variables for predictions of the overall survival of gastric cancer patients who underwent limited lymphadenectomy

The objective of this study was to explore the prognostic prediction rationality of the seventh edition N stage for gastric cancer (GC) patients who underwent the limited lymphadenectomy. Clinicopathological data of 769 GC patients who underwent the curative resection between 1997 and 2006 were analyzed for demonstration that the seventh edition N stage had the significant superiorities of prognostic prediction to the patients who underwent the limited lymphadenectomy. Although the extent of lymphadenectomy was associated with the overall survival (OS) of gastric cancer (GC) patients, the N stages of the seventh edition of the TNM Classification were identified as the most intensively independent predictors of GC prognosis. Using stratum analysis, the 5-year survival rate of patients who underwent limited lymphadenectomy was observed to be significantly different from that of patients who underwent extended lymphadenectomy, regardless of the extent of lymph node metastasis. Multinomial logistic regression analysis revealed that combining the extents of lymph node metastasis and lymphadenectomy could improve the prediction accuracy of patient survival status. Case control analysis showed that regardless of the extent of lymphadenectomy, the seventh edition N stages featured significant superiority for OS evaluation of GC patients. The seventh edition N stage had the prediction rationality for the OS of GC patients who underwent the limited lymphadenectomy.

Prognostic value of surgical margin status in gastric cancer patients

It has been reported that positive surgical margin is one of the most significant risk factors for local recurrence and poor survival. However, the survival of gastric cancer (GC) patients with positive margin is still controversial.

Positive impact of adding No.14v lymph node to D2 dissection on survival for distal gastric cancer patients after surgery with curative intent

BACKGROUND D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), while the necessity of No.14v lymph node (14v) dissection for distal GC is still controversial. METHODS A total of 920 distal GC patients receiving at least a D2 lymph node dissection in Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital were enrolled in this study, of whom, 243 patients also had the 14v dissected. Other 677 patients without 14v dissection were used for comparison. RESULTS Forty-five (18.5%) patients had 14v metastasis. There was no significant difference in 3-year overall survival (OS) rate between patients with and without 14v dissection. Following stratified analysis, in TNM stages I, II, IIIa and IV, 14v dissection did not affect 3-year OS; in contrast, patients with 14v dissection had a significant higher 3-year OS than those without in TNM stages IIIb and IIIc. In multivariate analysis, 14v dissection was found to be an independent prognostic factor for GC patients with TNM stage IIIb/IIIc disease [hazard ratio (HR), 1.568; 95% confidence interval (CI): 1.186-2.072; P=0.002]. GC patients with 14v dissection had a significant lower locoregional, especially lymph node, recurrence rate than those without 14v dissection (11.7% vs. 21.1%, P=0.035). CONCLUSIONS Adding 14v to D2 lymphadenectomy may be associated with improved 3-year OS for distal GC staged TNM IIIb/IIIc.

Elevated preoperative plasma D-dimer dose not adversely affect survival of gastric cancer after gastrectomy with curative intent: A propensity score analysis

Objective Elevated plasma D-dimer has been reported to be associated with advanced tumor stage and poor survival in several types of malignancies. The purpose of this study was to assess the potential impact of preoperative plasma D-dimer level (PDL) on overall survival (OS) of gastric cancer (GC) patients undergoing curative surgery by applying propensity score analysis. Methods A total of 1,025 curatively resected GC patients in Tianjin Medical University Cancer Institute & Hospital were enrolled. Patients were categorized into two groups based on preoperative PDL: the elevated group (EG) and the normal group (NG). To overcome bias due to the different distribution of covariates for the two groups, a one-to-one match was applied using propensity score analysis, after matching, prognostic factors were analyzed. Results In analysis for the whole study series, patients in the EG were more likely to have a larger proportion of tumor size ≥5 cm (67.5% vs. 55.8%, P=0.006), elder mean age (64.0±10.8 years vs. 60.5±11.6 years, P<0.001) and advanced tumor (T), node (N), and TNM stage. Patients with elevated PDL demonstrated a significantly lower 5-year OS than those with normal PDL (27.0%vs. 42.6%, P<0.001), however, the PDL was not an independent prognostic factor for OS in multivariate analysis [hazard ratio: 1.13, 95% confidence interval (95% CI): 0.92-1.39, P=0.236]. After matching, 163 patients in the EG and 163 patients in the NG had the same characteristics. The 5-year OS rate for patients in the EG was 27.0% compared with 25.8% for those in the NG (P=0.809, log-rank). Conclusions The poor prognosis of GC patients with elevated preoperative PDL was due to the advanced tumor stage and elder age rather than the elevated D-dimer itself.