A Substage Increase in The AJCC Classification System Improves Prognostic Prediction in Stage III Gastric Cancer With Insufficient Lymph Nodes Removed.

BACKGROUND: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. METHODS: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). RESULTS: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). CONCLUSIONS: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer.

Extensive Dissection at No. 12 Station During D2 Lymphadenectomy Improves Survival for Advanced Lower-Third Gastric Cancer: A Retrospective Study From a Single Center in Southern China.

BACKGROUND: D2 lymphadenectomy including No. 12a dissection has been accepted as a standard surgical management of advanced lower-third gastric cancer (GC). The necessity of extensive No. 12 nodes (No. 12a, 12b, and 12p) dissection remains controversial. This study aims to explore its impact on long-term survival for resectable GC. METHODS: From 2009 to 2016, 353 advanced lower-third GC patients undergoing at least D2 lymphadenectomy during a radical surgery were included, with 179 patients receiving No. 12a, 12b, and 12p dissection as study group. A total of 174 patients with No. 12a dissection were employed as control group. Surgical and long-term outcomes including 90-day complications incidence, therapeutic value index (TVI), 3-year progression-free survival (PFS), and 5-year overall survival (OS) were compared between both groups. RESULTS: No. 12 lymph node metastasis was observed in 20 (5.7%) patients, with 10 cases in each group (5.6% vs. 5.7%, p = 0.948). The metastatic rates at No. 12a, 12b, and 12p were 5.7%, 2.2%, and 1.7%, respectively. The incidence of 90-day complications was identical between both groups. Extensive No. 12 dissection was associated with increased TVI at No. 12 station (3.9 vs. 0.6), prolonged 3-year PFS rate (67.0% vs. 55.9%, p = 0.045) and 5-year OS rate (66.2% vs. 54.0%, p = 0.027). The further Cox-regression analysis showed that the 12abp dissection was an independent prognostic factor of improved survival (p = 0.026). CONCLUSION: Adding No. 12b and 12p lymph nodes to D2 lymphadenectomy might be effective in surgical treatment of advanced lower-third GC and improve oncological outcomes compared with No. 12a-based D2 lymphadenectomy.

Systemic immune-inflammation index for predicting prognosis of colorectal cancer.

AIM: To investigate the clinical significance of preoperative systemic immune-inflammation index (SII) in patients with colorectal cancer (CRC). METHODS: A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII = (P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with CRC. RESULTS: The optimal cut-off point for SII was defined as 340. The overall survival (OS) and disease-free survival (DFS) were better in patients with low NLR, PLR, and SII (P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics (ROC) curve for SII (0.707) was larger than those for NLR (0.602) and PLR (0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION: SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.

Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer.

We previously performed long non-coding RNA (lncRNA) expression microarray analyses to identify novel indicators for gastric cancer (GC) metastasis and prognosis in which we identified lncRNA XLOC_010235 (XLOC) as a candidate RNA. However, XLOC_010235 molecular mechanism of action remains unclear. Gain and loss of function approaches were used to investigate the biological role of XLOC in vitro. The effects of XLOC on cell viability were assessed by CCK-8 proliferation assays. Real-time PCR, western-blot and immunofluorescence were used to evaluate the mRNA and protein expression of Snail and multiple EMT related molecules. The positive XLOC/Snail1 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Ectopic expression of XLOC facilitate cell viability, migration and invasion, leading to the acceleration of metastasis, while depletion of XLOC expression hindered cell migration and invasion. Moreover, over-expression of XLOC was found to play a important role in epithelial-to-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression, in which transcriptional factor Snail1 was involved. These results advance our understanding of the role of lncRNA XLOC_010235 as a active regulator of EMT by associating with Snail1, which may help in the development of new therapeutics.

Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell proliferation and colorectal cancer growth.

The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The effectiveness of the interference was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction, and the cell proliferation was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed by subcutaneously inoculating the constructed cells into BALB/c nude mice. The protein expression levels of CRMP-4 were markedly increased in colon tumor tissue of the human samples. The proliferation of SW480 cells and the tumor growth rate in nude mice of the si-CPMR-4 group were evidently depressed compared with the si-scramble group. Thus, the present results suggest that CRMP-4 may be involved in the pathogenesis of CRC.

Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature.

Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients' follow up for colorectal cancer with or without subsequent adrenal metastasis.

XRCC1 R399Q polymorphism and colorectal cancer risk in the Chinese Han population: a meta-analysis.

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in DNA repair, genetic instability, and tumorigenesis. The XRCC1 R399Q polymorphism has been reported in some studies to influence the risk of colorectal cancer (CRC), though this remains controversial. We performed a meta-analysis to determine the association of XRCC1 R399Q polymorphisms with CRC risk in the Chinese Han population. A literature search was conducted using PubMed, EMBASE, and the China National Knowledge Infrastructure to identify eligible studies published before June 2014. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the effect of XRCC1 R399Q polymorphisms on CRC risk. Eleven case-control studies with a total of 3194 CRC cases and 4472 controls were identified. No significant association between the XRCC1 R399Q polymorphism and CRC risk was observed in the Chinese Han population (Gln/Gln vs. Arg/Arg, OR = 1.26, 95% CI = 0.85-1.87, P OR = 0.242; Arg/Gln vs. Arg/Arg, OR = 0.95, 95% CI = 0.70-1.18, P OR = 0.651; dominant model, OR = 1.09, 95% CI = 0.86-1.38, P OR = 0.480; and recessive model, OR = 1.24, 95% CI = 0.91-1.70, P OR = 0.177). After excluding two studies that deviated from the Hardy-Weinberg equilibrium, there remained no significant association between XRCC1 R399Q and CRC risk. No publication bias was found using the funnel plot and Egger's test. Our meta-analysis results suggest that the XRCC1 R399Q polymorphism is not associated with increased risk of CRC in the Chinese Han population.

Survival prognosis and clinicopathological features of the lymph nodes along the left gastric artery in gastric cancer: implications for D2 lymphadenectomy.

The Japanese Gastric Cancer Treatment Guidelines (third edition) have assigned No. 7 station left gastric artery lymph nodes (LNs) to the D1 range of lymphatic dissection. We investigated the clinicopathological characteristics, survival impact, and appropriateness of ascribing No. 7 station LNs to D1 lymphadenectomy in gastric cancer. Patients (n=608) undergoing radical resection with No. 7 station LN dissection were recruited between January 1997 and June 2008. They were subdivided into four groups: N0, no LN metastasis; D1, LN without No. 7 station LN metastasis in the D1 lymphadenectomy region; No. 7, No. 7 station LN without LN metastasis in the D2 lymphadenectomy region; and D2, LN without No. 7 station LN metastasis in the D2 lymphadenectomy region. Of these, 17.2% (n=105) were positive for No. 7 LN metastasis, an important, independent prognostic factor associated with poor clinicopathological parameters, advanced tumor stage, and reduced survival. Tumor behavior in the No. 7 group was similar to that in the D2 group, but poorer than in the D1 group in terms of advanced tumor stage, with 5-year survival rates of 34.3%, 25.9% and 54.6%, respectively. Five-year survival rates in the No. 7 group were comparable to those in the D2 group (P>0.05), but significantly lower than in the D1 group (P<0.05). Logistic multivariate regression analysis established No. 3 and 9 station LN metastasis, node classification, and tumor-node-metastasis stage as independent risk factors for No. 7 station LN metastasis. Thus, No. 7 station LNs should be ascribed to D2 lymphadenectomy in gastric cancer.