Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro.

BACKGROUND: Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM: To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS: Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS: TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION: Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

Combination of endoscopic submucosal dissection and laparoscopic sentinel lymph node dissection in early mucinous gastric cancer: Role of lymph node metastasis.

BACKGROUND: Recent evidence showed that combining endoscopic submucosal dissection (ESD) and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer (EMGC) patients with risks of positive lymph node metastasis (pLNM). AIM: To explore the predictive factors for pLNM in EMGC, and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC. METHODS: Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016. Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors, providing odds ratio (OR) with 95% confidence interval. And the association between the number of predictors and the pLNM rate was also investigated. RESULTS: Depth of invasion (OR = 7.342, 1.127-33.256, P = 0.039), tumor diameter (OR = 9.158, 1.348-29.133, P = 0.044), and lymphatic vessel involvement (OR = 27.749, 1.821-33.143, P = 0.019) turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis. For patients with 1, 2, and 3 risk factors, the pLNM rates were 9.1%, 33.3%, and 75.0%, respectively. pLNM was not detected in seven patients without any of these risk factors. CONCLUSION: ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size ≤ 2 cm, and when lymphatic vessel involvement is absent by postoperative histological examination. Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.

Comparison of endoscopic submucosal dissection with surgical gastrectomy for early gastric cancer: An updated meta-analysis.

BACKGROUND: There are several surgical options for treating early gastric cancers (EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with low risk of lymph node metastasis has been widely accepted as a therapeutic alternative. The role of endoscopic submucosal dissection (ESD) in treating EGC is not well established, especially when compared with resection surgery cases in a long-term follow-up scope. AIM: To compare the safety and efficacy of the short- and long-term outcomes between ESD and resection surgery. METHODS: We searched the databases of PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1990 to June 2018, enrolling studies reporting short- or long-term outcomes of ESD in comparison with resection surgery for EGC. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. Stata software (version 12.0) was used for the analysis. Pooling analysis was conducted using either fixed- or random-effects models depending on heterogeneity across studies. RESULTS: Fourteen studies comprising 5112 patients were eligible for analysis (2402 for EGC and 2710 for radical surgery). Our meta-analysis demonstrated that the ESD approach showed advantages through decreased operation time [weighted mean difference (WMD): -140.02 min, 95%CI: -254.23 to -34.82 min, P = 0.009], shorter hospital stay (WMD: -5.41 d, 95% CI: -5.93 to -4.89 d, P < 0.001), and lower postoperative complication rate [Odds ratio (OR) = 0.39, 95%CI: 0.28-0.55, P < 0.001). Meanwhile, EGC patients who underwent ESD had higher recurrence rate (OR = 9.24, 95%CI: 5.94-14.36, P < 0.001) than resection surgery patients. However, the long-term survival including overall survival [Hazard ratio (HR) = 0.51, 95%CI: 0.26-1.00, P = 0.05] and event-free survival (HR = 1.59, 95%CI: 0.66-9.81, P = 0.300) showed no significant differences between these two groups. CONCLUSION: In the treatment of EGC, ESD was safe and feasible in comparison with resection surgery, with advantages in several surgical and post-operative recovery parameters. Although the recurrence rate was higher in ESD group, the long-term survival was still comparable in these two groups, suggesting ESD could be recommended as standard treatment for EGC with indications.

Predictive factors for lymph node metastasis and defining a subgroup treatable for laparoscopic lymph node dissection after endoscopic submucosal dissection in poorly differentiated early gastric cancer.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC); to guide the individual application of a combination of endoscopic submucosal dissection (ESD) and laparoscopic lymph node dissection (LLND) in a suitable subgroup of patients with poorly differentiated EGC. METHODS: We retrospectively analyzed 138 patients with poorly differentiated EGC who underwent gastrectomy with lymphadenectomy between January 1990 and December 2015. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95% confidence interval (95%CI) were calculated. We further examined the relationship between the positive number of the significant predictive factors and the LNM rate. RESULTS: The tumor diameter (OR = 13.438, 95%CI: 1.773-25.673, P = 0.029), lymphatic vessel involvement (LVI) (OR = 38.521, 95%CI: 1.975-68.212, P = 0.015) and depth of invasion (OR = 14.981, 95%CI: 1.617-52.844, P = 0.024) were found to be independent risk factors for LNM by multivariate analysis. For the 138 patients diagnosed with poorly differentiated EGC, 21 (15.2%) had LNM. For patients with one, two and three of the risk factors, the LNM rates were 7.7%, 47.6% and 64.3%, respectively. LNM was not found in 77 patients that did not have one or more of the three risk factors. CONCLUSION: ESD might be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2 cm in size and when LVI is absent upon postoperative histological examination. ESD with LLND may lead to the elimination of unnecessary gastrectomy in poorly differentiated EGC.

Feasibility study on expanded indication for endoscopic submucosal dissection of intramucosal poorly differentiated early gastric cancer.

AIM: To identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using endoscopic submucosal dissection (ESD) for the treatment of intramucosal poorly differentiated EGC. METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component. RESULTS: Tumor size (OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement (OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component (OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7 (8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors. CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.

Risk clinicopathological factors for lymph node metastasis in poorly differentiated early gastric cancer and their impact on laparoscopic wedge resection.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC), and enlarge the possibility of using laparoscopic wedge resection (LWR). METHODS: We retrospectively analyzed 85 patients with poorly differentiated EGC who underwent surgical resection between January 1992 and December 2010. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95%CI were calculated. We further examined the relationship between the positive number of the three significant predictive factors and the LNM rate. RESULTS: In the univariate analysis, tumor size (P = 0.011), depth of invasion (P = 0.007) and lymphatic vessel involvement (P < 0.001) were significantly associated with a higher rate of LNM. In the multivariate model, tumor size (OR = 7.125, 95%CI: 1.251-38.218, P = 0.041), depth of invasion (OR = 16.624, 95%CI: 1.571-82.134, P = 0.036) and lymphatic vessel involvement (OR = 39.112, 95%CI: 1.745-123.671, P = 0.011) were found to be independently risk clinicopathological factors for LNM. Of the 85 patients diagnosed with poorly differentiated EGC, 12 (14.1%) had LNM. The LNM rates were 5.7%, 42.9% and 57.1%, respectively in cases with one, two and three of the risk factors respectively in poorly differentiated EGC. There was no LNM in 29 patients without the three risk clinicopathological factors. CONCLUSION: LWR alone may be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size, and when lymphatic vessel involvement is absent at postoperative histological examination.

Identification of clinicopathological factors predicting lymph node metastasis in differentiated submucosal gastric cancer: Impact on surgical strategy.

The aim of this study was to identify the clinicopathological factors predictive of lymph node metastasis (LNM) in differentiated submucosal gastric cancer (SGC), and to establish a simple criterion which may be useful in selecting the optimal treatment for cases with SGC. A total of 70 patients with differentiated and surgically treated SGC were retrospectively examined, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated. In the univariate analysis, tumor size, lymphatic vessel involvement and the presence of intermingled components of undifferentiated cancer cells were significantly associated with a higher rate of LNM (all P<0.05). In the multivariate analysis, lymphatic vessel involvement (OR=392.269; 95% CI 1.380-1115.032; P=0.038) and presence of intermingled components of undifferentiated cancer cells (OR=98.515; 95% CI 2.687-3612.400; P=0.012) were found to be independent pathological risk factors for LNM. LNM was observed in 75.0% (3/4) of patients with the two risk factors, but in none of the 45 patients without the two risk factors. Lymphatic vessel involvement and presence of intermingled components of undifferentiated cancer cells are independently associated with the presence of LNM in differentiated SGC. Thus, these two risk factors may be used to establish a simple criterion to guide further surgical procedures in cases with SGC revealed after endoscopic mucosal resection (EMR).

Defining a subgroup treatable for laparoscopic surgery in poorly differentiated early gastric cancer: the role of lymph node metastasis.

OBJECTIVE: The present study aims to identify the clinicopathologic factors predictive of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to expand the possibility of using laparoscopic surgery for the treatment of poorly differentiated EGC. METHODS: Data from 70 cases of poorly differentiated EGC treated with surgery were collected. The association between clinicopathologic factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size, depth of invasion, and lymphatic vessel involvement (LVI) were the significant and independent risk factors for LNM (all P<0.05). The LNM rates were 6.9%, 45.5%, and 60.0%, respectively. There was no LNM in 25 patients without the above three risk factors. CONCLUSIONS: Laparoscopic surgery is a sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size and when LVI is absent upon postoperative histological examination.