Mechanism of reversing cisplatin resistance by Xiaoyan Decoction in lung cancer / 中草药

Objective: To investigate the possible mechanism of reversal of cisplatin resistance in lung cancer by Xiaoyan Decoction. Methods: The migration ability of cancer cells was observed by the scratch test, and the MTT was used to test the mobility of cancer cells. The siRNA transfection was applied to demonstrate the possible molecular mechanisms. The mRNA and protein expression levels were detected by real-time quantitative reverse transcription PCR and Western Blot. Results: MTT showed that A549/DDP could significantly inhibit cell proliferation at later points of time. Similarly, cisplatin combined with Xiaoyan Decoction could significantly inhibit cell proliferation at 48, 72 and 96 h. Scratch test showed that the migration distance was shorter in A549/DDP/siRNA-Beclin1 cell line than NC. MTT showed the proliferation of A549/DDP/siRNA-Beclin1 cell line was decreased when compaired with NC. Western blot also showed that the protein expression of P-gp and LRP was decreased. MTT also detected that cisplatin and Xiaoyan Decoction significantly inhibited cell proliferation of A549/DDP/siRNA-Beclin1 cell at later points of time. Cisplatin combined with Xiaoyan Decoction significantly inhibited cell proliferation in the whole course. The results showed that protein expression level of YAP1, P-gp and LRP in A549/DDP/siRNA-Beclin1 cell line was significantly lower than those in NC. Conclusion: Xiaoyan Decoction may improve the sensitivity to cisplatin may via Beclin 1-YAP1 pathway.

The prognostic influence of D2 lymphadenectomy with para-aortic lymph nodal dissection for gastric cancer in N3 stage / 中华外科杂志

<p><b>OBJECTIVE</b>To elucidate the necessity of para-aortic lymph nodal dissection in D2 lymphadenectomy for gastric cancer in N3 stage.</p><p><b>METHODS</b>A total of 278 gastric cancer patients staged N3 who underwent gastrectomy between January 2003 and December 2007 were enrolled. There were 180 male and 98 female patients, and the patients' age were 26-93 years (median was 61 years). All patients had undergone surgical treatment. There were R0 resection in 246 cases and R1 resection in 32 cases. Lymph node dissection included D1 lymphadenectomy with 125 cases, D2 lymphadenectomy with 109 cases and D2+para-aortic lymph nodal dissection(PAND) with 44 cases. The surgical approach were total gastrectomy (98 cases) and subtotal gastrectomy (180 cases). Potential prognostic factors were analyzed.</p><p><b>RESULTS</b>The lymph node metastasis of each station was high in gastric cancer patients staged N3 and 34.1% patients had the para-aortic lymph nodal metastasis. Borrmann type (HR = 1.350, 95%CI: 1.018-1.790, P = 0.037), curability (HR = 1.580, 95%CI: 1.076-2.322, P = 0.020), depth of invasion (HR = 1.697, 95%CI: 1.005-2.864, P = 0.048), metastatic lymph node ratio (HR = 1.631, 95%CI: 1.261-2.111, P = 0.000), extranodal metastasis (HR = 1.336, 95%CI: 1.027-1.738, P = 0.031), postoperative adjuvant chemotherapy (HR = 1.312, 95%CI: 1.015-1.696, P = 0.038), extent of lymphadenectomy (HR = 1.488 and 2.114, P = 0.054 and 0.000) and number of retrieved lymph node (HR = 1.503 and 2.112, P = 0.025 and 0.000) were found to be factors correlated to overall survival. In multivariate analysis, only Borrmann type (HR = 1.399, 95%CI: 1.050-1.863, P = 0.022), metastatic lymph node ratio (HR = 1.353, 95%CI: 1.016-1.802, P = 0.039) and extent of lymphadenectomy (HR = 1.725, 95%CI: 1.111-2.678, P = 0.015) were independent prognostic factors for gastric cancer patients in N3 stage.</p><p><b>CONCLUSIONS</b>Patients in N3 stage should at least have 30 lymph node examined. D2 lymph node dissection plus PAND may improve the overall survival for gastric cancer patients in N3 stage.</p>

Analysis of clinicopathologic characteristics and prognosis on mixed histology type of gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinicopathologic characteristics and prognosis of mixed histological type (MHT) gastric cancer.</p><p><b>METHODS</b>Clinical and follow-up data of 1108 gastric cancer patients undergoing radical operation in Tianjin Cancer Hospital between 2003 and 2006 were analyzed retrospectively. Clinicopathologic characteristics of MHT gastric cancer were summarized and the prognosis was analyzed by Kaplan-Meier analysis and COX regression.</p><p><b>RESULTS</b>Among the 1108 patients, 144 (13.0%) had mixed histology type of gastric cancer. Compared to the unitary histological type (UHT), MHT gastric cancer had bigger tumor size, higher proportion of T4 tumor, and was easier for lymph node and distant metastasis (all P<0.05). The 3- and 5-year survival rates of patients with MHT were 26.5% and 10.8% respectively, which were lower than those with UHT (58.8% and 35.0%, P<0.01). Univariate and multivariate analyses showed TNM classification was an independent prognostic factor (P<0.01).</p><p><b>CONCLUSIONS</b>MHT gastric cancer shows worse prognosis than UHT gastric cancer. There is no difference in prognosis among various combination of MHT gastric cancer. TNM classification is an independent prognostic factor of MHT gastric cancer.</p>

Prognostic value of metastatic lymph node ratio for gastric cancer patients with less than 15 lymph nodes dissection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of metastatic lymph node ratio (MLR) for gastric cancer patients with less than 15 lymph nodes dissected.</p><p><b>METHODS</b>Clinical data of 610 gastric cancer patients undergoing operation in Tianjin Cancer Hospictal from January 2003 to July 2007 were analyzed retrospectively. Patients were divided into two groups: <15 lymph nodes dissected group (n=320) and ≥ 15 lymph nodes dissected group (n=290). MLR was classified based on the following intervals: rN1 ≤ 10%, rN2 10%-30%, rN3 30%-60% and rN4 >60%. Survival was determined by Kaplan-Meier method and difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. Survival rates were compared between two groups in pN and rN stages respectively.</p><p><b>RESULTS</b>In <15 nodes group, all the survival differences among various rN stages were not significant (all P>0.05), while in same rN stage, all the survival differences among various pN stages were not significant (all P>0.05). Significant differences of 5-year cumulative survival rates were found between the two groups in pN2 and pN3a stage patients (both P<0.05) while no significant differences were found among different rN stages (all P>0.05). Multivariate analysis demonstrated rN stage was an independent prognostic factor for gastric cancer patients with <15 lymph nodes dissected (P=0.012, RR=1.617, 95%CI:1.111-2.354).</p><p><b>CONCLUSION</b>The rN staging system based on MLR can predict the prognosis of gastric cancer patients with less than 15 lymph nodes dissected.</p>

Mode of lymph node metastasis in early gastric cancer and risk factors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the status of lymph node metastasis (LNM) and to discuss reasonable lymphadenectomy in early gastric cancer (EGC).</p><p><b>METHODS</b>Between January 1991 and December 2010, 242 EGC patients underwent surgery in the Tianjin Cancer Hospital. Their clinical characteristics, pathologic features, and lymph node metastasis were analyzed retrospectively.</p><p><b>RESULTS</b>LNM was observed in 22 of 242 patients (9.1%), and 10 (5.5%) in 182 mucosal lesions and 12 (20.0%) in 60 submueosal lesions. There were 14 patients had LNM in the first tier alone, 4 patients had skipped metastasis, and 4 patients had LNM in the first, second, and third ties. The LNM was identified in 18 patients at the first tier with groups 7 and 3 being the most common (8 patients in each group), 7 patients at the second tier (4 patients in group 8a and 3 in group 9), and 2 patients at the third tier (one 16b, and one 4sa). Multivariable analysis showed that the depth of invasion (P=0.003, OR=4.386, 95%CI:1.656-11.617), and lymphatic vessel involvement(P=0.002, OR=13.621, 95%CI:2.711-68.447) were independent risk factors for LNM.</p><p><b>CONCLUSIONS</b>LNM in EGC is mainly correlated with depth of invasion, and lymphatic vessel involvement. Precise evaluation of LNM pre- and intra-operatively is very important for the reasonable surgery.</p>

The significance of No.13 lymph node dissection in D2 gastrectomy for lower-third advanced gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and necessity of No.13 lymph node dissection in D2 radical gastrectomy for lower-third advanced gastric cancer (AGC).</p><p><b>METHODS</b>Data of 379 cases who were diagnosed as TNM II-III stage AGC were collected from January 2001 to June 2007. One hundred cases who undergone No.13 lymph node dissection during D2 gastrectomy for lower-third AGC were selected as study group. Other 279 cases (control group) received only D2 gastrectomy. The differences in clinicopathologic and intraoperative and postoperative parameters and 5-years survival rate were compared using the SPSS 17.0 software.</p><p><b>RESULTS</b>There were no significant differences between the two groups in patients' gender, age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth, lymph node metastasis, TNM classification, operative time, blood loss and the incidence of postoperative complications (P > 0.05). In the study group, there were 9 patients with positive No. 13 lymph node, and its 5-year survival rate (46.0%) was higher than the control group (36.5%, χ² = 4.452, P < 0.05). The Univariate analysis showed that age (χ² = 7.539), No.13 lymph node dissection (χ² = 4.452), tumor size (χ² = 7.100), duodenum invasion (χ² = 9.106), tumor depth (χ² = 7.428), lymph node metastasis (χ² = 45.046), TNM classification (χ² = 57.008) are associated with prognosis of lower-third AGC (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 - 0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR = 5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 - 3.394) as independent prognostic factors (P < 0.05).</p><p><b>CONCLUSION</b>No. 13 lymph node dissection for TNM II-III stage lower-third advanced gastric cancer is feasible and necessary.</p>

The prognostic analysis of tumor size in T4a stage gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of tumor size in the prognosis of T4a stage gastric cancer.</p><p><b>METHODS</b>The best cut-off point depending on tumor size was selected by Kaplan-Meier. Compare cliniclópathological characteristics between small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate analysis was done by Log-rank test and multivariate analysis was performed using the Cox proportional hazard regression model. The independent prognostic factors of patients were performed subgroup analysis.</p><p><b>RESULTS</b>Eight centimetre was the optimal cut-off of tumor size for T4a stage gastric cancer. There were significantly differences between SSG and LSG in tumor location (χ² = 15.695), histological grade (χ² = 4.393), macroscopic type (χ² = 5.629) and early recurrence (χ² = 4.292). Univariate analysis showed age (χ² = 4.463), tumor size (χ² = 9.057), macroscopic type (χ² = 6.679), histological grade (χ² = 5.122), location of tumor (χ² = 8.707) and N stage (χ² = 132.954) are related to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192) were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR = 1.876) was independent risk factor for survival (P = 0.000). Further stratified analysis indicated that the 5-year survival rate of LSG is significantly lower than that of SSG in T4a stage patients of gastric cancer without lymph nodes metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01).</p><p><b>CONCLUSIONS</b>Tumor size is an independent prognostic factor in patients of T4a stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant impact on the prognosis of T4a stage gastric cancer without lymph nodes metastasis or poorly differentiated.</p>

The value of negative lymph node count in prediction of prognosis of advanced gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of negative lymph node count (NLNC) in prediction of prognosis of advanced gastric cancer after radical resection.</p><p><b>METHODS</b>The 544 cases of radical gastrectomy patients with complete clinical and follow-up data between January 2011 and July 2007 were collected. Survival was determined by the Kaplan-Merier method and univariate analysis was done by Log-rank test, Multivariate analysis was performed using the Cox proportional hazard regression model.</p><p><b>RESULTS</b>Univariate analysis showed age (χ(2) = 4.449), T stage (χ(2) = 30.482), N stage (χ(2) = 205.452), location of tumor (χ(2) = 16.649), tumor size (χ(2) = 35.117), macroscopic type (χ(2) = 4.750), histological grade (χ(2) = 6.130), NLNC stage (χ(2) = 150.369) and type of gastrectomy (χ(2) = 25.605) were related to survival. Among them, T stage, N stage, tumor size and NLNC stage were independent risk factors for survival (P < 0.05). The prognostic factors of patients were performed subgroup analysis, NLNC > 15 group can prolong the survival than NLNC ≤ 15 group in the T2 stage (HR = 0.315), T4 stage (HR = 0.401), the same classification of location of tumor (HR = 0.286-0.493), tumor size (HR = 0.336, 0.465), macroscopic type (HR = 0.306, 0.418), histological grade (HR = 0.411, 0.365) and type of gastrectomy (HR = 0.444, 0.358 and 0.356, all P < 0.05). More NLNC can prolong Disease-Free Survival for patient of early recurrence (χ(2) = 8.648, P = 0.003).</p><p><b>CONCLUSIONS</b>Sufficient negative lymph node count can prolong the survival and decrease the risk of early recurrence.</p>

Significance of No.14v lymph node dissection for advanced gastric cancer undergoing D2 lymphadenectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To elucidate the necessity of No.14v lymph node dissection in D2 lymphadenectomy for advanced gastric cancer.</p><p><b>METHODS</b>Clinicopathological data of 131 cases of advanced gastric cancer receiving D2 or D2+ plus No.14v lymph node dissection were reviewed retrospectively. Clinicopathological factors associated with No.14v lymph node metastasis were analyzed and prognostic value of No.14v lymph node metastasis was evaluated.</p><p><b>RESULTS</b>Of the 131 patients, 24 (18.3%) had positive No.14v lymph node. The incidence of 14v metastasis was associated with tumor location, tumor size, depth of invasion, N staging, TNM staging, No.1, No.6, and No.8a lymph nodes metastasis. Tumor location and N staging were independent risk factors for No.14v metastasis (all P<0.05). The 5-year survival rate was 8.3% and 37.8% in patients with and without No.14v metastasis respectively. The difference was statistically significant (P<0.01). Multivariate analysis revealed that metastasis of No.14v was an independent prognostic factor for advanced gastric cancer after D2 lymphadenectomy (P=0.029, RR=1.807, 95%CI:1.064-3.070).</p><p><b>CONCLUSIONS</b>For advanced middle and lower gastric cancers, especially those with larger size, serosa invasion and possibility of No.6 lymph node metastasis, it is necessary and feasible to remove the No.14v lymph node.</p>

The reasonable surgery for gastric body cancer and prognostic analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the reasonable surgery for gastric body cancer.</p><p><b>METHODS</b>From January 2001 to December 2006, the clinicopathological data of 145 patients with a tumor in the middle third of the stomach underwent radical gastric resection were analyzed retrospectively. We conducted comparative analysis for the differences in clinicopathological characteristics and prognosis between total gastrectomy (TG) and subtotal gastrectomy (STG).</p><p><b>RESULTS</b>The 98 patients underwent TG, 47 received STG. There were significant differences in aspects of tumor size, depth of tumor, nodal status and TNM stage between the 2 groups. Patients with more advanced cancer were more likely to receive TG. The 5-year survival rate for TG was lower (25.5%) than STG (63.8%) (χ(2) = 11.707, P = 0.000). However, if tumor stages were stratified, there was no significant difference in the 5-year survival rate. TNM stage (P = 0.044) and histologic type (HR = 1.834, 95%CI: 1.073 - 3.135, P = 0.027) were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The overall survival rate of STG for gastric cancer in the middle third of the stomach is better than that of TG. If the radical resection margin can be obtained for gastric body carcinoma, STG is considered instead of TG.</p>