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Objective To investigate the expression and clinical significance of pro-inflammation S100A9 protein in intestinal type gastric cancer.Methods We retrospectively analyzed the clinicopathological materials of the 278 patients who were diagnosed as Lauren classification intestinal gastric cancer and underwent surgical treatment between January and December 2008 at the Department of General Surgery,Zhongshan Hospital Fudan University.Immunohistochemistry was used to analyze the expression of S100A9 protein in tumor tissues and para-tumor tissues.Results High expression of S100A9 protein was associated with the depth of tumor invasion (P =0.013),lymph node metastasis (81.4％,53.9％,47.3％ vs.84.7％,69.3％,60.7％,x2 =4.220,P =0.041) and TNM stage (P =0.010).The overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.In stage Ⅲ/Ⅳ patients,the overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.Moreover,for those patients who received postoperative chemotherapy,the prognosis of the patients with high expression of S100A9 protein was poorer than those with low expression.By multivariable analysis,the expression of S100A9 protein was not an independent risk factor for the prognosis of intestinal gastric cancer patients.Conclusions High expression of S100A9 protein in intestinal gastric cancer was associated with poor prognosis.
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Objective To investigate the prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis.Methods The retrospective case-control study was conducted.The clinicopathological data of 995 patients with stage Ⅲ gastric cancer who were admitted to the Zhongshan Hospital of Fudan University between January 2003 and December 2014 were collected.There were 690 males and 305 females,aged from 20 to 75 years,with an average age of 61 years.After clinical staging according to results of preoperative accessory examinations,patients with early gastric cancer underwent D1+ lymphadenectomy,patients with advanced gastric cancer underwent D2 lymphadenectomy and patients with serosa invasion underwent D2+ lymphadenectomy.Observation indicators:(1) treatment situations;(2) follow-up and survival situations;(3) prognostic factors analysis after operation;(4) stratified analysis:① stratified analysis of tumor pathological N staging;② stratified analysis of number of lymph node dissected;③ stratified analysis of tumor pathological TNM staging;(5) receiver operating characteristic (ROC) curve.Patients were followed up using outpatient examination and telephone interview to detect postoperative survival up to January 2016.The overall survival time was from the operation data to last follow-up or time of death.Measurement data with normal distribution were represented as Mean±SD.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and Log-rank test was used for survival analysis.The COX proportional hazard model was used for univariate and multivariate analysis.The ROC curve and area under curve (AUC) were used to check the accuracy of number of positive lymph nodes and metastatic lymph node ratio for prognosis.Comparison of the AUC was analyzed by the Z test.Results (1) Treatment situations:of 995 patients underging gastrectomy,677 underwent distal gastrectomy,85 underwent proximal gastrectomy,233 underwent total gastrectomy.There were 117 undergoing D1+ lymphadenectomy and 878 undergoing D2 lymphadenectomy or D2+ lymphadenectomy.The number of lymph node dissected,number of positive lymph nodes,metastatic lymph node ratio were 27± 12,10± 9 and 0.41±0.28,respectively.(2) Follow-up and survival situations:995 patients were followed up for (35± 32)months.During the follow-up,the 1-,3-,5-year overall survival rates were 77.9％,47.8％,36.2％.(3) Prognostic factors analysis after operation:results of univariate analysis showed that sex,tumor histological type,vascular embolus,degree of tumor invasion,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were related factors affecting prognosis of radical gastrectomy for stage Ⅲ gasteric cancer (hazard ratio =0.817,1.486,1.268,2.173,1.957,1.737,3.357,2.169,95％ confidence interval:0.686-0.973,1.059-2.086,1.074-1.497,1.195-3.954,1.480-2.588,1.390-2.170,2.476-4.602,1.740-2.704,P＜0.05).Results of multivariate analysis showed that sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging were independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer (hazard ratio =0.805,1.476,0.237,1.475,3.811,3.600,95％ confidence interval:0.673-0.963,1.049-2.087,0.083-0.678,1.140-1.909,2.259-6.428,1.317-9.839,P＜0.05).(4) Stratified analysis:of the 995 patients,the postoperative l-,3-,5-year overall survival rates were 93.7％,69.6％,60.5％ in the patients with metastatic lymph node ratio ≤ 0.1,86.9％,60.6％,44.3％ in the patients with 0.1 ＜ metastatic lymph node ratio ≤0.4 and 64.3％,28.9％,21.0％ in the patients with metastatic lymph node ratio ＞ 0.4,showing a statistically significant difference (x2 =121.300,P＜0.05).There were statistically significant differences between patients with metastatic lymph node ratio ≤0.1 and patients with 0.1＜ metastatic lymph node ratio ≤0.4,between patients with metastatic lymph node ratio ≤0.1 and patients with metastatic lymph node ratio ＞0.4 (x2=7.580,65.320,P＜0.05).There was a statistically significant difference between patients with 0.1 ＜ metastatic lymph node ratio ≤0.4 and patients with metastatic lymph node ratio＞0.4 (x2 =80.806,P＜0.05).① Stratified analysis of tumor pathological N staging:the average metastatic lymph node ratio was 0.09 in the 132 stage N1 patients,who were divided into the patients with metastatic lymph node ratio ≤ 0.1 and ＞ 0.1.The postoperative 1-,3-,5-year overall survival rates were 92.2％,68.6％,59.1％ in the 108 patients with metastatic lymph node ratio ≤ 0.1 and 79.2％,32.8％,21.9％ in the 24 patients with metastatic lymph node ratio ＞0.1,respectively,showing a statistically significant difference (x2 =14.499,P＜0.05).The average metastatic lymph node ratio was 0.23 in the 265 stage N2 patients,who were divided into the patients with metastatic lymph node ratio ≤0.2 and ＞0.2.The postoperative 1-,3-,5-year overall survival rates were 92.3％,73.8％,61.0％ in the 138 patients with metastatic lymph node ratio ≤0.2 and 76.5％,40.1％,22.2％ in the 127 patients with metastatic lymph node ratio ＞0.2,respectively,showing a statistically significant difference (x2 =42.536,P＜0.05).The average metastatic lymph node ratio was 0.56 in the 598 stage N3 patients,who were divided into the patients with metastatic lymph node ratio ≤0.4 and ＞0.4.The postoperative 1-,3-,5-year overall survival rates were 88.5％,62.8％,47.0％ in the 194 patients with metastatic lymph node ratio ≤ 0.4 and 64.3％,29.8％,21.0％ in the 404 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =51.860,P＜ 0.05).② Stratified analysis of number of lymph node dissected:7 of 117 patients with the number of lymph node dissected ＜ 15 had metastatic lymph node ratio ≤0.1,who were divided into patients with metastatic lymph node ratio ≤0.4 and ＞0.4.The postoperative 1-,3-,5-year overall survival rates were 78.2％,40.0％,28.6％ in the 44 patients with metastatic lymph node ratio ≤0.4 and 78.1％,18.7％,12.9％ in the 73 patients with metastatic lymph node ratio＞0.4,respectively,showing a statistically significant difference (x2 =4.727,P＜0.05).③ Stratified analysis of tumor pathological TNM staging:of 262 patients with stage Ⅲa gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 88.5％,65.0％,54.3％ in the 230 patients with metastatic lymph node ratio ≤0.4 and 77.5％,35.4％,29.5％ in the 32 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =6.132,P＜0.05).Of 296 patients with stage Ⅲb gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.4％,60.7％,42.7％ in the 200 patients with metastatic lymph node ratio ≤ 0.4 and 59.9％,26.8％,21.7％ in the 96 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2 =23.699,P＜0.05).Of 437 patients with stage Ⅲ c gastric cancer,the postoperative 1-,3-,5-year overall survival rates were 84.7％,59.9％,38.7％ in the 133 patients with metastatic lymph node ratio ≤0.4 and 64.0％,27.9％,18.3％ in the 304 patients with metastatic lymph node ratio ＞0.4,respectively,showing a statistically significant difference (x2=36.215,P＜ 0.05).(5) ROC curve:ROC curves of postoperative overall survival rates in patients with stage Ⅲ gastric cancer were drawn using the number of positive lymph nodes and metastatic lymph node ratio,of which AUC were 0.619 (95％ confidence interval:O.588-0.649) and 0.706 (95％ confidence interval:0.677-0.734),showing a statistically significant difference (Z=8.842,P＜0.05).Conclusions Sex,tumor histological type,tumor pathological N staging,number of lymph node dissected,metastatic lymph node ratio,tumor pathological TNM staging are independent factors affecting prognosis of radical gastrectomy for stage Ⅲ gastric cancer.There is different prognosis of patients with different metastatic lymph node ratios in the subgroup of the same tumor pathological TNM staging,number of lymph node dissected,tumor pathological TNM staging.Compared with tumor pathological N staging,metastatic lymph node ratio has a more accurate predictive value for prognosis.
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<p><b>OBJECTIVE</b>To establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance.</p><p><b>METHODS</b>Clinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity.</p><p><b>RESULTS</b>Among 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28.2%). Neutrophil/lymphocyte ratio (NLR) of 26 patients was ≥ 2.37(26/231, 11.3%). Multivariate analysis showed that Lauren classification (HR=8.95, 95%CI:1.32-60.59, P=0.025), CA125(HR=17.45, 95%CI:5.54-54.89, P=0.001), CA72-4(HR=20.06, 95%CI:5.05-79.68, P=0.001), and NLR (HR=4.16, 95%CI:1.17-14.75, P=0.032) were independent risk factors of peritoneal metastasis in gastric cancer. In the nomogram, the highest score was 241, including diffuse or mixed Lauren classification (54 score), CA125 ≥ 35 kU/L (66 score), CA72-4 ≥ 10 kU/L (100 score), and NLR ≥ 2.37 (21 score), which represented a highest risk of peritoneal metastasis (more than 90%). The AUC of nomogram was 0.912, which was superior than any single variable (AUC of Lauren classification: 0.678; AUC of CA125: 0.720; AUC of CA72-4: 0.792; AUC of NLR: 0.613, all P=0.000). The total score of nomogram increased according to the TNM stage, and was highest in the peritoneal metastasis group (F=49.1, P=0.000). When the cut-off value calculated by ROC analysis was set at 140, the model could best balanced the sensitivity (0.79) and the specificity (0.87). Only 5% of patients had peritoneal metastasis when their nomogram scores were lower than 140, while 58% of patients had peritoneal metastasis when their scores were ≥ 140(χ=69.1, P=0.000).</p><p><b>CONCLUSION</b>The risk evaluation model established with Lauren classification, CA125, CA72-4 and NLR can effectively predict the risk of peritoneal metastasis in gastric cancer, and provide the reference to preoperative staging and choice of therapeutic strategy.</p>
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Female , Humans , Male , Middle Aged , Antigens, Tumor-Associated, Carbohydrate , Blood , Area Under Curve , CA-125 Antigen , Blood , CA-19-9 Antigen , Blood , Leukocyte Count , Logistic Models , Lymphocytes , Pathology , Neoplasm Metastasis , Diagnosis , Neutrophils , Pathology , Nomograms , Peritoneal Neoplasms , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment , Methods , Risk Factors , Sensitivity and Specificity , Stomach Neoplasms , Blood , Classification , Diagnosis , PathologyABSTRACT
Objective To investigate the correlation between clinicopathological features and lymph node metastasis (LNM) in early gastric cancer (EGC).Methods From January 2006 to June 2009,the clinical data of 473 patients with EGC were collected.The data of patients including gender,age,tumor size,tumor number,general classification,differentiation degree,invasion depth,ulcer in tumor,nerve invasion,and lymphatic tumor cell embolus were analyzed.Chi-square test was performed to analyze the correlation between clinicopathological features and LNM in EGC.Logistic regression analysis was used to analyze the independent risk factor of LNM in EGC.Results Among 473 patients with EGC,77 patients had LNM and the metastasis rate was 16.3％.The metastasis rate of the female patients (24.6％,41/167) was higher than that of the male (11.8 ％,36/306).The metastasis rate of the tumors with maximum diameter over 2 cm (22.0％,39/177) was higher than that of the tumors less than 2 cm (12.8％,38/296).The metastasis rate of the elevated lesions (26.1％,6/23) was higher than that of flat and concave lesions (9.0 ％,15/167;19.8％,56/283).The metastasis rate of poorly differentiated tumors was higher than moderate differentiated and high differentiated tumors (12.7 ％,23/181; 7.1％,3/42).The metastasis rate of tumors invading into submucosa (22.9％,41/179) was higher than that of tumors invading into mucosa (12.2％,36/294).The metastasis rate of tumors with lymphatic embolus (40.7％,11/27) was higher than that of tumors without lymphatic embolus (14.8％,66/446) and the differences were statistically significant (x2 =12.960,6.873,10.704,7.382,9.277 and 12.572,all P＜0.05).The results of multifactor analyzed by Logistic regression analysis revealed that female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa were the independent risk factors of LNM in EGC (relative risk (RR)=2.53,2.14,1.63 and 2.39,all P＜0.01).Conclusion Female,maximum diameter over 2 cm,poorly differentiated type and invasion to submucosa are the independent risk factors of LNM in EGC.
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<p><b>OBJECTIVE</b>To explore the risk factors associated with the prognosis in poorly differentiated(G3) advanced gastric cancer (AGC) and the effect of number of harvested lymph nodes on the prognosis.</p><p><b>METHODS</b>Clinical data of 484 patients with G3 advanced gastric cancer undergoing gastrectomy combined with lymphadenectomy in Zhongshan Hospital from December 2002 to October 2007 were retrospectively analyzed. The χ(2) test or Fisher's exact probability method was used to test measurement data. Survival was calculated using Kaplan-Meier method. Clinicopathological factors such as age, invasion depth, number of harvested lymph nodes, lymph node metastasis, ratio of metastatic lymph node, lymphatic vessels involvement were analyzed using the Cox regression model.</p><p><b>RESULTS</b>Number of lymph node dissected, lymph node metastasis, ratio of metastatic lymph node and lymphatic vessels involvement were significantly affected by groups of 15 lymph node dissected in G3 AGC patients (P<0.05). Invasion depth, number of lymph node dissected, lymph node metastasis, ratio of metastatic lymph node and lymphatic vessels involvement were significantly independent predictors of survival in G3 AGC patients (all P<0.05). Patients with at least 20 lymph nodes had a better survival rate than those with less than 20(P<0.01).</p><p><b>CONCLUSIONS</b>Invasion depth, number of harvested lymph nodes, lymph node metastasis, ratio of metastatic lymph node and lymphatic vessels involvement are important factors influencing the prognosis of G3 AGC. At least 20 lymph nodes should be recommended to ensure the quality of lymphadenectomy for gastric cancer.</p>
Subject(s)
Humans , Gastrectomy , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Prognosis , Retrospective Studies , Risk Factors , Stomach Neoplasms , Pathology , General Surgery , Survival RateABSTRACT
Objective This study investigates the epithelial-mesenchymal transition effects exerted on human liver cancer cells HepG2 by THP-1 derived macrophages.The roles of tumor-associated macrophages (TAMs) on liver cancer progression and its mechanisms were explored.Methods HepG2 cells were cultured with THP-1 derived macrophages to mimic the microenvironment of liver cancer.After the culture treatment,morphological changes of the liver cancer cells were observed.Decreased E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT),and the Ecadherin protein variations in the HepG2 cells were detected by immunofluorescence (IF) and Westernblot.FlowCytomix was carried out to screen the cytokines in the supernanants of THP-1 cells and THP-1 derived macrophages.Results After culture with macrophages,HepG2 cells revealed a morphological change.These cells lacked epithelial morphology and became a spindle-like mesenchymal cell phenotype.Additionally,the E-cadherin protein expression was reduced dramatically as measured by IF and Western-blot.IL-8 and IL-1β expression in the supernatants were increased 40 and 20 times,respectively,after THP-1 cells were activated to macrophages (P＜0.01).TNF-α expression was increased 8 times (P =0.056).Conclusion THP-1 derived macrophages could induce EMT effects on HepG2 cells,which may relate to the increased secretion of IL-1β,IL-8 and TNF-α.
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Objective To investigate the relationship between various clinicopatholngic factors and prognosis of early gastric cancer. Methods The clinical data of 459 patients with early gastric cancer who had undergone gastrectomy combined with extended (D2) lymphadenectomy at Zhongshan Hospital from January 2002 to October 2007 were retrospectively analyzed. Survival was calculated using the Kaplan-Meier method, and clinicopathologic factors such as age, sex, tumor size, gross morphology, tumor differentiation, depth of invasion, lymphatic vessels involvement and lymph node metastasis were analyzed using the Cox regression model. Univariate analysis was done by Log-rank test. Results Univariate analysis demonstrated that tumor size and differentiation, depth of invasion, lymphatic vessels involvement and lymph node metastasis significantly affected survival in patients with early gastric cancer (χ~2 = 8.476, 6.210, 4.014, 14. 197, 55.027, P < 0.05). The status of lymph node metastasis was an independent predictor of survival in patients with early gastric cancer, and the more metastatic lymph nodes detected, the greater the influence on the prognosis. Conclusions Lymph node metastasis is the most important factor influencing the prognosis of early gastric cancer. Appropriate lymph node dissection is necessary, especially for patients with risk factors associated with lymph node metastasis.
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Objective To investigate the expression of muhidrug resistance-related protein 1 (MRP1),lung resistance-related protein(LfuP)and glutathione S-transferase-π(GST-π)in carcinoma of the gallbladder and cholangiocarcinoma. Methoils MRP1,LRP,GST-πwere measured in experimental group(18 cases of carcinoma of the gallbladder,36 CSSeS Of cholangiocarcinoma)and control group(13cases of cholecystitis and cholangeitis)by immunohistochemistry.Statistical analysis used chi-square test and spearman test. Results The positive rate of MRP1,LRP,GST-π in carcinoma of the gallbladder and eholangiocarcinoma were 72%(13/18),78%(14/18),61%(11/18)and 86%(31/36),75%(27/36),69%(25/36),respectively,significantly higher than those of 23%(3/13),23%(3/13),23%(3/13)(X2=4.5,P＜0.05)in control group.The expression of LRP[93%(13/14)]in pafients＞60 years old was significantly higher than 64%(14/22)in patients younger than 60 yrs old(x2=3.9,P ＜0.05).In addition,their expression was not related to gender,age,staging,tumor differentiation and lymph node metastasis(P＞0.05).The expression of MRP1 was related with tllose Of GST-π,Spearman correlation coefficient=0.569(P＜0.05).Conclusions MRP1,LRP,GsT-π were over expressed in various degrees in carcinoma Of the gallbladder and cholangiocarcinoma witllout chemotherapy.and related to the primary muhidrug resistance Of cholangiocarcinoma and carcinoma of the gallbladder.
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Background and purpose:Arsenic trioxide,verified as a breakthrough in the management of acute promyelocytic leukemia,has been applied to a variety of solid tumors.Gall bladder carcinoma,lacking specific clinical manifestations,is usually diagnosed at advanced stages of the diseases and few cases can be resected by operation.Chemotherapy has not shown significant activity in gall bladder carcinoma.This study was to investigate the biological effect of As2O3 on the growth of human gall bladder carcinoma cell and its mechanism.Methods:GBC cells were cultured with different concentrations of As2O3,the proliferative activity of the cells was detected by MTT methods,and the cell cycle status was carried out by flow cytometry(FCM).Western blot and RT-PCR were performed to analyse the expression of cyclin D1,D2,D3,CDK4 and CDK6.GBC cells were transient transfected with cyclin D1 promoter construct pGL3 and then treated by different doses of As2O3.The luciferase activity was measured.Results:The treatment of As2O3 in gall bladder carcinoma cells could inhibit the growth of cells in a time and dose dependent manner,make cells arrest in G1 phase and down regulate the expression of cyclin D1.In addition,the activity of cyclin D1 promoter was down-regulated by As2O3 in a dose-dependent manner and decreased about 70 percent when treated with 4 ?mol/L As2O3.Conclusions:As2O3 can significantly inhibit the growth of human gall bladder carcinoma cells as well as down-regulate the expression of cyclin D1 in vitro.