ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the features of clinicopathology and prognosis in young gastric cancer patients.</p><p><b>METHODS</b>Clinicopathological data of 90 young gastric cancer patients (≤40 years old) who received radical gastrectomy in the Department of General Surgery of Zhongshan Hospital, Fudan University from January 2013 to December 2014 were retrospectively analyzed. Survival data were obtained by follow-up and the last follow-up time was October 2016. Log-rank test and Cox regression model were used to analyze the risk factors of prognosis and these factors included gender, age, tumor size, degree of differentiation, histological type, Lauren pattern, T stage, N stage, vessel carcinoma embolus, clinical symptom, anemic condition, CA19-9 level, et al.</p><p><b>RESULTS</b>The median age of 90 patients was 35 years old, of whom, 20(22.2%) patients were ≤30 years old and 70(77.8%) patients were between 31 and 40 years old. There were 70(77.8%) female patients, 38(42.2%) patients with anemia, 11(12.8%) patients with elevated CA19-9 level and 9(10.0%) patients with family history of gastrointestinal tumors. The mean time of all the patients from presence of symptom to consultation was 8.2 months. Postoperative pathology revealed 65(72.2%) patients with poorly differentiated adenocarcinoma, 6(6.7%) patients with mucinous adenocarcinoma, 9(10%) patients with signet-ring cell carcinoma, and 10(11.1%) patients with papillary-canalicular adencarcinoma. Sixty-nine (76.7%) patients were diagnosed as advanced gastric cancer and 67(74.4%) patients were involved with lymphatic metastasis when they visited our hospital. Univariate analysis showed that gender (P=0.021), tumor size (P=0.001), depth of tumor infiltration (P=0.016), lymphatic metastasis (P=0.000), vessel carcinoma embolus (P=0.001), elevated CA19-9 level (P=0.001), and anemia (0.024) were statistically related with postoperative survival. Multivariate analysis showed that lymphatic metastasis was an independent risk factor of the poor prognosis of young patients (HR:2.774, 95%CI:1.435 to 5.364, P=0.002).</p><p><b>CONCLUSIONS</b>The majority of young gastric cancer cases are female with poorly differentiated adenocarcinoma. Most patients are diagnosed as advanced gastric cancer with lymphatic metastasis when they visit hospital at the first time. The lymphatic metastasis is an independent risk factor of prognosis in young gastric cancer patients.</p>
ABSTRACT
<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>