1.Research on DNA microarray chip method for detecting drug resistance of Mycobacterium tuberculosis
Yaqin LIU ; Zhenbin YANG ; Dongxia FENG ; Haiying WANG
International Journal of Laboratory Medicine 2014;(14):1910-1913
Objective To evaluate the feasibility of the DNA microarray method used in detecting the drug resistance of Myco-bacterium tuberculosis by comparing the traditional proportion method and the DNA microarray method for detecting the drug re-sistance of Mycobacterium tuberculosis.Methods 54 strains of Mycobacterium tuberculosis isolated from clinical specimens in our hospital from January 2012 to March 2013 were randomly extracted and their resistance to isonicotinic acid hydrazide (INH)and rifampicin(RFP)was detected by the DNA microarray method and the proportion method.The detection results were performed the comparative analysis.Results With the proportion method as the golden standard,the coincidence rates of the DNA microarray method for detecting the Mycobacterium tuberculosis resistance to INH and RFP were 75% and 91.0% respectively.Conclusion The DNA microarray technique is suitable for the rapid screening of clinical first-line drug resistant Mycobacterium tuberculosis.
2.Expression of multidrug resistance-related proteins MRP1/LRP/GST-π in carcinoma of the gallbladder and cholangiocarcinoma
Yunjie JIN ; Houbao LIU ; Zhenbin SHEN ; Saixiong TONG ; Bingsheng WANG
Chinese Journal of General Surgery 2008;23(5):356-359
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.
3.Correlations between serum macrophage migration inhibitory factor and active rheumatoid arthritis
Zhixia YANG ; Zhenbin LI ; Zhongcheng SUN ; Yanqing LIU
Chinese Journal of Tissue Engineering Research 2008;12(37):7390-7393
BACKGROUND: Macrophage migration inhibitory factor (MIF) is mainly concerned with macrophage mobilizing function, as the upper stream cytokine of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), which may have critical effect in the process of the onset of rheumatoid arthritis. OBJECTIVE: To explore the correlations between the change of serum MIF and the activity of rheumatoid arthritis (RA) disease.DESIGN, TIME AND SETTING: Non-randomized control and case study, which was carried out in the Bethune International Peace Hospital of Chinese PLA from September in 2005 to October in 2006.PARTICIPANTS: Sixty RA patients were included in this study, and other thirty healthy subjects were selected as the control group. There were significant differences in age and sex between the two groups. METHODS: Clinical data of sixty RA patients were selected by carrying out retrospective analysis, then on the basis of disease activity score (DAS) accumulated points, they were divided into active and inactive group respectively, who were contrasted with 30 health adults. MAIN OUTCOME MEASURES: ① Morning stiffness (in minutes), joint tenderness index, arthrocele index, semi-quantity rheumatoid factor (RF), C-reactive protein concentration (CRP), erythrocyte sedimentation rate (ESR), and platelet count (PLT) were recorded; ② To compare the level of serum MIF, IL-1β and TNF-α among active group, inactive group, and control group; ③ The correlation analysis was carried out among the level of serum MIF, inflammatory index and clinical observation index.RESULTS: There was significantly increased in serum MIF of patients in the active group compared to of inactive and normal groups (P < 0.05), but there were no significantly differences between inactive and control groups (P > 0.05). There were significant correlations between the serum MIF concentration and active inflammatory index of RA disease, blood sedimentationrate (ESR), C-reactive protein (CRP), platelet counting (PLT), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), swell joint index (SJI) and tenderness joint, but no significant difference was observed between the serum MIF, age, disease course, morning stiffness and rheumatoid factor (RF).CONCLUSION: The serum MIF concentration is significantly increased in patients with RA, and it may be a useful parameter for monitoring disease activity of RA.
4.Effects of Bushen Huoxue Fang on estrogen receptor alpha mRNA in pituitary body of ovariectomized rats with collagen-induced arthritis
Lifen GENG ; Kunshen LIU ; Hua MA ; Baoquan JIAO ; Zhenbin LI
Chinese Journal of Tissue Engineering Research 2009;13(28):5539-5543
BACKGROUND: Pharmacological researches demonstrate that Chinese crude drugs of invigorating the kidney contain flavonoids such as prepared rhizome of rehmannia and kudzuvine root, they possess phytoestrogenic effect, among them, isoflavone acts as a regulator of estrogen receptor.OBJECTIVE: To approach the effects of self-planned Bushen Huoxue Fang (BSHXF) on the serum estradiol and estrogen receptor α mRNA expression in pituitary gland in rats with collagen-induced arthritis. DESIGN, TIME AND SETTING: Randomized grouping controlled animal experiment was performed in the central laboratory of Bethune Intemational Peace Hospital of Chinese PLA between May 2006 and May 2008. MATERIALS: Sixty female and healthy Wistar rats were randomly divided into sham operated group (n=10) and operation group (n=50). Operation group was reproduced collagen-induced arthritis model at 2 weeks following ovariectomy. The rats of arthritic index ≥ 5 were assigned into model group, BSHXF group, methotrexate (MTX) group, and MTX + BSHXF group, each group included 10 rats. The Chinese crude drugs were bought from LERENTANG drugstore in Shijiazhuang, including rhizoma drynariae, safflower, prepared rhizome of rehmannia, Herba Epimedii, danshen root, kudzuvine root and so on. After routine decoction, centrifugalization, rogue and condensing 1.3 kg/L decoction, the solution was sealed up, divided pack and reserved at 4℃.METHODS: Sham operated group and model group were intragastrically administered with normal saline 2 mL per day; BSHXF group with BSHXF decoction 2 mL per day; MTX group with MTX 2.6 mg/kg (2 mL) once a week, and normal saline 2 mL per day at other time points; MTX + BSHXF group with MTX 2.6 mg/kg (2 mL) once a week and BSHXF juice 2 mL per day. Each group was given 6 weeks.MAIN OUTCOME MEASURES: After blooding by abdominalis aorta, magnetic-split enzyme linked immunosorbent assay was applied to detect the level of serum estradiol. Reverse transcription-polymerase chain reaction detected the expression of estrogen receptor a mRNA in rat pituitary gland.RESULTS: Compared with model group, the expression of estrogen receptor a mRNA in pituitary gland increased in the MTX group, but there was not statistically significant. BSHXF + MTX group showed a significantly increased expression (P < 0.01). The expression of estrogen receptor α mRNA in BSHXF group was higher than MTX group, but lower than BSHXF + MTX group (P < 0.05). No significant difference existed between BSHXF group, BSHXF + MTX group and sham operation group. Compared with sham operation group, there were statistically significant decrease of estradiol in the model group. Compared with model group, the estradiol levels were shown to increase in three treatment groups. Among them, MTX group had slightly slower level with no significant difference (P > 0.05), while BSHXF + MTX group had the most obvious increase, which was close to normal level (P < 0.01). There was a significantly positive correlation between estradiol and the expression of estrogen receptor o mRNA (r=0.483, P < 0.05).CONCLUSION: Serf-planned BSHXF possessing oestrogenic hormonelike role can elevate the level of serum estradiol and upregulate the expression of estrogen receptor a mRNA in pituitary gland.
5.Percutaneous vertebroplasty with high-viscosity bone cement injection for repair of osteoporotic vertebral compression fractures in the elderly:evaluation of vertebral height recovery
Guangxu NIU ; Zhenfeng LIU ; Zhenbin WANG ; Wenfei GU ; Laiyong TU ; Jiang ZHAO
Chinese Journal of Tissue Engineering Research 2015;(38):6126-6132
BACKGROUND:Whether there is a necessary connection or internal patterns between the amount of bone cement-recovery of vertebral height-clinical efficacy has no evidence-based medicine findings in the treatment of osteoporotic vertebral compression fractures using percutaneous vertebroplasty with high-viscosity bone cement injection.
OBJECTIVE: To observe the change of vertebral height in the elderly with osteoporotic vertebral compression fractures after percutaneous vertebroplasty with high-viscosity bone cement injection.
METHODS:A total of 110 elderly patients with osteoporotic vertebral compression fractures (139 vertebrae) were admitted at the Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region from January 2011 to December 2012. Al the patients received percutaneous vertebroplasty by the same group of surgeons. Bone cement at drawing stage was injected into the fractured vertebra. During the 12-month folow-up, visual analogue scale, Barthel index and vertebral height restoration were observed as evaluation indexes.
RESULTS AND CONCLUSION:The surgical treatment was done successfuly in the 110 patients (139 vertebrae). The amount of bone cement per vertebra was 3-6 mL, with a mean of 3.5 mL. At 12 months after surgery, the visual analog scale scores were decreased from 7.9 to 1.8, Barthel index was increased from 40.25 to 82.21, both of which were improved significantly (P < 0.05). After surgery, the vertebral heights at the anterior and middle parts were increased by (81.25±9.26)% and (78.22±10.65)%, respectively, and there was significant differences before ant at 24 hours, 3 months and 12 months after surgery (P < 0.05). During the folow-up, there were five vertebrae with bone cement leakage, but no clinical symptoms occurred, and no nerve injury or pulmonary embolism happened. These findings indicate that percutaneous vertebroplasty with high-viscosity bone cement injection can effectively relieve pain, restore the vertebral height, reduce the incidence of complications and shorten the recovery time in patients with osteoporotic vertebral compression fractures.
6.Analysis of TRRAP as a Potential Molecular Marker and Therapeutic Target for Breast Cancer.
Ji WANG ; Ming SHAN ; Tong LIU ; Qingyu SHI ; Zhenbin ZHONG ; Wei WEI ; Da PANG
Journal of Breast Cancer 2016;19(1):61-67
PURPOSE: This study was designed to assess the protein levels of transformation/transcription domain-associated protein (TRRAP) in invasive ductal breast carcinomas, and investigated the association between TRRAP and the clinicopathological features of breast cancer. METHODS: We examined TRRAP protein expression in 470 breast cancer tissues and normal breast tissues by tissue microarray to study the correlation between TRRAP expression and clinicopathological features. This was analyzed using the chi-square test. Kaplan-Meier survival curves and log-rank tests were applied to analyze the survival status. Cox regression was applied for multivariate analysis of prognosis. RESULTS: The data demonstrated that expression of TRRAP was significantly lower in breast carcinomas (36.6%) than in corresponding normal breast tissues (50.8%). In addition, TRRAP protein levels negatively correlated with tumor size, and indicated poor differentiation, increased nodal involvement, and low p53-positive rates. Analysis of survival revealed that lower TRRAP expression correlated with shorter survival time. Univariate analyses identified TRRAP and progesterone receptor as independent protective factors for breast cancer prognosis. However, Ki-67, tumor size, and nodal involvement appeared to be independent risk factors. CONCLUSION: The findings indicate a significant correlation between TRRAP protein levels and adverse prognosis in breast cancer. Therefore, TRRAP could be a prognostic biomarker for breast cancer. In addition, TRRAP is also a predictive biomarker of breast cancer treatment.
Biomarkers
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Breast Neoplasms*
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Breast*
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Kaplan-Meier Estimate
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Multivariate Analysis
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Prognosis
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Receptors, Progesterone
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Risk Factors
7.Prognostic factors of radical gastrectomy for stage Ⅲ gastric cancer and predictive value of metastatic lymph node ratio for prognosis: a report of 995 cases
Rongjian ZHOU ; Heng ZHANG ; Ping SHU ; Hongshan WANG ; Zhenbin SHEN ; Fenglin LIU ; Jing QIN
Chinese Journal of Digestive Surgery 2019;18(3):250-258
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.
8.The expression and clinical significance of S100A9 protein in gastric cancer of intestinal type
Rongjian ZHOU ; Heng ZHANG ; Ping SHU ; Hongshan WANG ; Zhenbin SHEN ; Fenglin LIU ; Jing QIN
Chinese Journal of General Surgery 2019;34(1):53-57
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.
9.Impact of the number of lymph nodes dissected on the prognosis of G3 advanced gastric cancer.
Jiaqian LING ; Cong WANG ; Xuefei WANG ; Zhenbin SHEN ; Weidong CHEN ; Jing QIN ; Xinyu QIN ; Kuntang SHEN ; Yihong SUN ; Fenglin LIU
Chinese Journal of Gastrointestinal Surgery 2014;17(7):667-671
OBJECTIVETo 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.
METHODSClinical 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.
RESULTSNumber 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).
CONCLUSIONSInvasion 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.
Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate
10.Establishment of risk evaluation model of peritoneal metastasis in gastric cancer and its predictive value.
Junjie ZHAO ; Rongjian ZHOU ; Qi ZHANG ; Ping SHU ; Haojie LI ; Xuefei WANG ; Zhenbin SHEN ; Fenglin LIU ; Weidong CHEN ; Jing QIN ; Yihong SUN
Chinese Journal of Gastrointestinal Surgery 2017;20(1):47-52
OBJECTIVETo establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance.
METHODSClinical 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.
RESULTSAmong 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).
CONCLUSIONThe 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.
Antigens, Tumor-Associated, Carbohydrate ; blood ; Area Under Curve ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Female ; Humans ; Leukocyte Count ; statistics & numerical data ; Logistic Models ; Lymphocytes ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Neutrophils ; pathology ; Nomograms ; Peritoneal Neoplasms ; secondary ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Assessment ; methods ; Risk Factors ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; classification ; diagnosis ; pathology