The Relationship Of Spectral Computed Tomography Imaging Parameters And Angiogenesis And Their Prognostic Value In Gastric Adenocarcinoma

Part I:Influence of region of interest to spectral CT iodine basedimaging in advanced gastric cancerObjectiveTo determine the measurement consistency of spectral CT parameters in advanced gastric cancer based on different region of interest(ROIs)and their relationship with tumor micro-vessel density(MVD).Material and methodsThirty patients with histologically proven advanced gastric cancer were examined using spectral-dual-phase-abdominal CT.Two observers independently acquired iodine concentration(IC),normalized IC(nIC),and CT value at workstation using three different ROI protocols:10mm2 circular ROI near tumor border where enhanced obviously,30mm2 near the tumor center and the freehand outline ROI.Data of the two observers were calculated for the interclass correlation coefficient(ICC)and Bland-Altman plot.Differences of each group of ROI data were compared using paired t test.And the relationship of each parameter to tumor MVD was analyzed by Pearson correlation.Results1.The IC,nIC and CT values obtained by ROI-outline had the highest inter-observer ICC than that of smaller circular ROI,and the differences were more centered.2.Significant differences were observed between the means of the all parameters with ROI-10mm2,ROI-30mm2 and ROI-outline protocols(P<0.001).3.The nIC in venous phase(VP)had good correlations with intra-tumoral MVD especially for the ROI-outline(r = 0.67,P<0.001).ConclusionDifferent selection of tumor ROI has significant impact on the final CT parameters.Analysis using by outlined ROI protocol improves inter-observer consistency and provide more stable data.Part Ⅱ:The relationship of spectral computed tomography imaging parameters and angiogenesis in advanced gastric adenocarcinoma——a pilot studyObjectiveTo investigate the role of iodine concentration(IC)and slope of spectral curve generated from spectral computed tomography(CT)in the evaluation of angiogenesis and other clinical pathological features with advanced gastric adenocarcinoma(AGC).Material and methodsForty-two AGC patients who underwent preoperative abdominal spectral CT were prospectively analyzed.First of all,the primary lesion was measured by freehand outline region of interest(ROI),the nornal gastric wall and the abdominal aorta at the same level was measured by round ROI in the axial CT images.The iodine concentrations in the arterial and venous phase(IC-AP,IC-VP)of all the ROIs were automatically acquired in the iodine images.The normalized iodine concentration(nIC)was calculated as the ratio of the target IC to the abdominal aorta IC.The attenuation value of the lesion-ROI on 40 keV and 70 keV monochromatic images was measured respectively and the duel-phasic slope were calculated(Slope-AP,Slope-VP).After that,the total RNA was extracted from the primary cancer and normal gastric tissue and then reversed to cDNA.Fluorescence reverse transcription real-time polymerase chain reaction(RT-PCR)detection was used to verify the relative expression of vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor C(VEGFC).Paraffin blocks comprising gastric cancer were sectioned and immunohistochemically stained with CD34 and D2-40 antigens respectively.The expressions of micro-vessel density(MVD)and micro-lymphatic vessel density(MLVD)were measured.CT parameters and the expressions of angiogenesis molecules between gastric cancer and normal tissues were compared using t-test or Mann-Whitney U test.The correlation between spectral CT parameters and angiogenesis molecular expressions was performed by spearman correlation.At the same time,clinicopathological TNM staging,lymphovascular invasion(LVI)were also documented.ROC curves were performed to evaluate the diagnostic value of CT parameters in LVI.The area under the curve(AUC)was used as a criterion to evaluate its value,and the best diagnostic threshold was selected to calculate its sensitivity and specificity.Results1.The IC、nIC and the slope values of gastric cancer were higher than those of normal gastric tissue in duel-phasic spectral CT.RT-PCR revealed that the relative RNA expression of VEGFA and VEGFC in cancer tissue was higher than that of normal gastric mucosa.2.VEGFA-RNA expression was moderately and mildly correlated with nIC-VP and Slope-VP,respectively;VEGFC-RNA expression was positively correlated with Slope-VP in gastric cancer.3.When divided MVD and MLVD into categories,the IC and slope values were higher in high MVD group,and the nIC-AP was statistically significant between different MLVD group(P = 0.02).4.There was a moderate positive correlation between nIC-AP and MVD(r =0.41,P = 0.01),nIC-VP and Slope-VP were both well corelated with MVD(r = 0.62,P<0.001,r =0.69,P<0.001,respectively).nIC-AP was negatively correlated with MLVD(r =-0.35,P＝ 0.02).5.IC-AP,IC-VP and nIC-AP were significantly different between the groups with or without LVI(IC-AP,P = 0.02;IC-VP,P = 0.04;nIC-AP,P = 0.02).IC-AP combined with nIC-AP had a better efficacy in diagnosing LVI with the AUC =0.765.6.While there was no significant correlation between spectral CT parameters and serosal invasion,lymph node metastasis and pathological TNM staging of gastric cancer.ConclusionIodine concentration parameters from spectral CT can reflect the angiogenesis status of AGC,which would be a noninvasive tool in evaluating the prognosis in advanced gastric adenocarcinoma patients.Part III:Prognostic value of spectral CT and clinicopathologicalparameters in gastric cancer patients after radical surgeryObjectiveTo analyze the factors that influencing the prognosis of patients with gastric cancer after radical surgery and to explore the value of preoperative spectral CT parameters in the prediction model.Material and methodsAccording to the criteria of inclusion and exclusion,148 patients with gastric cancer were enrolled.The clinical data of gender,age,location,with or without postoperative chemotherapy were documented.Spectral CT with its anatomical features such as Borrmann’s classification,clinical T staging(cT),clinical N staging(cN),and other quantitative parameters such as thickness,iodine concentration(IC-AP,IC-VP)in arterial phase(AP)and venous phase(VP),normalized iodine concentration(nIC-AP,nIC-VP),slope from 40 keV to 70 keV(Slope-AP,Slope-VP)in arterial and venous phase,as well as the pathological indicators such as:differentiation,Lauren classification,pathological T staging(pT),pathological N staging(pN),pathological TNM staging(pTNM),and immunohistochemical VEGF,HER2 expression were all collected and re-examined.The recurrence and death time of all the patients were followed-up.All the indexes and parameters were compared with different endpoint of recurrence in disease free survival(DFS)and of death in overall survival(OS)using x 2 test or contingency table test,independent sample t-test or Mann-Whitney U test.Survival analysis were using Kaplan-Meier method and then log-rank test to find univariate factors.Multivariate Cox regression analysis was performed for the factors that satisfied the test level(a<0.05).Results1.Eleven indicators of gastric cancer such as Borrmannn’s classification,cT staging,thickness,IC-VP,nIC-VP,slope-VP,differentiation,Lauren classification,pT,pN,pTNM staging were related to DFS and OS.2.pTNM staging,Lauren classification,pN staging and Slope-VP of spectral CT were independently influencing the postoperative DFS of gastric cancer patients.3.pTNM staging and Slope-VP were the independent factors affecting the OS rate of postoperative gastric cancer patients.ConclusionPreoperative CT morphological and quantitative parameters combined with postoperative pathological parameters can predict the prognosis of gastric cancer survival.The slope of 40 keV-70 keV in venous phase of spectral CT is expected to be a non-invasive indicator to predict the recurrence and survival for postoperative gastric cancer patients.