The Study On The Relationship Between Force Dual-energy CT And Enhanced CT Features And Pathologic Micro-structure In Renal Cell Carcinoma

Background:Renal cell carcinoma(RCC)is one of the most common urological malignancy,which include clear cell renal carcinoma(ccRCC),papillary renal carcinoma(pRCC),Chromophobe renal cell carcinoma(cRCC)and so on.And hypervascular ccRCC has the highest incidence.On enhanced computed tomography(CT)scans,the appearance of ccRCC has been described as rapid wash-in and wash-out.Its enhancement varies greatly and some can manifest as hypovascular on enhanced CT imaging,which is similar to papillary RCC(pRCC).However,the enhancement mechanism of RCC remains unclear.The treatment of RCC includes radical nephrectomy(RN),nephron-sparing surgery(NSS),tumor enucleation,and some newly ways,such as minimally invasive ablation and target therapy developed in recent years.Conservative surgery,minimally invasive ablation or active surveillance(AS)should be conducted to RCC with low pathologic grade.The selection of treatment mainly depends on tumor malignant degree and particular situation of the patient.Tumor malignant degree mainly depends on microstructure of tumor cells and surrounding stroma,which will require assessment before surgery or treatment.The carcinoma is an angiogenesis dependent disease.Angiogenesis plays an important role in tumor invasion and metastasis.The gold standard for the measurement of tumor angiogenesis currently is microvessel density(MVD),whose relationship with tumor growth,metastasis,and prognosis has been confirmed.Both MVD and vascular architecture can affect the biological behaviour of the tumor.It has been reported that anti-tumor angiogenesis drugs mainly target intratumoral immature vessels instead of mature ones.The maturity of vessels reflects in the morphology of the microvessels,especially vessels with lumen.Therefore,a comprehensive assessment on tumor angiogenesis requires the combination of MVD and other vascular architecture parameters.The microvascular architecture of liver has been studied.However,there is no report of microvascular architecture in RCC.MVD has several substantial limitations.For example,it is a kind of invasive,vitro and non-functional measurement and requires the precision of tissue preparation.Hence it may not be an ideal indicator for evaluating tumor angiogenesis.The pathologic evaluation before therapies is needed.Fuhrman grade is the most widely used pathologic grade system and is the important indicator of malignancy degree for RCC.Preoperative noninvasive prediction for ccRCC pathological Fuhrman grade is very necessary and significant to make the therapy and evaluate prognosis.Evaluating Fuhrman grade in imaging view is a hotspot of the research,and the research findings confirmed the value of imaging tests,but authoritative and widely accepted conclusion is not yet formed.As a simple,noninvasive and widely-used imaging modality,enhanced CT scan is reliable in RCC examination,which can provide an effective means of diagnosis and evaluating prognosis of RCC.In order to correct errors from contrast agent load,relative CT enhancement value was used.Recent years,with the rapid development of spectral CT,CT imaging has become multiple parameters from single parameter(CT value),and can reflect the microstructure characteristics of the pathological changes.Force Dual source dual energy CT is one of the most advanced spectrum CT,with the technique of pure spectrum,the dual energy CT imaging realize precise separation of the material composition.The iodine-based image and monoenergetic image can be automatically generated,parameters of ROI such as iodine concentration,VNC value,iodine overlay value and so on can be obtained at the same time.Therefore,this can accurately evaluate histopathology changes of tumor.Many scholars apply it to the diagnosis of renal cancer and obtained certain effect.But there's very little study on tumor grade.This Study is divided into two parts.Part OneCorrelation Of Parameters On Enhanced CT With Microvascular Architecture Parameters In Renal Cell Carcinoma Aims:To study the correlation between parameters on enhanced CT and microvascular architecture parameters in renal carcinoma(RCC).To investigate enhancement mechanism of RCC on enhanced CT.To evaluate of enhanced CT in the pathologic micro-structure in RCC.Methods:A retrospective review was conducted on the clinical,radiological and pathological records of 51 patients(44 cases of ccRCC,7cases of PRCC)who underwent radical or partial nephrectomy and received a histologic diagnosis of RCC.Surgical specimens of 51 patients were stained for HE and CD34 immunohistochemical staining,and then analyzed for micro-vascular architecture using Image Plus 6.0 image processing software.According to fuhrman grade,the 44 cases of ccRCC were classified into high grade(Fuhrman grade 1 and 2)and low grade(Fuhrman grade 3 and 4).The CT value of tumor(VTA),the CT value ratio of tumor to aorta(RTA),tumor to cortex(RTC)and tumor to medulla(RTM)during arterial phase were measured.The CT value difference of tumor and cortex(DTC),tumor and medulla(DTM)and tumor in arterial and venous phases(DAV)were also calculated.Pearson's correlation of parameters on enhanced CT and micro-vascular architecture parameters was investigated.44 cases of ccRCC were divided into different groups according to cystic changes and pseudo-capsule.The differences between every two groups were compared using t-test.44 cases of ccRCC were divided into three groups according to RTC.The difference among the 3 groups was compared using one-way ANOVA test(Student-Newman-Keuls,SNK test).By means of the t-test,the difference between hypovascular ccRCC(RTC?0.6)and PRCC has been compared.Results:MVD2 was significantly higher in the cyst-present group than cyst-absent group(t=2.10,P=0.043).There was no significant difference with regard to MVD1,Sl,Dl,L1,S2,D2 and L2 between the cyst-present and cyst-absent groups(P>0.05).The capsule-present group showed a significant higher value of S1,MVD2,S2,D2 and L2 than the capsule-absent group(P<0.05).As to other parameters no significant difference was found(P>0.05).MVD1 was positively correlated with VTA,RTC,DTC,and DTM(r=0.47,0.36,0.33,0.44,respectively;P<0.05 for all),but was not correlated with RTA or RTM(r=0.30 and 0.34,respectively;P>0.05 for both;).Microvascular parameters(MVD1,D1,L1)of high grade group were greater than the low group,high group parameter(S2)was less than the low group,and the difference was statistically significant.Other microvascular parameters(S1,MVD2,D2,L2)between high and low grade group were of no statistical significance.Significant difference was noted in MVD1 in the group of RTC<0.6 with the other groups(F=7.98,p<0.01),while MVD1 did not differ significantly from the groups of 0.6<RTC<1 and RTC?1.MVD2 was significantly different among the groups of RTC<0.6,0.6<RTC<1 and RTC?1(F=18.62,p<0.001).The vascular parameters were generally higher in hypovascular ccRCCs than pRCCs with significant difference in MVD1 and S1 and no difference in D1,L1,MVD2,S2,D2 and L2.Conclusions:The parameters on enhanced CT is associated with vascular architecture parameters including MVD,area and perimeter.Microvascular parameters of RCC have been linked to nuclear grade.Quantitative and semi-quantitative parameters of RCC on spiral enhanced CT imaging can shed some light on the tumor vasculature and function as the indicators of the biological behaviour of RCC.The limitation is that the present study concentrated on ccRCC and pRCC and did not investigate the correlations in other subtypes.Further studies on the correlations between microvascular architecture parameters and parameters on enhanced CT in other subtypes are warranted.Part TwoThe Value Of Force Dual-Energy CT And Enhanced CT Features In Predicting Of Pathologic Grading In CcRCCAims:To investigate the correlation between features of Force dual-energy CT and enhanced CT and Fuhrman grade,to assess the value of dual-energy CT and enhanced CT in predicting of pathologic grading in ccRCC.Expect to assist with clinical treatment and prognosis.Methods:68 cases of ccRCC underwent contrast-enhanced CT scanning while 35 cases Force dual-energy CT,which were pathologically confirmed ccRCC were included in the present study.The clinical,radiological and pathological records were collected.Surgical specimens of those patients were stained for HE and classified into high grade(Fuhrman gradel and 2)and low grade(Fuhrman grade3 and4).In the 68 cases,The feature of enhanced CT was described,the CT value of tumor(VTA),the CT value ratio of tumor to aorta(RTA),tumor to cortex(RTC)and tumor to medulla(RTM)during arterial phase were measured,The CT value difference of tumor and cortex(DTC),tumor and medulla(DTM)were calculated along with that of tumor in arterial and venous phases(DAV).In the 35 patients,the dual-energy parameters including VNC value(VNCV),iodine overlay value(IOV),mixed energy value(MEV),iodine concentration(IC)and normalized iodine concentration based on aorta,cortex,medulla(NICA,NICC,NICM),were measured,and the CT value of tumor(VTA)in Mono-energetic 40-160kev image were also measured.The slope of spectrum curve(K)were calculated.The differences between high grade and low grade were compared using t-test.68 cases were divided into two groups,respectively,according to sex,age,side(right and left kidney),tumor size(>7cm and ? 7cm,>4cm and ? 4cm),tumor shape(quasi-circular and irregular),cystic changes(cystic-absent and cystic-present)and pseudo-capsule(pseudo capsule-absent and pseudo capsule-present).The differences of high and low grads ratio in every two groups were compared using ? 2 test(Chi-square test).Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and specificity.Results:The high grade ratios of>7cm and>4cm groups were greater than ? 7cm and ? 4cm groups,but the difference was significant only between>7cm and ? 7cm groups.The high fuhrman grade ratios of the irregular and oval groups were 30%and 10.53%respectively,and the difference was significant.The cystic-present group showed a significant higher furman grade than cystic-absent group(P=0.039).The high fuhrman grade ratios of pseudo capsule-absent group and pseudo capsule-present group were 21.74%,13.64%respectively,pseudo capsule-absent group tend to have higher fuhrman grade,whereas the difference was not significant.There were no difference between male and female,= 60yr and<60yr,right and left kidney groups(p>0.05).The differences of VTA,RTC and DTC were significant(P<0.05),whereas no significant difference was found in RTM,DTM and DAV(P>0.05).IOV,MEV,IC,NICA,NICC and K of high fuhrman grade group were less than that of low group,and the differences were significant,The VTA in Mono-energetic 40-100kev image were difference between the two groups(P<0.05).The AUC of IOV,MEV,IC in arterial phase and IOV,IC in venous phase were 0.81,0.78,0.80,0.80,0.81,respectively,and that of NICA,NICC,K were 0.76,0.80,0.79,The sensitivity and specificity of IOV in arterial phase to diagnosis high fuhrman grade is 0.86 and 0.75,with the threshold of 57.3.when the threshold of NICC is 0.66,the sensitivity and specificity is 0.76 and 0.88 respectively.The AUC of RTC is 0.74,the largest one of the enhanced CT parameters,the sensitivity and specificity is 0.80 and 0.69,with the threshold of 7.72.Conclusions:Quantitative and semi-quantitative parameters of ccRCC on Force dual energy CT and enhanced CT imaging can reflect the tumor tissue microstructure,and shed some light on tumor grading as the indicators of the biological behaviour of ccRCC.This may provide imaging basis for clinical treatment and prognosis assessment.Parameters of Force dual energy CT may be of better value than enhancement CT in the diagnosis of RCC.The limitation is that the number of cases from Force dual energy CT is inadequate,and did not analyze the other types of kidney cancer.Further study is still needed to do after supplementing materials.CONCLUSIONSThe parameters on enhanced CT is associated with tumor stroma vascular architecture parameters including MVD,area and perimeter.Micro-vascular parameters of RCC have been linked to nuclear grade.Quantitative and semi-quantitative parameters of ccRCC on Force dual energy CT and enhanced CT imaging are associated with nuclear grade of tumour cells.Parameters on Force dual energy CT have a larger AUC in diagnosing nuclear grade than common enhanced CT.Therefore,parameters on Force dual energy CT have a higher tissue specificity and accuracy.Parameters of Force dual energy CT may be of better value than enhanced CT in the diagnosis of RCC.In short,parameters on Force dual energy CT and enhanced CT imaging can reflect the tumor tissue micro-structure,and shed some light on tumor grading as the indicators of the biological behaviour of ccRCC.This may provide imaging basis for clinical treatment and prognosis assessment.The limitation is that the number of cases from Force dual energy CT is inadequate,and did not analyze the other types of kidney cancer.Further study is still needed to do after supplementing materials.