| Part ⅠThe correlation of abdominal visceral fat as measured via CT with clear cell renal cell carcinoma T stageBackgroundCcRCC(clear cell renal cell carcinoma,ccRCC)is the most common pathological type of renal cancer,with a high incidence in men than in women.In recent years,there has been evidence that obesity is an independent risk factor for ccRCC.The most commonly used indicators to clinically define obesity are BMI and abdominal circumference,which can only roughly assess the degree of obesity in human body,but cannot accurately reflect the extent and proportion of fat accumulation.Two people with the same BMI and abdominal circumference may have completely different fat accumulation patterns,one may be predominantly subcutaneous fat and the other may be predominantly visceral fat.Studies have found that subcutaneous fat and visceral fat have different functions,and their roles in the development of cancer are not the same or even contradictory.The mechanism of obesity promotion of cancer is complex and may result from a combination of changes in secretory function,biochemical indicators or tumor synergism.Visceral fat can produce a range of inflammatory or pro-tumor factors and is thus more harmful than subcutaneous fat,given this the concept of relative visceral fat is proposed.It is worth noting that relative visceral fat area(relative visceral fat area,rVFA)is an individual standardized fat variable,which greatly reduces the impact of individual differences.Recently,rVFA has been used by more and more scholars in fat-related researches.Some scholars have found that sex hormones can affect the distribution pattern of human adipose tissue,men tend to accumulate more intra-abdominal fat,and women tend to accumulate more subcutaneous fat,and with different and changed hormone levels,the fat accumulation pattern will change.Therefore,fat measurements stratified by gender are important to study the association between obesity and ccRCC.ObjectiveTo investigate the predictive value of gender-specific abdominal visceral fat composition for T staging of ccRCC based on CT(computed tomography,CT)images combined with Image J software measurement.Materials and MethodsThis study retrospectively analyzed 253 patients(including 182 male patients and 71 female patients)with pathologically confirmed ccRCC from January 2014 to January 2020.T1 and T2 patients were defined as low-stage patients,and T3 and T4 patients were defined as high-stage patients(including 178 patients with low T stage and 75 patients with high T stage).The age of the patients was 59.6(±10.8)years,and BMI was 25.5(±3.9)kg/m2.The CT image at the navel level was selected,the image was opened using ImageJ software,and continuous line-like landmarks were manually delineated along the abdominal wall to divide the abdominal fat into VFA(visceral fat area,VFA)and SFA(subcutaneous fat area,SFA).TFA(Total fat area,TFA)and rVFA(relative VFA,rVFA)were then calculated according to the formula:TFA=VFA+SFA;rVFA=VFA/TFA.Clinical characteristics(age,sex,and BMI)were also included in the assessment factors.Continuous variables were tested formally(Kolmogorov-Smirnov test for groups of>50 patients and Shapiro-Wilk test for groups of ≤50 patients)and tested for homogeneity of variance.The following statistical methods were used for comparison:two-sample t-test was used for continuous data that met normal distribution and met homogeneity of variance in the group,Mann-Whitney U test was used for continuous variables that were not normally distributed or did not meet homogeneity of variance;chi-square test was used for categorical variables.The generalized linear model was used to compare the indicators again with age as a covariate;the correlation between each continuous variable and age was assessed with correlation analysis.Logistic regression analysis was used to assess the association of each variable with ccRCC stage under univariate and multivariate conditions.ROC curves were used to analyze the discriminant ability of univariate and multivariate models by gender.ResultsThere was no statistically significant difference in BMI of the patients.In male patients,age was negatively correlated with BMI(r=-0.312,P=0.001)and positively correlated with rVFA(r=0.156,P=0.035);in female patients,age was positively correlated with VFA(r=0.381,P=0.001)and positively correlated with rVFA(r=0.397,P<0.001).After adjusting for age,rVFA was higher in men with high T stage ccRCC than in men with low T stage(50.96 vs 42.03,P<0.001);rVFA was higher in women with high T stage ccRCC than in women with low T stage(42.16 vs 33.21,P<0.001).RVFA was a stable independent predictor of high-T stage ccRCC in both men and women in univariate(men:OR 1.100,95%CIs 1.054-1.153,P<0.001;women:OR 1.131,95%CIs 1.045-1.245,P=0.005)and multivariate(men:OR 1.097,95%CIs 1.050-1.151,P<0.001;women:OR 1.109,95%CIs 1.008-1.239,P=0.045)models,but had better correlative performance in women(AUC:0.737 vs 0.791,respectively).Conclusions1)Preoperative higher relative visceral fat area(rVFA)was associated with high T stage in patients with ccRCC,and the discrimination performance was better in female patients.2)There is no correlation between subcutaneous fat and the T stage of ccRCC patients,suggesting that the risk of tumor stage in patients with peripheral obese is lower than that in patients with central obesity.Part ⅡCT quantification of abdominal fat in overweight/obese patients with associated sex hormones screening and preliminary understanding of sex-differentiated adiposity effects in renal carcinomaBackgroundWith the increasing number of obese people,obesity is becoming an important public health concern all over the world.It is well-known that obesity is closely associated with endocrine and metabolic disorders,and there is increasing evidence that adipose tissue is sex-specific.The rVFA(relative fat area,rVFA)was shown to predict the higher level of Foreman’s grade in women with renal carcinoma,but did not have similar predictive power in men.Studies have shown that women are more vulnerable to excess adipose tissue in obesity than men.Our correlative study also found that adipose tissue had a higher predictive power for ccRCC(clear cell renal cell carcinoma,ccRCC)stage in women than in men.However,the underlying biological mechanism of the phenomenon is not clear.This may be related to the target population selected for the study and individualized differences in hormone levels.Therefore,it is important to screen out sex hormones associated with adipose tissue and quantify changes in the levels of these hormones with fat-related variables to explain the differentiated mechanism of action of fat-renal carcinoma.ObjectiveScreening fat-related sex hormones in overweight/obese patients based on CT quantification of abdominal fat provides possible inspiration to explain sex-differentiated effects of fat in ccRCC patients to provide possible inspiration for explaining the role of fat sex-difference in patients with renal carcinoma.Materials and MethodsAbdominal CT images of 250 female and 114 male overweight or obese(BMI>25 kg/m2)patients were retrospectively collected for analysis and measurement.The patients’ age,height,weight,BMI,waist circumference,hip circumference,waist-to-hip ratio,and serum sex hormone levels were also collected.The image selection and measurement methods are the same as those described in part I.All measurements and calculations were performed by two well-trained radiologists in a blind manner.All variables were first tested for distribution by using normality tests.Correlations between serum sex hormone levels,abdominal fat area-related variables,and clinical characteristics were tested using spearman’s correlation test.Associations between serum sex hormone levels and abdominal fat-related variables were assessed after adjusting for age and BMI.Multiple linear regression analyses of hormone levels and fat-related variables were performed after log-transformation and β-transformation.ResultsThe overall baseline characteristics and the correlation between clinical characteristics of different genders and serum sex hormone levels and abdominal fat area-related variables1)A total of 250 females and 114 males were enrolled in this study.The mean age of the female patients was 32.5(±7.5)years,and the BMI was 38.5(±5.2)kg/m2.The mean age of the male patients was 31.1(±7.4)years,and the BMI was 41.9(±6.1)kg/m2.2)The variables that were negatively correlated with age in female patients were AMH(anti-Samuel tube hormone,AMH),PRL(prolactin,PRL),PROG(progesterone,PROG),TEST(testosterone,TEST),TFA(total fat area,TFA)and SFA(subcutaneous fat areas);the variables positively correlated with age were FSH(follicle-stimulating hormone,FSH),VFA(visceral fat areas,VFA)and rVFA(relative VFA,rVFA).The variables negatively correlated with age in male patients were PRL,E2(estradiol,E2)and SFA;the variables positively correlated with age were FSH,VFA and rVFA.3)The variables negatively correlated with BMI in female patients were PROG and rVFA;variables positively correlated with BMI were TFA,VFA and SFA.In male patients,BMI was negatively correlated with TEST and rVFA,but positively correlated with PRL,E2,TFA,VFA and SFA.Correlations between abdominal fat area-related variables and serum sex hormone levels1)In female patients,VFA was negatively correlated with PROG and E2,but positively correlated with FSH;SFA was positively correlated with PRL;rVFA was positively correlated with FSH,and negatively correlated with PRL,PROG and E2.In male patients,TFA was positively correlated with PRL and E2,but negatively correlated with TEST;VFA was negatively correlated with TEST;SFA was negatively correlated with FSH but positively correlated with PRL and E2;rVFA was positively correlated with FSH but negatively correlated with PRL and E2.2)After adjusting for age and BMI,in female patients,PRL was positively correlated with both TFA and SFA;PROG was negatively correlated with VFA and rVFA;E2 was negatively correlated with both VFA and rVFA and positively correlated with SFA;other than that,correlation between other fat variables and sex hormones disappears.In male patients,E2 was positively correlated with SFA,but negatively correlated with rVFA;TEST was negatively correlated with VFA and rVFA;otherwise,the correlations between other fat variables and sex hormones among men disappeared.3)β-transformation([(2β)-1]x 100)showed that in female patients,TFA increased by 3.14%(95%CIs 0.311 to 6.044,P=0.029)and SFA increased by 4.70%(95%CIs 0.633 to 8.929,P=0.023)when PRL concentrations were doubled;when PROG concentration was doubled,VFA decreased by 2.53%(95%CIs-4.115 to-0.928,P=0.002)and rVFA decreased by 2.64%(95%CIs-4.287 to-0.956,P=0.002);when E2 concentration was doubled,VFA decreased by 3.83%(95%CIs-6.407 to-1.184,P=0.005),rVFA decreased by 4.61%(95%CIs-7.269 to c1.879,P=0.001),and SFA increased by 2.54%(95%CIs 0.090 to 5.055,P=0.042).In male patients,SFA increased by 3.10%(95%CIs 0.507 to 5.766,P=0.019)and rVFA decreased by 3.61%(95%CIs-6.468 to-0.671,P=0.017)when E2 concentrations were doubled;when TEST concentrations were doubled,VFA decreased by 9.87%(95%CIs-18.351 to-0.501,P=0.040)and rVFA decreased by 9.37%(95%CIs-16.884 to-1.174,P=0.026).Conclusions1)E2 was negatively correlated with visceral fat and positively correlated with subcutaneous fat in both women and men,and PROG in females and TEST in males were also negatively correlated with visceral fat,which may have a synergistic effect with the adiposity correlation of E2.2)The negative feedback between PROG in men and TEST in women and visceral fat disappeared,reflecting obvious sex differences which may be related to the lower levels of corresponding sex hormones in different sexes of the organism not being sufficient to produce fat correlation.3)Interaction between visceral fat and sex hormones may jointly influence the mechanism of fat-cancer action and may be one of the mechanisms of action for sex differentiation in fat-renal carcinoma.Part ⅢThe value of abdominal fat variables as measured via CT and haematological indicators of nutrition and inflammation on the prediction of short-term postoperative complications in patients with clear renal cell carcinomaBackgroundRecent studies have shown that the progression of ceRCC is usually related to a series of inflammatory reactions in adipose tissue.Similar to most tumors,the occurrence and development of ccRCC is usually closely related to the changes of patients’ nutritional status.Some scholars have found that obesity can affect the progression of ccRCC.At present,there are various studies on the relationship between adipose tissue and the prognosis of ccRCC.However,the results are not consistent.As we all know,tumor staging not only affects the choice of treatment,but also is closely related to the prognosis of patients.Existing obesity-tumor prognosis correlation studies rarely consider tumor populations with specific stages,which inevitably affects the assessment of the predictive value of adiposity on patient prognosis and may be one of the reasons for the inconsistent findings.Therefore,post-sample stratification studies of different staged populations are necessary to assess the individualized prognostic predictive value of adipose tissue for ccRCC.ObjectiveThe aim of this study was to investigate whether preoperative body fat distribution and nutritional inflammatory status are associated with short-term postoperative complications in patients with different T-stage ccRCC,and to provide preliminary basis for the establishment of preoperative noninvasive prognostic biomarkers for clinical purposes.Materials and methodsThis study retrospectively analyzed 250 patients(176 male patients and 74 female patients)with pathologically confirmed ccRCC between January 2014 and April 2021.Clinical information collected included age,gender,surgical procedure,short-term postoperative complications(within 30 days),T-stage,and preoperative serum biochemical indices.Subsequently,patients were divided into low T-stage(T1 and T2)and high T-stage(T3 and T4)groups.The image selection and measurement methods are the same as those described in part Ⅰ.A one-way logistic regression analysis followed by a two-way stepwise regression analysis was performed to screen patients for significant predictors of short-term postoperative complications.Predictive performance was assessed using the AUC(area under curve,AUC)of the ROC(receiver operating characteristic,ROC)curve.Correlations between fat area-related variables and biochemical indicators were analyzed using spearman and pearson correlation tests.Results1)In the low-T staging group,patients with short-term postoperative complications had lower VFA(visceral fat area,VFA)(110.0 vs 148.1,P<0.001)and rVFA(relative visceral fat area,rVFA)(33.6 vs 47.5,P<0.001)and higher SFA(subcutaneous fat area,SFA)(201.9 vs 171.3,P=0.007)compared to patients without complications.2)In the high T-stage group,there were no statistically significant differences in preoperative abdominal fat-related variables between patients with or without short-term postoperative complications.3)In the one-way logistic regression analysis,gender(OR 6.081,95%CIs 3.049-12.494,P<0.001),VFA(OR 0.979,95%CIs 0.971-0.987,P<0.001),SFA(OR 1.008,95%CIs 1.003-1.012,P=0.001)and rVFA(OR 0.793,95%CIs 0.734-0.845,P<0.001)were significantly associated with short-term postoperative complications in patients in the low T-stage group.In the high T-stage group,only gender(OR 0.105,95%CIs 0.006-0.569,P=0.034)was an independent predictor of short-term postoperative complications in patients,while no variable related to patients’ preoperative abdominal fat was screened as a significant predictor.4)All variables with prognostic value in univariate logistic regression were included in the subsequent two-way stepwise regression.The results of multivariate analysis showed that rVFA(OR 0.809,95%CIs 0.746-0.865,P<0.001)was a predictor of short-term postoperative complications in patients in the low T-stage group,whereas in the high T-stage group,only gender(OR 0.105,95%CIs 0.006-0.569,P=0.034)was an independent predictor.5)In the low-T staging group,HSP(heat shock protein,HSP)90a was positively correlated with TFA(total fat area,TFA)and SFA;neutrophils were positively correlated with VFA and rVFA;lymphocytes were positively correlated with VFA and rVFA.In the high T-stage group,PNI(prognostic nutrition index,PNI)was positively correlated with TFA and SFA;serum albumin was positively correlated with TFA and SFA.In addition,in the high T-stage group,SII(systemic immune-inflammation index,SII)was negatively correlated with TFA and SFA;NLR(neutrophil to lymphocyte ratio,NLR)was negatively correlated with SFA;lymphocytes were negatively correlated with rVFA.6)RVFA was a higher predictor of short-term postoperative complications in patients with low T-stage ccRCC(AUC=0.895);whereas in patients with high T-stage ccRCC,gender was a weaker predictor of short-term postoperative complications in patients(AUC=0.642).Conclusion1)Higher preoperative rVFA suggests a lower incidence of short-term postoperative complications in patients with low T-stage ccRCC,but no predictive value for patients with high stage.2)Inflammatory and nutritional indicators vary widely among patients with ccRCC at different stages,while inflammatory and nutritional parameters,heat shock proteins,and tumor stage may act synergistically with adipose tissue as one of the factors influencing patient prognosis. |
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