Visceral Fat Tissue And Its Importance In The Diagnosis, Treatment And Outcome Of Renal Cell Carcinoma

Part one. Diagnosis1)Visceral Fat Accumulation is Associated with Different Pathological Subtypes of Renal Cell CarcinomaPurpose:Evidence showed that obesity is a risk factor for renal cell carcinoma (RCC) and it is associated with higher risk of clear-cell subtype than with other histology. Visceral adipose tissue is characterized byendocrine function which may play a certain roll in carcinogenesis. The aim of the current study was to investigate how visceral obesity is associated with histological subtypes of RCC in a Chinese cohort.Material and Methods:The kidney tumor database was collected from Shanghai Cancer Center, patients with localized RCC and complete CT/MRI information was enrolled. In each subject, a single sliced computer tomography image was used to measure the area of visceral and subcutaneous adipose tissue. Univariate and multivariate logistic regression model was performed to analyze clear cell or non-clear cell RCC in relation to age, gender, tumor size, diabetes, hypertension, total fat area, visceral fat area, and body mass index (BMI).Results:A total of487were enrolled.418patients were of clear cell subtype whereas69patients had non-clear cell RCC. Among which there were327male and160female, the mean age was54.8years, the mean tumor size was5.1cm and the mean visceral fat area was102cm2while the mean BMI was26.7. Visceral fat area is associated with BMI, gender, and increased simultaneously with age. Multivaraate analysis showed that age (OR=1.04, p<0.001) and visceral fat area (OR=1.006, p=0.025) were independent predictors of clear cell RCC, instead, BMI and gender didn’t show statistical significance.Conclusion:Increased visceral fat was found to strongly associate with clear cell subtype of RCC. Visceral fat tissue may have played an important roll in the carcinogenesis of clear cell RCC instead of non-clear cell RCCs. Part one. Diagnosis2) Visceral Obesity and Risk of High Grade Disease in Clinical T1a Renal Cell CarcinomaPurpose:Accurate assessment of disease characteristics is a prerequisite for treatment decision making regarding small renal masses. In this study we evaluate the association between visceral obesity and Fuhrman grade in patients with cT1a renal cell carcinoma, in order to help physicians build a preliminary awareness of the tumor grade before surgery.Materials and Methods:We retrospectively collected data on186patients with surgically treated cT1a renal cell carcinoma. Single slice computerized tomography was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Other analyzed factors included clinical characteristics (age, gender, body mass index and tumor size) and anatomical features of the tumor defined by the R.E.N.A.L. nephrometry score. The association between predictors and high grade disease (Fuhrman grade III or IV) were assessed using logistic regression analyses.Results:The mean age was56years old,68.3%patients were male and the mean tumor size was3.4cm.174patients had clear cell carcinoma while12patients had papillary renal cell carcinoma. A total of47(25.3%) tumors were classified as high grade. The percentage of visceral adipose tissue was higher in male participants but did not correlate with body mass index, age or tumor size. In univariate analyses the percentage of visceral adipose tissue and tumor size were significantly associated with higher Fuhrman grade. Multivariate analysis showed that the percentage of visceral adipose tissue (OR1.06, p=0.0018) and tumor size (OR1.91, p=0.047) were independent predictors of high grade cancer. Addition of the percentage of visceral adipose tissue to a model including clinical characteristics and anatomical features of the tumor remarkably improved its discriminatory ability (p=0.0010).Conclusions:Increased visceral obesity was found to be strongly associated with higher Fuhrman grade in patients with cT1a renal cell carcinoma. Further studies are needed to confirm these findings and discover the underlying biological mechanism. Part two. Treatment Decision MakingHow does Obese Status Influence Treatment Decision Making:Multicenter Study in ChinaPurpose:It is reported that in some part of China, there is more than50%middle-aged people who is overweight. Hence many renal tumor patients were also obese patients who suffers other complications. The aim of this research is to observe whether obese status will influence the treatment decision made by Chinese urologists for renal tumor patients.Material and Methods:The database of localized kidney tumor patients who undergone surgery from2008to2011was collected from three tertiary centers in China. Only patients with complete CT information was enrolled. Surgery types were noted, which included open radical nephrectomy(RN), open nephron sparing surgery(NSS), laparoscopic radical nephrectomy(LAPRN) and laparoscopic nephron sparing surgery(LAPNSS). We used the R.E.N.A.L. nephrometry score to define the anatomical features of the tumor. In each subject, a single sliced computer tomography image was used to measure whole the area of abdomen adipose tissue using specific image software and then the patients were divided into obese group and non-obese group. Univariate and multivariate logistic regression model was performed to analyze the state of obese in relation surgical decision.Results:A total of577were enrolled. Among which there were62.1%male and37.9%female, the mean age was54.4years, the mean tumor size was5cm, the mean BMI was23.7and the mean total abdomen fat area(TFA) was238cm2.245patients(42.4%) undergone open RN,127patients (22%) undergone LAPRN,177patients (30.7%) undergone open NSS,28patients (4.9%) undergone LAPNSS. Patients with high RENAL score(≥9) were more likely to undergone radical nephrectomy while low score patients take nephron sparing surgery no matter open or laparoscopic. Chi-square test showed that obese statement significantly influenced the decision of laparoscopic surgery(p=0.001) but not nephron sparing surgery(p=0.79). Multivariate analysis revealed that tumor size, TFA, RENAL nephrometry score were strongly associated with the decision of laparoscopic surgeries; age, tumor size and RENAL nephrometry score strongly influence the decision of nephron sparing surgeries. For those patients with low RENAL nephrometry score, TFA still changes the surgical decision of laparoscopic surgeries(p=0.005) as well as a trend for nephron sparing surgeries(p=0.068). After adjusting the year of surgery we didn’t observe a change in surgery type.Conclusion:Obese status is one of the influence factors of surgery decision making. The accumulation of abdomen fat will prevent urologists to perform laparoscopic surgeries but not nephron sparing surgeries. This change of surgery types will not change by year. Part Three. Outcome of Advanced DiseaseBody Fat Distribution is Associated with the outcome of advanced renal cell carcinoma patients who takes target therapiesBackgrouds:It is well known that obesity is associated with the prevalence as well as the outcome of renal cell carcinoma. However, less is known about the link between visceral fat and the outcome of renal tumors. The purpose of the article was to investigate how the visceral fat is associated with the outcome of advanced renal cell carcinoma patients who takes target therapies.Methods:Patients who takes part in the Famitinib clinical trial which is held in Shanghai between2011and2013was enrolled. We collected patient’s data including age, gender, BMI, drug type, MSKCC score, ECOG score and drug related adverse events. Progression free survival and overall survival was counted. In each subject, a single sliced computer tomography image was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Continuous variables were turned into binary variables using the median value. Log-rank analysis was used to estimate the association between PFS and obese status. The correlations between other covariables and PFS were evaluated by multivariate analysis using COX regression analysis. Fisher test was used to reveal the link between adverse events and obese status.Results:in total26patients were enrolled. Among which there were18male and8female, the mean age was56.3years and the mean BMI was23.6. The median PFS was8.4months, however the median overall survival was not reached. Univariate analysis failed to observe and link between drug type or BMI and outcome, but the proportion of visceral adipose tissue(Visceral Fat Area%, VFA%) showed significant association with PFS, p=0.037, OR=0.32. Multivariate analysis confirmed that VFA%was the only significant predictive factor. It have to be noted that most patients with low VFA%had severe adverse advents and undergone dose reduction. Some patients with low visceral fat area also undergone dose related side effects but there was no statistic significance(p=0.114). There was no association between BMI or subcutaneous fat area and side effects.Conclusions:VFA%was one of the predictive factors of advanced renal cell carcinoma patients who take target therapy. Patients with high proportion of visceral fat had worse outcomes, resulting in a reduction of PFS for4months. Further studies are needed to confirm these findings and discover the underlying biological mechanism.