| Colorectal cancer(CRC)is one of the most common malignancies in the world,and its incidence and mortality are on the rise worldwide.in 2020,there were more than 1.9 million new cases and 935,000 deaths of CRC worldwide.Obesity is an important risk factor for morbidity and mortality of many cancers,including CRC.According to data published by WHO,the global prevalence of obesity in 2020 is 15.62%of the total population,an increase of 2.21%from 13.40%in 2016.The China Nutrition and Chronic Disease Status Report(2020)states that by 2020,overweight or obese adult residents in China will account for more than half of the total population,and obesity is already a worldwide public health problem.A growing number of studies have focused on the impact of obesity on the prognosis of CRC patients;however,the current findings are inconsistent.Traditional measures of obesity,BMI,waist circumference and waist-to-hip ratio,have their inherent limitations.Although BMI is generally considered to be a proxy for body composition,it cannot accurately reflect the degree of obesity and quantify body composition,especially the amount and distribution of adipose and muscle tissue.Waist circumference and waist-to-hip ratio are better estimates of central obesity than BMI,but have limitations in inter-and intraobserver reproducibility and in distinguishing between visceral,subcutaneous adipose tissue and skeletal muscle tissue.Accurate quantification of subcutaneous and visceral adipose tissue and skeletal muscle tissue by manual and semi-automated imaging techniques can provide potentially valuable clinical information in addition to traditional measures of obesity.Numerous studies have assessed the impact of visceral adiposity on the prognosis of CRC patients by this method and have demonstrated that visceral adiposity is an independent risk factor for long-term prognosis in CRC patients.However,existing cohort studies are difficult to answer clinicians’and patients’questions about each individual’s survival rate and to be efficiently applied in individualized medical models.The construction of prognostic prediction models is an important technical tool for cancer prevention and treatment,and column line graphs,a graphical computational tool based on statistical prediction models,can assist clinical decision making by generating accurate predictions based on the assessment of important factors and providing accurate and personalized risk predictions for individuals to estimate the conditional probability of disease outcomes.This study takes"the clinical needs of CRC patients"as the starting and ending point,explores the correlation between abdominal obesity and CRC prognosis from clinical evidence-based medical evidence,and constructs a prognostic model for CRC patients based on abdominal obesity-related indicators applicable to Chinese population,with the aim of compensating for the lack of abdominal obesity factors in existing prognostic models.It is important for guiding cancer prevention and treatment,identifying high-risk groups,timely weight intervention,and improving patients’prognosis.This study was divided into three parts.First,the significance of abdominal obesity in the prognosis of CRC patients was systematically analyzed by Meta-analysis method to provide evidence-based medical evidence for the correlation between abdominal obesity and the prognosis of CRC patients.Subsequently,it was hypothesized that the choice of CT scan level might lead to differences in the results of abdominal obesity affecting the prognosis of tumor patients,based on the problem that the measurement of fat area and skeletal muscle area using computed tomography(CT)may result in large differences in measurement results due to differences in the location of CT scan levels.To this end,the optimal CT scan level for measuring fat area versus skeletal muscle area in CRC patients was investigated.Finally,the correlation of abdominal obesity-related indicators with postoperative pathological indicators and short-term prognosis of CRC patients was investigated,and a prognostic prediction model for CRC patients based on abdominal obesity-related indicators was constructed.Clinical study I:Impact of abdominal obesity on survival of patients after CRC surgery:a systematic review and Meta-analysisObjective:To quantitatively analyze the existing clinical studies and objectively evaluate the impact of abdominal obesity-related indicators on the prognosis of colorectal cancer patients.Methods:This Meta-analysis was designed according to the PRISMA guidelines.The study questions were developed using the PICOS strategy:(Population,P)was defined as patients with CRC;(Intervention,I)as patients with low skeletal muscle content and/or patients with high abdominal adiposity;(Comparison,C)was patients with high skeletal muscle content and/or low abdominal adiposity;(Outcomes,O)was a prognostic indicator and(Study design,S)was an observational or randomized controlled trial.Pub Med,Embase,Web of Science,MEDLINE,The Cochrane Library,CNKI,and Wanfang databases were searched for literature exploring the prognostic impact of abdominal obesity-related indicators on colorectal cancer patients published since their creation until October 31,2022.Data extracted included:author name,publication date,country,study type,patient time,number of patients(male/female),age,included patients,method of body composition analysis(including measurement location,measurement parameters,cut-off values,and measurement time),follow-up time,and outcome indicators(including OS,RFS,DFS and CSS).Data were pooled using a random effects model.Heterogeneity between studies was evaluated using the Q test and the I~2 statistic.For the I~2 statistic,heterogeneity was defined as low(I~2:25%-50%),medium(I~2:50%-75%),and high(I~2>75%).For the Q statistic,P≤0.1 was considered as significant heterogeneity.Qualitative and quantitative methods,including funnel plots and Egger’s test,were used to study publication bias.Statistical analysis was performed using Stata 16.0(Stata Corp,College Station,TX)software.Results:A total of 27 articles were included in this study.The results showed that CRC patients with high abdominal skeletal muscle index(SMI)had better OS(HR:1.51;95%CI,1.37-1.68),DFS(HR:1.56;95%CI,1.20-2.02),RFS(HR:1.14;95%CI,0.87-1.50)and CSS(HR:1.40;95%CI,1.12-1.74),thus demonstrating that skeletal muscle is a favorable prognostic factor for CRC patients.In addition,CRC patients with high visceral-to-subcutaneous adipose tissue area ratio(VSR)had worse OS(HR:1.89;95%CI,1.35-2.63),DFS(HR:1.89;95%CI,1.38-2.58),and RFS(HR:3.32;95%CI,1.22-9.06),suggesting that high VSR is an unfavorable prognostic factor for CRC patients.Conclusion:Abdominal obesity-related indicators are a strong prognostic indicator for the prognosis of CRC patients.Clinical studyⅡ:Impact of abdominal obesity on survival of postoperative CRC patients:finding the optimal CT scan levelObjective:To evaluate the optimal CT scan level for predicting prognosis of colorectal cancer patients by using abdominal obesity-related metrics at a total of six CT scan levels from the T12/L1 disc to the L5/S1 disc to predict OS and CSS in colorectal cancer patients.Methods:Patients who underwent surgical treatment and were pathologically diagnosed with CRC from May 01,2015 to April 30,2016 at Xijing Gastroenterology Hospital,Air Force Military Medical University were included.General clinical data of the enrollees were collected and adipose and muscle tissues in different parts of the abdomen were measured according to the abdominal CT images of all study subjects.Statistical analysis was performed using EXCEL with SPSS 20.0 and R.OS and CSS were analyzed using COX proportional risk model and competing risk analysis,respectively,and multifactorial analysis was performed using stepwise regression model to identify independent risk factors,and predictive models for OS and CSS were constructed based on these factors,and Akaike Akaike Information Criteria(AIC)was used to evaluate the model fit and select the best candidate model.Variance Inflating Factor(VIF)was used to check the multicollinearity among the independent variables,and the area under the curve(AUC)of Receiver Operating Characteristic(ROC)was used for model validation.The model recognition performance was evaluated.The validity of the prediction model in clinical practice was evaluated using Decision Curve Analysis(DCA).Results:A total of 450 patients were included in this study,including 186 cases of colon cancer and 264 cases of rectal cancer.The results showed that comparing the prediction models of OS and CSS for colon cancer,the L2/L3 level model had the lowest AIC(OS:449.21;CSS:301.31)and the highest AUC(OS:1 year:AUC=0.901(95%CI,0.855,0.947),3 years:AUC=0.792(95%CI,0.717,0.867),5 years:AUC=0.820(95%CI,0.752,0.887);CSS:1 year:AUC=0.926(95%CI,0.877,0.975),3 years:AUC=0.784(95%CI,0.701,0.867),5 years:AUC=0.795(95%CI,0.719,0.872)),the decision curve showed the best performance;comparing the prediction models of OS and CSS for rectal cancer,the L4/L5 level model showed the smallest AIC(OS:725.41;CSS:535.08)and the highest AUC(OS:1 year:AUC=0.730(95%CI,0.641,0.820),3 years:AUC=0.807(95%CI,0.752,0.863),5 years:AUC=0.840(95%CI,0.791,0.889);CSS:1 year:AUC=0.705(95%CI,0.611,0.799),3 years:AUC=0.802(95%CI,0.743,0.860),5 years:The greater the VSR and the smaller the SMI,the worse the prognosis of CRC patients;CRC patients with a moderate total fat index(TFI)had a better prognosis than those with a higher or lower TFI.Conclusion:The L2/L3 level model was the best CT scan level for OS and CSS prediction in colon cancer patients;the L4/L5 level model was the best CT scan level for OS and CSS prediction in rectal cancer patients.Clinical studyⅢ:The effect of abdominal obesity on short-term outcomes and the construction of long-term survival nomogram in postoperative CRC patientsObjective:To investigate the correlation between abdominal obesity-related indicators and postoperative pathological indicators and short-term prognosis of CRC patients,and to pioneer the construction of a prognostic prediction model for CRC patients based on abdominal obesity-related indicators.Methods:688 patients who underwent surgical treatment and were pathologically diagnosed with colorectal cancer from May 01,2015 to August 31,2016 at the Xijing Gastroenterology Hospital of the Air Force Military Medical University were included.General clinical data of the enrollees were collected and adipose tissue and muscle tissue in different parts of the abdomen were measured according to the abdominal CT images of all study subjects.After surgery,the patients’operative time,number of intraoperative lymph node dissection,postoperative complications,length of hospital stay,nerve infiltration and choroidal carcinoma emboli were collected.Discrete data were tested by chi-square test or Fischer exact test.Independent t-test was used for continuous data.Continuous variables that were not normally distributed were log-transformed before analysis.For the construction and validation of column nomogram,colorectal cancer patients from May 01,2015 to April 30,2016 at Xijing Hospital were the training set of 450 patients;colorectal cancer patients from May 01,2016 to August 31,2016 were the validation set of 238 patients.OS curves were plotted by Kaplan-Meier method and evaluated by log-rank test.CCS was evaluated using Fine and Gray’s competing risk regression model for univariate and multifactor analysis to select prognostic factors affecting survival time,and predictive nomogram were constructed based on the results of multifactor analysis.Results:With higher VSR,patients had significantly longer operative time and hospital days,fewer intraoperative lymph nodes,and higher rates of complications,nerve infiltration,and vascular thrombosis.Patients with colorectal cancer with lower SMI had higher complication rates and longer hospitalization days,with no significant effects on operative time,number of intraoperative detected lymph nodes,nerve infiltration and choroidal carcinoma embolism rates.Univariate and multifactorial analyses revealed that age,TNM grade,Carcinoembryonic Antigen(CEA)level,L2/L3-TFI and L2/L3-SMI were independent risk factors for OS and CSS in colon cancer,and age,TNM grade,CEA level,histological grade,L4/L5-TFI,L4/L5-VSR and L4/L5-SMI were independent risk factors for OS and CSS of rectal cancer.The model could well assess OS and CSS in colorectal cancer patients at 1,3 and 5 years and had high AUC at all time points.in addition,the calibration curves showed that the predicted survival at 1,3 and 5 years was very close to the actual survival rate.Thus,this prognostic prediction model can be used to better assess the clinical outcomes of individual patients.Conclusion:1.Indicators related to abdominal obesity(TFI,VSR and SMI)were independent risk factors associated with CRC patients.2.Strong correlation of VSR and SMI with postoperative pathological indicators and short-term prognosis of CRC patients.3.Pioneering the construction of a prognostic prediction model for CRC patients based on indicators related to abdominal obesity,and the model has good identification and calibration capabilities.4.The use of the model allows individualized prognosis prediction and early weight intervention in high-risk groups,which can be easily applied in medical institutions at all levels and provides a reference for improving the long-term prognosis of CRC patients through weight management. |
PDF Full Text Request