Risk Factors Related To Postoperative Death In Patients With Rectosigmoid Junction Tumor Perforation And Related Experimental Research

BackgroundColorectal cancer is a common gastrointestinal tumor with serious threat to human life and health.according to the national cancer registration data in 2016 the National Cancer Registry collected,colorectal cancer have ranked fourth cancer of male,and third malignant tumor of female,the incidence of colorectal cancer have ranked second in the city area,and fifth in rural areas.according to the national reports of malignant tumor death cases,colorectal cancer have ranked fifth in male,fourth in female.With the development of social economy and the improvement of people's living standard,the incidence of colorectal cancer is increasing year by year in both rural and urban areas,both sexes.Perforation of colorectal cancer is not uncommon in clinical practice,and there were corresponding reports at home and abroad.Most of them were based on clinical case reports and experience communication.Colorectal perforation can occur in the ascending colon,descending colon,sigmoid colon,rectum and other parts,and the rectosigmoid junction tumor perforation is common.With the increase of population aging and the change of people's lifestyle,the perforation of tumor at the junction of rectum and sigmoid is increasing.Perforation of rectosigmoid junction tumor is critical illness for colorectal cancer,Which often require emergency surgery.patients are often older with poor organ function,Some of them are still difficult to survive and have high mortality even after the surgery.At present,the research about perforation of rectosigmoid junction tumor is seldom in domestic or aboard.Considering the present clinical situation with poor treatment effects,high expense and high morbidity about perforation of colorectal cancer,which even have Potential disputes,the clinical data of patients with perforation of rectosigmoid junction tumor from January 2000 to October 2015 in Huangshi Central Hospital were collected.By logistic regression analysis of single factor and multiple factors risk factors associated with death in postoperative were investigated;at the same time,aimed at the renal dysfunction in preoperative mice model of sepsis induced by cecal ligation and puncture(CLP)method,to investigate the effects of NAMPT inhibitor FK866 on renal damage of mice with sepsis by cecal ligation and puncture(CLP)method.Objective(1)The aim of this study was to investigate risk factors related to postoperative death of patients with rectosigmoid junction tumor perforation.This may improve the survival rate of patients via treating correctly according to these risk factors for postoperative mortality,and may also improve the compliance of patients and reducing the occurrence of medical disputes via assessment of death risk of patients.(2)Renal dysfunction is a major risk factor related to postoperative death of patients with rectosigmoid junction tumor perforation.To investigate the acute renal damage caused by sepsis,experimental sepsis was induced in mice using the cecal ligation and puncture(CLP)method.Furthermore,the effect of NAMPT inhibitor FK866 on the renal damage caused by sepsis was investigated.This may provide new insights into the functional mechanism of FK866 and an important framework for developing novel targeted clinical therapies for acute renal dysfunction.Methods(1)The clinical data of 76 cases with rectosigmoid junction tumor perforation which confirmed by pathological examination postoperative in our hospital from January 2000 to October 2015 was collected.(2)Healthy male C57BL/6J mice were selected as the object of study to establish the cecel ligation and puncture(CLP)sepsis model.(3)Forty-eight male C57BL/6J mice were randomly divided into six groups(n=8):Sham group,vehicle group,FK866 group,CLP group,vehicle + CLP group and FK866 + CLP group.FK866(10mg/kg)were given intraperitoneally in mice at 24,12,and 0.5 h prior to CLP.The histological changes of renal tissues were examined.Serum urea nitrogen(1BUN)and creatinine(Cr)levels were measured.Serum levels of NAMPT,tumor necrosis factor(TNF)-a and interleukin(IL)-6 were measured by ELISA,The mRNA expression of TNF-??IL-6 and IL-10 were measured by real-time quantitative PCR,The protein expression of NAMPT,cleaved caspase-3,cytoplasmic I?B? and nuclear NF-?B p65 were measured by western blot.The activity of NF-?B p65 and caspase-3 were measured by colorimetry.Results(1)Of the 76 cases,17 patients died postoperative,the mortality rate was 22%,the single factor analysis showed that age(x2=4.649,p=0.031),duration of abdominal pain(x2=8.218,p=0.016),severe heart and lung diseases(x2=11.996,p=0.007),circulatory and renal function(x2= 10.360,p= 0.016),serum albumin(x2=7.252,p=0.027),white blood cellcount(x2=7.633,p=0.022),perforation diameter(x2=9.770,p=0.008),Geroge grade of intraperitoneal contamination(x2=10.086,p=0.006)were related to postoperative death(P<0.05),multivariate analysis showed that complicated with severe heart and lung diseases,complicated with circulatory and renal dysfunction,white blood cell count<4*109/1,hole diameter was larger than 3cm,over one quadrant of Geroge grade of intraperitoneal contamination were independent risk factors for postoperative death.(2)Renal and serum NAMPT protein levels were significantly increased after CLP compared to those in sham group(P<0.01).Compared with the sham group,the pathological scores of renal tubular injury in CLP group were significantly increased(P<0.01).Serum levels of BUN and Cr were significantly increased in the CLP group(P<0.01).Both serum TNF-a,IL-6 and renal TNF-a,IL-6 and IL-1? mRNA levels were significantly increased in the CLP group(P<0.01).CLP significantly increased NF-?B activation as indicated by higher NF-?B p65 activity,higher levels of NF-?B p65 in the nucleus and lower levels of I?Ba in the cytoplasm(P<0.01).Furthermore,CLP significantly increased cellular apoptosis as indicated by higher levels of cleaved caspase-3 protein and caspase-3 activity(P<0.01).In contrast,FK866 treatment significantly attenuated renal injury,inhibited proinflammatory cytokine production,cellular apoptosis,and NF-?B activation(P<0.01).Conclusion(1)Risk factors related to postoperative death of rectosigmoid junction tumor perforation were mainly associated with preoperative important organ function state and intraperitoneal infection factors.(2)NAMPT expression was increased in septic mice.FK866 treatment significantly decreased NF-?B activation and subsequently reduced proinflammatory cytokine production.Furthermore,FK866 treatment significantly inhibited cellular apoptosis.FK866 acts as a novel therapeutic compound for sepsis-induced acute renal acute renal injury via the inhibition of inflammation and cellular apoptosis.