| Part 1 Effects of Immunonutrition Intervention on Gut Microbiota and Tumor proliferation in Gastric Cancer Transplanted 615 Mouse ModelBackground:One of the most common toxic and side effects of chemotherapy for gastric cancer is gastrointestinal adverse reactions,the main manifestations include gastrointestinal motility dysfunction,intestinal flora dysfunction and intestinal mucosal barrier damage.Immunonutrition plays an important role in nutritional supplementation,regulation of immunity and maintenance of gut microbiota.Current evidence indicates that immunonutrition such as n-3 polyunsaturated fatty acids(PUFA)play a role in maintaining the balance of gut microbiota in colorectal cancer and inflammatory bowel disease,and at the same time,help reduce the dysbiosis caused by chemotherapy in colorectal cancer,even might has a certain correlation with tumor prognosis.At present,the effect of chemotherapy on gut microbiota in gastric cancer is still unclear.The impact of immunonutrition intervention on gut microbiota of gastric cancer and its relationship with tumor proliferation need to be studied.Objective:By constructing an animal model of gastric cancer xenograft-chemotherapy in 615 mice,the initial exploration of the effects of chemotherapy and xenograft establishment on the gut microbiota in gastric cancer,and then aim to investigate the effects of supplemental immunonutrition including glutamine(GLN)and fish oil on gut microbiota and tumor proliferationMaterials and Methods:Randomly we divide 36 6-week-old female 615 mice into the following 6 groups:Group 1,chemotherapy group(CON1,n=6),intraperitoneally inject 5-Fu on days 3,6,and 9;Group 2-5,615 mice were subcutaneously injected with MFC pregastric cancer cells(5× 106)to construct a transplanted gastric cancer model(recorded as day 0),followed by 5-Fu chemotherapy(on day7,10 and 13)to construct an animal model of gastric cancer-chemotherapy,group 2 without other interventions(CON2,N=6),group 3 as saline intervention group(NS,n=6),group 4 as low-dose glutamine intervention group(Low GLN/LG,n=6),group 5 as high-dose valley The aminoamide intervention group(High GLN/HG,n=6),and group 6 as the fish oil intervention group(PUFA,n=6).Before the intervention at baseline(Day-7),before transplantation of tumor(Day-1),before the first chemotherapy in Group 2-5(Day 6),and on the 21st day after the completion of the intervention,fresh stool samples were taken at each timepoint and used 16S rRNA method for determination of gut microbiota.Compare the growth rate of transplanted tumors in groups 2-5.Define p<0.05 as a statistically significant difference.Results:The results of the baseline gut microbiota characteristics show that the Firmicutes and Bacteroidetes dominate,with the former accounting for 41%-57%,the latter accounting for 39%-56%,and the sum 92%-98%.The F/B ratio ranges from 0.73 to 1.46.After chemotherapy intervention,the relative abundance of the Firmicutes phy lum was significantly increased,the Bacteroidetes was significantly decreased,the F/B ratio was increased to 2.39.At the genus level,the proportion of Akkermansia(Akk)was significantly decreased(2%-4%→1%,p<0.01).In the PUFA group,the abundance of the Firmicutes phylum is significantly reduced,and the Bacteroidetes is significantly increased.The F/B ratio is back to 1.0,which is maintained at the baseline range(0.73-1.46).At the genus level,the relative abundance of the genus Akk was significantly increased.In the HG group,the abundance of Firmicutes was significantly reduced,and the Bacteroides was significantly increased,with an F/B ratio of 1.48.The size of the transplanted tumor in the PUFA group was 0.26 ± 0.23g,and the size of the transplanted tumor in the HG group was 0.32± 0.18g,which was smaller than the 0.72 ± 0.41 g in the CON2 group.However,there were no significant differences statistically(P=0.13,0.10,respectively)Conclusion:5-Fu chemotherapy increased the relative abundance of the Firmicutes phylum in the gut microbiota of mice with transplanted gastric cancer,reduced the ratio of Bacteroides phylum,the F/B ratio was significantly increased,the proportion of Akk bacteria decreased,and the structure of the gut microbiota was changed by the chemotherapy.Supplementation with fish oil and glutamine can reverse the structural changes of the gut microbiota caused by chemotherapy and maintain the intestinal flora F/B ratio within a normal range.Supplementation with fish oil can significantly increase the relative abundance of Akk and might help to inhibit tumor proliferationPart 2 Preliminary Study on the Influence of Nutritional Intervention on Gut Microbiota and Clinical Outcomes in Gastrointestinal TumorsBackground:Research on the impact of nutritional interventions on gut microbiota is rising.On the one hand,specific nutritional interventions may affect the structure of gut microbiota.On the other hand,different nutritional support approaches may also affect the structure of gut microbiota.Studies have suggested that parenteral nutrition intervention may result in decreased the diversity of gut microbiota and changes in the structure.At the same time,studies have suggested that changes in gut microbiota may be related to infection complications.The concepts of pre-rehabilitation and early enteral nutrition in gastrointestinal cancer patients are getting more and more attention.The effects of perioperative nutrition support on gut microbiota and postoperative infection,is worth conducting a preliminary researchObjective:To preliminarily explore the impact of perioperative enteral nutrition intervention on the gut microbiota in patients with gastrointestinal tumors and the clinical outcome after surgeryObjects and Methods:Patients with gastrointestinal tumors undergoing elective surgery in the Department of General Surgery at Peking Union Medical College Hospital were enrolled.According to whether patients were given oral enteral nutrition support for pre-rehabilitation and early enteral nutrition postoperatively,will patients be divided into study group and control group.In the study group,enteral nutrition was taken orally for at least 3 days before surgery,and at least 500 ml of enteral nutrition liquid per day.According to the concept of enhanced recovery after surgery(ERAS),enteral nutrition support was given early(day 1-2)after surgery.In the control group,enteral nutrition support was not given before the operation,and fasting for 3 days after the operation as well as given parenteral nutrition and/or with fluid support.Fresh feces were collected before operation and 5-7 days after operation,1 6S rRNA sequencing was performed to analyze the characteristics of gut microbiota,and postoperative infection complications,total complications and postoperative hospital stay were recorded.Define p<0.05 as a statistically significant differenceResults:We included 3 7 patients with elective gastrointestinal tumors from December 2017 to April 2018,including 24 in the control group(CON group)and 13 in the study group(EN group).At the genera level,Akkermansia(Akk)was 2%and<0.1%in the study group and the control group,respectively,and 4%and 0.4%after the operation.After perioperative enteral nutrition support,the proportion of Akk is increasing without significance Preoperative Escherichia Shigella was 9%and 5%in the EN and CON groups,respectively,and 11%and 19%after the operation.Postoperative infection complications were 1 case(8%)in the EN group and 5 cases(21%)in the CON group.The total postoperative complications were 1 case(8%)and 9 cases(38%).The average postoperative hospital stays were 8.0±2.1 days and 1 2.3± 7.5 days,but no statistical difference was testedConclusion:Enhanced perioperative enteral nutrition intervention can increase the relative abundance of Akk and reduce the proportion of E.Shigella,and may help reduce postoperative infection complications and achieve ERAS.Akk bacteria as a potential new microbiota biomarker may suggest better postoperative clinical outcomes.Part 3 Impact of Immunonutrition Intervention on Clinical Outcomes in Patients with Gastrointestinal TumorBackground:Enteral nutrition support during the perioperative period may help to optimize postoperative clinical outcomes and enhance postoperative recovery.Immunonutrition such as fish oil can help reduce the inflammatory cascade produced after surgery and inhibit the excessive activation of pre-inflammatory factors,which may help reduce the incidence of postoperative complications,especially infection complications.At present,the application of immunonutrition in patients with gastrointestinal tumors during the perioperative period reduces infection complications and achieves ERAS,is still inconsistently conclusive.Objective:To study the effect of supplementing immunonutrition during the perioperative period on the clinical outcomes in patients with gastrointestinal tumors.Objects and Methods:Patients with gastrointestinal tumors undergoing elective surgery in the Basic Surgery of Peking Union Medical College Hospital,the study group,5 consecutive days before surgery and 7 days after surgery were supplemented with immune nutrition(IMPACT/Nestle or Supportan)600-800ml per day,sequential increased supplementation after operation,and the perioperative nutritional support plan of the control group is ordinary enteral nutrition or parenteral nutrition(without supplementation of fish oil,arginine,nucleotide and other immunonutrients).Prospectively collect patients postoperative infection complications,total complications and postoperative hospital stays.For the definition of infection complications,we referred to the health care-associated infection specified by the National Center for Diseases and Prevention.P<0.05 is a statistically significant difference.Results:A total of 190 gastrointestinal tumor patients admitted to the Department of General Surgery at Peking Union Medical College Hospital from September 2016 to December 2019 were included,of which 69 were in the study group,121 were in the control group,105 were gastric cancer,39 cases of colorectal cancer,38 cases of gastrointestinal stromal tumors and 8 cases of small intestine tumors.The incidence of postoperative infection complications in the study group and the control group was 4.3%(3/69)and 13.2%(16/121),respectively.The study group had significantly lower incidence than the control group(p=0.003),in which the main infections with clear causes were 4.2%(8/190)of gastrointestinal leak and 2.6%(5/190)of pulmonary infection.The study group also had significantly lower incidence of total postoperative complications than the control group(p=0.039).The average postoperative hospital stay in the study group was 8.2 ± 2.1 days,which was significantly shortened than that in the control group,10.8 ±9.4 days(p=0.030).Conclusion:Perioperative immunonutrition intervention may help reduce postoperative infection complications and total postoperative complications,shorten the average postoperative hospital stay,and help to achieve ERAS in clinical practice.Part 4 The Effect of Neoadjuvant Chemotherapy Combined with Nutritional Support on Long-term Survival of Gastric CancerBackground:The incidence of gastric cancer(GC)in China is high.The main treatment of locally advanced gastric cancer is surgery combined with postoperative or perioperative chemotherapy.Recently,there are increasing studies on neoadjuvant chemotherapy for gastric cancer.Besides,patients with GC have a high prevalence of malnutrition.Nutritional support during neoadjuvant chemotherapy may affect these patients’ long-term survival.Aim:To investigate the effects of nutritional support during neoadjuvant chemotherapy on long-term survival in patients with GC.Methods:We included patients with GC undergoing neoadjuvant chemotherapy and had elective surgery at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences.Patients who had remained or increased body weight preoperatively were included in the study group,and no nutritional support or weight loss 1-3 months before surgery were as the control group.We followed up the patient’s long-term survival.Kaplan-Meier method was used to do survival analysis.Results:We finally included 274 patients who met the inclusion criteria from January 2014 to December 201 9,including 214 in the study group and 60 in the control group.At baseline,there were no significant differences in age,gender,BMI,surgical methods,pathological differentiation,and TNM stage between the two groups.The five-year overall survival rate of the study group was 58.2%,which was significantly higher than the control group,32.6%.Conclusion:Neoadjuvant chemotherapy combined with nutritional support may help to improve the nutritional status,improve chemotherapy tolerance,and may even improve long-term survival in locally advanced GC patients.Part 5 Application of Long-term Parenteral Nutrition in Gastrointestinal Dysfunction and Establishment of infection risk modelsBackground:Enteral nutrition intake of patients with gastrointestinal dysfunction or intestinal failure is not sufficient or feasible,and these patients have to rely on long-term parenteral nutrition.The transition from hospital to home mode makes home parenteral nutrition(HPN)in the future a trend.Among long-term parenteral nutrition patients,central line-associated bloodstream infection(CLABSI)is one of the most serious and life-threatening complications of HPN.Studying the risk factors associated with infection can help identify high-risk groups early and prevent CLABSIObjective:To investigate the potential risk factors of CLABSI and to determine a predictive model in a cohort of adult HPN patients.Objects and Methods:Patients who were managed by the HPN service at the Hospital of the University of Pennsylvania on January 1,2018 were included and followed up to 6/30/2019.We used electronic medical records to collect demographic and clinical data.CLABSI was reported by infectious disease experts.Variables with p<0.05 are significant,and variables with p<0.2 are included in the logistic regression model.Results:We included 114 patients undergoing HPN,with an average age of 54 ± 16 years,68%of women,and an average BMI of 25 ± 5.6 kg/m2.The median HPN days was 5 16(15-10281)days,and 26%had a history of CLABSI.Catheter types include PICC 72.6%,tunneled type 23.9%and Port 3.5%.The incidence of CLABSI was 0.89/1000 catheter days.Logistic regression model analysis results show that the presence of ostomy(OR=22.0;95%CI,4.8-101.7),tunneled and port catheters(OR=4.4;95%CI,1.4-13.9)and BMI<18.5(OR=5.9;95%CI,1.4-24.2)as risk index for CLABSI.Conclusion:In adult HPN patients,the presence of ostomy,the use of tunneled or port catheters,and low BMI are associated with the occurrence of CLABSI.Standardized ostomy care and nutritional support may help reduce the occurrence of CLABSI. |
