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Study On The Therapeutic Effect And Mechanism Of Endoscopic Ultrasonography-guided Gastrointestinal Anastomosis Under Gastrointestinal Obstruction On Lipid Metabolism Of Metabolic Dysfunction-associated Fatty Liver Disease

Posted on:2022-08-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:H X GaoFull Text:PDF
GTID:1484306563454884Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: metabolic dysfunction-associated fatty liver disease(MAFLD)is a clinicopathological syndrome characterized by steatosis and fat accumulation of liver parenchymal cells without excessive drinking history.With the increase of obesity,metabolic dysfunction-associated fatty liver disease(MAFLD)has become a major cause of liver disease worldwide.The increase in the incidence of MAFLD from 15% in 2005 to 25% in 2015 has been linked to a sharp increase in obesity worldwide.MAFLD occurs in 70% of obese people and 85% of morbidly obese people.Insulin resistance is a risk factor for obese MAFLD.In patients with type 2 diabetes,the incidence of MAFLD is76%.Early detection and timely intervention to prevent the deterioration of MAFLD will undoubtedly play a positive role in the diagnosis and treatment of MAFLD.Endoscopic gastro-intestinal anastomosis after pyloric closure is a new surgical procedure.After pyloric closure,gastro-intestinal anastomosis under the guidance of endoscopic ultrasound can achieve open location of duodenum and part of jejunum,reduce the absorption of food,and further alleviate liver injury in MAFLD.Because other intervention measures(including exercise,health education,lifestyle intervention)in the treatment of obesity has a short effect,not easy to control and so on.Metabolic surgery for weight loss is undoubtedly the treatment of choice.Compared with non-operation,it has the advantages of stability and long duration.From the simple restriction of food intake and absorption to the intestinal flora pathway,epigenetic pathway,bile acid pathway to improve the metabolic level of patients,weight loss and metabolic surgery methods have been constantly improved.At present,the three most widely used in the world include: Laparoscopic Roux-en-Y gastric bypass(LYRGB);and Biliopancreatic diversion with Duodenal switch(BPD-DS).Although laparoscopic surgery is less invasive in appearance,it is characterized by excision of the stomach,anatomical structure changes,and difficult recovery,resulting in more postoperative complications.For pyloric closure,the retrievable double balloon method can be used to perform EUS-GE.After the control of liver function is restored and improved,the balloon and stent can be removed at a selected time,so as to complete the recovery of the anatomical structure and the cure of the disease.In this study,endoscopic ultrasound gastro-intestinal anastomosis was performed on patients with clinical upward gastrointestinal obstruction to observe the major postoperative complications.And intervene.On this basis,pyloric closure and ultrasound-guided gastro-intestinal anastomosis were performed on MAFLD animals through modeling,so as to explore the postoperative alleviating effect on liver function and the study on lipid metabolism and the possible potential mechanism.Methods: In this study,the patients who received endoscopic ultrasonography guided gastro-intestinal anastomosis in our hospital from January 2018 to October 2020 were revisited and included in the study.The observation indexes were the success rate of endoscopic ultrasonography gastro-intestinal anastomosis,white blood cell count,postoperative survival time,stent removal time and stent displacement rate.The stent was fixed with double anchor lockers to evaluate the safety and effectiveness of endoscopic ultrasound-guided double anchor lockers for stent fixation,and to intervene in postoperative complications of EUS-GE.By building MAFLD model,the complications and survival rate of experimental animals were recorded after surgery,and the following indexes were detected :(1)body weight and food intake;(2)Serological indicators: Blood samples were collected on the day of operation and 4,8 and 12 weeks after operation to detect the levels of albumin,ALT,R-GT,triglyceride and cholesterol;(3)The animals were sacrificed 12 weeks after the operation.Liver samples were collected for HE staining and oil red O staining,respectively,to determine the fat accumulation.(4)WB and PCR methods were used to detect the key enzymes of lipogenic fatty acids: fatty acid synthase(FAS)and non-esterified fatty acids(FFA),which are products of triglyceride decomposition.Acetyl-Co A carboxylase(ACC)was detected by immunohistochemical method.To evaluate the efficacy of endoscopic ultrasonography-guided gastrointestinal anastomosis in the treatment of obese non-alcoholic fatty liver disease and the remission of dyslipidemia.Experimental animal specimens were collected after surgery,and the following indicators were detected: the expression of GLP-1,GIP,leptin,adiponectin,insulin and inflammatory factors were detected by ELISA method to explore the possible mechanism of endoscope-guided gastrointestinal anastomosis on the reduction of lipid metabolism in obese non-alcoholic fatty liver disease.Results: 1.Fifteen patients were included in the study,including 12 patients with malignant etiology and 3 patients with benign etiology.In malignant etiologies,the surgical success rate is 100%.Postoperative transient leukocyte elevation in 2 cases improved with antibiotics.The mean survival time of the 11 patients was 2.7-4.5 months.One is still alive.No stent removal was found in malignant etiology.Two of them had stent displacement and were treated with stent sleeve under endoscopy.In benign etiologies,the surgical success rate is 100%.There was no transient leukocyte elevation after operation.Three patients are still alive after surgery.At the same time,stents were removed 6 months after surgery in 3 cases.No stent displacement was observed during stent placement.2.During the operation,endoscopic gastro-intestinal anastomosis was successfully completed in both the experimental group and the control group,with a success rate of100%.In the experimental group,the mean time of pyloric annulus incision was30.5±3.46 min,and the mean time of stent implantation was 29.37±8.53 min.The fixation time of the stent was 10.75±1.49 min.In the course of operation,a stent was successfully placed again after the wound in the stomach was closed due to stent placement in the abdominal cavity.One of the recent adverse reactions was pneumoperitoneum.Additional bleeding and perforation did not occur.In the long-term adverse reactions,no stent obstruction occurred in 8 animals,and stent displacement occurred in 1 animal.The average weight loss was-1.39±3.12 kg.In the control group,the mean time of pyloric annulus incision was 30.13±2.41 min,and the mean time of stent implantation was22.86±4.48 min.No recent adverse reactions occurred.Among the long-term adverse reactions,no stent obstruction occurred in 8 animals,and stent displacement occurred in7 of them.The average weight loss was-0.55±4.47 kg.The animals in the experimental group and the control group could eat normal food after the operation.Autopsy of the experimental group showed complete adhesion between the intestinal wall and the stomach wall,and the anchors and lockers were intact.In the control group,the stent fell off and a fistula could be observed anatomically.3.In the experiment,there was no obvious difference in food intake among the three groups.The weight of the control group showed a significant upward trend,while the weight gain of the surgery group and the drug group showed a smaller upward trend than that of the control group,which was statistically significant.4.Compared with the control group,AST and R-GT in liver function were significantly improved by endoscopic gastro-intestinal anastomosis and drug operation.5.The animals had lower serum triglycerides and cholesterol after the drugs,and the surgery also improved,but not as much as the drugs.6.Both HE staining and oil red 0 staining suggested that the degree of hepatic steatosis was alleviated in the gastroenterostomy group and the drug group under the guidance of endoscopic ultrasound.7.WB and PCR results at 12 weeks after operation indicated that the expressions of Fas,ACC and FFAR in liver of the operation group were decreased.8.Postoperative insulin resistance was relieved.9.The levels of GLP-1 and GIP in serum of the animals after gastroenterostomy under endoscopic ultrasound showed an increasing trend after surgery,but the changes were not obvious in the drug group.10.In the operation group,leptin decreased significantly in the first month after operation,but had little change in the second and third months after operation.The trend of adiponectin was not obvious.11.Inflammatory cytokines TNF-A,IL-6 and IL-1 in the operation group increased significantly in the first month after surgery,and returned to normal in the second and third months after surgery.Conclusion: 1.Endoscopic gastro-intestinal anastomosis is a safe,effective,minimally invasive,scarless,simple and widely applicable treatment that can alleviate the treatment effect of upper gastrointestinal obstruction.However,stent displacement in patients after surgery is the main cause of adverse reactions in patients with gastro-intestinal anastomosis under the guidance of endoscopic ultrasound.2.The method of fixing the stent with double anchor lockers can effectively prevent the stent from shifting,and this operation is safe and effective,with little trauma and high safety.3.Gastrointestinal anastomosis under the guidance of endoscopic ultrasound has a alleviating effect on liver function and blood lipid.It has ameliorative effect on the elevation of blood lipid and hepatic steatosis.4.Gastrointestinal anastomosis under endoscopic ultrasound improved insulin resistance,which was closely related to the improvement of lipid metabolism.5.Elevation of GLP--L and changes in bile acid metabolism may be the reasons for recovery of insulin sensitivity and improvement of lipid metabolism.6.EUS-GE was applied to the obstruction of digestive tract caused by malignant diseases,but it did not have more obvious effects on metabolism,and the complications were small and controllable.It has mild effect on benign diseases and can regulate the absorption of metabolic nutrients according to the length of open small intestine.
Keywords/Search Tags:Pyloric obstruction, endoscopic ultrasound-guided gastrointestinal anastomosis, MAFLD, lipid metabolism
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