Study On The Conditions And Pathophysiological Mechanism Of Gallbladder-digestive Fistula After EUS-guided Gallbladder Drainage

Purpose: The per-oral cholecystoscope using EUS-guided gallbladder drainage(EUS-GBD)can safely and efficiently complete gallbladder interventional treatments such as stone removal and biopsy.The strength of the fistula formed between the gallbladder and the upper gastrointestinal tract after EUS-GBD severely affected the success rate of subsequent per-oral cholecystoscope operations.However,little was known about the time of fistula formation and related mechanisms.Therefore,this study used clinical retrospective research and animal experiments to study the formation process,regulatory factors and mechanism of fistula after EUS-GBD and to provide a basis for determining the time for stent removal and interventional treatment after EUS-GBD.Method: A retrospective study was conducted on patients who underwent EUS-GBD and per-oral cholecystoscope in our hospital from June 2014 to January 2021 to verify the safety and effectiveness of EUS-GBD and per-oral cholecystoscope,and to analyze the factors influencing the formation of gallbladder-gastrointestinal tract fistula formed after EUS-GBD and the tolerance of the fistula to different per-oral cholecystoscope interventional procedures.After that,Bama pigs were used as experimental animals to use traction experiments and histological studies(HE staining,Masson staining and immunohistochemical staining)to explore the effect of stent indwelling time on the formation and strength of the fistula after EUS-GBD and to study the histological changes and related mechanisms during the formation of the fistula.Results: A total of 52 patients underwent EUS-GBD and per-oral cholecystoscopy in our hospital from June 2014 to January 2021.All of them showed a complete fistula surrounding the stent.Except for 2 patients whose stent indwelling time was too short(7days and 10 days)suffered fistula rupture,the rest of the patients(50 cases)successfully completed the per-oral cholecystoscope treatment,suggesting that this method is safe and effective.The size and kind of gallbladder stones were the key factors that affect the stent indwelling time and the operation time of the per-oral cholecystoscope.Animal experiments found that the formation of a fistula can be seen 1 week after EUS-GBD,and the intensity of the fistula gradually increases with time,reaching a peak at 4 weeks,and then maintaining stability.The intensity of the fistula exceeded the intensity of the autologous duodenal tissue at 2 weeks after the operation,and the intensity of the fistula was 2.6 times the intensity of the duodenum at 4 weeks after the operation.The formation of the fistula undergone the process of inflammation,granulation hyperplasia,fibrosis and epithelialization,which was in line with the process of wound healing.During the formation of fistula,the expression of TGF-? and Smad3 peaked at 2 weeks after surgery and then decreased.The expression of S100A4 peaked at 2 and 8 weeks after surgery.The expression of ?-SMA and the accumulation of extracellular fibrin continued to increase.Conclusion: EUS-GBD and per-oral cholecystoscope operation have high safety and effectiveness in the treatment of calculous cholecystitis;Both the gastric route and the duodenal route of EUS-GBD can form a stable fistula;operations such as lithotripsy and fistula orifice angiography increase the risk of fistula rupture.The formation of the fistula goes through the three processes of granulation,fibrosis,and epithelialization,which is in line with the wound healing process;the strength of the fistula increases with the extension of the stent indwelling time,and balances at 4 weeks after the operation.The strength of the fistula is related to the degree of tissue fibrosis.The fibrosis of the fistula is related to the up-regulation of S100A4 and ?-SMA Controled by the TGF-?/Smad3 pathway.