Interventional treatment of esophagogastric varices in cirrhosis Portal hypertension with esophagogastric variceal bleeding is a common emergency in gastroenterology, with a mortality rate of 48-62% for initial bleeding and a 60-70% risk of rebleeding within 2 years in surviving patients. How to control ruptured esophagogastric variceal bleeding and prevent rebleeding has become the key to save the lives of patients with cirrhosis. It is also an urgent clinical problem to be solved. Now, the advantages and disadvantages of various therapeutic techniques from anatomical structure are combined with recent interventional techniques carried out by the Department of Gastroenterology of Shandong Provincial Hospital in this field at home and abroad. 1.Esophageal varices applied anatomy esophageal veins are located in the submucosa and muscle layer of esophagus or in the wall of the subplasma membrane, esophageal varices usually refer to varices in the lower part of esophagus, especially varices located in the submucosa of esophagus are easy to rupture and bleed, which are better observed on CT axial and MPR, TSMIP two-dimensional images, which show nodular, striated, earthworm-like, clustered vascular cross-sectional images in the thickened esophageal wall , the inner wall of the esophagus is uneven and jagged, mild varices are not easily revealed by CT and are less sensitive than endoscopy [ 10]. The paraoesophageal vein is located in the posterior mediastinum outside the esophageal wall, and its patency can play a shunting role to reduce the degree of esophageal varices, and CT shows varices outside the esophageal wall, which can be easily distinguished from varices on CT 2D images, but they are not easily distinguished on 3D images, especially when the varices are significant. Both the varices and the paraoesophageal veins merge directly or indirectly into the dilated odd and/or hemi-odd veins and finally into the superior vena cava. According to Shinichi Nakamura et al [12], there are four types of connections between the esophageal vein, the paraoesophageal vein and the coronary vein (see the figure below): type I, where the coronary vein ends in a branch that enters the cardia and connects to the esophageal vein, and no paraoesophageal vein exists outside the esophageal wall; type II, where the coronary vein is divided into two branches, the anterior branch enters the cardia and connects to the esophageal vein, and the posterior branch connects to the paraoesophageal vein outside the esophageal wall. The blood of this type of esophageal varices mainly comes from the anterior branch of the coronary vein; Type III, the end of the coronary vein is also a branch that connects with the paraesophageal vein outside the esophageal wall, and then continues with the varices of the esophagus through the perforating vein, and the paraesophageal vein of this type is generally thickened significantly; Type IV, the end of the coronary vein is also divided into two branches, which connect with the anterior and posterior branches respectively. In type IV, the coronary vein is also divided into anterior and posterior branches, which are connected with esophageal vein and paraoesophageal vein respectively, and there is a penetrating vein traffic between them. For type II without intervening veins, the paraoesophageal veins should be preserved during surgery or intervention to play the role of shunt, but it is difficult to distinguish the intervening veins by CT, which is the limitation of CT, while ultrasound endoscopy can clearly show the distribution and course of the intervening veins; in conclusion, in portal hypertension, the esophageal veins mainly receive the retrograde blood from the coronary veins, but also partly from the fundic veins [13], and occasionally the left branch of the portal vein is coexisting The ectopic high esophageal branches that develop, which can be clearly shown on CT images when the above-mentioned vessels are dilated. 2, Advantages and limitations of endoscopic ligature and sclerotherapy Endoscopic ligature and sclerotherapy is the conventional treatment for esophagogastric varices and is the first-line treatment technique for ruptured esophageal varices and bleeding. It is widely used clinically because of the advantages of easy operation, small trauma and reliable effect of emergency hemostasis. Reproducible and easy to promote, it is the current standardized treatment option for esophagogastric varices. However, EVL and ESI have unavoidable congenital defects. Although endoscopic ligation or sclerotherapy can cause scarring of the esophageal mucosa and submucosa and temporary disappearance of the esophageal veins, because endoscopic treatment, especially the currently popular microscopic ligation – this mechanical ligation – cannot adequately obstruct the penetrating veins connecting the parietal and submucosal esophagus, the high pressure blood flow around the esophagogastric fundus can flow through the penetrating veins to the submucosal veins, causing The varices of the esophagogastric fundus can be re-formed in a relatively short time (Figure-2). Therefore, endoscopic treatment is currently considered to be an effective method to stop bleeding in acute cases, but the recurrent bleeding is high, the long-term efficacy is uncertain, and the cut requires repeated treatment, which increases the traumatic nature of copying and the economic burden. Endoscopic treatment is not infallible. 3, transjugular intrahepatic portosystemic stent shunt (TIPS) In 1989, German radiologists such as richrer introduced an interventional radiology technique for the treatment of ruptured variceal bleeding caused by portal hypertension in hepatic sclerosis into clinical practice. This interventional technique has been carried out in our hospital since 1993. TIPSS mainly emphasizes that all interventional operations are performed in the liver, and its approach is the classic transjugular approach, which establishes a partial portal shunt in the liver, thus reducing portal pressure, and simultaneously embolizing the collateral circulation of the variceal bleeding, It also allows simultaneous embolization of the collateral circulation of the variceal bleeding, achieving the dual treatment goal of shunting and disconnecting the flow. TIPSS has important advantages: (1) it is less invasive and can be performed under local anesthesia in patients with acute illnesses, child C patients can tolerate the procedure, and the effect of lowering pressure is precise and effective; (2) due to the adjustability of the shunt channel (using balloon expansion of the stent), individualized flow is achieved according to individual needs, and the disadvantages of hepatic encephalopathy caused by transitional shunts can be minimized; (3) in TIPSS, a partial portal shunt channel is established to reduce portal pressure; and the collateral circulation of variceal bleeding can be embolized at the same time to achieve the dual purpose of treatment with both shunt and dissection. (3) the operation of TIPSS with simultaneous small-bore shunt and portal dissection is conducive to greater utilization of their respective therapeutic advantages and reduction of side effects. At present, TIPSS is more than “quiet” in China, while the basic and clinical applications in Europe and the United States are developing steadily. The results of several overseas studies on the clinical application of TIPSS have shown that compared with medical methods, TIPSS is more effective for acute gastrointestinal hemorrhage caused by portal hypertension; especially hemorrhage caused by fundic varices, and the combination of embolization of esophageal and fundic varices is beneficial to the prevention of reissue of blood; compared with surgical bypass, TIPSS is less invasive, safer, and relatively easy to perform. Compared with surgical bypass, TIPSS is less invasive, safer, and relatively simple to perform, and the bypass effect is the same as that of surgical bypass. Therefore, TIPSS should be included as a treatment option in acute gastrointestinal hemorrhage when medical treatment is not effective. It can be concluded that TIPSS is still a valuable and practical technique among the existing treatments for portal hypertension in cirrhosis, and has advantages that are not available with medical and surgical approaches. On the contrary, in the domestic situation, some scholars have changed from the initial excitement to the current “cold” situation, for various reasons, and the gap between expectations and actual results is the main problem. Indeed, the relatively wide grasp of indications for some patients at the early stage of TIPSS application has caused some blindness; the occurrence of stenosis or even occlusion of the internal stent in some patients after surgery, especially the expensive cost does not bring satisfactory long-term results, is also one of the reasons for the current relative stagnation. The problem of postoperative shunt stenosis and restenosis is also a hot spot and a difficult problem. Despite the efforts of many parties, no breakthrough has been achieved yet. The results demonstrate that the incidence of restenosis tends to increase with time. And postoperative stenosis mainly occurs within one year after surgery. It can be seen that the problem of postoperative stenosis and restenosis after TIPSS has become one of the main problems and difficulties affecting the medium and long-term outcomes. In recent years, the application of overlapping stents seems to improve the long-term patency rate, and if this difficulty can be broken through, TIPSS is expected to be re-recognized and more widely used as a treatment tool. 4, percutaneous transhepatic tissue adhesive interventional dissection Because of the limitations of endoscopic treatment and the re-occlusion of TIPS distant frame, the development of interventional dissection has provided an opportunity. This technique is aimed at the anatomical characteristics of varicose veins and blood supply veins, and embolization is thorough and reasonable. TH glue is a domestic tissue adhesive, which belongs to the a-cyanoenolate class of glue, and its structural formula a-carbon atom combines CN and COOR groups, so that the carbon atom in the β-position has strong electric absorption, and in the presence of trace anions, it can produce instant polymerization reaction and curing, The purpose of permanent occlusion of the lumen is achieved. TH gel is a liquid embolic agent, and after injection through the coronary vein of the stomach, TH gel enters the lower esophagus and the submucosal varices of the gastric fundus through the perforating veins between the muscular layer, and blocks the paradoxical blood flow inside and outside the esophageal wall, so that the traffic branches between the portal veins are completely and permanently embolized to ensure the long-term efficacy of the interventional embolization. and TH gel embolization simulation. Figure: TH glue completely embolizes the varices and their blood supplying veins, submucosal and peri-oesophageal blood supplying veins. 5. Several factors influence the long-term efficacy of TH gel embolization. (1) Focus on embolization of the lower esophagus, gastric fundus and varices around the cardia at 5cm above and below the cardia When injecting TH gel, the catheter should be inserted into the distal end of the gastric coronary vein, so that TH gel is infused into all vascular branches of the lower esophagus and cardia area of the gastric fundus, making the vascular shape there and completely blocking the paradoxical blood flow in the bleeding area of the gastric fundus and lower esophagus. The varices of the lower esophagus 3-5 cm above the cardia and the varices of the fundus within 5 cm below the cardia are the appropriate sites for ruptured variceal bleeding in combination with portal hypertension, and only permanent embolization of this site can achieve the desired long-term effect. As early as 1979, Bengmark et al. reported the use of octyl cyanoacrylate for embolization of the gastric coronary vein, but the amount of adhesive used at that time was only 0.5-2 ml, which mainly embolized the main trunk of the gastric coronary vein, and the varicose vein was rarely filled with embolic agent. In our group, the amount of TH gel used was 4-22 ml, with an average of 7.5 ml, and TH gel was required to embolize not only the main trunk of the coronary vein but also all branches around the cardia of the fundus. According to the results of our 146 patients, the embolization results can be divided into three types according to the range of TH glue filling in the vessels: 1) esophagogastric-fundus type, where the embolization is more complete, with TH glue filling in the anterior and posterior branches of the coronary vein, the vessels around the cardia of the fundus, and the varices of the lower esophagus of at least 5 cm or more (Figure); 2) fundus-cardia type3, where TH glue embolizes the coronary vein and the cardia of the fundus but not the varices of the cardia. 3) Trunk type 3, TH gel embolized in the trunk of the coronary vein of the stomach and did not reach the fundus of the stomach around the cardia (Figure). The results of our application in the past 4 years show that the rebleeding rate is less than 10% in the case of TH gel embolization reaching the peripancreatic vessels of the fundus or the varices of the lower esophagus, while the rebleeding rate is as high as 67% in the case of embolization of the trunk of the coronary vein only. This suggests that complete embolization of the varices in the lower esophagus and gastric fundus is a key factor in ensuring long-term outcome. a b c Figure-2, TH glue 3 types of embolization: a. esophagogastric-fundus type; b. gastric fundus type; c. trunk type 2) Combined partial splenic embolization In portal hypertension, 60-70% of the blood flow in the portal vein comes from the spleen, and splenic artery embolization can reduce splenic blood flow and portal blood flow, Embolization of the splenic artery can reduce splenic blood flow and portal venous blood flow, and subsequently reduce portal venous pressure and block portal venous hyperdynamic circulation. In our study, we found that the basal portal pressure increased by 8.6% after gastric coronary vein embolization, and decreased by 19.5% after splenic embolization. This indicates that the combined intervention can significantly reduce portal pressure. Gao Huan et al. reported a group of intraoperative TH gastrointestinal coronary vein embolization cases [8], in which 38.3% rebleeding was observed in embolization alone and 8.9% in combined splenectomy, suggesting that the high blood flow status of the spleen affects the long-term outcome of coronary vein embolization. We advocate splenic embolization at 50-80% to minimize portal vein pressure and reduce postoperative neovascularization and recurrent bleeding from varicose veins. However, the abdominal pain, fever and ascites aggravation after splenic embolization should be taken seriously and actively prevented. (3) Reasonable application of endoscopic ligature and sclerotherapy In esophagogastric fundic type with more complete variceal embolization, TH glue has been filled in the peripancreatic vessels of the fundus and at least 5 cm above the variceal veins of the lower esophagus, endoscopic treatment is not necessary. However, in the case of fundic-cardia embolism or coronary trunk embolism where TH glue does not reach the lower esophagus, endoscopic ligation or sclerotherapy can be considered as an extension and supplement to the scope of interventional embolization, which will also reduce the risk of endoscopic treatment because the main source of blood supply to the varices of the esophagus is blocked by the embolization of the varices at the base of the stomach. The efficacy of combined treatment: 1+1〉2. Figure-3 Simulation of combined treatment 4) Prevention of ectopic embolism The curing time of TH gel after encountering blood flow is 6-10 seconds, because the varices are twisted and the blood flow is slow, TH gel has enough time to coagulate and embolize in the varices, and it usually collects in the varices of the lower esophagus and the cardia of the gastric fundus and does not flow to distant areas. Pulmonary embolism occurs. However, in patients with abnormally large varices, excessive blood flow rate or abnormally large traffic branches, ectopic embolism should be prevented. In such patients, we recommend that after the catheter has been superselected for the gastric coronary vein, an appropriate amount of anhydrous alcohol should be injected or a ciliated steel ring should be placed at the beginning of the gastric coronary vein to partially block the blood flow in the gastric coronary vein, and then the catheter should be injected with TH gel across the ring to prevent ectopic embolism caused by the rapid “downstream” flow of TH gel. In addition, during TH gel injection, if coronary venous flow is blocked, the injection should be stopped in time to avoid portal vein embolism caused by reflux. In our group, only one case of minor pulmonary embolism occurred at the beginning of the study, but the injection was stopped in time after the intraoperative discovery of ectopic TH glue wandering, and no significant adverse consequences occurred. 6.Technical advantages and postoperative regression of TH glue infusion embolization TH glue is an a-cyanoacrylate octyl ester containing contrast agent, which solidifies and forms thrombus within 6 seconds after encountering blood, and then mosaic with tissues to achieve the purpose of permanent occlusion of the official cavity. As early as 1983, Liu Xiaogong and other scholars in China proposed TH glue embolization of the gastric coronary vein under direct vision in the open abdomen, during which TH glue was injected into the lower esophagus and the venous plexus at the base of the stomach by a gastric coronary vein cannula. The TH gel was shown to be a permanent mucoadhesive agent, which is not easily recanalized after embolization, and its long-term efficacy is equivalent to that of conventional surgical dissection or bypass. However, the intravascular distribution of TH glue cannot be shown dynamically during surgery, and the possible ectopic traffic branches cannot be detected in time, and fatal pulmonary embolism may occur [10], which limits the clinical application. This technique is operated under X-ray surveillance, and TH gel is injected along the esophageal and gastric branches of the gastric coronary vein and flows towards the end, eventually filling the varices in the lower esophagus, cardia and fundus, solidifying the lumen and completely eliminating the anomalous blood flow forming the varices in the esophagogastric fundus. Compared with intraoperative TH glue embolization, the X-ray operation can accurately understand all the portal branches, including high or ectopic side branches, and avoid ectopic embolization caused by blind injection; it can observe the flow range of TH glue in the blood vessel in real time, and by adjusting the injection speed and dosage, it is possible to completely eliminate the ectopic flow of varices. It is possible to observe the intravascular flow of TH gel in real time and adjust the injection speed and volume to achieve a satisfactory embolization site. In conclusion, although endoscopic sclerotherapy and ligation can better control emergency bleeding, endoscopic treatment mainly deals with superficial vessels under the mucosa, and it is difficult to completely embolize the peripheral veins of the esophagogastric fundus and the perforating veins of the muscular layer, so the rate of recurrent bleeding is higher. In recent years, in view of the limitations of endoscopic treatment, our hospital has actively carried out clinical application research on percutaneous transhepatic tissue glue infusion embolization, and in some cases combined with necessary endoscopic treatment or transjugular intrahepatic portosystemic shunt (TIPSS), forming a comprehensive treatment mode with interventional flow dissection (PTVE) as the mainstay and interventional shunt (TIPSS) and endoscopic treatment as the supplement, which has obviously improved the level of esophagogastric fundus The level of varices treatment has been significantly improved.