For splenomegaly and hypersplenism due to cirrhosis and various other causes, the traditional approach is open or laparoscopic splenectomy. Since surgical splenectomy reduces antibody production, it involves more serious complications such as overwhelming post-splenectomy infection (OPSI), sepsis, hemorrhage, portal vein thrombosis, etc. The post-splenectomy spleneless state, immunosuppressive therapy especially radiation therapy may be the basis of OPSI.
Therefore, finding an effective and minimally invasive treatment method is of clinical importance. Partial splenic embolization (PSE) can be used to achieve non-surgical splenectomy, and Pinto et al. showed that transcatheter arterial embolization of 60% to 70% of the spleen significantly improved hypersplenism, while the residual 30% to 40% of splenic tissue was immunoprotective against sepsis. PSE also provides a chance of survival for inoperable patients and has become an important alternative to surgical splenectomy.
1. Indications and contraindications for PSE.
1.1 Indications for PSE.
PSE is mainly used in the early stage of cirrhosis due to portal hypertension with splenomegaly and hypersplenism. It has been proved [2~28] that for splenomegaly and hypersplenism caused by various diseases are suitable for interventional treatment.
(1) Diseases related to cirrhotic portal hypertension: they can be treated alone or in combination with other methods, such as endoscopic variceal ligation (EVL), percutaneous transhepatic varices embolization (PTVE ), etc;
②Hematologic diseases;
③Neoplastic diseases: supportive treatment for hepatocellular carcinoma combined with cirrhosis and splenomegaly, and targeted treatment for splenic neoplastic diseases;
④Adjuvant therapy for liver transplantation: treatment of hypersplenism before and after liver transplantation, which can reduce the risk of perioperative complications due to splenectomy, as well as treatment of splenic artery steal syndrome to improve post-transplant liver perfusion;
⑤ Splenic trauma and splenic vascular lesions;
(6) Others: pain syndrome due to giant spleen, and patients who do not want surgery but require non-surgical treatment.
1.2 Contraindications to PSE.
Mainly include.
①Iodine allergy;
(ii) Significant disorders of coagulation mechanism;
③Severe jaundice;
④Extremely low plasma albumin;
⑤ intractable ascites with primary peritonitis;
⑥Child C grade liver function with extreme failure;
(7) Severe cardiopulmonary and renal organ insufficiency;
⑧Patients with secondary splenomegaly and hypersplenism, whose primary disease has reached the end stage;
⑨ Patients with sepsis, splenic embolism with a high risk of splenic abscess;
⑩ splenic artery superselective cannulation failure may not be injected in the abdominal arterial trunk embolic agent.
2. Basic PSE operations.
2.1 PSE-related splenic application anatomy.
The splenic artery originates from the abdominal trunk in 81.2% and travels along the superior margin of the pancreas in a wavy bend, and its segmental distribution features provide an anatomical basis for PSE procedures. The splenic lobe artery usually emanates 1.5-2.5 cm from the splenic hilum. The splenic lobar artery is superiorly and inferiorly branched in 93.8% of cases and superiorly, medially, and inferiorly branched in 6.2% of cases. Each branch is further divided into two to three splenic segmental arteries, which then gradually branch. The splenic artery sends out many branches to supply the tail of the pancreatic body, the largest branch is the dorsal pancreatic artery, followed by the large pancreatic artery, they all originate from the middle segment of the splenic artery, when making a plan for splenic embolization, the pancreatic artery must be visualized to reduce the risk of ectopic embolization.
2.2 Choice of embolization methods.
The commonly used methods are superselective splenic artery embolization and nonselective splenic artery embolization. The splenic artery can be superselectively cannulated to some distal branches of the splenic artery and made to embolize completely. In order to accurately estimate the embolization area and reduce the occurrence of serious adverse effects after embolization, scholars at home and abroad now mostly use superselective cannulation of the middle and lower pole splenic artery followed by injection of embolic agent. The use of coaxial microcatheters can reduce the difficulty of operation when the splenic artery is severely tortuous and make super-selective cannulation possible to achieve precise embolization and prevent regurgitation.
Non-selective splenic artery embolization is performed by placing the tip of the catheter in the main trunk of the splenic artery and injecting an appropriate amount of embolic agent, which randomly embolizes the splenic artery branches of the appropriate diameter with the blood flow. This method is prone to infarction foci of different degrees in all parts of the spleen, and it is difficult to accurately judge and control the embolization area during operation, which can easily lead to over-embolization and severe reactions due to large infarcts in the splenic area.
2.3 Selection of embolization materials.
Scholars at home and abroad have studied and compared the embolization effect by applying a variety of embolization materials, and most of them choose gelatin sponge as embolization material. Zhu Kongshun et al. pointed out that although gelatin sponge particles are absorbable embolic agents, infarction of splenic tissue occurred long before its absorption, and the possibility of postoperative revascularization could be disregarded when PSE was applied.
Han et al. used 100-150 gelatin sponge particles of 1 to 2 mm as the upper limit of safe embolization, and most of the embolized splenic parenchyma could reach 50% to 70%, regardless of whether the blood flow in splenic artery branches was slowed down. Stainless steel rings can permanently occlude larger vessels and are used for embolization of the main trunk or larger branches of the splenic artery.
Polyvinyl alcohol (PVA) pellets are permanent end-embolization materials that can be easily released and controlled via microcatheters, and embolization can reach the level of the splenic sinus, resulting in complete infarction of the functional splenic area, which is not easily recanalized. In addition, there are studies on the application of detachable balloons, anhydrous ethanol, iodized oil, sodium cod liver oil and real silk threads as embolic agents.
3, PSE postoperative complications.
In the early application of PSE surgery, Trojanowski et al [7] reported in 1980 that its complication rate was 30% to 40% and mortality rate was 20% to 30%. With the increasing research and improvement of treatment methods and operation techniques, the incidence of complications and mortality have been greatly reduced. Drooz et al. 2003 concluded that the success rate of embolization for splenic trauma and hypersplenism was 87%-100%, and the overall serious complication rate after embolization was 8%-22%.
3.1 Common complications.
3.1.1 Puncture site hematoma: Mostly due to short local compression hemostasis time or abnormal coagulation mechanism.
3.1.2 Post-embolization syndrome: Sakai et al [9] reported that the most common side effects were abdominal pain (82.4%) and fever (94.1%), and nausea and vomiting, which are usually tolerable. han et al [4] observed that left upper abdominal pain could last from 8 to 18 days, while severe pain was only 2 to 6 days. In case of sudden and persistent hyperthermia splenic abscess and other foci of infection should be excluded.
3.2 Serious complications.
3.2.1 Pneumonia, atelectasis or pulmonary insufficiency and pleural effusion: Infarction of the upper pole of the spleen stimulates reactive inflammation of the left diaphragm and pleura. Patients with pain in the splenic region resulting in restricted respiratory movements, poor bronchial drainage resulting in left pneumonia and pulmonary insufficiency. pinto et al [2] studied that fever and leukocytosis associated with pulmonary embolic syndrome (PES) can occur in more than 50% of patients with excessive embolism, usually lasting 3 to 5 days.
C-reactive protein (CRP) can be measured to distinguish PES from infection. The characteristic peak of CRP appears on postoperative day 4-5 and decreases to normal on day 10, while the peak of CRP does not decrease or continues to increase in case of infection.
3.2.2 Peripleural inflammation and transient ascites: they are caused by exudation and irritation from the surface of splenic infarction.
3.2.3 Splenic abscess: a more serious complication of PSE, resulting from aseptic laxity and the return of blood from the portal venous system containing intestinal bacteria into the splenic embolic area along the splenic vein. Once a splenic abscess develops, it should be treated by local puncture intervention or surgery.
3.2.4 Splenic rupture: the fourth postoperative week is the most dangerous period for rupture of the splenic envelope [10].
3.2.5 Splenic vein or portal vein thrombosis: postoperative erythrocytes and platelets are sharply elevated and slow blood flow in the splenic vein is caused.
3.2.6 Misembolization: Insufficient depth of catheter insertion, poor selectivity or high injection pressure causing regurgitation of embolic agent and misembolization of liver, pancreas and gastrointestinal organs, etc.
3.2.7 Others: such as paralytic intestinal obstruction, bacterial peritonitis, hepatorenal syndrome, etc. In EVL-PSE [11], EVL-related angina and/or retrosternal pain may occur, which usually resolves spontaneously after 3 to 5 days.
3.3 Complication prevention and control.
The general guidelines for the prevention and treatment of complications arising are.
① Application of broad-spectrum antibiotics from 8 to 12 hours preoperatively until 1-2 weeks postoperatively, and local application of embolic substances mixed with antibiotics (e.g., gentamicin) and strict asepsis;
② Selective cannulation over the opening of the main pancreatic artery branches to prevent misembolization;
③Effective pain control;
④Avoid excessive embolization.
4. PSE application and efficacy assessment.
PSE weakens splenic phagocytosis and suppresses immune hemocytopenia in patients with cirrhosis, thereby correcting hypersplenism and reducing the occurrence of complications related to portal hypertension. The efficacy of PSE was significant in both the immediate and long term, independent of age, gender, duration of disease and platelet count before treatment.
Palsson et al. followed up 26 patients (total follow-up time 1715 months) and evaluated their physical status, hematological parameters, and number of esophageal variceal bleeds. 19 patients improved (improvement in at least 2 parameters), 5 patients maintained their status quo (improvement or deterioration in 1 parameter and no change in other parameters or no change in all 3 parameters), and 2 patients deteriorated (decrease in at least 2 parameters).
4.1 Splenic changes.
CT 2 days after PSE showed heterogeneous multifocal peripheral infarct formation in the spleen, and within 2 weeks the spleen volume increased to 110%-140% of that before PSE. 2-4 weeks CT scans could show infarct formation and liquefaction as well as well-demarcated splenic infarct foci, and within 1 month there was almost no splenic wrinkling, and after 2 months it showed liquefied tissue absorption and the whole spleen volume decreased significantly and remained stable. Grossly, the spleen appeared as a gray area of segmental infarct formation, and microscopic examination suggested degenerative necrosis of the splenic parenchyma and proliferation of surrounding fibrous tissue.
Watanabe et al. studied a group of children whose spleen volume before PSE was 7.2 to 14.2 times that of a normal spleen, and after PSE the spleen volume did not decrease to normal size but remained 2 to 7 times larger than normal.Killeen et al. studied pre- and post-operative CT scans of blunt splenic trauma with PSE: 63% of proximal splenic artery trunk emboli had splenic infarcts, which were mostly small, multiple, and The distal embolization, on the other hand, was 100% infarcted, and the infarcts were larger and solitary; statistics showed that distal embolization was more prone to infarct formation than proximal embolization. The degree of spleen volume reduction correlated with the embolic area, and less than 20% had no spleen reduction.
4.2 Peripheral blood picture changes.
4.2.1 Platelets.
Platelet values increase at 24 hours after surgery, peak at about 1 week, and can be 3-fold higher than preoperative values at 2 weeks, and can increase by 185% and 95% at 1 month and 6 months, respectively [15,16], after which they continue to increase steadily or decline slowly to normal levels. increase in platelet thrombopoietin (TPO) and platelet-associated immunoglobulins after PSE The increase in thrombopoietin (TPO) and platelet-associated immunoglobulins after PSE may promote platelet repair and increase platelet counts.
Rios et al. studied the effect of TPO before and after PSE or liver transplantation in 33 cases of cirrhosis. Plasma TPO levels were negatively correlated with spleen volume, TPO half-life was prolonged after PSE, TPO and platelet count increased significantly at 90 days, and TPO levels increased rapidly on day 7 in most cases, and the physiological relationship between TPO and platelets was restored.
4.2.2 Leukocytes.
They can be elevated to normal one week after surgery due to inflammatory response, drop to (4.0-7.0)×109/L after 3 weeks and remain stable, and can be elevated by 51% and 30% after 1 and 6 months, respectively [15].Sakai et al [9] reported that leukocyte and platelet counts were elevated in 16 of 17 cases and persisted for at least 1 year. In contrast, arterial chemoembolization of hepatocellular carcinoma can cause fluctuations or decreases in leukocyte counts.
4.2.3 Erythrocytes and hemoglobin.
Recent postoperative elevations are not significant, and after 6 months the red blood cell count increases significantly and can persist for 7.5 years. red blood cell destruction and clearance rates slow after PSE, and hemoglobin values increase mildly over time, although they are difficult to assess due to confounding factors such as variceal rupture and bleeding and transfusion.
4.3 Altered liver function.
After PSE, splenic artery blood flow decreased and hepatic artery blood flow increased compensatingly, while the superior mesenteric vein return flow increased due to reduced portal vein pressure, thus improving the nutrition of liver tissue, enhancing protein synthesis, improving the patient’s liver function and raising the Child classification standard. follow-up results of Tajiri et al. showed no significant increase in blood AST and ALT, and 6 months after PSE, serum albumin and Cholinesterase increased significantly 6 months after PSE and lasted for 6 and 7 years, respectively.
4.4 Portal system hemodynamic changes.
Since 60%-70% of portal venous blood flow comes from the splenic vein, PSE reduces portal venous pressure by partially decreasing blood flow through the splenic vein. Han et al [4] determined that hepatic wedge venous pressures (HWVP) decreased from 19.6±8 mmH2O before surgery to 14.2±7 mmH2O, reducing The hepatic sinusoidal gap pressure was reduced by 30%-50%.
After combined EVL-PSE treatment for ruptured esophageal varices bleeding from portal hypertension, ultrasonography showed no significant change in the diameter of the main trunk of the portal vein, but blood flow and blood velocity were significantly reduced, as were blood flow and blood velocity in the left and odd veins of the stomach.
4.4.1 Reduction in the frequency of esophageal variceal bleeding.
The reduction of HWVP, portal venous pressure and portal venous blood flow after PSE significantly reduced the frequency of esophageal variceal bleeding. Application of EVL-PSE combination for esophageal varices can completely eradicate esophageal varices in the long term. Cui Yi et al. applied PTVE combined with PSE for the treatment of portal hypertension in cirrhosis, and the hemostasis rate of active bleeding reached 100%.
4.4.2 Improvement of portal circulation encephalopathy.
PSE can be used as a complementary treatment for portal-systemic circulatory encephalopathy due to portal-systemic shunts (PSS) in cirrhosis. occlusion of PSS restores portal perfusion and reverses hepatic encephalopathy. blood ammonia levels and grade of hepatic encephalopathy are lower after PSE at 6 months, 9 months, 1 year, and 2 years postoperatively compared with the non-PSE group [22].
4.4.3 Improvement of portal hypertensive gastropathy.
Gastric mucosal hemodynamic assessment after PSE showed that despite no increase in oxygen saturation, hemoglobin levels could be restored by 11% (P < 0.01) and symptoms of portal hypertensive gastropathy were significantly improved in 71% of patients [19].
4.5 Splenic disease
4.5.1 Splenic trauma.
The use of PSE has led to a fundamental shift in the management of splenic trauma from surgical to non-surgical treatment. Hemostasis is simple and easily tolerated, and is an effective management method for bleeding from splenic rupture.
About 30% of patients with blunt splenic trauma with normal post-traumatic hemodynamics require PSE, with a success rate of about 93% to 97% [14]. In high-grade (grade 4-5) splenic trauma, PSE can also achieve an efficiency of more than 80%. The choice of embolization method should be based on the characteristics of splenic artery injury. Superselective embolization should be performed to ensure complete hemostasis in cases of extravasation of contrast beyond the splenic parenchyma, and combined superselective embolization and splenic artery trunk embolization is recommended in cases of multiple injuries and/or bleeding within the splenic parenchyma and arteriovenous fistula.
4.5.2 Splenic aneurysms and pseudoaneurysms.
The incidence of splenic artery aneurysms is greatly increased in patients with portal hypertension, with an incidence of approximately 7% to 20% in patients with cirrhosis. PSE significantly reduces morbidity and mortality compared with surgical procedures. The location of occlusion must be precisely chosen to preserve collateral flow through the gastric, omental, and pancreatic vessels, and the recommended treatment is sandwiching of the aneurysm sac to eliminate the neck of the aneurysm.
4.5.3 Splenic tumors.
The release of yttrium-90 microspheres via the splenic artery is feasible for radiotherapy of congestive splenomegaly and thrombocytopenia, with fewer side effects, but significantly lower postoperative platelet peaks. Recently, PSE combined with radiofrequency ablation has been applied to treat malignant tumors of the splenic parenchyma, and the application of PSE procedure before radiofrequency ablation helps to improve the effectiveness of experimental and clinical embolization.
4.6 Splenic artery steal syndrome.
In situ liver transplantation for liver failure is often complicated by a shift in blood flow to the donor liver, and the recipient’s own disease such as hepatitis or graft rejection can lead to increased resistance of the hepatic artery, eventually leading to blood flow from the abdominal trunk to the spleen, called splenic artery steal syndrome. PSE can significantly reverse splenic artery piracy and improve liver function.
5. Factors affecting the efficacy of PSE.
5.1 Embolization area.
If the embolization area is too small, the efficacy is poor and the chance of recurrence and re-embolization is significantly higher; if the embolization area is too large, the postoperative reaction is severe and the purpose of preserving spleen function is not achieved. palsson et al. showed a positive correlation between the elevated level of platelets and the embolization area of splenic parenchyma (r = 0.53, p = 0.003). However, embolization area is directly related to the occurrence of complications, so embolization of 50% to 70% is appropriate.
PSE does not affect the treatment of hepatocellular carcinoma, but the degree of splenic artery embolization needs to be controlled. In weak, large tumor and obviously impaired liver function, the area of splenic embolization at one time should not be too large, and repeated and multiple restrictive splenic embolization can be adopted to reach or approach the effective embolization area.
5.2 Child classification of liver function.
Serious complications are related to embolization area and liver function, and Child B and C grades of cirrhosis can increase the risk of mortality and long-term sepsis during the procedure. serious complications after PSE in decompensated cirrhosis by Sakai et al. all occurred in Child B grade. However, Han et al. reported four cases of Child C grade without serious complications. Therefore, poor liver function is not an absolute contraindication to proper control of embolization area.
6. Regarding post-PSE recurrence.
Splenic regeneration is more common after PSE, and distant postoperative splenomegaly often implies recurrence of hypersplenism. kimura et al. studied a postoperative recurrence rate of 30%, similar to splenectomy.
The degree of embolization directly affects postoperative splenomegaly, and PSE can be repeated to correct hemocytopenia if necessary to achieve the desired outcome. Zhu Kongshun et al. used low-pressure flow control method to slowly inject gelatin sponge or PVA particles into the distal splenic artery trunk, which can embolize the peripheral splenic tissue more uniformly and form “armor”-like fibrosis to limit postoperative splenic hyperplasia and reduce recurrence. Patients with immune thrombocytopenic purpura often have recurrence after surgery, in which case complete splenic embolization is required to eliminate splenic function.