Due to its minimally invasive nature, HIFU has attracted much attention in recent years. It has been a mature approach in the treatment of malignant or benign tumors8,9. Recently, investigators also aimed to use HIFU for the treatment of other diseases, such as secondary hypersplenism. Previous studies have investigated the safety and efficacy of HIFU in the treatment of secondary hypersplenism caused by cirrhosis7.
In our study, we found that HIFU was safe and effective in the treatment of secondary hypersplenism in most cirrhotic patients whose liver function was classified as Child–Pugh A or B. Postoperatively, subcutaneous ecchymosis of the waist was found in 7 patients (63.6%). Two patients (18.2%) complained of mild pain in the left upper abdomen. Hematologic analysis revealed that HIFU treatment resulted in an approximately 50% increase in the mean PLT count and a 25% increase in the mean WBC count 4 weeks post-HIFU relative to the baseline WBC count pre-HIFU. This result is in accordance with those of previous studies. Zhu et al7 reported that HIFU is safe and effective in the treatment of cirrhotic secondary hypersplenism in patients whose liver function is classified as Child–Pugh A or B. No major complications, such as gastrointestinal perforation, peritonitis, splenic rupture or abscess, occurred peri-HIFU and/or post-HIFU. Minor adverse events, such as abdominal pain and dermal ecchymosis, occurred in some patients. The PLT counts, WBC counts and red blood cell (RBC) counts increased after HIFU treatment and peaked 1 year after HIFU. Another study compared the safety and efficacy of HIFU with those of surgical splenectomy and partial splenic embolization (PSE). HIFU was safer and less invasive than splenectomy and traditional PSE10. Thus, HIFU seems to be promising in the treatment of cirrhotic secondary hypersplenism. However, few studies have investigated the potential contraindications for HIFU in the treatment of secondary hypersplenism.
The main finding of this study is that multiple small gallstones might be a contraindication for HIFU in the treatment of secondary hypersplenism. However, we enrolled only 11 patients with decompensated cirrhosis. Two of these 11 patients (2/11, 18.2%) with multiple small gallstones developed gallstones that incarcerated in the common bile duct post-HIFU. An earlier related study on patients with cholelithiasis reported that the annual risk of developing an acute biliary complication was 3.1%11. Our study found a higher occurrence of acute biliary complications (18.2% vs. 3.1%). The higher occurrence of acute gallstone incarceration into the common duct might be explained by three main reasons. First, we included cirrhotic patients with hypersplenism and gallstones but not patients with gallstones only. It has been proven that changes in bile acid composition and increased nucleation of bile combined with decreased motility of the gallbladder may contribute to the development of gallstones in patients with liver cirrhosis. Thus, cirrhotic patients have a higher incidence and prevalence of gallstones12,13,14,15. The portal vein diameter and hypersplenism are risk factors for developing gallstones in patients with cirrhosis15. Gallstones are more than two times more common in cirrhotic patients with portal hypertension than in cirrhotic patients without portal hypertension16. Second, smaller stones, especially stones ≤ 0.55 cm, have been reported to be an independent risk factor for the development of common bile duct stones17. This may explain why the two patients with multiple small stones developed common bile duct stones post-HIFU, while the other three patients with a single large gallstone did not experience any related complications. Third, HIFU treatment of the spleen led to coagulation necrosis of the targeted tissues. This phenomenon can directly damage spleen tissues and vessels, which may lead to damage to multiple RBCs in a short time. The latter may result in the production of a large amount of UCB. In addition, perioperative fasting may lead to bile stasis12. The CCK level has been reported to be higher in cirrhotic patients than in noncirrhotic patients, which indicates that the gallbladder may be stimulated to contract once a patient starts to eat, especially with a greasy diet. We speculate that the increased level of CCK combined with the large burden of UCB and bile stasis may contribute to the development of common bile duct stones18,19.
This study had some limitations. First, the number of patients enrolled was limited. Only 11 patients were included in this study. Decompensated cirrhosis with gallstones incarcerated in the common bile duct indicates that some invasive procedures, such as ERCP, might be required for treatment. However, procedural risks and complications, such as acute-on-chronic-liver failure, have been reported to be quite common in patients with decompensated cirrhosis undergoing ERCP20. This suggests that prevention could be much better than salvation. Since two patients with multiple small gallstones developed small stones incarcerated in the common bile duct post-HIFU, before we go further, it is necessary to consider whether we chose the wrong patients for HIFU treatment. Second, this study was not placebo controlled. This was a retrospective study, and the small number of enrolled patients did not allow us to study some patients as controls. However, all 11 enrolled patients were well defined and homogenous. Third, the percentage of ablation required for better outcomes is not clearly stated. In our study, the ablated volume to spleen volume rate was 35%-61%. Up to now, no study has reported the best percentage of HIFU ablation in the treatment of secondary hypersplenism. Thus, this is from the experience of PSE in the treatment of secondary hypersplenism21. It has been reported that it could be dangerous when splenic necrosis is over 70% after PSE, as subsequent splenic abscess may lead to death. Finally, the targeted ablated region of the spleen hasn’t been determined yet. In our study, we prefer to choose the middle and/or lower pole of the spleen or the hilum of the spleen in order to avoid stimulating the pleura and/or damaging the adjacent organs. Actually, the small sample size neither allow us to determine the most appropriate ablation spleen volume nor the best targeted ablation area. A large-sample multicenter clinical trial with a long-term follow-up is required to illustrate the proper indications, contraindications, ablation volume as well as the most appropriate ablation area for HIFU in the treatment of secondary hypersplenism.