Clinical Research On High-intensity Focused Ultrasound Ablation Of Hypersplenism

BackgroundHypersplenism is a common manifestation,70-80%patients withcirrhotic hypertension present with various degrees of splenomegaly andhypersplenism. Hypersplenism refers to a clinical syndrome characterizedby splenomegaly, a variable combination of anemia, leucopenia and/orthrombocytopenia, compensatory bone marrow hyperplasia, reducedimmunity and improvement after splenectomy. The conventional treatmentfor patients with hypersplenism is splenectomy. However, after the firstreport of overwhelming post-splenectomy infection by King andSchumacher was published in1952, surgeons experienced fundamentalchange in the understanding of the spleen. What’s more, surgery isassociated with increased risk of splenic vein thrombosis, secondarythrombocythemia and infection, particularly with encapsulatedmicro-organisms. Recent studies have shown that the spleen is an organ ofa variety of important functions such as anti-infection and anti-tumorimmunity. It is recommended to reserve the splenic tissue and function asmuch as in the treatment of benign conditions of the spleen. With the development of Interventional Radiology, partial splenic embolization(PSE) has been applied in clinical practice for the treatment ofsplenomegaly and hypersplenism, but the incidences of complications arehigh, meanwhile, it is hard to control the embolization extent because ofthe lack of monitoring. Local ablation therapy such as radiofrequencyablation (RFA) and microwave ablation (MWA) has also markedimprovement for the treatment of hypersplenism, RFA attracts the mostattention. However, secondary hypersplenism is usually found withhyperkinesis of portal vein and fragile spleen tissues, thus in the process ofpuncture, it is very easy to cause splenic injuries, so deeper study on RFA isneeded. Therefore, new, safe, and effective modalities which can reservemore splenic tissue and function should be considered for secondaryhypersplenism.High intensity focused ultrasound (hereinafter referred as HIFU) mayprovide an effective and safe method for hypersplenism. High intensityfocused ultrasound (HIFU), which was introduced in the1940s as a viablethermal tissue ablation approach, has been applied to treat a variety of solidmalignant tumors in a well-defined volume, including the pancreas, liver,prostate, breast, uterine fibroids, and soft-tissue sarcomas. The mainmechanism is thermal effect, which means heat generation due toabsorption of the acoustic energy with a rapid elevation of temperature inthe local tissue. Tissue temperature elevated to higher than60℃will generally lead to instantaneous and irreversible cell death via coagulationnecrosis in most tissues. Meanwhile, mechanical effect and cavitation effectalso play a role in HIFU treatment. Noble ML, et al found that HIFU waseffective in achieving hemostasis in hemorrhagic spleen models of pigs andrabbits. Experimental study on HIFU ablation of the spleen for thetreatment of hypersplenism has shown that HIFU is feasible and effectivein the treatment of animal experimental study for splenomegaly andhypersplenism.Objective1.To assess the safety, efficacy and clinical prospects of high-intensityfocused ultrasound (HIFU) in treatment of hypersplenism.2. To study the value of dynamic contrast enhanced MRI in evaluating thecurative effect of high intensity focused ultrasound (HIFU) forhypersplenism.3. To explore the preliminary mechanism of high intensity focusedultrasound ablation on hypersplenism.Research content1. Patients with hepatocellular carcinoma （HCC） complicated withhypersplenism were treated with the ultrasound-guided HIFU.Complications were recorded. The laboratory examination and MRI imaging were used to evaluate the efficacy.2. Patients who suffered the disease of hypersplenism were treated withHIFU ablation. All patients underwent HIFU ablation were closelyfollowed-up. MRI scan was performed and the spleens were observed.Blood counts and liver function tests were also determined.3. Retrospective analysis of dynamic contrast enhanced MRI was done inpatients with hypersplenism before and after HIFU treatment, the signalchanges and enhanced features of lesions before and after HIFU treatmentwere observed.Materials and methodsPart one1. Patients selectionFrom September2008to September2012, a total of nine patients withHCC complicated with hypersplenism who refused surgical operationunderwent HIFU ablation for liver tumor and spleen at the Clinical Centerfor Tumor Therapy of the Second Affiliated Hospital of ChongqingMedical University, Chongqing, China.2. EquipmentsThe Model JC Focused Ultrasound Tumor Therapeutic System(Chongqing Haifu Medical Technology Co., Ltd., Chongqing, China). 3. MethodsA total of nine patients with HCC complicated with hypersplenism,consisting of5males and4females (the median age was56, ranging51-66years), were treated with the ultrasound-guided HIFU. Complications wererecorded. The laboratory examination and MRI imaging were used toevaluate the efficacy.4. Statistical methodsSPSS16.0package was applied for statistical analysis.Part two1. Patients selectionFrom September1,2008, a total of28patients,15males and13females with a median age of53(range26-71) years old, with severehypersplenism who refused surgical operation underwent HIFU ablation ofthe spleen at the Clinical Center for Tumor Therapy of the SecondAffiliated Hospital of Chongqing Medical University, Chongqing, China.2. EquipmentsThe Model JC Focused Ultrasound Tumor Therapeutic System(Chongqing Haifu Medical Technology Co., Ltd., Chongqing, China).3. MethodsA total of28patients who suffered the disease of hypersplenism weretreated with HIFU ablation. All patients underwent HIFU ablation wereclosely followed-up. MRI scan was performed and the spleens were observed. Blood counts and liver function tests were also determined.4. Statistical methodsSPSS16.0package was applied for statistical analysis.Part three1. Patients selectionFrom September,2008, a total of15patients with severehypersplenism who refused surgical operation underwent HIFU ablation ofthe spleen at the Clinical Center for Tumor Therapy of the SecondAffiliated Hospital of Chongqing Medical University, Chongqing, China.2. EquipmentsThe Model JC Focused Ultrasound Tumor Therapeutic System(Chongqing Haifu Medical Technology Co., Ltd., Chongqing, China),Siemens Magnetom Symphony A Tim1.5T MR.3. MethodsRetrospective analysis of dynamic contrast enhanced MRI was done in15patients with hypersplenism before and after HIFU treatment, the signalchanges and enhanced features of lesions before and after HIFU treatmentwere observed. ResultsPart oneAfter HIFU, an averagely28.76%±6.1%ablation of spleen werediscoverd, meanwhile the white blood cell count, platelet count and liverfunction of patients were substantially improved during the follow upperiod. In addition, the symptoms such as epistaxis and gingival bleedingwere ameliorated or even eliminated and the quality of life was improved.Follow-up imaging showed a non-perfused volume in the spleen and anabsence of tumor blood supply at treated lesions in the liver.Part twoIn the follow-up process, the levels of white blood cell, Platelets andliver function in the blood after HIFU were significantly higher than thoseof levels before HIFU. The MRI in the days of14after HIFU treatmentshowed the ablation area turned into non-perfused volume in the spleen.The percentage of damaged part of the spleen from HIFU is（27.20%±6.07%）(range16.90%~42.34%). The symptoms (eg, epistaxis and gingivalbleeding) were ameliorated significantly or even disappeared and thequality of life was improved.Part threeCompared with pre-operation, the signal increased or reduced orstayed the same on T1WI, it has no specificity. The signal reduced onT2WI after HIFU treatment. Dynamic contrast enhanced MRI showed theablation area was larger than those of T1WI and T2WI, no enhancementwas found in lesions. Conclusions1. For the first time, HIFU ablation was used to treat HCC complicatedwith hypersplenism. HIFU may be an effective and safe alternative fortreatments of HCC complicated with hypersplenism, but futher studies arenecessary to clarify the mechanisms.2. Splenic HIFU ablation is a safe, effective and noninvasive approach forhypersplenism and it has a potential good prospect in clinical application. Itprovides a better choice for the treatment of hypersplenism.3. T2WI has specificity in demonstrating coagulation necrosis ofhypersplenism after HIFU ablation, dynamic contrast-enhanced MRI hashigher sensitivity in demonstrating ablation area, by demonstrating theblood supply of the lesion and enhancement characteristics. MRI isefficient and noninvasive in follow-up for the change of signals of treatedregion after HIFU and can reflect the histological change of treated regionprecisely.