High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.

Ventral hernia after high-intensity focused ultrasound ablation for uterine fibroids treatment:A case report

BACKGROUND High-intensity focused ultrasound(HIFU) ablation is a minimally invasive approach in gynecology that is used to manage uterine fibroids.Although this procedure is safe and effective,adverse outcomes are becoming a major problem.CASE SUMMARY We present a case of ventral hernia that occurred as a rare and delayed complication of HIFU ablation for uterine fibroids treatment.The patient came to the hospital with abdominal bloating that occurred 6 mo after ultrasound-guided HIFU ablation for managing uterine fibroids.The ventral hernia,which occurred due to atrophied muscle layers following the procedure,was confirmed by imaging studies and intraoperative findings.She required a hernia repair with mesh and hysterectomy for definitive treatment of uterine fibroid.CONCLUSION High-intensity ultrasound ablation should be performed only on appropriate candidates.Patients should be educated about potential complications of the procedure and the possibility of subsequent treatment.Post-procedural long-term follow-up for detecting delayed adverse effects is important.

Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized with HIFU-generated vaccine,tumor-generated vaccine,and saline,respectively.In addition,20 mice bearing H22 tumors were successfully treated with HIFU ablation. The protective immunity of the vaccinated mice was investigated before and after a subsequent H22 tumor challenge.Using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay,the cytotoxicity of splenic lymphocytes co-cultured with H22 cells wasdetermined in vitro before the tumor challenge,and tumor volume and survival were measured in vivo after the challenge in each group.The mechanism was also explored by loading the vaccines with bone marrowderived dendritic cells(DCs). RESULTS:Compared to the control,HIFU therapy, tumor-generated and HIFU-generated vaccines significantly increased cytolytic activity against H22 cells in the splenocytes of the vaccinated mice(P<0.001). The tumor volume was significantly smaller in the HIFU vaccine group than in the tumor vaccine group(P <0.05)and control group(P<0.01).However,there was no tumor growth after H22 rechallenge in the HIFU therapy group.Forty-eight-day survival rate was 100%in mice in the HIFU therapy group,30%in both the HIFU vaccine and tumor vaccine groups,and 20% in the control group,indicating that the HIFU-treated mice displayed significantly longer survival than the vaccinated mice in the remaining three groups(P< 0.001).After bone marrow-derived DCs were incubated with HIFU-generated and tumor-generated vaccines, the number of mature DCs expressing MHC-Ⅱ + ,CD80 + and CD86 + molecules was significantly increased,and interleukin-12 and interferon-γlevels were significantly higher in the supernatants when compared with immature DCs incubated with mouse serum(P<0.001). However,no differences of the number of mature DCs and cytokine levels were observed between the HIFU- generated and tumor-generated vaccines(P>0.05). CONCLUSION:Tumor debris remaining after HIFU can improve tumor immunogenicity.This debris releases tumor antigens as an effective vaccine to develop host antitumor immune response after HIFU ablation.

A review on radiofrequency,microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis

Importance:Hepatocellular carcinoma(HCC)is usually accompanied by liver cirrhosis,which makes treatment of this disease challenging.Liver transplantation theoretically provides an ultimate solution to the disease,but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients.In an ideal situation,a treatment that is safe and effective should provide a better outcome for patients with the dilemma.Objective:This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC.Evidence Review:Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy.Various types of ablative therapy have their unique ability,and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients.Findings:Radiofrequency ablation(RFA)has a relatively longer history and more evidence to support its effectiveness.Microwave ablation(MWA)is gaining momentum because of its shorter ablation time and consistent ablation zone.High-intensity focused ultrasound(HIFU)ablation is a relatively new technology that provides non-invasive treatment for patients with HCC.It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis.Conclusion and Relevance:Selective use of different loco-ablative therapies will enhance clinicians’treatment options for treatment of HCC.

Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Multi-element Ultrasound Phased Array Applicator for the Ablation of Deep-seated Tissue

High-intensity focused ultrasound (HIFU) has attracted increasing interests as a promising noninvasive modality for the treatment of deep tumors in the thoracic and abdominal cavity.A 90-element HIFU spherical phased array applicator operated at 1 MHz has been developed for deep tissue ablation.The spherical array with a 5 cm wide central hole has a 21 cm diameter and an 18 cm radius of curvature.Annular element distribution with unequal element spacing is used to reduce the number of elements.The array is constructed with piezoelectric lead zirconate titanate (PZT-8) circular elements that are 1.4 cm in diameter and have a wall with thickness of 0.2 cm.The array offers an effective ablating depth of at least 8 cm in the tissue for both simulations and ex vivo experiments.The simulations demonstrate that the developed array can steer the focus with good quality of intensity distributions up to 6 mm off center over ranges from 17 to 21 cm when the water depth is set at 11 cm.We also present the beam focusing capability in deep tissue through a series of ex vivo experiments by measuring discoloration areas after sonications.These results indicate that the developed array is ideal for the ablation of deep-seated tissue.

Focused ultrasound induces apoptosis in pancreatic cancer cells

Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades. Focused ultrasound （FU） has been somewhat successful in treating pancreatic cancer. The purpose of this study was to investigate apoptosis in pancreatic cancer cells induced by FU. Methods Suspension of human pancreatic carcinoma cell line PaTu 8988t was radiated by FU, using five doses with different radiation parameters and patterns, including one blank control. Temperature increase of the cell suspension was monitored. Cell apoptosis and death after FU radiation was observed using fluorescence microscopy and was tested by flow cytometer at 3, 6, 12, 24, and 48 hours after ultrasound radiation. Results The maximum cell suspension temperatures following five radiation doses were 28℃, （42.20±2.17）℃, （50.80±0.84）℃, （55.80±2.17）℃, and （65.20±3.11）℃; differences between the doses were statistically significant （P 〈0.05）. The apoptosis rate peaked at 24 hours after radiation, at （0.56±0.15）%, （1.28±0.16）%, （1.84±0.29）%, （5.74±1.15）%, and （2.00±0.84）% for the five doses; differences between the doses were statistically significant （P 〈0.05）. Between doses 1--4, cell apoptosis rates increased as the Tmax increased, in dose 5, as the Tmax was above 60℃, the apoptosis rate decreased. Conclusion Sub-threshold thermal exposures of FU radiation with a continuous radiation pattern could result in higher percentage of apoptosed cells.

MRI引导的聚焦超声术治疗症状性子宫肌瘤的前瞻性研究

目的探讨MRI引导的聚焦超声术（MRgFUS）治疗育龄期妇女症状性子宫肌瘤的安全性和有效性。方法选择2010年4月至2012年4月在北京协和医院门诊自愿接受MRgFUS治疗的子宫肌瘤患者80例，对其中已完成生育且有症状、可以清晰地表达治疗中的感受、子宫体积〈16孕周、子宫肌瘤直径为2．5±10．0cm、数量〈10个的23例患者进行MRgFUS治疗。记录治疗参数、非灌注体积率（NPVR）和不良反应。并于术后1周，1、3、6个月，1年及2年随访。术前筛查及术后每次随访时均填写子宫肌瘤症状与生命质量问卷（UFS-QOL），该问卷包括症状严重程度评分（SSS）和健康相关生命质量（HRQL）评分两部分，分别比较治疗前后各问卷的评分变化。术后半年及1年时行MRI检查，比较肌瘤及子宫体积变化。术前所有患者均行血常规检查，贫血者于术后3个月、1年时复查血常规。结果（1）治疗参数及不良反应：平均治疗温度为（69±7）℃，平均治疗时间为（144±62）min，平均NPVR为（62±23）％；主要出现的不良反应有皮肤红斑（1／23）、下腹部痉挛性疼痛（8／23）、阴道血性分泌物（5／23）、下肢酸胀或麻木感（4／23），程度均较轻且能自行缓解。（2）治疗后再手术率：1年内选择手术治疗的患者1例，两年内选择手术治疗的患者共4例（包括肌瘤剔除或子宫切除）。（3）治疗前后肌瘤及子宫体积变化：术前、术后半年及1年时子宫肌瘤体积分别为75．6（P25=43．8，P75=128．9）、52．3（Pz5=23．8，P75=111．2）、45．9（P25=26．3，P75=71．7）cm^3，子宫体积分别为270．0（P25=208．4，P75=390．3）、216．4（P25=151．1，P75=290．0）、200．0（P25=149．1，P75=267．6）cm^3，术后肌瘤及子宫体积均呈缩小趋势，差异均有统计学意义（P〈0．01）。（4）治疗前后UFS-QOL测评结果：术前、术后3个月、术后1年的SSS分别为（34±13）、（22±11）、（19±12）分，术后较术前显著降低，差异有统计学意义（P〈0．01）。术前、术后3个月、术后1年的HRQL评分分别为（74±15）、（82±13）、（89±10）分，术后较术前明显提高，差异也有统计学意义（P〈0．01）。（5）治疗前后血红蛋白水平变化：治疗前11例患者贫血，平均血红蛋白为（87±6）g／L，治疗后3个月及1年时的血红蛋白含量分别为（106±14）、（112±10）g／L，术后较术前血红蛋白含量明显升高，差异有统计学意义（P〈0．01）。结论MRgFUS是治疗症状性子宫肌瘤安全的无创疗法，其短期疗效确定，术后1年时子宫肌瘤症状及患者生命质量均明显改善，但两年内有一定的再手术率。