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.

Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer

AIM:To evaluate the safety and clinical application of high-intensity focused ultrasound(HIFU)therapy for unresectable pancreatic cancer(PC).METHODS:Thirty PC patients(16 cases in stage III and 14 cases in stage IV)with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy.Informed consent was obtained.This study began at the end of 2008 and was approved by the ethics committee of our hospital[Institutional Review Board(IRB):890].The HIFU device used was the FEP-BY02(Yuande Bio-Medical Engineering,Beijing,China).RESULTS:The mean tumor size after HIFU therapy changed to 30.9±1.7 mm from 31.7±1.7 mm at pre-therapy.There were no significant changes in tumor size,mean number of treatment sessions(2.7±0.1 mm),or mean total treatment time(2.4±0.1 h).The rate of symptom relief effect was 66.7%.The effectiveness of primary lesion treatment was as follows:complete response,0;partial response,4;stable disease,22;progressive disease,4.Treatment after HIFU therapy included 2 operations,24 chemotherapy treatments,and 4 best supportive care treatments.Adverse events occurred in 10%of cases,namely pseudocyst formation in 2 cases and mild pancreatitis development in 1.However,no severe adverse events occurred in this study.CONCLUSION:We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound （HIFU） combined with （＋） low-dose external beam radiotherapy （LRT） as supplemental therapy for advanced prostate cancer （PCa） following hormonal therapy （HT）. Our definition of HIFU＋LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy （CRT）. We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU＋LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU ＋LRT treatment. There were significant differences among four groups with regard to overall survival （OS） and disease-specific survival （DSS） curves （P=0.018 and 0.015）. Further comparison between each pair of groups suggested that the long-term DSS of the H IFU ＋ LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU＋LRT group and the CRT group. Multivariable Cox＇s proportional hazard model showed that both HIFU＋LRT and CRT were independently associated with DSS （P=0.001 and 0.035） and had protective effects with regard to the risk of death. Compared with CRT, HIFU ＋LRT significantly decreased incidences of radiation-related late gastrointestinal （GI） and genitourinary （GU） toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and reRional lymph node metastases after HT. As an alternative to CRT, HIFU＋LRT showed Rood efficacy and better safety.

Long-Term Outcomes and Prognosis of Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Localized Prostate Cancer—Therapy after Recurrence and Predictive Factors

Objectives: To evaluate the outcomes and prognosis of high-intensity focused ultrasound (HIFU) therapy for patients with localized prostate cancer, and identify suitable candidates for this therapy by investigating the predictive factors. Methods: The 224 patients (low 54, intermediate 111 and high-risk patients 59) with T1-2 stage were treated using the Sonablate device and followed for over 12 months after treatment. Recurrence was determined based on histological findings, prostate-specific antigen (PSA) failure and local or distant metastasis. The factors which are predicting variables with potential effects were investigated by Kaplan-Meier and multivariate analysis. Results: A total of 255 treatment sessions (193 with one, 31 with two) were performed. No patients died of prostate cancer, but 15 died of other causes and 14 patients were lost during follow-up. The 7-year recurrence-free survival (RFS) rates in all patients were 75%, and 5-year RFS rates were 98%, 84% and 59% in the low, intermediate and high-risk patients respectively. In the 216 patients who underwent histological examination at 6 months or later after HIFU, 25 (12%) were positive. In 77 patients with recurrence after first-HIFU, the second treatments were hormonal therapy and HIFU. Of the 31 patients who underwent a second HIFU, the 5-year RFS rates were 64%, and 5-year RFS rates were 100%, 74% and 33% in the low, intermediate and high-risk patients. The significant predictor for recurrence was risk-group, T-stage (T1 vs T2), Gleason score (≤3 + 4 and ≥4 + 3), pretreatment PSA (Conclusions: Prognosis of HIFU for Patients with localized prostate cancer was good, and the low and intermediate-risk patients with T1-staging are suitable indications for HIFU. Effective predictors for outcomes were risk-group, T-stage, Gleason score, pretreatment PSA and nadir PSA.

Intermittent ice-cooling to prevent skin heat injury caused by highintensity focused ultrasound therapy targeting desmoid-type fibromatosis:A case report

Introduction:Desmoid-type fibromatosis(DF)is a fibrous tumor characterized by low-grade malignant and easy invasive growth and high recurrence.High-intensity focused ultrasound(HIFU)therapy has been identified as a novel non-invasive approach for DF treatment;however,the ultrasonic energy generated by HIFU can cause skin heat injury.Case:A 31-year-old female patient with signs and symptoms of DF received treatment in our institution.The patient had undergone HIFU treatment six times from April 27,2018,to August 21,2019.After HIFU therapy for the third time,she had a third-degree skin burn showing as orange peel-like change and spent three months to promote the recovery of the skin lesions.An intermittent ice-cooling strategy was used to avoid skin damage during the fourth HIFU treatment.This patient did not have any apparent skin injury during the last three HIFU therapy and acquired satisfactory anti-tumor therapeutic effect.Conclusions:There are differences in the thermal selectivity of tumor tissues,which leads to different critical thermal injury temperature values that the tissue can tolerate.Ice-cooling can lower skin tissue temperature and reduce the thermal damage caused by HIFU treatment.

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.

High-intensity focused ultrasound with large scale spherical phased array for the ablation of deep tumors

Under some circumstances surgical resection is feasible in a low percentage for the treatment of deep tumors. Nevertheless, high-intensity focused ultrasound （HIFU） is beginning to offer a potential noninvasive alternative to conventional therapies for the treatment of deep tumors. In our previous study, a large scale spherical HIFU-phased array was developed to ablate deep tumors. In the current study, taking into account the required focal depth and maximum acoustic power output, 90 identical circular PZT-8 elements （diameter=1.4 cm and frequency=l MHz） were mounted on a spherical shell with a radius of curvature of 18 cm and a diameter of 21 cm. With the developed array, computer simulations and ex vivo experiments were carried out. The simulation results theoretically demonstrate the ability of the array to focus and steer in the specified volume （a 2 cm×2 cm×3 cm volume） at the focal depth of 15 to 18 cm. Ex vivo experiment results also verify the capability of the developed array to ablate deep target tissue by either moving single focal point or generating multiple foci simultaneously.

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.

复生康胶囊联合高强度聚焦超声消融术治疗胃癌肝转移临床研究

目的:探讨复生康胶囊联合高强度聚焦超声消融术(HIFUA)治疗不可切除的胃癌肝转移的临床治疗效果。方法:运用随机数字表法将226例不可切除的胃癌肝转移患者分为观察组和对照组,各113例。两组均采用HIFUA进行治疗,观察组另给予复生康胶囊,而对照组则给予安慰剂。治疗前后,检测两组患者免疫功能指标,主要包括IgG、IgA、IgM、CD3^+及CD4^+水平;检测两组患者肿瘤标记物含量,主要包括AFU、GP73、CA242及Frr;检测两组患者肝功能指标,主要包括TBIL、AST、ALP及ALT。治疗后,对两组进行为期3年的随访,分别比较两组患者的1年和3年生存率、PFS和OS。结果:治疗后,观察组IgG、IgA、IgM、CD3^+及CD4^+均显著高于对照组(P<0.05),而AFU、GP73、CA242及Frr含量均显著低于对照组,且TBIL、AST、ALP及ALT含量亦均显著低于对照组(P<0.05)。相较于对照组,观察组患者的1年和3年生存率、PFS及OS均显著升高,且差异具有统计学意义(P<0.05)。结论:复生康胶囊联合HIFUA可有效改善不可切除的胃癌肝转移患者的免疫和肝功能,延长患者的生存时间。

高强度聚焦超声治疗进展期肝癌的临床疗效

目的探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)治疗进展期肝癌的近期和远期疗效。方法151例失去手术治疗机会或不愿意接受手术治疗的进展期原发性肝癌患者接受以HIFU为中心的序贯治疗,30例同期仅接受对症支持治疗的进展期肝癌患者作为对照组。两组患者一般情况及肿瘤分期等具可比性。治疗前后及随访期间定期观察患者的疼痛症状评分(Karnofsky评分),肿瘤指标(AFP、CA199),影像学改变及应答率、生存期、生存质量改变。结果与对照组相比,HIFU组患者的影像学、AFP及症状评分均明显好转(P<0.05)。HIFU组患者的显效和有效率分别为28.5%和60.3%;对照组分别为0%和16.7%;总体有效率HIFU组(88.8%)明显高于对照组(16.7%),P<0.01。HIFU组患者的1年、2年生存率(分别为50%、30.9%)均明显高于对照组(分别为3.6%、0%),P<0.01。HIFU组患者接受治疗后3个月的生存质量评分为83.1±8.0,明显优于治疗前评分67.7±5.9及同期对照组评分69.0±8.5(P<0.05)。HIFU治疗期间无严重并发症发生。结论HIFU是治疗进展期肝癌安全、有效的治疗方法。

高强度聚焦超声联合微波消融治疗大肝癌的疗效与不良反应

目的探讨高强度聚焦超声(HIFU)联合微波消融(MWA)治疗大肝癌的疗效与不良反应。方法采用随机、对照、抽样研究方法,选择肝癌患者122例作为研究对象,按照随机信封抽签原则分为观察组与对照组,各61例。对照组给予高强度聚焦超声,观察组在对照组治疗的基础上给予微波消融治疗,所有患者都治疗观察3个月,记录治疗疗效与不良反应,随访生存情况。结果观察组与对照组的治疗总有效率分别为68.9%和49.2%,观察组高于对照组(P<0.05)。治疗期间观察组与对照组的肝区疼痛、消化道反应、肝功能异常与骨髓抑制等不良反应发生情况对比无统计学差异(P>0.05)。观察组与对照组治疗前后CD3^+CD4^+T比例对比无统计学差异(P>0.05),观察组治疗后的CD3^+CD8^+T比例低于对照组(P<0.05),且都低于治疗前(P<0.05)。观察组的总体生存时间与疾病进展时间为(31.44±4.29)个月和(26.29±5.11)个月,都长于对照组的(25.63±5.19)个月和(20.41±4.89)个月(P<0.05)。结论高强度聚焦超声联合微波消融治疗大肝癌能改善患者的免疫功能,提高治疗效果,延长患者的生存时间,且不会增加不良反应的发生。

CAO方案化疗联合高频聚焦超声消融治疗Ⅲ/Ⅳ期肝母细胞瘤患儿疗效分析

目的分析应用长春新碱、阿表霉素联合环磷酰胺(CAO方案)化疗联合高频聚焦超声消融治疗Ⅲ/Ⅳ期肝母细胞瘤(HB)患儿的疗效。方法回顾性分析2010年12月~2016年1月我科收治的34例Ⅲ/Ⅳ期HB患儿的临床资料,其中16例接受CAO方案化疗联合高频聚焦超声消融治疗,18例仅接受CAO方案化疗治疗。比较两组各项血和生化指标、肿瘤缓解率、化疗不良反应发生率和转归情况。结果在治疗3m末,联合组血清AFP水平为(43.2±5.4)μg/L,ALT水平为(93.5±26.3)U/L,AST水平为(91.2±30.2)U/L,显著低于对照组【分别为(55.3±6.2)μg/L、(197.1±57.8)U/L和(213.7±66.2)U/L,P<0.05】,而两组外周血Hb水平比较,差异无统计学意义(P>0.05);联合组肿瘤缓解率为81.3%,显著高于对照组的61.1%,差异具有统计学意义(P<0.05);联合组化疗不良反应发生率为18.8%,与对照组的27.8%比,差异无统计学意义(P>0.05);在随访24m末,联合组病死率为6.3%,与对照组的11.1%比,差异无统计学意义(P>0.05),但联合组肿瘤复发率为13.3%,显著低于对照组的25.0%,差异具有统计学意义(P<0.05)。结论采取CAO方案化疗与高频聚焦超声消融联合治疗Ⅲ/Ⅳ期HB患儿能有效延缓病情发展,提高肿瘤缓解率,降低复发率。

手术切除、射频消融及海扶刀治疗结直肠癌肝转移患者的不同预后比较

目的比较肝切除术(HR),射频消融(RFA)和海扶刀(HIFU)治疗结直肠癌肝转移(CRLM)的不同预后。方法我院经HR、RFA及HIFU治疗的CRLM患者71例,提取患者临床一般资料、诊断、治疗、病理结果、随访无复发生存率(RFS)和总生存率(OS)进行分析。结果 41例HR,20例RFA,10例HIFU进行了有效随访。HR和RFA组及HR和HIFU组的复发模式差异有统计学意义(P <0. 05)。HR组与HIFU组OS、RFS差异有统计学意义(P <0. 05),HR组与RFA组OS、RFS差异无统计学意义(P> 0. 05)。多因素分析显示转移灶的治疗和肝转移灶数目是预后的独立预测因子。结论 RFA治疗结直肠癌肝转移的疗效与HR相似,HIFU治疗结直肠癌肝转移的疗效低于HR治疗结直肠癌肝转移的疗效。