高强度聚焦超声(HIFU)肿瘤热消融技术的关键问题简析

目的 1988年,王智彪萌发了用高强度聚焦超声(high intensity focused ultrasound,HIFU)从体外对体内肿瘤进行非侵入切除的灵感.在之后的10年中,他和他的团队在该领域提出了"生物学焦域"、"超声治疗剂量学"、"组织声环境"等概念.在实时超声监控、治疗系统优化、远程医疗系统、临床方案等方面突破了相应的关键技术壁垒.将HIFU治疗技术成功运用于外科治疗,在国际上积累了数量最多的临床病例.在该领域的设备研制、临床应用及若干基础研究方面走在了世界前列.

Abstract：

In 1988, Zhibiao Wang had an inspiration of ablating tumor in vivo non-invasively by high intensity focused ultrasound (HIFU). In the following 10 years, he and his team first proposed concepts such as "biological focal region", "ultrasound therapy dosimetry", "acoustic environment in tissue" and so on. They had broken down the key technical barriers in real-time ultrasound monitoring, treatment system optimization, telemedicine system, clinical protocols and other aspects, making HIFU therapy successfully applied to surgery and accumulated the largest number of clinical cases internationally. They have been playing a leading role around the world in equipment development, clinical application and some basic research in this field.     

Anaesthesia for high intensity focused ultrasound (HIFU) therapy

High intensity focused ultrasound (HIFU) is a treatment modality for tissue ablation with an expanding range of indications. It is helpful to understand its basic principles, the physiological changes induced, and the pathophysiology of the patient groups undergoing HIFU. HIFU is usually performed in a radiology suite, and requires co-ordinated efforts between the radiologist/surgeon and anaesthetist during ablation therapy to enhance accuracy of treatment and patient safety. Planning of the equipment, ventilation strategies and drugs needed during the procedure would reduce potential anaesthetic and procedure-related complications.     

Prospective multicentre study using high intensity focused ultrasound (HIFU) for the focal treatment of prostate cancer: Safety outcomes and complications

PurposeTo investigate focal therapy using High Intensity Focused Ultrasound (HIFU) for the treatment of localized prostate cancer (CaP), we analyzed the safety and complications of this procedure.MethodsPatients (pts) eligible for this multicenter prospective cohort study suffered from low to intermediate risk localized CaP with no prior treatment. After tumor identification on multiparametric MRI and in prostate biopsy, the lesions were treated with HIFU observing a safety margin of 8 to 10 mm. Adverse events (AE) after 30 and 90 days, as well as the required interventions were assessed and stratified for treatment localizations.ResultsOf the 98 men included in the study in two European centers, 35 (35.7%) experienced AEs in the first 30 days after HIFU intervention with Clavien-Dindo grade ≤ II: 15 pts (15.3%) had a postoperative urinary tract infection and 26 pts (26.5%) a urinary retention. Four pts (4.1%) underwent subsequent intervention (Clavien-Dindo grade IIIa/b). The number of late postoperative complications occurring between 30 and 90 days after intervention was low (2.0%). The highest complication rate was associated with tumors located at the anterior base (50.0%). The inclusion of the urethra in the ablation zone led to AEs in 20 out of 41 cases (48.8%) and represented a significant risk factor for complications within 30 days (odds ratio = 2.53; 95% confidence interval: 1.08–5.96; P = 0.033).ConclusionsFocal therapy of CaP lesions with a robotic HIFU-probe is safe and renders an acceptable rate of minor early AEs. The inclusion of the urethra in the ablation zone leads to an increase in early complications and should be avoided whenever possible.     

Outcomes of partial gland ablation using high intensity focused ultrasound for prostate cancer

BackgroundTo evaluate the clinical and oncological outcomes of partial gland ablation (PGA) using high intensity focused ultrasound (HIFU) technique for the clinically unilateral prostate cancer.MethodsWe performed a retrospective analysis for the 163 patients who treated by PGA for clinically unilateral prostate cancer. The PGA was performed using Focal one system with concurrent trans-urethral prostatectomy. The oncological and functional outcomes were evaluated as well as risk factors for remnant disease after PGA. Clinically significant cancer was defined as grade group ≥2.ResultsAmong the entire subjects, grade group 2 or greater was present at pre-treatment biopsy in 76.7%. Median follow-up time was 17 months and 60.1% of total subjects had follow-up biopsy at postoperative 1 year. There were 25 subjects (24.2%) with any cancer and 13 subjects (12.6%) with CS cancer at the follow-up biopsy. The preoperative age and number of positive cores at preoperative biopsy were significantly associated with positive results at follow-up biopsy. Incontinence which requires 2 or more pads per day was observed at 4 subjects (2.5%) postoperatively. There were no subjects who needed intensive care or experienced rectal complications.ConclusionThe PGA with HIFU was safe and showed good preservation of functional outcomes as well as satisfactory oncological control. The remnant disease was observed in the 24.5% of patients who underwent follow-up biopsy in the present study. Thus, further prospective study is needed to evaluate oncological and functional outcomes of PGA with HIFU more accurately.     

Current state of high intensity focused ultrasound (HIFU) as treatment of prostatic carcinoma

ObjectiveTo evaluate the current state of high intensity focused ultrasound as therapeutical option of prostatic carcinoma (PCa)MethodsWe completed an extense review of urologic literature on the role of HIFU on the treatment of PCa.ResultsThis technique is nowadays usually being indicated in Europe as treatment of many cases of either primary or relapsed PCa after radiotherapy. Although some reports suggest that HIFU is very effective as treatment for low and medium risk localized PCa patients, no randomized series comparing this technique with conventional therapies have been presented yet. Great disparity in criteria to define free-disease survival is detected, which make difficult the interpretation of results.ConclusionsExperience of some groups in HIFU is highly promising. Local tumour destruction is evident both in primary and relapsed PCa cases. To make conclusions in the long-term, controlled-randomized trials must be designed, with follow-up to measure benefits in global survival and quality of live. Comparisons must be completed with conventional techniques, and a uniform definition of disease free-survival is necessary.     

高强度聚焦超声消融局限型子宫腺肌症

目的探讨高强度聚焦超声(HIFU)消融治疗局限型子宫腺肌症的应用价值。方法回顾性分析经HIFU消融治疗的60例局限型子宫腺肌症患者,观察其治疗前及治疗后1、3、6个月的影像学表现、子宫肌瘤症状严重程度及健康相关生活质量调查问卷评分情况。结果 HIFU治疗后3天内复查MRI提示平均消融率为(70.30±12.27)%。不同部位治疗前及治疗后1、3、6个月的症状严重程度评分和健康相关生活质量评分总体差异均有统计学意义(P均0.05)。局限性子宫腺肌症病灶不同时间点的体积差异均有统计学意义(P均0.05)。未见严重并发症发生。结论 HIFU治疗局限型子宫腺肌症无创、安全、有效。     

Location of residual cancer after transrectal high-intensity focused ultrasound ablation for clinically localized prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? Transrectal High‐Intensity Focused Ultrasound (HIFU) ablation has been used as a minimally invasive treatment for localized prostate cancer for 15 years. Five‐year disease‐free survival rates of 66–78% have been reported, challenging the results of external‐beam radiation therapy. Usually, a 6‐mm safety margin is used in the apex to preserve the urinary sphincter and potency. The influence of this 6‐mm margin on the results of the treatment has never been assessed. This retrospective study of a cohort of 99 patients who underwent systematic biopsy 3–6 months after HIFU ablation for prostate cancer (with a 6‐mm safety margin in the apex) shows that post‐HIFU residual cancer is found more frequently in the apex. Therefore, new strategies improving the prostate destruction at the apex while preserving the urinary continence need to be found.

OBJECTIVE

? To evaluate whether the location (apex/midgland/base) of prostate cancer influences the risk of incomplete transrectal high‐intensity focused ultrasonography (HIFU) ablation.

PATIENTS AND METHODS

? We retrospectively studied 99 patients who underwent prostate cancer HIFU ablation (Ablatherm; EDAP, Vaulx‐en‐Velin, France) with a 6‐mm safety margin at the apex, and had systematic biopsies 3–6 months after treatment. ? Locations of positive pre‐ and post‐HIFU sextants were compared. ? The present study included two analyses. First, sextants negative before and positive after treatment were recoded as positive/positive, hypothesizing that cancer had been missed at pretreatment biopsy. Second, patients with such sextants were excluded.

RESULTS

? Pre‐HIFU biopsies found cancer in all patients and in 215/594 sextants (36.2%); 55 (25.6%) positive sextants were in the apex, 86 (40%) in the midgland and 74 (34.4%) in the base. ? After treatment, residual cancer was found in 36 patients (36.4%) and 50 sextants (8.4%); 30 (60%) positive sextants were in the apex, 12 (24%) in the midgland and eight (16%) in the base. ? Both statistical analyses found that the locations of the positive sextants before and after HIFU ablation were significantly different (P < 0.001), with a higher proportion of positive apical sextants after treatment. ? At the first analysis, the mean (95% confidence interval) probability for a sextant to remain positive after HIFU ablation was 8.8% (3.5–20.3%) in the base, 12.7% (5.8–25.9%) in the midgland and 41.7% (27.2–57.89%) in the apex. ? At the second analysis, these same probabilities were 5.9% (1.9–17%), 9.9% (3.9–23.2%) and 27.3% (13.7–47%), respectively.

CONCLUSION

? When a 6‐mm apical safety margin is used, residual cancer after HIFU ablation is found significantly more frequently in the apex.     

The utility of intraoperative contrast-enhanced ultrasound in detecting residual disease after focal HIFU for localized prostate cancer

Background and objectivesFocal high intensity focused ultrasound (HIFU) is an emerging treatment for selected men with localized prostate cancer. A limitation of HIFU is the absence of a reliable tool to measure treatment effect intraoperatively. Contrast-enhanced ultrasound (CEUS) has been shown to be a promising modality for assessing the extent and boundaries of tissue ablation. The aim of this study was to assess the value of CEUS immediately after focal HIFU.Materials and methodsRetrospective analysis of a prospectively maintained registry including consecutive men undergoing focal HIFU (Focal One). Candidates for focal HIFU were treatment naive men with ≥10 years life expectancy, prostate-specific antigen (PSA) ≤ 20 ng/ml, TNM primary tumor, regional lymph nodes, distant metastasis stage ≤ T2c N0 M0 with a multiparametric MRI (mpMRI) visible lesion concordant with histologically proven prostate cancer. CEUS evaluation was performed immediately at the end of the procedure. Based on the surgeon's estimation of CEUS imaging, re-HIFU was performed, followed by another CEUS evaluation. To test our hypothesis, the results of the CEUS were compared to the results of early mpMRI to rule out clinically significant cancer. The concordance between the 2 tests was measured using the Cohen's kappa. The best model including relevant predictors was calculated with CEUS or with mpMRI to determine their respective added value.ResultsOf 66 men who underwent HIFU, 32 met eligibility criteria. Bifocal treatment was performed in 1 man, increasing the number of treated lesions to 33. Further ablation based on CEUS was delivered intraoperatively to 13 lesions (39%). The positive biopsy rate for clinically significant cancer in the treated zones was 30% (10/33). The negative predictive value of CEUS and early mpMRI was 71% (95% confidence interval: 59%–82%). Concordance between CEUS and mpMRI was significant with a 72.7% agreement (P = 0.001). The model with CEUS showed the best accuracy with an area under the curve of 0.881.ConclusionCEUS has a higher added value compared to early mpMRI in ruling out clinically significant cancer after focal HIFU. It should be evaluated whether the use of CEUS intraoperatively enhances the efficacy of focal HIFU.     

Localized prostate cancer treatment in renal transplant patient with high intensity focalized ultrasound (HIFU)

We report a 62 years old kidney transplant (KT) patient who was diagnosed of localized prostatic cancer (PC) after 6 years of the implant. Transrectal prostatic High Intensity Focused Ultrasound (HIFU) was applied. Results have been satisfactory, achieving pathologic and biochemical success. The discharge was completed at 24 hs, the morbidity was minimal. We have not found any reference in the literature on the appliance of HIFU in PC KT patients. We think that HIFU may represent a good alternative for these patients.     

高强聚焦超声(HIFU)无创治疗肿瘤技术的崛起

20世纪40年代,美国学者首次提出了高强聚焦超声治疗技术的概念,并进行了初步的工程和临床研究.70、80年代间,治疗肿瘤的温热疗法曾盛行一时.90年代之后,高强聚焦超声外科肿瘤治疗技术在国际上重新崛起,我国率先推出了大型高强聚焦超声肿瘤治疗系统,并成功地应用于临床治疗乳腺癌、骨肿瘤、肝癌等多种实体肿瘤.迄今,该"JC型高强聚焦超声肿瘤治疗系统"已出口到英国、意大利、西班牙、日本、韩国等许多欧亚国家,在诸如欧洲肿瘤治疗中心等20多个医疗中心运行,治疗肿瘤患者达数万例.我国持续保持着引领世界超声无创治疗技术发展的领先地位.

Abstract：

In the 40 years of last centry American scientists put forward a concep of high intensity focused ultrasound (HIFU) therapeutic technique and had done some technical and clinical studies. Since 90 years the HIFU surgery technique treating tumors anew rised abruptly in the world. China firstly put out a comprehensive HIFU tumor treating sistem and successfully treated many solid tumors such as breast cancer, bone tumor, liver cancer etc.. Now the treating sistem has already exported to England, Italy,Spain, Japan, Colea etc. and treated tens thousands tumor patients. In the field of noninvasive ultrasound treating tumor technique China has continually kept the leading position in the world.     

Anesthetic management for high-intensity focused ultrasound (HIFU) therapy in prostate cancer patients

HIFU therapy is one of epoch-making, low-invasive treatments for prostate cancer. We investigated 71 patients who had undergone HIFU therapy from June 2004 through September 2005. We mainly gave a single spinal injection followed by epidural catheterization with a combined spinal-epidural anesthesia kit. Three patients received general anesthesia because of various problems such as allergy for local anesthetics, ankylosing spondylitis and severe spinal deformity causing difficulty in lumbar puncture. Spinal anesthesia was successfully achieved in most patients. Twelve patients with insufficient anesthetic levels required additional local anesthetics via epidural catheters. We found no serious perioperative complications.     

高强度聚焦超声肿瘤治疗技术原理

高强度聚焦超声波(high-intensity focused ultrasound,HIFU)是利用超声波良好的方向性、可穿透性、生物组织吸声特性等,将体外超声换能器发射的低声强超声波准确聚焦于体内的肿瘤靶组织处.聚焦后局部组织所吸声能转化为热能可使组织瞬间升温至蛋白变性阈值温度(60℃以上).该技术可使肿瘤细胞发生不可逆凝固性坏死,但不伤及焦点周围正常组织.

Abstract：

High intensity focused ultrasound (HIFU) is a novel physical tumor therapeutic technology which applies the ultrasound well targeting, focusing, tissue absorbing property, and so on. It focused outer transducer low intensity ultrasound wave and targeted in the tumor, whichcan raise the temperature above 60℃ rapidly and induce tissue irreversible coagulation necrosis, with no damage to the surrounding normal tissue. It is a new physical tumor treatment technology.     

Health‐related quality of life after salvage high‐intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer

Objective: To evaluate health‐related quality of life (HRQOL) after salvage high‐intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Methods: Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA‐PCI) questionnaire at baseline and at follow‐up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow‐up. Results: Fifty‐seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6–29 months). The mean score for urinary function decreased from 79.7 ± 12.1 prior to HIFU to 67.4 ± 17.8 after HIFU (P < 0.001). The mean score for sexual function decreased from 32.1 ± 24.1 prior to HIFU to 17.2 ± 17.0 after HIFU (P < 0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Conclusion: Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow‐up of 17.5 months.