高强度聚焦超声肿瘤消融术麻醉管理的研究进展

高强度聚焦超声（HIFU）是一种无创的局部热消融技术,是治疗实体肿瘤的一种新方法,其安全性和可靠性已得到证实,目前已广泛应用于肝脏、胰腺、子宫以及前列腺等器官肿瘤的治疗。由于采用HIFU进行肿瘤治疗的患者通常处于肿瘤的终末期,全身情况较差,麻醉方式的选择须十分谨慎,不同部位的肿瘤其麻醉关注点也有所不同。本文就各种HIFU肿瘤消融术麻醉方式的选择、相关并发症和麻醉管理要点进行综述。     

高强度聚焦超声治疗肝癌的麻醉探讨

目的探讨高强度聚焦超声(h igh intensity focused u ltrasound,H IFU)治疗肝癌病人的麻醉特点。方法21例全部采用静吸复合全麻,丙泊酚、咪达唑仑、芬太尼和维库溴铵静脉注射诱导,气管内插管行控制呼吸,持续吸入异氟烷或恩氟烷,间隙追加芬太尼、丙泊酚和维库溴铵,保持术中病人良好的肌松和完善的镇痛,维持病人血流动力学和体温的稳定。结果21例均在全麻下成功完成H IFU治疗,2例H IFU治疗时须加深麻醉抑制焦点区刺激反应。手术时间245~423 m in,(329±48)m in;术毕苏醒时间7~18 m in,(11±3)m in;拔除气管导管时间9~24 m in,(15±4)m in。1例术后并发少量胸腔积液,2周后自行消失。结论静吸复合全麻是高强度聚焦超声治疗肝癌病人安全有效的麻醉方法。     

经直肠高强度聚焦超声(HIFU)治疗良性前列腺增生的临床研究

目的探讨经直肠高强度聚焦超声（high-intensity focused ultrasound，HIFU）治疗良性前列腺增生（BPH）的有效性和安全性。方法对150例BPH患者采用Sonablate 500型“经直肠超声聚能刀”进行前列腺消融术。在术前、术后30min，1、2、6和12个月，经直肠超声观察前列腺和前列腺部尿道的影像学变化，通过尿液分析、国际前列腺症状评分（IPSS）、生活质量评分（QOL）、最大尿流率（Qmax）和残余尿量（PVR）进行疗效评估，同时观察术后并发症。23例术后12个月行排尿期膀胱尿道造影。结果对143例进行了12个月的观察随访，术后IPSS评分和QOL评分降低，PVR减少，Qmax明显提高（P〈0．01），前列腺体积缩小（P〈0．05）。前列腺消融时间25—90min。术后留置尿管时间为3—19d，7例术后反复排尿困难、药物治疗效果不佳者行TURP手术，3例患者出现附睾炎，1例术后15d发生尿道直肠瘘。术后经直肠超声观察和膀胱尿道造影，证实术后前列腺部尿道较术前明显增宽。结论“经直肠超声聚能刀”前列腺消融术，能对前列腺组织进行选择性破坏，具有微创（无血手术）、安全和并发症少等优点。对前列腺中叶增生明显者可联合TURP治疗。“经直肠超声聚能刀”治疗BPH近期疗效满意，远期疗效有待进一步观察。     

聚焦超声消融治疗胰腺癌的临床观察

目的探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)消融治疗胰腺癌的疗效和安全性.方法采用JC型高强度聚焦超声治疗系统,消融治疗44例胰腺癌患者.观察治疗前后的影像学变化及临床症状,评价HIFU治疗的疼痛缓解程度、生存期及不良反应.结果44例患者经HIFU治疗后,疼痛缓解率为94.74%,1、3、5年生存率分别为15.91%、6.82%、2.27%,中位生存时间为8个月(3～71个月).无上消化道出血或胃肠穿孔等严重并发症.增强CT或MRI显示HIFU治疗区内组织消融.结论HIFU是一种治疗胰腺癌的有效方法.该法无创、安全性较高、止痛效果明显,适合病情较重、不能耐受其他方法治疗的患者.     

Extracorporeal application of high-intensity focused ultrasound for prostatic tissue ablation

OBJECTIVE: To investigate the efficacy and safety of extracorporeal prostatic tissue ablation using high-intensity focused ultrasound (HIFU) in vivo in animals, and in a clinical feasibility study in men, as this is an investigational minimally invasive treatment alternative for locally confined prostatic carcinoma, but may have significant side-effects. PATIENTS, MATERIALS AND METHODS: Ultrasound (1.04 MHz excitation frequency) was generated by an extracorporeal cylindrical piezo-ceramic element and focused by a paraboloidal reflector to a focal size of 32 x 4 mm. The focal distance and aperture diameter were both 100 mm. HIFU was applied extracorporeally at different intensities and pulse duration (up to 6 s) to 11 dog prostates in vivo (median intensity 1192 W/cm2) and eight patients (median intensity 3278 W/cm2, range 2384-3576) under general anaesthesia. The lesions were assessed macroscopically and histologically after HIFU and any side-effects evaluated. RESULTS: Thermoablation was feasible in vivo and in all patients. Macroscopic analysis and histology showed sharply demarcated coagulative necrosis. Side-effects, including skin and rectal burns, occurred only after transvesical application in the in vivo study. There were no side-effects in patients after perineal application. CONCLUSION: Extracorporeal HIFU is technically feasible and induces sharply demarcated tissue damage in the prostate. From the early results of this phase 1 study, the perineal approach seems to be safe.     

High‐intensity focused ultrasound for localized prostate cancer: initial experience with a 2‐year follow‐up

OBJECTIVE

To report on the short‐term functional and oncological results, from one institution, of high‐intensity focused ultrasound (HIFU) for treating localized prostate cancer.

PATIENTS AND METHODS

Over a 3‐year period, 43 patients with localized prostate cancer were scheduled for HIFU in the primary (31) and salvage (12) settings using a second‐generation Ablatherm^TM device (EDAP, Lyon, France). Oncological failure was defined by several criteria, including biochemical failure (assessed using both the Phoenix definition of the nadir + 2 ng/mL) and the current Food and Drug Administration (FDA) trial endpoint of a prostate‐specific antigen (PSA) level of ≥0.5 ng/mL, or starting salvage therapy, or the presence of cancer on biopsy after treatment.

RESULTS

Three patients had their procedures abandoned due to technical limitations/rectal wall thickness. The mean PSA levels in the primary and salvage groups were 9.2 and 5.1 ng/mL, respectively. The mean HIFU treatment time in the primary and salvage groups was 71.1 and 63.3 min, respectively. Using the Phoenix definition of biochemical failure, HIFU treatment failed in 13 patients in the primary group (46%) and five in the salvage group. Using the FDA trial endpoint, HIFU failed in 21 patients in the primary group (75%) and eight in the salvage group. One man died from metastatic prostate cancer 18 months after salvage HIFU. There were two urethral strictures in the primary (7%) and one in the salvage treatment group. There were two prostato‐rectal fistulae in the salvage HIFU group.

CONCLUSIONS

HIFU is proposed to be a minimally invasive low‐morbidity ablative treatment for localized prostate cancer, and with good efficacy. The present limited series is unable to support these claims. There were significant rates of complications and oncological failure in both the primary and salvage setting. As a result we have suspended our programme pending further evidence of its safety and efficacy.     

Microbubbles improve the ablation efficiency of extracorporeal high intensity focused ultrasound against kidney tissues

Objective  The necrosis rate is low when ablating kidney tissues with extracorporeal high intensity focused ultrasound (HIFU), and this drawback has been limiting the application of ultrasonic therapy. The aim of the present study was to determine whether microbubbles increased the ablation efficiency in vivo. Methods  Goat kidneys were exposed to HIFU (control group) or microbubble-assisted HIFU (experimental group). Microbubbles were intravenously injected before focused ultrasound exposure. The linear scan was employed and tissue ablation was performed in manner of a clinical regime. The necrosis rate was determined 24 h after HIFU. Pathological examinations were performed to confirm tissue necrosis and to determine whether there were unaffected tissues within the exposed volume. Results  The necrosis rate was increased in experimental group (4.17 ± 1.33 vs. 9.32 ± 2.27 mm³/s, P = 0.0007). Ablated tissues formed a hemorrhagic volume on gross examinations, and the boundary between treated and untreated areas was sharp. There was no intact tissue within the exposed volume. Hemorrhage frequently occurred in insonated parenchymas. Destructed ghost cells just inside the demarcation were full of vacuoles, when introducing microbubbles. In control group, the volumes of ablated tissues varied drastically between animals despite a same treatment template. Conclusion  Microbubbles increased the ablation efficiency of HIFU against kidney tissues. A preoperative regime might poorly predict the therapeutic outcome. T. Yu and D. Hu contributed equally to this paper.     

高强度聚焦超声对淋巴管的生物学效应

目的 用高强度聚焦超声(HIFU)辐照大鼠淋巴管,观察产生的生物学变化,探讨HIFU治疗乳糜尿的可行性.方法 将SD大鼠32只随机均分为4组;用高强度聚焦超声辐照大鼠右侧腹股沟区,左侧对照;分别于辐照后24 h、72 h、7 d、30 d观察辐照区及周围组织肉眼及病理改变.结果 HIFU辐照后,大鼠腹股沟淋巴管24 h及72h组表现为管腔变形、破裂等急性损伤改变,7 d及30 d组表现为淋巴管数量减少、管腔闭塞、管周瘢痕形成;各时间组实验侧淋巴管密度(LVD)比自身对照侧明显减少:24 h组为1.100±0.428比1.450±0.411(P＜0.01);72 h组为0.725±0.238比1.575±0.362(P＜0.01);7 d组为0.375±0.198比1.575±0.249(P＜0.01);30 d组为0.175±0.198比1.500±0.400(P＜0.01);辐照后,随时间延长,实验侧LVD明显减少(F=16.669,P＜0.01);辐照后7 d,LVD减少不明显(P＞0.05).结论 高强度聚焦超声可靶向损伤淋巴管,最终使管腔粘连闭塞,因此高强度聚焦超声治疗乳糜尿有可行性.

Abstract：

Objective To investigate the use of high-intensity focused ultrasound ( HIFU) to noninvasively produce biological effect in rat lymphatic vessels in vivo, and the feasibility of HIFU in the treatment of chyluria. Methods Thirty-two SD rats were divided into four groups randomly. The right inguinal regions were irradiated and the left served as controls. At the 1st, 3rd, 7th and 30 day after HIFU irradiation, the gross and pathological changes were observed. Results There were acute changes such as the lymphatic vessels rupture and deformation on the experimental sides at 1st and 3rd day after HIFU irradiation. The number of lymphatic vessels was reduced, lumen was occluded, scar formed around the lumen at 7th and 30th day. The lymphatic vessec density (LVD) on the experimental side was significantly decreased as compared with the controls after HIFU irradiation (experimental sides vs controls: 1st day,1.100 ±0.428 vs 1.450 ±0.411 (P＜0.01); 3rd day, 0. 725 ±0. 238 vs 1.575 ±0.362 (P＜0.01);7th day, 0. 375 ± 0. 198 vs 1. 575 ± 0. 249 ( P ＜ 0. 01); 30th day, 0.175 ± 0.198 vs 1. 500 ± 0.400 (P＜0. 01). There was a significant decrease in LVD on the experimental side with the time going (F = 16.669,P＜0.01). However, there was no significant decrease in LVD at the 7th day (P＞0.05).Conclusion HIFU could precisely damage lymphatic vessels of rats and make lumen occlusion finally,suggesting the feasibility of HIFU for chyluria treatment.     

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.     

放射性粒子125Ⅰ联合高强度聚焦超声治疗肝癌的临床疗效

目的 探讨应用放射性粒子125Ⅰ联合高强度聚焦超声治疗肝癌的临床疗效及可行性.方法 四川大学华西医院自2006年6月～2007年4月采用放射性粒子125Ⅰ联合高强度聚焦超声治疗肝癌10例,其中5例为原发性肝癌患者,5例为肝癌术后复发患者.在治疗计划指导下,利用放射性粒子125Ⅰ联合高强度聚焦超声进行治疗.结果 10例患者手术均顺利完成.所有患者术后未发生出血、感染等严重并发症,部分患者肝功能出现损害,经常规保肝治疗后恢复.术后经腹部摄片证实放射性粒子的位置无变化,于术后1、3、6月作CT复查肿瘤体积变化,提示肿瘤不同程度缩小.术后1月存活8例,术后3月存活7例,术后6月存活5例,术后1年存活2例.随访3～18个月,其中最短存活1个月,最长存活22个月,有2例患者现仍然存活.其余患者死于术后全身广泛转移.结论 放射性125l粒子和高强度聚焦超声联合应用具有安全、微创及并发症发生率低的特点,是综合治疗肝癌的有效手段之一.     

经直肠高能聚焦超声与经尿道前列腺切除术治疗前列腺增生症近期疗效比较

目的研究经尿道前列腺切除术(TURP)与经直肠高强度聚焦超声系统(HIFU)治疗前列腺增生症(BPH)的临床疗效。方法对80例BPH手术患者随机分为2组,每组40例,分别行TURP、HIFU前列腺消融术治疗,回顾分析并比较各组术后一般情况及并发症等。复查IPSS、QOLS、PV、Qmas、RUV等疗效指标,对所测指标进行统计学分析。结果两组病人术前一般情况比较差别无显著性(P>0.05)。HIFU组在术后相关指标及并发症发生率与TURP组有显著差异(P<0.05),HIFU组的并发症发生率明显低于TURP组。各组术后主、客观症状均较术前明显改善,比较有显著性差异(P<0.05)。HIFU组在术后3个月主、客观指标比较中与TURP组有显著差异(P<0.05),但在术后1年时HIFU组、TURP组各主、客观指标比较差别无显著性(P>0.05)。结论HIFU前列腺消融术与TURP近期疗效相当,但它在治疗BPH患者中,较TURP更安全,更具微创,术中无出血,手术时间、住院时间短,并发症少等优点。     

Salvage high‐intensity focused ultrasound for biopsy‐confirmed local recurrence of prostate cancer after radical prostatectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To present experience in high‐intensity focused ultrasound (HIFU) used as a salvage therapy for biopsy‐confirmed local recurrence at the vesico‐urethral anastomosis after radical prostatectomy (RP).

PATIENTS AND METHODS

From July 2006, four patients diagnosed with prostate cancer recurrence after RP were treated with HIFU, with or without salvage radiotherapy, using the Sonablate® 500 (Focus Surgery, IN, USA). Biochemical failure was defined as in increase in prostate‐specific antigen (PSA) level of >0.2 ng/mL. No patients received any adjuvant therapy after HIFU therapy before reporting failure.

RESULTS

The mean age and initial PSA level before RP was 74 years and 10.0 ng/mL, respectively. After RP, one patient was stage T2aN0M0, two were stage T3N0M0 and the last had an unknown pathological stage. Three patients received external beam radiotherapy as salvage therapy after RP. The mean PSA level before HIFU, tumour volume at the vesico‐urethral lesion and operative duration were 4.3 ng/mL, 4.6 mL and 27 min, respectively. Adenocarcinomas were confirmed by biopsy of the tumour at the vesico‐urethral anastomotic lesion before HIFU. At 24 months of follow‐up, patients 2 and 4 were classified a biochemically disease‐free. Biopsies at the anastomotic site after HIFU in three patients showed no malignancy, with fibrosis. There were no complications.

CONCLUSION

Salvage HIFU for patients with recurrence after RP is feasible, even though they received salvage radiotherapy before HIFU. More patients and a longer follow‐up are needed to evaluate the safety and oncological adequacy of this new approach.     

靶区血管与声轴成角对脉冲高强度聚焦超声表面消融的影响:实验研究

目的探讨靶区血管与声轴成角对脉冲高强度聚焦超声(PHIFU)表面消融的影响。方法选取30只新西兰大白兔,获取胸主动脉。采用仿组织蛋清体模,在预定消融靶区埋入兔胸主动脉,根据其与声轴成角分为0°、45°和90°组,并设空白对照组,每组10个。在B超监控下采用PHIFU行表面消融,每组治疗参数设置相同。消融过程中对血管面靶区测温,消融后逐层切开体模行肉眼和超声观察,计算每组总体积(V)并进行比较,对辐照区血管行病理检查。结果空白对照组体模边缘为完整强回声带,而0°、45°、90°组血管周围部分呈低回声。空白对照组血管后面最高温度为(98.60±5.76)℃,0°组为(98.90±7.09)℃,45°组为(71.10±13.85)℃,90°组为(70.20±9.14)℃;空白对照组与45°组、90°组比较差异均有统计学意义(P均0.05)。空白对照组总坏死体积为(40 709.70±3 193.31)mm~3,0°组为(40 029.02±3 580.17)mm~3,45°组为(34 562.59±3 883.26)mm~3,90°组为(36 737.01±3 278.68)mm~3;空白对照组与0°组比较差异无统计学意义(P0.05)。血管病理检查示部分弹性纤维断裂,45°和90°组可见碎裂的细胞核。结论当靶区血管与声轴夹角为0°时,对靶区能量沉积影响最小,夹角为45°、90°时对血管壁破坏作用更强。     

海扶刀联合吉西他滨在中晚期胰腺癌治疗中的应用

[摘 要] 目的 探究采用高强度聚焦超声联合吉西他滨治疗中晚期胰腺癌的效果及安全性。方法 将2012年6月至2017年6月间郑州大学第一附属医院诊治的165例中晚期胰腺癌患者随机分为高强度聚焦超声联合静脉滴注吉西他滨治疗组（联合组,92例）和吉西他滨治疗组（化疗组,73例）。对比两组患者治疗2个月后的疼痛缓解率、外周血CA19-9水平、肿瘤体积变化、并发症的发生情况以及治疗后3、6个月的生存率。结果 治疗两个月后,联合组患者疼痛缓解率明显高于化疗组（94.4% vs 21.1%）;联合组治疗2个月后VAS评分[（2.7±3.2）vs（6.2±2.8）]及CA19-9水平[（204.6±195.6）U/mL vs（537.2±274.5）U/mL]明显下降（P<0.05）;肿瘤体积[（20.13±13.25）cm 3 vs （33.45±13.68） cm 3 ]明显缩小（P<0.05）。治疗3个月后,联合组生存率为97.6%,化疗组生存率为94.3%,两组对比无统计学差异（P>0.05）;治疗6个月后,联合组生存率为69.5%,化疗组生存率为24.3%,两组对比有统计学差异（P<0.05）。联合组患者均未出现胃肠道穿孔、胰瘘和出血等HIFU治疗并发症。结论 高强度聚焦超声联合吉西他滨治疗中晚期胰腺癌可明显缩小肿瘤体积,减轻患者的疼痛症状,且并发症少,有效改善生活质量,延长患者的生存期。     

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.     

高强度聚焦超声治疗晚期胰腺癌128例分析

目的 评价高强度聚焦超声(HIFU)治疗晚期胰腺癌的作用、安全性和有效性.方法 分析了128例晚期胰腺癌患者(Ⅲ期41例,Ⅳ期87例)接受HIFU治疗,通过临床症状、实验室检查、影像学变化和生存期等观察疗效.结果 全组病例未发生严重不良反应,22.9％患者癌抗原19-9下降,疼痛缓解,有效率为72.5％.局灶近期疗效为部分缓解11.7％,稳定70.3％,进展18.0％.1年生存率为16.7％,中位生存期为7.0个月.其中Ⅲ期患者1年生存率为28.5％,中位生存期为9.0个月;Ⅳ期患者1年生存率为10.8％,中位生存期为6.0个月.结论 HIFU治疗能够有效稳定瘤灶、缓解疼痛、延长患者生存期且不良反应少,显示了良好的临床价值.