Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound

The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(-2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogeneous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.     

Extracorporeal high intensity focused ultrasound in the treatment of patients with solid malignancy.

The ideal treatment of localized cancer should cause the complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which can induce complete coagulation necrosis of a targeted tumor, at depth, through the intact skin. The concept of using HIFU as a non-invasive therapy has attracted attention in medicine for 60 years. Recently, it has received increasing interest as a promising modality for the treatment of localized solid malignancies. The goal of this article is to introduce recent clinical developments in the use of extracorporeal HIFU ablation for solid tumors, including those of liver, breast, bone, kidney, pancreas, soft tissue, and uterus. It describes the physical principles and ablative mechanisms, three-dimensional therapeutic regimes, and medical imaging used in HIFU. Currently, large numbers of patients with solid malignancy are already treated using HIFU, and short-term clinical results are very encouraging. However, large-scale randomized clinical trials are necessary to evaluate long-term efficacy of HIFU treatment for solid malignancies. It is concluded that this non-invasive ablation can be considered as a conventional therapy for widespread clinical use only when the results from prospective, randomized clinical trials worldwide are available.     

高强度聚焦超声体外治疗恶性实体肿瘤的临床安全性研究

目的：研究高强度聚焦超声（HIFU）体外治疗恶性实体肿瘤的临床安全性。方法：HIFU体外治疗恶性实体肿瘤患者164例,观察治疗过程中,治疗后的全身和局部的变化。结果：治疗中,治疗后患者生命体征稳定,主要器官功能基本正常;局部瘤灶无破裂或出血,无黄疸或胆汁漏溢,未发现瘤灶邻近脏器或血管损伤,结论：HIFU体外治疗恶性实体肿瘤是安全的。     

High-intensity focused ultrasound ablation assisted using color Doppler imaging for the treatment of hepatocellular carcinomas

Purpose

We evaluated the usefulness of color Doppler flow imaging to compensate for the inadequate resolution of the ultrasound (US) monitoring during high-intensity focused ultrasound (HIFU) for the treatment of hepatocellular carcinoma (HCC).

Materials and methods

US-guided HIFU ablation assisted using color Doppler flow imaging was performed in 11 patients with small HCC (<3 lesions, <3 cm in diameter). The HIFU system (Chongqing Haifu Tech) was used under US guidance. Color Doppler sonographic studies were performed using an HIFU 6150S US imaging unit system and a 2.7-MHz electronic convex probe.

Results

The color Doppler images were used because of the influence of multi-reflections and the emergence of hyperecho. In 1 of the 11 patients, multi-reflections were responsible for the poor visualization of the tumor. In 10 cases, the tumor was poorly visualized because of the emergence of a hyperecho. In these cases, the ability to identify the original tumor location on the monitor by referencing the color Doppler images of the portal vein and the hepatic vein was very useful. HIFU treatments were successfully performed in all 11 patients with the assistance of color Doppler imaging.

Conclusion

Color Doppler imaging is useful for the treatment of HCC using HIFU, compensating for the occasionally poor visualization provided by B-mode conventional US imaging.     

高强度聚焦超声破坏深部组织超声图像变化

为阐明高强度聚焦超声(HIFU)对体内肝组织的生物学效应,本研究用超声图像定量分析方法观察小型香猪肝脏受损组织的形态学变化.用超声定位的HIFU体外断层切除肝脏靶区.并用定量分析系统检测靶区,发现HIFU治疗前后超声图像有明显差异.结果提示:超声图像定量分析可用于监测HIFU治疗后受损组织的形态学变化.     

高能超声聚焦治疗子宫肌(腺)瘤临床报告

目的评价高能超声聚焦(HIFU)治疗子宫肌瘤及腺肌症的近期疗效及安全性。方法选择不愿意手术的已生育的育龄期妇女为治疗对象,在B超定位并实时监视下,应用FEP-BY01型高能超声聚焦肿瘤治疗机治疗340例。定期随访观察患者临床症状、体征及瘤体内超声影像学变化。结果经HIFU治疗后的340例患者近期患者有效率达95%,无效率5%。发生皮肤烫伤2例。结论高强度超声体外聚焦热疗治疗子宫肌瘤安全有效,可作为一种无创伤治疗子宫肌瘤及腺肌症的新方法。     

Extracorporeal ablation of uterine fibroids with high-intensity focused ultrasound: imaging and histopathologic evaluation.

OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy of high-intensity focused ultrasound (HIFU) in the treatment of uterine fibroids by using imaging and histopathologic examination. METHODS: From May 2004 to June 2005, 119 consecutive patients with 187 uterine fibroids were treated with HIFU. Sixty-two fibroids received ultrasonographically guided needle puncture biopsy 1 week before and after HIFU treatment, respectively, to confirm the diagnosis and to assess the early therapeutic efficacy. Hematoxylin-eosin staining and electron microscopy were performed to characterize more subtle phenotypic changes to determine treatment success. Immediate therapeutic effects were assessed at follow-up with Doppler ultrasonography and computed tomography or magnetic resonance imaging. All patients were followed for 6 to 12 months to observe long-term therapeutic effects. Fibroid mean diameters, volumes, and reduction rates 1, 3, 6, and 12 months after HIFU treatment were calculated and compared with 1-way analysis of variance and Student-Newman-Keuls tests. RESULTS: No severe complications were observed after HIFU ablation. Fifty-one (82.3%) of 62 biopsy specimens revealed obvious signs of necrosis under light microscopy, and more subtle changes in cellular structure that indicated nonviability could be found in 60 specimens (96.8%) under electron microscopy. However, viable cells still could be found in 16 specimens (25.8%). Follow-up images showed absence or reduction of blood supply in the lesions after HIFU ablation. Median reductions in tumor size as a percentage of initial tumor volume at 1, 3, 6, and 12 months after HIFU treatment were 21.2%, 29.6%, 44.8%, and 48.7%, respectively. CONCLUSIONS: Imaging and histopathologic evidence directly validate HIFU ablation as an effective treatment of uterine fibroids.     

Contrast‐Enhanced Transrectal Ultrasound for Follow‐up After Focal HIFU Ablation for Prostate Cancer

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast‐enhanced transrectal ultrasound (TRUS) in follow‐up of patients after high‐intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast‐enhanced TRUS findings were as follows: (1) contrast‐enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast‐enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image‐guided prostate biopsy, which showed prostate cancer; and (3) contrast‐enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.     

高强度聚焦超声单次治疗子宫肌瘤的临床研究

目的探讨高强度聚焦超声（HIFU）单次治疗子宫肌瘤的安全性和近期疗效。方法采用JC型HIFU肿瘤治疗系统对确诊的33例子宫肌瘤患者共46个肌瘤进行治疗性研究。比较治疗前后患者的临床症状和超声影像变化。结果治疗后超声造影显示肌瘤平均灭活率为（80．7±16．3）％,其中灭活率90．0％以上的肌瘤占69．6％（32／46）;治疗后1、3、6、12个月超声检查显示肌瘤体积较治疗前明显缩小（P〈0．01）,平均缩小率分别是（37．8±9．2）％、（47．1±11．4）％、（61．0±13．2）％、（76．5±15．4）％。子宫肌瘤相关临床症状评分较治疗前有所改善（P〈0．05）。无严重并发症发生。结论HIFU单次治疗子宫肌瘤近期疗效好,安全,副作用小,值得进一步研究。     

超声用于评价高强度聚焦超声联合射频治疗大肝癌的研究

目的探讨超声图像监控在高强度聚焦超声（HIFU）联合射频（RFA）治疗大肝癌（直径〉5cm）肿瘤时的作用。方法利用HIFU联合RFA治疗大肝癌患者76例,观察肝癌组织术中、术后超声图像的变化,并对照手术前后腹部MRI结果进行对比分析。结果HIFU及RFA治疗时,可见超声灰阶增强,术后随访癌灶血流减少或消失,术后MRI显示治疗靶区坏死明显,坏死区与超声定位治疗靶区相一致,提示超声定位及监控准确,周围邻近脏器未见损伤。结论超声是目前HIFU及RFA治疗大肝癌时较好的定位及治疗监控手段。     

Neoadjuvant HIFU treatment for malignant fibrous histiocytoma: report of a case

High-intensity focused ultrasound (HIFU) is an innovative, noninvasive, extracorporeal technique that induces coagulative necrosis of tumor tissue by thermal effects and cavitation. In published studies, HIFU has usually been used as an alternative to surgery, with or without other treatment modalities, to achieve curative tumor ablation or palliative tumor cytoreduction. Neoadjuvant HIFU treatment for primary inoperable malignant fibrous histiocytoma has never been reported, and neoadjuvant radiotherapy, chemoradiation, or chemotherapy is routinely under consideration. This is the first case in which HIFU ablation contributed as a neoadjuvant therapy to facilitate function-sparing resection, not as a replacement for surgery. It suggests that HIFU ablation may have some unique major advantages for treating inoperable huge soft-tissue sarcomas as a neoadjuvant local treatment modality, especially for patients for whom neoadjuvant chemotherapy or radiotherapy is not indicated.     

MRI在高强度聚焦超声消融子宫肌瘤中的应用进展

高强度聚焦超声（HIFU）已广泛应用于子宫肌瘤治疗,疗效确切。MRI软组织分辨率高,在妇科实体肿瘤检测中优势明显。MR多参数成像技术在术前拟定治疗计划、术中实时监测、术后疗效评估中具有不可替代的作用。本文对MRI各参数在HIFU消融子宫肌瘤术前、术中及术后的应用进行综述。     

高强度聚焦超声治疗子宫平滑肌瘤的病理变化及其超声随访研究

目的通过病理穿刺及超声随访探讨高强度聚焦超声（HIFU）治疗子宫肌瘤的有效性。方法62例经HIFU治疗的子宫肌瘤患者，术前、术后1周分别进行超声引导下穿刺活检，标本行光镜和电镜观察。并分别在术后1、3、6和12个月进行超声检查，计算瘤体均径并与治疗前均径比较。结果光镜和电镜显示HIFU治疗后子宫肌瘤组织明显的细胞坏死、核固缩浓染、核碎裂溶解以及细胞器的破坏；同时可见血管的破坏以及空泡的形成。超声随访显示治疗后1个月肌瘤出现缩小，治疗后3个月瘤体明显缩小，与治疗前相比有显著差异（P〈0．05）。结论病理检查和超声随访证实HIFU治疗子宫平滑肌瘤明确有效。     

Fast and Selective Ablation of Liver Tumors by High-Intensity Focused Ultrasound Using a Toroidal Transducer Guided by Ultrasound Imaging: The Results of Animal Experiments

This study demonstrated that high-intensity focused ultrasound (HIFU) produced with an intra-operative toroidal-shaped transducer causes fast, selective liver tumor ablations in an animal model. The HIFU device is composed of 256 emitters working at 3 MHz. A 7.5 MHz ultrasound imaging probe centered on the HIFU transducer guided treatment. VX2 tumor segments (25 mg) were implanted into the right lateral liver lobes of 45 New Zealand rabbits. The animals were evenly divided into groups 1 (toroidal HIFU ablation), 2 (surgical resection) and 3 (untreated control). Therapeutic responses were evaluated with gross pathology and histology 11 d post-treatment. Toroidal transducer-produced HIFU ablation (average ablation rate 10.5 cc/min) allowed fast and homogeneous tumor treatment. Sonograms showed all ablations. VX2 tumors were completely coagulated and surrounded by safety margins without surrounding-organ secondary HIFU lesions. HIFU group tumor volumes at autopsy (39 mm³) were significantly lower than control group volumes (2610 mm³, p < 0.0001). HIFU group tumor metastasis (27%) was lower than resected (33%) and control (67%) group metastasis. Ultrasound imaging, gross pathology and histology results supported these outcomes. HIFU procedures had no complications. Rabbit liver tumor ablation using a toroidal HIFU transducer under ultrasound imaging guidance might therefore be an effective intra-operative treatment for localized liver metastases.     

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging

High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US) imaging were synchronized to develop a system for real-time visualization of HIFU treatment. The system was tested in vivo in pig liver. The HIFU application resulted in the appearance of a hyperechoic spot at the focus that faded gradually after cessation of HIFU exposure. The duration of HIFU exposure needed for a hyperechoic spot to appear, was inversely related to the HIFU intensity. The threshold intensity required to produce a hyperechoic spot in liver in < 1 s was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was observed, providing a potential for pretreatment targeting. The real-time visualization method was used in hemostasis of actively bleeding internal pelvic vessels, allowing targeting and monitoring of successful treatment. Real-time US imaging may provide a useful tool for image-guided HIFU therapy.     

高强度聚焦超声治疗子宫肌瘤疗效研究

目的探讨高强度聚焦超声治疗子宫肌瘤的有效性,评价超声造影对HIFU治疗的疗效判断。方法选择HIFU治疗的子宫肌瘤患者88例,共检出肌瘤138枚,于治疗前和治疗后彩色多普勒血流显像及超声造影检查,观察瘤体大小、内部及周边组织回声和血流灌注对比变化。结果治疗2~5d后肌瘤内部回声不均匀性增强,血流信号减少,肌瘤内无造影剂显示,肌瘤内时间强度曲线幅度减低。治疗3个月后肌瘤缩小,平均有效率52%,肌瘤内部回声均发生变化,血流信号消失,临床症状改善。结论HIFU治疗子宫肌瘤有效。超声造影可早期客观评估子宫肌瘤血流灌注状态,有效评价HIFU治疗的效果,作为治疗后判断疗效是一项较好的检测指标。     

高强度体外聚焦超声热疗治疗盆腹部转移癌疗效的超声观察

目的：评价高强度体外聚焦超声热疗（HIFU）治疗盆腹部转移癌的临床应用价值及彩色多普勒超声治疗前后声像图变化。方法：15例转移癌共21个癌瘤HIFU治疗前后均进行彩超检测。观察其大小，内部回声及血供改变情况。并观察HIFU治疗后癌瘤病理组织学改变。结果：治疗有效率76%（16/21），治疗后彩超表现为癌瘤缩小，回声增强，血供明显减少或消失，病理组织学上表现为凝固性坏死或纤维化形成。结论：HIFU对盆腹部转移癌治疗有效。彩超能直观反映其疗效。     

Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment

Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.     

高强度聚焦超声联合动脉栓塞治疗恶性实体肿瘤的初步视察

目的：高强度聚焦超声（HIFU）是治疗恶性实体肿瘤的新方法，本文主要探讨HIFU联合TACE治疗恶性肿瘤的近期临床疗效。方法：本文观察了19例HIFU联合TAE/TACE治疗恶性实体肿瘤，14例术中B超监测出现明显回声增强。根据患者术前后的临床症状、B超、肝功能检查、AFP、MRI等评价HIFU的临床疗效。结果：术后AFP呈不同程度下降，MRI示肿瘤体内血供减少，肿瘤有不同程度坏死，部分瘤体直径缩小。仅少数患者有轻度的局部烧伤，无一例严重并发症。结论：HIFU对实体肿瘤有确切疗效，TAE/TACE和HIFU在肿瘤治疗中有协同作用，新鲜碘油沉积可能在其中起较大作用。