高强度聚焦超声治疗晚期胰腺癌对机体免疫功能的影响

目的：探查高强度聚焦超声治疗胰腺癌对机体细胞免疫功能的影响。方法：应用HIFUNIT-9000型治疗仪对65例Ⅲ～Ⅳ期的胰腺癌病人进行治疗；VAS法评估治疗前后病人疼痛程度的改变；超声、CT观察治疗前后肿瘤大小及影像学特征的改变；流式细胞仪检测治疗前后病人外周血T淋巴细胞亚群的变化。17例未行HIFU治疗的中晚期胰腺癌病人作为对照。结果：65例病人治疗后，疼痛减轻52例（80．0％），治疗后评分疼痛下降程度明显大于对照组（P〈0．01）；56例（86．1％）治疗后肿瘤癌组织多普勒B超显示血供减少；CT证实HIFU组治疗前、后肿瘤增长幅度小于对照组（P〈0．05）；外周血γδT细胞及CD4^＋／CD8^＋比例均高于治疗前（P〈0．05）。结论：HIFU治疗晚期胰腺癌不仅安全有效，还可增强机体的抗肿瘤免疫功能。     

乌司他丁对肝癌患者高强度聚焦超声治疗后细胞免疫功能的影响

目的 探讨乌司他丁对肝癌患者高强度聚焦超声（HIFU）治疗后细胞免疫功能的影响。方法 择期行HIFU治疗的肝癌患者20例，ASAⅡ或Ⅲ级，随机分为2组（n=10）：对照组（C组）和乌司他丁组（U组）。U组于麻醉诱导后缓慢静脉注射乌司他丁20万U，C组输注等量生理盐水。于HIFU治疗前即刻（T1）、治疗结束即刻（T2）及治疗结束后24h（T3）采取肘静脉血样2ml，使用流式细胞仪检测CD3^＋、CD4^＋、CD8^＋T淋巴细胞和NK细胞百分率。结果 与T1比较，C组T2、T3时CD3^＋、CD4^＋、CD8^＋T淋巴细胞百分率差异无统计学意义（P〉0．05），T2时CD4^＋，CD8^＋比值增高，T2、T3时NK细胞百分率增高（P〈0．05），U组T2、T3时CD3^＋T淋巴细胞百分率差异无统计学意义（P〉0．05），T2时CD4^＋、CD8^＋T淋巴细胞百分率增高（P〈0．05），T2、T3时CD4^＋／CD8^＋比值、NK细胞百分率增高（P〈0．01）；与C组比较，T2、T3时U组NK细胞百分率增高（P〈0．05）。结论 乌司他丁可有效提高HIFU治疗肝癌患者的细胞免疫功能。     

高强度聚焦超声对恶性实体肿瘤血管的破坏作用

目的：探讨高强度聚焦超声（HIFU）体外破坏恶性实体肿瘤血管的临床影像学变化和病理学变化。方法：HIFU治疗恶性实体肿瘤患者164例，通过数字减影血管造影、彩超、放射性核素显影分析肿瘤血管治疗前后的功能状态；30例患者治疗后常规外科手术，观察肿瘤血管的病理学变化。结果：临床影像学检查显示与治疗前比较，治疗后肿瘤异常血管网被破坏，肿瘤内血供减少或消失；光镜下肿瘤毛细血管、小血管管壁结构出现不可逆性损伤表现，腔内有血栓形成。结论：HIFU能从体外破坏肿瘤血管，加强了HIFU杀死肿瘤细胞的直接效应，这种选择性破坏血管作用有重要的临床意义。     

高强度聚焦超声治疗原发性肝癌相关并发症分析及处理

目的 对高强度聚焦超声（HIFU）治疗原发性肝癌的并发症进行分析,提高HIFU治疗的安全性.方法 回顾性分析郑州大学第一附属医院自2009年12月-2014年9月收治的165例经高强度聚焦超声治疗的原发性肝癌患者的资料,统计其发生的并发症并分析相关处理措施.结果 HIFU治疗原发性肝癌常见的并发症包括治疗区皮肤软组织损伤（118/165）、肝功能一过性损伤（83/165）、术后低热（81/165）、自限性胸腔积液（42/165）及术区疼痛麻木（33/165）;比较严重的并发症主要包括肋骨骨折（2例）、脏器穿孔损伤（1例）、癌灶破裂出血（1例）及皮肤Ⅱ（5例）、Ⅲ（1例）度烧伤;所有并发症积极治疗后均未引起严重后果.结论 高强度聚焦超声治疗原发性肝癌严重并发症少,安全性高.     

高强度聚焦超声治疗高危前列腺增生症的临床疗效

目的 评价高强度聚焦超声（HIFU）治疗高危前列腺增生症的近期疗效及安全性。方法 选择高危前列腺增生症患者102例，超声定位实时监视下，从体外将高能量超声聚焦于增生的前列腺组织，应用FEP-BY02型高强度聚焦超声治疗机进行HIFU治疗，治疗后定期随访观察患者临床症状、体征及瘤体超声影像学变化。结果 102例患者治疗后近期总有效率为92.2%（显效＋有效＋部分有效），其中显效11例（10.8%），有效43例（42.2%），部分有效40例（39.2%），无效8例（7.8%）。结论 HIFU体外治疗可作为一种无手术创伤治疗高危前列腺增生症安全有效方法之一。     

高强度聚焦超声治疗中晚期原发性肝癌对患者免疫状态的影响

目的 观察高强度聚焦超声（HIFU）治疗中晚期原发性肝癌对患者免疫状态的影响。方法 对2003年3月至2003年12月我院收治的40例原发性肝癌患者行HIFU治疗，对其治疗前后进行自身比较并与射频治疗组进行比较，观察分析原发性肝癌患者在接受HIFU治疗后的免疫指标（cD3、cD4、CD8、CD4／CD8、NK、IL-2、TNF）变化。结果 HIFU治疗组与射频治疗组3、6、9个月及1年生存率比较，差异无统计学意义；患者上述各项免疫指标于HIFU治疗前后相比较差异无统计学意义，与射频治疗组比较，差异亦无统计学意义。结论 HIFU治疗中晚期原发性肝癌对患者早期免疫状态的影响不明显。     

载阿霉素的液-固相变型原位凝胶注射治疗兔VX2肝癌HIFU消融后残癌

目的观察载阿霉素液一固相变型原位注射凝胶（DOX-ISFI）治疗高强度聚焦超声（HIFU）消融兔、,x2肝癌后残癌的疗效。方法以24只兔建立VX2肝癌模型,对肿瘤行HIFU不全消融,随机分为HIFU消融与DOX—ISFI联合治疗组（HIFU＋DOX—ISFI组）、HIFU消融与空白液一固相变原位注射凝胶联合治疗组（HIFU＋N—ISFI组）,每组12只,比较两组肿瘤生长率、PCNA表达情况,并以冰冻切片荧光显像观测药物瘤内分布。结果处理后HIFU＋DOX—ISFI组肿瘤生长明显减慢,其生长率明显低于HIFU＋N—ISFI组（P〈O．05）;HIFU十D0X-ISFI组肿瘤增殖指数明显低于HIFU＋N—ISFI组（P〈0．05）;荧光显像姓示药物从注射中心向剧围呈阶梯状分布。结论DOXISFI能钉效治疗HIFUiVX2肝癌后的残癌。     

肝癌的影像学检查与病理结果的对比研究

目的评价目前常用的几种影像学技术对肝硬化肝癌检查的准确性。方法将74例肝癌肝移植病例的术前彩色多普勒超声（BUS）、CT、MRI检查结果与术后病理解剖结果对照分析，从肿瘤大小（以长径进行对比，若术前影像学检查与标本解剖误差〈1cm认为是符合）和数目两方面的诊断符合率来评估术前常用的影像学检查的可靠性。结果肿瘤数目术前影像学检查与术后病理解剖结果的符合率分别是：BUS38．8％（26／67），CT56．6％（30／53），MRI61．0％（36／59）；肿瘤直径的符合率分别是：BUS38．3％（57／149），CT42．5％（54／127），MRI48．3％（71／147）。随着瘤灶直径增加，检查符合率逐步提高。直径≤1cm的肿瘤BUS、CT、MRI三者漏诊率分别为90．2％（37／41）、89．5％（34／38）及78．3％（36／46）。结论对肝硬化肝癌，目前常用的术前影像学检查方法均不完全符合于病理结果，并存在一定数量的假阳性及假阴性，仅依术前影像学检查报告确定治疗方案，尤其是作为肝切除与肝移植适应证的绝对标准时应考虑到这一因素。肝硬化肝癌影像学检查的准确性有待于进一步提高。     

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.     

高能聚焦超声治疗晚期胰腺癌的近期疗效观察

目的：观察高强度体外聚焦超声（HIFU）热疗治疗晚期胰腺癌的安全性及近期疗效。方法：应用FEP—BY02肿瘤超声治疗机治疗胰腺癌17例，共接受治疗135次（每例平均8次）。结果：完全缓解率2例，部分缓解10例，总有效率70％。临床受益反应率82.36％，无效率17.64％。癌性疼痛缓解率80％。结论：HIFU治疗晚期胰腺癌能取得一定的疗效，治疗安全性高。     

HIFU消融治疗不同MRI特征子宫肌瘤的效果

目的探讨HIFU消融治疗不同MRI特征子宫肌瘤的效果。方法回顾性分析经HIFU治疗的96例子宫肌瘤患者资料,比较HIFU治疗不同位置、类型、MRI信号特征和强化程度的子宫肌瘤的消融率和能效因子,并评估其安全性。结果平均肌瘤体积、消融率、能效因子分别为(107.14±70.85)cm3、(72.48±11.04)%和(7.45±3.05)J/mm3。不同位置、类型、信号特征和强化程度的子宫肌瘤之间,HIFU消融率和能效因子差异均有统计学意义(P均0.05),对前壁、肌壁间、T2WI低信号、T1WI轻度强化肌瘤的消融率更高、能效因子更低(P均0.05)。术中、术后未发现严重不良反应。结论 HIFU治疗子宫肌瘤相对安全,消融效果确切,其对前壁、肌壁间、T2WI低信号、T1WI轻度强化的子宫肌瘤的消融效果更好。     

MRI appearance of prostate following transrectal HIFU ablation of localized cancer.

OBJECTIVES: To evaluate the accuracy of gadolinium-enhanced MRI in gauging the extent of the tissue damage induced by transrectal high intensity focused ultrasound (HIFU) therapy and to assess how well the results obtained with this modality correlate with histological findings (control biopsies). METHODS: Twenty-one patients with biopsy-proven prostate cancer (T1-T2-T3a, Nx, M0) who gave informed consent were included in the protocol. They underwent pre- and postoperative (2-5 days after HIFU treatment) MR examinations. Fifteen patients also underwent a follow-up MR examination 1-5 months postoperatively. MR findings were compared with the results of postoperative transrectal biopsy examinations. RESULTS: The prostate volume increased after the HIFU session from 43.9+/-18.6 to 52.1+/-21 cm(3) by day 2 (p<0.001). On fat-saturated gadolinium-enhanced T1-weighted images, the treated area appeared as a hypointense zone surrounded by a peripheral rim of enhancement in all patients. A positive correlation (r = 0.75) was found between the volume of the hypointense zone measured at days 2-5 (30+/-11 cm(3), 67% of the posttreatment prostate volume) and the theoretical target volume (22+/-5 cm(3), 61% of the initial prostate volume). MRI showed that the anterior part of the base was not reached by the ultrasound beam. The mean volume of the untreated zone (prostate without any MRI modifications) was 8 cm(3) (range, 0.4-36). No correlation was found between the MRI appearance of the treated area and the intensity of the necrosis or the presence of foci of residual, viable cancer. CONCLUSION: Gadolinium-enhanced MRI is an accurate way of determining the extent of tissue damage induced in HIFU ablative therapy, but cannot predict histological results.     

高强度聚焦超声消融单发性子宫肌瘤能效因子的影响因素

目的分析单发性子宫肌瘤高强度聚焦超声(HIFU)消融过程中能效因子(EEF)的影响因素。方法回顾性分析218例接受HIFU治疗的单发性子宫肌瘤患者。选择可能影响EEF的因素作为自变量,以EEF为因变量,采用Stepwise regression方法建立多重线性回归模型。结果 HIFU治疗平均EEF为(7.62±5.39)J/mm3。6个预测因子被引入多重线性回归模型,包括靶皮距、前倾位(子宫位置)、贯穿型(肌瘤类型)、肌瘤最大径、低信号(T2WI信号强度)及增强T1WI强化程度。其中EEF与靶皮距、增强T1WI强化程度、贯穿型(肌瘤类型)呈正相关,与肌瘤最大径、低信号(T2WI信号强度)、前倾位(子宫位置)呈负相关,且肌瘤最大径对EEF影响最大(标准系数为-0.292)。结论对子宫呈前倾位且肌瘤血供少、含水量低、最大径长、靶皮距小的非贯穿型单发性子宫肌瘤,HIFU消融EEF小,难度低。     

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.     

高强度聚焦超声对21例中晚期原发性肝癌病人免疫状态的影响

目的　探讨高强度聚焦超声 (highintensityfocusedultrasound ,HIFU)对原发性肝癌(hepatocellularcarcinoma,HCC)病人机体免疫状态的影响。 方法　采用重庆海扶技术有限公司研制的HIFU系统 ,治疗中晚期HCC病人 2 1例。分别在治疗前和治疗后 3、7、14、2 1d抽取病人外周静脉血 ,检测细胞免疫和体液免疫的相关指标。HIFU治疗后又行癌灶切除的病例 ,对标本进行光学显微镜、电子显微镜观察。结果　光学显微镜、电子显微镜观察结果显示 ,HIFU治疗区内癌组织发生了不可逆性损伤。CD4治疗前 (34± 13)后 (3、7、14及 2 1d分别为 4 0± 7,37± 7,39± 9,37± 7)差异无显著意义 (F =0 89,P >0 0 5 ) ;其他细胞免疫指标 (CD3 ,CD8,CD4/CD8,CD16)以及体液免疫指标(IgG ,IgA ,IgM ,C3 )治疗前后间的差异亦均无显著意义。结论　HIFU能有效地破坏HCC组织。HIFU治疗中晚期HCC病人难以明显改善机体的免疫状态 ,此时若配合免疫治疗等手段 ,有望使病人获得更好的预后。     

Tolerance of High-Intensity Focused Ultrasound Ablation in Patients with Hepatocellular Carcinoma

Background

High-intensity focused ultrasound (HIFU) ablation is a relatively new, noninvasive way of ablation for treating hepatocellular carcinoma (HCC). Emerging evidence has shown that it is effective for the treatment of HCC, even in patients with poor liver function. There is currently no data on the safety limit of HIFU ablation in patients with cirrhosis. However, this information is vital for the selection of appropriate patients for the procedure. We analyzed HCC patients who had undergone HIFU ablation and determined the lower limit of liver function and other patient factors with which HCC patients can tolerate this treatment modality.

Methods

Preoperative variables of 100 patients who underwent HIFU ablation for HCC were analyzed to identify the risk factors in HIFU intolerance in terms of stress-induced complications. Factors that may contribute to postablation complications were compared.

Results

Thirteen (13?%) patients developed a total of 18 complications. Morbidity was mainly due to skin and subcutaneous tissue injuries (n?=?9). Five patients had first-degree skin burn, one had second-degree skin burn, and three had third-degree skin burn. Four complications were grade 3a in the Clavien classification and 14 were below this grade. Univariate analysis showed that age (p?=?0.022) was the only independent factor in HIFU intolerance.

Conclusions

HIFU ablation is generally well tolerated in HCC patients with cirrhosis. It is safe for Child-Pugh A and B patients and selected Child-Pugh C patients. With this new modality, HCC patients who were deemed unsalvageable by other surgical means in the past because of simultaneous Child-Pugh B or C disease now have a new hope.     

Prostate cancer treatment by the latest focal HIFU device with MRI/TRUS-fusion control biopsies: A prospective evaluation

Objectives

Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided focal high intensity focused ultrasound (HIFU) therapy of the prostate has recently been developed as a selective HIFU-therapy technique to enable targeted ablation of prostate cancer. Here we report a series of patients treated with focal HIFU therapy, discuss its potential pitfalls, and address controversies concerning the indications.

Heat fixation of cancer cells ablated with high-intensity-focused ultrasound in patients with breast cancer

BACKGROUND: High-intensity-focused ultrasound (HIFU) is a noninvasive thermal ablation technique. This study reports the use of histological techniques for the pathological assessment of HIFU effects in patients with breast cancer. METHODS: Twenty-three patients with biopsy-proven breast cancer underwent HIFU treatment for primary breast lesion. Mastectomy was performed on all patients after HIFU. By using histological examinations, the surgical specimens were assessed to explore HIFU effects on breast cancer. RESULTS: Coagulation necrosis of targeted tumors was confirmed by microscopy in 23 patients. Tumor cells presented typical characteristics of coagulation necrosis in the peripheral region of the ablated tumor in all patients. However, in 11 of 23 patients, hematoxylin and eosin staining showed normal cellular structure in the central ablated tumor. By using electronic microscopy and nicotinamide adenine dinucleotide-diaphorase stain, those who had normal-appearing cancer cells were not viable. CONCLUSIONS: HIFU can cause the heat fixation of ablated tumor through thermal effect.     

Expression of Tumor Antigens and Heat-Shock Protein 70 in Breast Cancer Cells After High-Intensity Focused Ultrasound Ablation

Background Previous results have shown that high-intensity focused ultrasound (HIFU) ablation can potentially activate a host antitumor immunity. The goal of this study was to investigate whether the tumor antigens expressed on breast cancer cells may be preserved after HIFU treatment, and to explore the potential mechanisms regarding the enhanced antitumor response. Methods The primary lesion in 23 patients with biopsy-proven breast cancer were treated with HIFU, then submitted to modified radical mastectomy. By using biotin-streptavidin-peroxidase immunohistochemical technology, a variety of cellular molecules expressed on breast cancer cells, including tumor antigens and heat-shock protein 70 (HSP-70), were stained in all breast specimens. A complete absence of staining was recorded as negative, and immunoreaction of the tumor cells was considered to be positive for antigen expression. Results Nuclear positivity of breast cancer cells for proliferating cell nuclear antigen, estrogen receptor, and progesterone receptor was detected in 0%, 9%, and 9% of the treated samples, respectively. The positive rate of cytoplasmic staining for matrix metalloproteinase 9, carbohydrate antigen 15–3, vascular endothelial growth factor, transforming growth factors β₁ and β₂, interleukin 6, and interleukin 10 was 0%, 52%, 30%, 57%, 70%, 48%, and 61% in the treated cancer cells, respectively. The positive rate of cellular membrane staining for epithelial membrane antigen, CD44v6, and HSP−70 was 100%, 0%, and 100% in the zones of treated cancer cells, respectively. Conclusions After HIFU ablation, some tumor antigens remained in the tumor debris. This could provide a potential antigen source to stimulate antitumor immune response.