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.     

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.     

Anti-angiogenesis in prostate cancer： knocked down but not out

Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors （stimulators and inhibitors）. This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms： by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration （FDA） approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and Dromising area of prostate cancer research.     

后腹腔镜技术治疗肾上腺肿瘤53例报告

Objectives To summarize the clinical experience of retroperitoneal laparoscopic adrenalectomy for adrenal tumor and facilitate the clinical application.Methods From June 2002 to October 2009,S3 caws of adrenal tumor were treated with retroperitoneal laparoscopic adrenalectomy,including 19 cases of primary aldosteronism,8 cases of Cushings syndrome,9 cases of pheochromocytoma,14 cases of nonfunctional adrenal adenoma,2 cases of adrenal cyst,1 case of adrenal paraganglioma.B ultrasound and CT/MRI were used to diagnose all patients.33 tumors were on the left side and 20 on the right.The size of the tumors ranged from 1.2 to 7.0cm(mean,2.2cm).Results 49 surgeries were successfully completed.4 surgeries converted to open surgeries.The mean of operating time was 92(56～220) min.The mean of estimated blood loss was 55 (20～300 ) ml.The mean of postoperative hospitalization was 7(4～12) days.There was no serious complication during perioperative period.Conclusions Retroperitoneal laparoscopic adrenalectomy for adrenal tumor is safe and effective with the advantages of minimal invasion,quick recovery and few complications.It should be considered as the first choice for treating benign adrenal diseases.     

后腹腔镜技术治疗肾上腺肿瘤53例报告

Objectives To summarize the clinical experience of retroperitoneal laparoscopic adrenalectomy for adrenal tumor and facilitate the clinical application.Methods From June 2002 to October 2009,S3 caws of adrenal tumor were treated with retroperitoneal laparoscopic adrenalectomy,including 19 cases of primary aldosteronism,8 cases of Cushings syndrome,9 cases of pheochromocytoma,14 cases of nonfunctional adrenal adenoma,2 cases of adrenal cyst,1 case of adrenal paraganglioma.B ultrasound and CT/MRI were used to diagnose all patients.33 tumors were on the left side and 20 on the right.The size of the tumors ranged from 1.2 to 7.0cm(mean,2.2cm).Results 49 surgeries were successfully completed.4 surgeries converted to open surgeries.The mean of operating time was 92(56～220) min.The mean of estimated blood loss was 55 (20～300 ) ml.The mean of postoperative hospitalization was 7(4～12) days.There was no serious complication during perioperative period.Conclusions Retroperitoneal laparoscopic adrenalectomy for adrenal tumor is safe and effective with the advantages of minimal invasion,quick recovery and few complications.It should be considered as the first choice for treating benign adrenal diseases.     

The current status of robot-assisted radical prostatectomy

Robot-assisted radical prostatectomy （RARP） is a rapidly evolving technique for the treatment of localized prostate cancer. In the United States, over 65% of radical prostatectomies are robot-assisted, although the acceptance of this technology in Europe and the rest of the world has been somewhat slower. This article reviews the current literature on RARP with regard to oncological, continence and potency outcomes-the so-called ＇trifecta＇. Preliminary data appear to show an advantage of RARP over open prostatectomy, with reduced blood loss, decreased pain, early mobilization, shorter hospital stay and lower margin rates. Most studies show good postoperative continence and potency with RARP; however, this needs to be viewed in the context of the paucity of randomized data available in the literature. There is no definitive evidence to show an advantage over standard laparoscopy, but the fact that this technique has reached parity with laparoscopy within 5 years is encouraging. Finally, evolving techniques of single-port robotic prostatectomy, laser- guided robotics, catheter-free prostatectomy and image-guided robotics are discussed.     

Targeted prostate biopsy： value of multiparametric magnetic resonance imaging in detection of localized cancer

Prostate cancer is the second most common cancer in men, with 1.1 million new cases worldwide reported by the World Health Organization in one recent year. Transrectal ultrasound （TRUS）-guided biopsy has been used for the diagnosis of prostate cancer for over 2 decades, but the technique is usually blind to cancer location. Moreover, the false negative rate of TRUS biopsy has been reported to be as high as 47%. Multiparametric magnetic resonance imaging （mp-MRI） includes T1- and T2-weighted imaging as well as dynamic contrast-enhanced （DCE） and diffusion-weighted imaging （DWI）. mp-MRI is a major advance in the imaging of prostate cancer, enabling targeted biopsy of suspicious lesions. Evolving targeted biopsy techniquesmincluding direct in-bore biopsy, cognitive fusion and software-based MRI-ultrasound （MRI-US） fusion--have led to a several-fold improvement in cancer detection compared to the earlier method. Importantly, the detection of clinically significant cancers has been greatly facilitated by targeting, compared to systematic biopsy alone. Targeted biopsy via MRI-US fusion may dramatically alter the way prostate cancer is diagnosed and managed.     

Pancreatic adenocarcinoma: Outstanding problems

Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%.Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma.About 40% of patients have locally advanced nonresectable disease.In the past,determination of pancreatic cancer resectability was made at surgical exploration.The development of modern imaging techniques has allowed preoperative staging of patients.Institutions disagree about the criteria used to classify patients.Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis.There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition ofborderline resectable pancreatic cancer is also lacking.Thus,there is much room for improvement in all aspects of treatment for pancreatic cancer.Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer.With improved surgical techniques and advanced perioperative management,vascular resection and reconstruction are performed more frequently;patients thought once to be unresectable are undergoing radical surgery.However,when attempting heroic surgery,a realistic approach concerning the patient’s age and health status,probability of recovery after surgery,perioperative morbidity and mortality and life quality after tumor resection is necessary.     

Malignant ovarian tumors complicating pregnancy: a clinicopathological study of twenty-one cases

<正>Objective: To study the clinicopathological characters of malignant ovarian tumors during pregnancy. The rationale for appropriate management was discussed. Methods: Twenty-one cases of malignant ovarian tumors complicating pregnancy treated between 1985 and 2002 were reviewed retrospectively. In reference with the reports from the current literatures, the rationale of the treatment for the best outcome of both mother and child was discussed. Results:In the patients reviewed, 9 were found with malignant germ cell tumors of the ovary, 6 with low malignant potential tumors, 4 with invasive epithelial tumors, and 2 with sex cord-stromal tumors. Sixteen (76. 2%) of the patients diagnosed in stage Ⅰ, and all had achieved complete response to the treatment. Three of the four patients in advanced stage died, of which two were invasive epithelial cancers and one stage Ⅳendodermal sinus tumor. All patients had surgery, and fourteen of them got conservative surgery. All sixteen patients accepted for chemotherapy took adjuvant chemotherapies after abortions or deliveries. Fourteen healthy live births were recorded in this group and there were no documented birth defects, but one died of respiratory distress syndrome. Conclusion: The managements of malignant ovarian cancers during pregnancy differed in different histological types. In ovarian borderline tumors and malignant germ cell tumors including stage Ⅰ,Ⅱ, and Ⅲ, surgery can be conservative. For advanced epithelial cancers, aggressive surgery should be instituted. Chemotherapy could be considered for the malignant germ cell tumor during the second and third trimester. Ovarian borderline tumors should not take chemotherapy. Epithelial cancer should be given combination platinum-based chemotherapy. Hysterectomy during pregnancy is rarely indicated unless it contributes significantly to tumor debulking, and pregnancy often could be allowed to continue until near-term.     

No-scalpel vasectomy outside China

Since 1985, the no-scalpel vasectomy technique has been widely used outside China. The prevalence of this technique has helped to increase the acceptability of male sterilization in many parts of the world. More than 5000 physicians in twenty-five developing countries have been trained in the no-scalpel vasectomy technique. In the United States in 1995, nearly one third of vasectomies employed the no-scalpel technique, and in the whole Northem American region, a total of 1100 doctors have been made familiar with the technique. Doctors believe that them are several advantages of the no-scalpel technique, including no incision, no stitches, faster procedure, faster recovery, less chance of bleeding, less discomfort and high efficacy. The key steps of the technique include fixation of the vas and infiltration anaesthesia of the spermatic cord, as well as grasping, delivering and isolating the vas. No-scalpel technique provides a good approach to expose the vas, in conjunction with which, different vas-end occlusion methods may be used.(Asian J Androl 2000; 2. 21 - 24)     

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.     

超声造影评价高强度聚焦超声治疗局限性前列腺癌早期疗效的临床研究

目的 探讨超声造影对高强度聚焦超声（HIFU）治疗局限性前列腺癌早期疗效评价的应用价值.方法 采用HIFU-2001型高强度聚焦超声肿瘤治疗系统,对17例局限性前列腺癌进行治疗.治疗前及治疗后1个月分别行超声造影检查,观察瘤体内部及周边组织血流灌注信号特点,据此判定疗效.同时根据直肠指检、经直肠前列腺B超检查前列腺肿块大小、血清PSA等结果进行客观疗效判定.将两疗效判定结果进行对比分析.结果 HIFU治疗前,所有前列腺低回声结节均呈快速高增强.HIFU治疗后,超声造影显示治疗有效15例,其中无增强12例、少量低增强3例;无效2例,仍表现为快速高增强.客观疗效判定有效15例,血清PSA下降幅度均≥50%,其中2例前列腺结节体积缩小≥50%;无效2例,血清PSA、前列腺低回声结节大小体积均与治疗前水平相当.客观疗效判定结果与超声造影结果相符.结论 超声造影能准确显示HIFU治疗局限性前列腺癌的消融范围及程度,是评价早期治疗效果的可靠方法.     

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侵袭性纤维瘤研究进展

侵袭性纤维瘤(AF)是一种交界性肿瘤,具有较强局部侵袭性和复发性而少见远处转移。近年来,影像学引导下高强度聚焦超声(HIFU)逐渐用于治疗AF,具有精准、无创、可重复等优点。本文对HIFU治疗AF研究进展进行综述。     

Das Lokalrezidiv des Prostatakarzinoms nach kurativer Therapie

In terms of effectivity and impact, no ideal approach is as yet available for treatment of local recurrence of prostate cancer. We direct our attention mainly toward high-intensity focused ultrasound (HIFU). HIFU therapy (Ablatherm) is only performed in our department when the following criteria are met: the recurrent tumor must be visualizable with imaging procedures (for HIFU, transrectal ultrasound is employed), the tumor must be accessible to the scanner head (penetration depth: 25 mm), and finally the diagnosis of recurrent tumor has to be histologically confirmed. An indisputable advantage of HIFU is the option of easily administering HIFU therapy for a second time in the presence of tumor remnants or in the event of cancer recurrence. Depending on the primary cancer treatment given, salvage HIFU achieves a biopsy-proven tumor-free state in 60-74% of patients. These results are in line with those that can be obtained with other salvage strategies (radical prostatectomy, radiation therapy). However HIFU shows reduced postoperative morbidity with less side effects.     

Tratamiento conservador del cáncer renal mediante HIFU. Técnica,indicaciones y resultados

This article reviews the mechanisms of action of high-intensity focused ultrasound (HIFU), as well as both experimental and clinical work related to renal tumor treatment.While most currently available experience in urological tumors with HIFU has been obtained with prostate cancer, an increasing number of studies support the efficacy and safety of this procedure for renal tumor destruction. HIFU completes, with cryotherapy and radiofrequency, the spectrum of minimally invasive surgery in renal cancer, intended to decrease surgical morbidity while achieving similar oncological control rates.It is still early to recommend this procedure for daily clinical practice because, while its safety and few side effects are known, many ongoing studies intended to confirm its mid- and long-term oncological efficacy should be completed.     

高强度聚焦超声体外治疗人恶性实体肿瘤的病理学变化

目的 研究高强度聚焦超声（HIFU）体外治疗人恶性实体肿瘤的病理学变化。方法 HIFU治疗164例恶性实体肿瘤病人,其中30例治疗后常规外科手术,观察治疗区组织的病理学变化。结果 HIFU治疗区与非治疗区边界清楚,治疗区内组织出现凝固性坏死。组织学检查显示治疗区内全部肿瘤细胞出现不可逆性损伤征象,其边缘有新生肉芽组织形成和淋巴细胞浸润。结论 HIFU体外治疗恶性实体肿瘤是安全、有效和可行的,该技术将为临床无创性治疗肿瘤提供一种全新的治疗手段。     

Ultrasonidos extracorpóreos de alta intensidad: alternativa terapéutica del tumor renal

ObjectivesHigh intensity focused ultrasound (HIFU) is known to be used for the treatment of solid tumors in minimally invasive procedures. Transducers allowing for application of ultrasound from an extracorporeal focus have recently been developed. A review is provided of the development, physical principles, and current status of this therapy, and our early experience with it for the treatment of renal tumors is reported.Materials and methodsExtracorporeal HIFU is currently being used for the treatment of tumors (mainly hepatic, gynecological, and bone tumors), and has been started to be used for renal tumors with good results. A literature review (structured search in the online MEDLINE electronic base) of the physical principles of this treatment and its biological action is provided. The therapeutic procedure used in the first few patients with renal carcinoma successfully treated with HIFU at our hospital is reported.ResultsThis therapy has been successfully used to treat solid tumors at several centers in Europe, America, and Asia. Our center has a wide experience in treatment of gynecological tumors using extracorporeal HIFU, and has already treated renal tumors with no complications, although follow-up is still short.ConclusionsExtracorporeal use of this energy appears as a new option among non-invasive therapies for renal cancer in selected cases. A low complication rate has been noted, but much longer follow-up times are required for assessment of oncological results.     

Principles and results of high-intensity focused ultrasound for localized prostate cancer

Focused ultrasound holds promise in a large number of therapeutic applications. It has long been known that high-intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible, with the development of high-power ultrasound arrays and noninvasive monitoring methods. In the last decade, HIFU have been adapted and used to treat localized prostate cancer and it is now commercially available in Europe. In this article, preclinical studies and clinical development of prostate HIFU as well as early clinical results from our center and international studies are reviewed. Early results demonstrated that prostate HIFU is efficient to obtain local control for low- and intermediate-risk localized prostate cancer; however, long-term follow-up is still needed to estimate the efficacy of prostate HIFU in terms of specific cancer mortality. This makes HIFU a viable alternative in patients not candidate for radical therapy.     

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。