Extracorporeal High-intensity Focused Ultrasound Research Articles

Intra-operative High Intensity Focused Ultrasound (HIFU) Pancreatic Ablation in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer

Introduction: Locally advanced pancreatic cancer (LAPC) has a poor prognosis and few therapeutic options. By definition, LAPC is not resectable. Radiotherapy showed no benefit in the LAP07 trial. Local ablative techniques could be an alternative with encouraging results reported. Extracorporeal HIFU is associated with improved quality of life but targeting the pancreas is difficult. We aimed to demonstrate the efficacy of an intra-operative HIFU transducer, initially developed for the treatment of liver metastases, for pancreatic ablation.

Fast and Large Extracorporeal HIFU Ablations of the Liver Using a Toroidal Transducer. Preclinical Study in an in vivo Porcine Model

Introduction: High intensity focused ultrasound (HIFU) is a recent, non-ionizing and non-invasive technology of focal destruction. Extra-corporeal approach is limited by targeting difficulties (bone interface and respiratory motion of the liver) and long-time treatment. We developed a new HIFU transducer based on toroidal geometry and assessed its efficacy on a porcine model. Method: The diameter and the radius of curvature of the toroidal transducer were 70 mm. The operating frequency was 2.5 MHz. An ultrasound imaging probe operating at 7.5 MHz was placed in the center of the HIFU transducer. In vivo experiments were conducted in eleven animals that were followed over 7 days after HIFU exposure. The HIFU exposure lasted about 40 seconds at an acoustic power of 140W. The toroidal device was hand held. Results: The thickness of intervening tissues was measured before each HIFU exposure and was on average 14.9±2.0 mm. The delivered acoustic energy was between 3870 to 7000 J according to the thickness and attenuation of intervening tissues. The dimensions of the HIFU ablations were 21.2±6.0 mm long by 14.7±5.3 mm large. HIFU ablations were visible on ultrasound images, transcutaneously and intra-operatively. No skin burns were observed. No post-operative complication occurred. Conclusions: A non-invasive HIFU treatment of the liver performed with a toroidal transducer is safe, feasible and well tolerated. Large volumes of ablation were obtained in 40s without resorting to mechanical scanning. Treatment parameters are strongly dependent to the thickness and to the attenuation of intervening tissues.

Preliminary study on ultrasound-guided high-intensity focused ultrasound ablation for treatment of broad ligament uterine fibroids

Objective To investigate the feasibility, efficacy and safety of ultrasound-guided high-intensity focused ultrasound (HIFU) ablation for treating the broad ligament uterine fibroid (BLUF). Methods A total of 236 patients with symptomatic uterine fibroids were enrolled and treated with JC-200 extracorporeal ultrasound-guided HIFU under conscious sedation between January 2017 and December 2018. Of them, data of 12 patients with 13 broad ligament fibroids were retrospectively analyzed. The patients’ mean age was 38.6 ± 6.3 years. The focused ultrasound target was deployed and moved from the deeper layer to the superficial layer of BLUFs. All patients underwent contrast-enhanced MRI (CE-MRI) before, immediate post-operation, and six months after the HIFU ablation procedure. The fibroid size, non-perfusion volume (NPV) ratio, the reduction of fibroid volumes, adverse events, symptom changes, and abnormal MRI findings associated with the HIFU treatment were analyzed. Results Ultrasound-guided HIFU ablation in the twelve patients was technically successful with one session treatment. The mean longest diameter of BLUFs was 6.2 ± 2.3 cm. The mean NPV ratio of fibroids was 84.08%± 9.4%. After HIFU ablation, lower abdominal pain occurred in 7 cases, sacrococcygeal pain in 3 cases, and mild skin pain in 6 cases. There were no severe adverse events and complications associated with the treatment. At 6 months post-treatment follow-up, the mean fibroid volume decreased by 56.2%± 9.0% (p < 0.05), and the symptoms related to broad ligament fibroids were improved or disappeared Conclusions Ultrasound-guided high-intensity focused ultrasound ablation is feasible, effective, and safe for treating broad ligament fibroids.

Characterization and Ex Vivo evaluation of an extracorporeal high-intensity focused ultrasound (HIFU) system.

BackgroundHigh‐intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required.MethodsThe acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo.ResultsAcoustic pressure mapping showed the insignificant presence of side/grating lobes and pre‐ or post‐focal peaks (≤−12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of −11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20‐mm target, which suggests the well‐controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750–1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling.ConclusionsOur characterization and ex vivo evaluation protocol met the IDE requirement. The in‐situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.

Vein wall shrinkage induced by thermal coagulation with high-intensity-focused ultrasound: numerical modeling and in vivo experiments in sheep

Background Varicose veins are a common disease that may significantly affect quality of life. Different approaches are currently used in clinical practice to treat this pathology. Materials and methods In thermal therapy (radiofrequency or laser therapy), the vein is directly heated to a high temperature to induce vein wall coagulation, and the heat induces denaturation of the intramural collagen, which results macroscopically in vein shrinkage. Thermal vein shrinkage is a physical indicator of the efficiency of endovenous treatment. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can thermally coagulate vein walls and induce vein shrinkage. In this study, we evaluated the vein shrinkage induced in vivo by extracorporeal HIFU ablation of sheep veins: six lateral saphenous veins (3.4mm mean diameter) were sonicated for 8 s with 3MHz continuous waves. Ultrasound imaging was performed before and immediately post-HIFU to quantify the HIFU-induced shrinkage. Results Luminal constriction was observed in 100% (6/6) of the treated veins. The immediate findings showed a mean diameter constriction of 53%. The experimental HIFU-induced shrinkage data were used to validate a numerical model developed to predict the thermally induced vein contraction during HIFU treatment. Conclusions This model is based on the use of the k-wave library and published contraction rates of vessels immersed in hot water baths. The simulation results agreed well with those of in vivo experiments, showing a mean percent difference of 5%. The numerical model could thus be a valuable tool for optimizing ultrasound parameters as functions of the vein diameter, and future clinical trials are anticipated.

Acoustic power measurement of high-intensity focused ultrasound transducer using a pressure sensor

The acoustic power of high-intensity focused ultrasound (HIFU) is an important parameter that should be measured prior to each treatment to guarantee effective and safe outcomes. A new calibration technique was developed that involves estimating the pressure distribution, calculating the acoustic power using an underwater pressure blast sensor, and compensating the contribution of harmonics to the acoustic power. The output of a clinical extracorporeal HIFU system (center frequency of ~1 MHz, p+ = 2.5–57.2 MPa, p− = −1.8 to −13.9 MPa, ISPPA = 513–22,940 W/cm2, −6 dB size of 1.6 × 10 mm: lateral × axial) was measured using this approach and then compared with that obtained using a radiation force balance. Similarities were found between each method at acoustic power ranging from 18.2 W to 912 W with an electrical-to-acoustic conversion efficiency of ~42%. The proposed method has advantages of low weight, smaller size, high sensitivity, quick response, high signal-to-noise ratio (especially at low power output), robust performance, and easy operation of HIFU exposimetry measurement.

High-intensity Focused Ultrasound Ablation of Soft-tissue Tumors and Assessment of Treatment Response with Multiparametric Magnetic Resonance Imaging: Preliminary Study Using Rabbit VX2 Tumor Model

Background High-intensity focused ultrasound (HIFU) is an emerging technique for noninvasive ablative treatment. However, HIFU has rarely been performed for the treatment of soft-tissue tumors. Thus, we aimed to assess the feasibility and safety of performing extracorporeal HIFU for the treatment of soft-tissue tumor. The treatment response was assessed using functional magnetic resonance imaging (MRI) techniques. Materials and methods In the rabbit VX2 intramuscular tumor model, HIFU was performed using an extracorporeal HIFU device (YDME FEP-BY02) by varying the electric power from 50 to 400 W, with the other parameters being fixed. The HIFU beam was insonated to one layer of focal spots having a depth of 8 mm. The degree of ablation was evaluated by histological examination and functional MRI techniques including dynamic contrast-enhanced MRI (DCE-MRI) and apparent diffusion coefficient (ADC) map. The presence of skin burn was also evaluated. Results Applying HIFU with an electric power of 200 W discretely produced the ablation zone without skin burn as planned before treatment (maximal depth: 8–9 mm), which shows the suitability of using HIFU (with 200 W electric power) for the treatment of soft-tissue tumors. By contrast, HIFU with an electric power of 100 W produced an ill-marginated ablation zone with internal residual tumor foci, and HIFU with 300–400 W produced ablation zones with a maximum depth of 13–24 mm, which far exceeded the planned depth and caused skin burn. Perfusion maps of DCE-MRI demonstrated the devascularized ablation zone more conspicuously than conventional contrast-enhanced T1-weighted images, and ADC map demonstrated the surrounding edema or granulation tissue better than conventional T2-weighted images. Conclusion Extracorporeal HIFU treatment for soft-tissue tumor may be a feasible approach with adjustment of input energy level. For post-treatment assessment, functional MRI techniques including DCE-MRI and ADC map may be useful and complementary to conventional MRI.

Thermal Fixation of Swine Liver Tissue after Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation

The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins.

Noninvasive Renal Sympathetic Denervation by Extracorporeal High-Intensity Focused Ultrasound in a Pre-Clinical Canine Model

This study investigated the feasibility of noninvasive renal sympathetic denervation (RSD) by using the novel approach of extracorporeal high-intensity focused ultrasound (HIFU). Catheter-based RSD has achieved promising clinical outcomes. Under the guidance of Doppler flow imaging, therapeutic ablations (250 W × 2 s) were performed by using extracorporeal HIFU on the bilateral renal nerves (36.3 ± 2.8 HIFU emissions in each animal) in a mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar procedures without acoustic energy treatment were conducted in 5 canines of the sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma noradrenaline (NA) level, and renal function were determined on days 0, 6, and 28. Pathological examinations were performed on all retrieved samples. All of the animals survived the treatment. After ablation, BP and NA significantly decreased compared with the baseline values (BP changed -15.9/-13.6 mmHg, NA changed -55.4% [p < 0.001] 28 days after ablation]) and compared with the sham group on days 6 and 28. Ablation lesions around the renal artery adventitia were observed on day 6. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation on day 28. No procedure-related complications were observed. Effective RSD was successfully achieved by using the extracorporeal HIFU method in canines. Thus, noninvasive HIFU may be further explored as an important and novel strategy for RSD.

Generation of uniform lesions in high intensity focused ultrasound ablation

High intensity focused ultrasound (HIFU) is emerging as an effective oncology treatment modality according to the clinical experience in the last decade. The temperature at the focus can reach over 65°C within seconds, denaturing cellular proteins and resulting in coagulative necrosis. HIFU parameters are usually kept the same for each treatment spot in tumor ablation. Because of the thermal diffusion from nearby spots, the lesion size will gradually increase as the HIFU therapy progresses, which leads to insufficient treatment of initial spots and over exposure of later ones. From the viewpoint of the physician, uniform lesions with the least energy exposure and the least energy are preferred in tumor ablation. In this study, an algorithm was developed to determine the number of HIFU pulses delivered to each spot in order to generate uniform lesions that fill the region-of-interest completely. The exposure energies required using different scanning pathways (raster scanning, spiral scanning from the center to the outside, and spiral scanning from the outside to the center), spot spacing (1mm, 2mm, 4mm, and 6mm) and motion time (from 0s to 400s) were compared with each other. It is found that spiral scanning from the outside to the center with spot spacing of 2mm and motion time less than 10s needs the least numbers of pulses or HIFU energy in uniform lesion production with the minimal temperature elevation. In addition, the effects of thermal properties of tissue (i.e., specific heat capacity, convective heat transfer coefficient, and thermal conductivity) on HIFU ablation were investigated in order to determine the HIFU treatment planning for various targets. Uniform lesion production in the transparent gel phantom and ex vivo bovine liver samples using the proposed algorithm proved effective and accord with the simulation for different scanning pathways by an extracorporeal clinical HIFU system. Therefore, dynamically adjusting ultrasound exposure energy can improve the efficacy and safety of HIFU ablation, and the treatment planning depends on the scanning protocol and thermal properties of the target.

Experimental Studies and Clinical Experiences on Treatment of Secondary Hypersplenism with Extracorporeal High-Intensity Focused Ultrasound

The aim of this study is to investigate the efficacy and safety of extracorporeal high-intensity focused ultrasound (HIFU) in treatment of hypersplenism. Fifteen adult dogs, weighing 13–18 kg were divided into three groups: sham group, SVL group undergoing splenic vein ligation (SVL) after laparotomy, and SVL + HIFU group receiving SVL followed by extracorporeal HIFU. Pathologic and hematologic analyses were performed. We also reviewed the clinical data of 19 patients with secondary hypersplenism caused by liver cirrhosis or hepatocellular carcinoma who underwent extracorporeal HIFU. Extracorporeal HIFU significantly diminished the volume of the spleen of animals, coupled with occurrence of coagulation necrosis and fibrosis in the target area. Both platelet and red blood cell counts were significantly restored by HIFU intervention. Similarly, HIFU treatment improved the hematologic parameters in patients with hypersplenism, and no major complications were encountered. Extracorporeal HIFU intervention is effective and safe in managing secondary hypersplenism.

Adverse Events of Extracorporeal Ultrasound-Guided High Intensity Focused Ultrasound Therapy

BackgroundHigh-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy.Methods and FindingsClinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0–280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58–44.38%, p<0.0001) and benign lesions (1.67–17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions.ConclusionThe frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared with MRgFU.

Experimental ablation of the pancreas with high intensity focused ultrasound (HIFU) in a porcine model

The aim of this study was to determine the feasibility and safety of high intensity focused ultrasound's (HIFU) in pancreatic diseases. Twelve pigs were divided into three groups. The pancreases of pigs in Group A were ablated directly with HIFU, but those in Group B and C ablated by extracorporeal HIFU. The pigs in Group C were sacrificed at day 7 after HIFU. Serological parameters were determined pre-operation and post-operation. The entire pancreas was removed for histological examination. Each animal tolerate the HIFU ablation well. The complete necrosis was observed in targeted regions. The margins of the necrotic regions were clearly delineated from the surrounding normal tissues. Infiltration of inflammatory cells and phorocytosis on the boundary were found in group C. Blood and urine amylase levels were relatively steady after HIFU. No acute pancreatitis or severe complications occurred. In conclusion, HIFU ablation on the pancreas was safe and effective in experimental pigs.

Laparoscopic high‐intensity focused ultrasound for renal tumours: a proof of concept study

Study Type--Therapy (case series) Level of Evidence What's known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib-cage limiting energy delivery. For this study, a purpose-built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications. • To test and establish clinical proof of concept for a laparoscopic high-intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface. • Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18-mm laparoscopic port. • HIFU treatment was targeted at a pre-defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed. • No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients. • The ablated zones were within the targeted area in all patients and no intra-lesional skipping was seen. • Subcapsular skipping was seen at the probe-tumour interface in two patients with viable tumour cells seen at microscopy. • One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells. • There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow-up of 15 (8-24) months with no evidence of metastatic disease or late complications. • Tumour ablation with laparoscopic HIFU is feasible. • Homogenous ablation can be achieved with no vital tissue within the targeted zone. • The technique is associated with low morbidity and may have a role in the definitive management of small tumours.

Extracorporeal high intensity focused ultrasound for renal tumours: a 3‐year follow‐up

To determine whether primary extracorporeal high-intensity focused ultrasound (HIFU) is safe, feasible and effective for managing small renal tumours. Although surgery currently remains the standard treatment for localized renal cell carcinoma (RCC), the increasing incidence of small renal cancers has led to a shift towards nephron-sparing surgery, with associated morbidity in 20-25% of cases, and minimally invasive ablative therapies present an alternative management. HIFU results in 'trackless' homogenous tissue ablation and when administered via an extracorporeal device, is entirely noninvasive. The study comprised 17 patients (mean tumour size 2.5 cm) with radiologically suspicious renal tumours who underwent extracorporeal HIFU using the Model-JC System (Chongqing HAIFU™, China), under general anaesthesia with one overnight hospital stay. Real-time diagnostic ultrasonography was used for targeting and monitoring. Patients were followed with a clinical review and gadolinium-enhanced magnetic resonance imaging at 12 days and every 6 months for a mean of 36 months. The outcomes measures were patient morbidity and oncological efficacy of HIFU treatment. Of the 17 patients, 15 were treated according to protocol; two procedures were abandoned due to intervening bowel. There were no major complications related to HIFU. Radiological evidence of ablation was apparent at 12 days in seven of the 15 patients. Before the 6-month follow-up one patient had surgery due to persisting central enhancement. Fourteen patients were evaluated at the 6-month follow-up; eight tumours had involuted (mean 12% decrease in tumour area). Four patients had irregular enhancement on imaging and had alternative therapies. Ten patients remain on follow-up at a mean (range) of 36 (14-55) months after HIFU (mean 30% decrease in tumour area). There was central loss of enhancement in all. Renal HIFU achieves stable lesions in two-thirds of patients, with minimal morbidity, and might be appropriate in selected cases. Further trials with accurate histological follow-up are essential to fully evaluate this novel technique.

Focal Therapy and Imaging in Prostate and Kidney Cancer: High-Intensity Focused Ultrasound Ablation of Small Renal Tumors

The rising incidence of small, incidentally detected renal masses in elderly, infirm patients has raised interest in minimally invasive, energy ablative techniques. High-intensity focused ultrasound (HIFU) delivers ultrasonic energy, resulting in heat and tissue destruction in the targeted tissue at a selected depth. In contrast to radiofrequency ablation and cryoablation, HIFU does not require puncturing the tumor, avoiding the high risk of hemorrhage or tumor spillage. While the extracorporeal approach shows unsatisfactory results, laparoscopic HIFU appears to be a promising alternative treatment option. Problems with respiratory movement and interphases, as seen in extracorporeal HIFU, are avoided when the transducer is brought directly to the target by laparoscopic HIFU. Potential benefits of laparoscopic HIFU are decreased morbidity, shorter hospitalization and convalescence, and preservation of renal function. Nevertheless, further prospective studies have to be performed to define the oncological success of HIFU as an alternative to open and laparoscopic surgery in small renal masses.

Ultrasonidos extracorpóreos de alta intensidad: alternativa terapéutica del tumor renal

Objectives High 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 methods Extracorporeal 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. Results This 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. Conclusions Extracorporeal 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.

High-intensity focused ultrasound for the treatment of renal masses: current status and future potential

To outline the current status of high-intensity focused ultrasound (HIFU) for the treatment of renal tumors. Application of extracorporeal HIFU for renal tumors is well tolerated with no serious perioperative complications. However, the techniques available do not permit sufficient tumor destruction that can be considered as an alternative to surgical extirpation. Laparoscopic HIFU avoids problems with respiratory movement and interphases and may achieve a greater rate of tumor destruction. At the current time, HIFU of renal tumors has to be considered an experimental treatment approach. Prospective evaluation of laparoscopic HIFU is necessary to evaluate its oncologic efficacy.

Preclinical in vivo Evaluation of an Extracorporeal HIFU Device for Ablation of Pancreatic Tumors

Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned. (E-mail: jooha@u.washington.edu)

High intensity focused ultrasound in the treatment of small kidney tumours— The Oxford experience

14645 Background: High-intensity focused ultrasound (HIFU) provides a potential non-invasive alternative to conventional therapies. We have been using the extracorporeal ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) in clinical trials to evaluate the safety and feasibility of treating small renal tumours. Methods: Patients with renal tumours less than 4cm diameter and unsuitable for surgery were treated with HIFU were enrolled into this phase II prospective trial. Treatment was delivered under general anaesthesia in a single session using the Model-JC Tumor Therapy System. Magnetic resonance imaging (MRI) 12 days after treatment provided an initial assessment of response (technical success). Patients are followed-up with further MR imaging at 6 months and one year to gauge technique effectiveness. A total of 14 patients will be included in the trial. Results: Eight patients with kidney tumours have been treated to date. All eight have had pre- and 12-day post-treatment MR imaging. One patient was not included in the analysis as treatment was suspended due bowel interposition in the treatment field during therapy. MRI changes suggestive of kidney tumour response have been seen in 4/7 (57%) cases. Complete ablation has been seen in two cases and partial ablation in two cases. One patient remains disease free 12 months after HIFU. Mild transient discomfort was reported by 4/8 patients (50%), and moderate discomfort in 3/8 (38%) but more severe pain needing opiate analgesia has not been encountered in this series. Minor skin toxicity (1mm blister at the treatment site) was seen in two patients. All patients were discharged the day after the procedure. There have been no adverse effects on renal, haematological or hepatic function. Conclusions: Extracorporeal HIFU has the ability to completely ablate small renal tumours. Our early clinical experience suggests that HIFU treatment of kidney tumours is safe and extremely well tolerated. The reasons for the variability in observed response remain obscure, and reliability of tumour ablation will need to improve before extracorporeal HIFU can be proposed for wider clinical use. [Table: see text]