lntraoperative and extracorporeal treatment of liver and pancreatic tumors by using toroidal high intensity focused ultrasound transducers

Les ultrasons focalisés de haute intensité (HIFU) permettent la destruction de tissus biologiques par élévation de la température. Cette technique reconnue est utilisée actuellement dans le monde médical afin de traiter certaines masses tumorales. Le projet décrit dans ce document détaille la mise au point et l'utilisation de deux systèmes thérapeutiques indépendants, ayant pour objectif principal le traitement peropératoire puis extracorporel des tumeurs hépatiques. Dans un premier temps, un système chirurgical existant, destiné au traitement des métastases hépatiques et en cours d'évaluation clinique, a été utilisé. La mise en place d'une modalité de traitement par focalisation électronique a permis d'augmenter le volume de coagulation initial et ainsi faciliter la procédure opératoire. Basée sur les conclusions de cette première étude, une seconde version de sonde peropératoire a été modélisée puis développée. La géométrie du transducteur utilisé a permis une modification de la forme des lésions produites. Les performances de cette sonde de traitement ont été évaluées numériquement puis validées lors d'expérience in vitro et in vivo. L'efficacité, la simplicité et la reproductibilité des traitements réalisés sur le foie ont conduit à une possible application du dispositif aux cancers du pancréas. Après étude numérique et évaluation de la faisabilité in vitro, une validation sur modèle animal a été entreprise. L'ensemble des résultats obtenus au cours de ces différents traitements peropératoires a permis d'envisager la faisabilité d'un dispositif de traitement par voie extracorporelle. Une étude théorique a donné lieu à la réalisation d'un prototype expérimental. Après calibrations et étalonnages, des résultats in vitro préliminaires ont été obtenusHigh intensity focused ultrasound (HIFU) allows the destruction of biological tissue by temperature increase. This technique is commonly used in the medical world for treating certain types of tumor masses. The project described in this document details the development and use of two independent therapy systems, with the main objective to treat intraoperatively and extracorporeally liver tumors. As a first step, an existing surgical system, intended to treat liver metastases and under clinical evaluation, was used. The establishment of a treatment modality based on electronic focusing has contributed to increase the coagulation volume and thus simplify the operative procedure. Based upon the findings of this first study, a second version of intraoperative probe was modeled and developed. The geometry of this new transducer allowed to change the shape of produced ablations. The performance of this probe were evaluated numerically and then validated with in vitro and in vivo studies. The effectiveness, simplicity and reproducibility of the treatments performed in the liver led to a possible application of the device to pancreatic cancer. After numerical study and in vitro feasibility assessment, animal model validation was also undertaken. All the results obtained during the peroperative treatments was used to study the feasibility of an extracorporeal treatment. A theoretical study has led to the development of an experimental prototype. After calibration, preliminary in vitro results were obtaine

lntraoperative and extracorporeal treatment of liver and pancreatic tumors by using toroidal high intensity focused ultrasound transducers

Les ultrasons focalisés de haute intensité (HIFU) permettent la destruction de tissus biologiques par élévation de la température. Cette technique reconnue est utilisée actuellement dans le monde médical afin de traiter certaines masses tumorales. Le projet décrit dans ce document détaille la mise au point et l'utilisation de deux systèmes thérapeutiques indépendants, ayant pour objectif principal le traitement peropératoire puis extracorporel des tumeurs hépatiques. Dans un premier temps, un système chirurgical existant, destiné au traitement des métastases hépatiques et en cours d'évaluation clinique, a été utilisé. La mise en place d'une modalité de traitement par focalisation électronique a permis d'augmenter le volume de coagulation initial et ainsi faciliter la procédure opératoire. Basée sur les conclusions de cette première étude, une seconde version de sonde peropératoire a été modélisée puis développée. La géométrie du transducteur utilisé a permis une modification de la forme des lésions produites. Les performances de cette sonde de traitement ont été évaluées numériquement puis validées lors d'expérience in vitro et in vivo. L'efficacité, la simplicité et la reproductibilité des traitements réalisés sur le foie ont conduit à une possible application du dispositif aux cancers du pancréas. Après étude numérique et évaluation de la faisabilité in vitro, une validation sur modèle animal a été entreprise. L'ensemble des résultats obtenus au cours de ces différents traitements peropératoires a permis d'envisager la faisabilité d'un dispositif de traitement par voie extracorporelle. Une étude théorique a donné lieu à la réalisation d'un prototype expérimental. Après calibrations et étalonnages, des résultats in vitro préliminaires ont été obtenusHigh intensity focused ultrasound (HIFU) allows the destruction of biological tissue by temperature increase. This technique is commonly used in the medical world for treating certain types of tumor masses. The project described in this document details the development and use of two independent therapy systems, with the main objective to treat intraoperatively and extracorporeally liver tumors. As a first step, an existing surgical system, intended to treat liver metastases and under clinical evaluation, was used. The establishment of a treatment modality based on electronic focusing has contributed to increase the coagulation volume and thus simplify the operative procedure. Based upon the findings of this first study, a second version of intraoperative probe was modeled and developed. The geometry of this new transducer allowed to change the shape of produced ablations. The performance of this probe were evaluated numerically and then validated with in vitro and in vivo studies. The effectiveness, simplicity and reproducibility of the treatments performed in the liver led to a possible application of the device to pancreatic cancer. After numerical study and in vitro feasibility assessment, animal model validation was also undertaken. All the results obtained during the peroperative treatments was used to study the feasibility of an extracorporeal treatment. A theoretical study has led to the development of an experimental prototype. After calibration, preliminary in vitro results were obtaine

Development of a hifu treatment using a toroidal transducer for pancreatic adenocarcinoma: Preliminary in vivo study

International audiencePancreatic adenocarcinoma is one of the most aggressive cancer. Regardless of the treatment used, the survival rate after 5 years is lower than 6%. Toroidal transducers can treat up to 60 cm3 of tissues in 370 seconds without the need to displace the HIFU probe. In this study, which included fourteen pigs, we evaluated in vivo the use of this device for treating the pancreas and peripancreatic vessels. The device was used intra-operatively. The transducer, working at 2.5MHz, has a toroidal shape with a radius of curvature of 70 mm focusing on a circle of 30 mm. An ultrasound-imaging probe working at 7.5 MHz was placed in the center of the HIFU transducer. Ablations were created in 440 seconds using an acoustic power of 85 or 100 watts. In total eight pigs were included in this study. Eight lesions were created in the pancreas and around peri-pancreatic vessels and observed immediately after treatment. Homogenous ablations were obtained in all cases and were confirmed histologically. The average diameter of the pancreatic ablations was 33.1 � 5.0 mm. These ablations were also homogeneous all around the peripancreatic artery and without occlusion as confirmed by Doppler examination. Using this toroidal HIFU transducer it is possible to treat the most challenging region of the pancreas and its surrounding vessels without any occlusion. This may allow to treat locally advanced pancreatic tumors which are the main contra-indication to curative resection

First Clinical Experience of Intra-Operative High Intensity Focused Ultrasound in Patients with Colorectal Liver Metastases: A Phase I-IIa Study

<div><p>Background</p><p>Surgery is the only curative treatment in patients with colorectal liver metastases (CLM), but only 10–20% of patients are eligible. High Intensity Focused Ultrasound (HIFU) technology is of proven value in several indications, notably prostate cancer. Its intra-operative use in patients with CLM has not previously been studied. Preclinical work suggested the safety and feasibility of a new HIFU device capable of ablating volumes of up to 2cm x 2cm in a few seconds.</p><p>Methods</p><p>We conducted a prospective, single-centre phase I-IIa trial. HIFU was delivered immediately before scheduled hepatectomy. To demonstrate the safety and efficacy of rapidly ablating liver parenchyma, ablations were performed on healthy tissue within the areas scheduled for resection.</p><p>Results</p><p>In total, 30 ablations were carried out in 15 patients. These ablations were all generated within 40 seconds and on average measured 27.5mm x 21.0mm. The phase I study (n = 6) showed that use of the HIFU device was feasible and safe and did not damage neighbouring tissue. The phase IIa study (n = 9) showed both that the area of ablation could be precisely targeted on a previously implanted metallic mark (used to represent a major anatomical structure) and that ablations could be undertaken deliberately to avoid such a mark. Ablations were achieved with a precision of 1–2 mm.</p><p>Conclusion</p><p>HIFU was feasible, safe and effective in ablating areas of liver scheduled for resection. The next stage is a phase IIb study which will attempt ablation of small metastases with a 5 mm margin, again prior to planned resection.</p><p>Trial Registration</p><p>ClinicalTrials.gov<a href="https://clinicaltrials.gov/ct2/show/NCT01489787" target="_blank">NCT01489787</a></p></div

HIFU Probe and schematic views of the ablated area.

<p>(a) Schematic diagram of a HIFU treatment with the HIFU focus placed in the liver such as HIFU ablations extent from the Glisson’s capsule. (b) Using less water in the cooling envelope the focus can be placed deeper in tissues (10 mm) such as HIFU ablations can be created deeper in the liver. (c) Photograph of the HIFU device. (d) Intraoperative view of the HIFU device.</p

Flowchart.

<p>Flowchart.</p

Macroscopic and echographic visualzation of HIFU ablated area.

<p>HIFU ablations were clearly visible in ultrasound images. Dimensions measured on sonograms were correlated to the dimensions measured on gross pathology. (a) Typical HIFU ablation observed on gross pathology, (b) on sonograms obtained with the integrated ultrasound imaging probe (IUSP) of the HIFU device and (c) on sonograms obtained with a higher resolution ultrasound imaging probe. (d) Correlation between dimensions measured on sonograms using IUSP and gross pathology.</p

Measures of HIFU ablations obtained with the integrated ultrasound imaging probe and at gross pathological examination.

<p>Measures of HIFU ablations obtained with the integrated ultrasound imaging probe and at gross pathological examination.</p

Additional file 1: of Efficacy of high-intensity focused ultrasound-assisted hepatic resection (HIFU-AR) on blood loss reduction in patients with liver metastases requiring hepatectomy: study protocol for a randomized controlled trial

SPIRIT checklist. (DOC 120 kb

Efficacy of high-intensity focused ultrasound-assisted hepatic resection (HIFU-AR) on blood loss reduction in patients with liver metastases requiring hepatectomy: study protocol for a randomized controlled trial

International audienceAbstractBackgroundLiver resection is the only potentially curative treatment for colorectal liver metastases (LM). It is considered a safe procedure, but is often associated with blood loss during liver transection. Blood transfusions are frequently needed, but they are associated with increased morbidity and risk of recurrence. Many surgical devices have been developed to decrease blood loss. However, none of them has proven superior to the standard crushing technique. We developed a new, powerful intra-operative high-intensity focused ultrasound (HIFU) transducer which destroys tissue by coagulative necrosis. We aim to evaluate whether HIFU-assisted liver resection (HIFU-AR) results in reduced blood loss.MethodsThis is a prospective, single-centre, randomized (1:1 ratio), comparative, open-label phase II study. Patients with LM requiring a hepatectomy for ≥ 2 segments will be included. Patients with cirrhosis or sinusoidal obstruction syndrome with portal hypertension will be excluded. The primary endpoint is normalized blood loss in millilitres per square centimetre of liver section plane. Secondary endpoints are: total blood loss, transection time, transection time per square centimetre of liver area, haemostasis time, clip density on the liver section area, rate and duration of the Pringle manœuvre, rate of patients needing a blood transfusion, length of hospital stay, morbidity, patients with positive resection margin, and local recurrence. Assuming a blood loss of 7.6 ± 3.7 mL/cm2 among controls, the study will have 85% power to detect a twofold decrease of blood loss in the experimental arm, using a Wilcoxon (Mann-Whitney) rank-sum test with a 0.05 two-sided significance level. Twenty-one randomized patients per arm are required. Considering the risk of contraindications at surgery, up to eight patients may be enrolled in addition to the 42 planned, with an enrolment period of 24 months. Randomization will be stratified by surgeon.DiscussionWe previously demonstrated the safety and efficacy of intra-operative HIFU in patients operated on for LM. We also demonstrated the efficacy of HIFU-AR in a preclinical study. Participants in the HIFU-AR group of this randomized trial can expect to benefit from reduced blood loss and decreased ischemia of liver parenchyma.Trial registrationClinicaltrial.gov, NCT02728167. Registered on 22 March 2016