Michele Diana, MD1, Bernard Dallemagne, MD2, Yu-Yin Liu, MD2, Veronique Lindner, MD, PhD3, Jacques Marescaux, MD, FACS, HonFRCS, HonFJSES, HonAPSA2. 1Institute for Image-Guided Surgery (IHU-Strasbourg), 2Research Institute against Cancer of the Digestive System (IRCAD), 3Pathology Department, University Hospital of Strasbourg, France
Objective of the technology or device
Advanced minimally invasive surgical endoscopic techniques, such as endoscopic submucosal dissection (ESD), are more and more frequently used in the management of early-stage gastrointestinal cancers. However, ESDs are challenging and time-consuming. The possibility to expand the indications of endoscopic heat-based ablative techniques, mainly used to treat dysplastic and/or premalignant tissues, to early-stage gastrointestinal malignancies could have a great clinical impact. This paradigm shift would require: the ability to deliver a tunable energy, with predictable results and a low risk of injuries to adjacent structures, and the possibility to monitor the efficacy of the treatment in real-time and obtain staging information. The aim of this experimental acute study was to evaluate a concept of submucosal ablation based on a fine-tuned emission of High-Intensity Focused Ultrasounds (HIFU) in direct contact with the mucosa.
Description of the technology and method of its use or application
The active part of the contact HIFU device is a 7MHz flat piezoceramic transducer, measuring 8 by 15mm. The transducer is mounted on the tip of a flexible endoscope. To lift the submucosa and protect the deeper layers (muscular and serosa) from the action of HIFU, a bolus of air (10cc) is injected into the submucosal space, before the application of the HIFU. The presence of an air interface, which reflects ultrasounds, creates an effective and long-lasting lifting of the submucosa/mucosa complex. The effects of the sonications can be evaluated in real-time with a probe-based confocal endomicroscopic system.
A total of 19 sonications have been performed in the stomach (n=7) and in the colon (n=12) of one anesthetized pig. Based on previous ex vivo and in vivo dose-response tests, the device was set to deliver an average of 500J for stomach sonications and 350J for colon sonications during 20 seconds to create an effective heat destruction on the submucosal layer. Mean depth of HICU lesions was 3±1.07mm and 1±0.6mm in the stomach and in the colon respectively. The most frequent histological signs of the sonications were architecture distortion, coagulation necrosis, congestion and edema. Those lesions were limited to the mucosa and submucosa. No damage to the muscular and serosal layers was noted, except in two colonic sonications, in which air cushion, due to technical error, was not properly created and full-thickness lesions were observed. Confocal imaging could identify specific clues for early mucosa coagulation damage such as deformation or disappearance of enterocytes’ borders. Comparable images were obtained at Hematoxylin-Eosin stained biopsies.
This contact HIFU device could create in vivo targeted lesions at submucosal level. The submucosal air cushion generates a reflective barrier to the HIFUs, avoiding any further progression down to the muscular and serosal layers and preventing energy transmission to adjacent organs. Confocal imaging can be useful for real-time monitoring of ablation efficacy, at least at mucosal level. A needle-based confocal probe could provide information on the deep aspect of the submucosa. The prototype is undergoing further refinements and dose-effects studies prior to evaluation in survival studies.