Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

Transrectal high-intensity focused ultrasound (HIFU) for management of rectosigmoid deep infiltrating endometriosis: results of Phase-I clinical trial.

OBJECTIVES: Deep infiltrating endometriosis (DIE) of the rectosigmoid is associated with painful symptoms. When medical treatment is ineffective, surgical resection remains the standard treatment, despite significant risk of adverse events. High-intensity focused ultrasound (HIFU) is a minimally invasive ablative procedure. Focal One® is a transrectal HIFU (TR-HIFU) device used in prostate cancer treatment. The primary objective of this study was to confirm the feasibility of treatment with TR-HIFU in patients presenting with posterior DIE with rectosigmoid involvement. We also assessed its safety and clinical efficacy in this context. METHODS: This was a non-controlled, prospective, Phase-I clinical trial in a French University Hospital which is a multidisciplinary center for management of endometriosis. Included were patients older than 25 years, without plans to conceive within 6 months, who presented with a single lesion of posterior DIE, with rectosigmoid invasion, after failure of hormonal therapy. All lesions were assessed preoperatively using transvaginal sonography and magnetic resonance imaging. Patients completed questionnaires on gynecological and intestinal symptoms (similar to a visual analog scale (VAS)), and on quality of life (Medical Outcomes Study 36-item short-form survey (SF-36) and, for the second half of patients recruited, symptom scoring system for constipation (KESS), female sexual function index (FSFI) and endometriosis health profile short-version score (EHP-5)), before, and at 1, 3 and 6 months after, TR-HIFU treatment with a Focal One real-time ultrasound-guided HIFU device. RESULTS: Twenty-three consecutive patients were included in the study between September 2015 and October 2019. All 23 lesions were visualized, giving a detection rate of 100%. Twenty lesions were treated ('feasibility rate', 87.0%): in 13 the whole lesion was treated and in seven the lesion was treated partially. The mean duration of the TR-HIFU procedure was 55.6 min. We observed a significant improvement in VAS score at 6 months, with differences relative to preoperative scores as follows, for: dysmenorrhea (-3.6, P = 0.004), dyspareunia (-2.4, P = 0.006), diarrhea (-3.0, P = 0.006), constipation (-3.0, P = 0.002), dyschezia (-3.2, P = 0.003), false urge to defecate (-3.3, P = 0.007), posterior pelvic pain (-3.8, P = 0.002) and asthenia (-3.8, P = 0.002). There was also a significant improvement in the SF-36 score, with an increase at 6 months relative to the preoperative score in both the physical component summary (+ 9.3%, P = 0.002) and mental component summary (+ 10.9%, P = 0.017). No major complications occurred during or after any procedure. CONCLUSIONS: TR-HIFU therapy for posterior DIE is feasible. If its efficacy and safety are confirmed, it could be a minimally invasive alternative to surgery for the treatment of rectosigmoid endometriosis. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Experimental evaluation of lesion prediction modelling in the presence of cavitation bubbles: intended for high-intensity focused ultrasound prostate treatment.

The accuracy of high-intensity focused ultrasound (HIFU) lesion prediction modelling was evaluated for a truncated spherical transducer designed for prostate cancer treatment The modelling adapted the bio heat transfer equation (BHTE) to take into account the activity of cavitation bubbles generated during HIFU exposure. This modelling was used to predict the lesions produced by three different transducer geometries: fixed-focus, concentric-ring and 1.5D phased-array. Lesions were predicted for different ultrasound exposure conditions close to those used in prostate cancer treatment. Twenty-one in vitro and nine in vitro experiments were performed on pig liver to validate the accuracy of the predictions. A good match was found between the predicted and experimental lesion shapes. Lesion dimensions (maximum depth and length, area at the centre of the lesion or central surface area) were measured on experimental and predicted lesions. The central surface area was predicted by the model with a range of error of 0.15-6.5% for in vitro tests and 0.97-9% in vivo. For comparison, BHTE without bubbles had a range of error of 0.4-55.5% (in vitro) and 9-25.5% (in vivo). The model should be accurate enough to predict HIFU lesions under ultrasound exposure conditions used in prostate cancer treatment.

1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery.

The aim of this study is to demonstrate the feasibility of a new spherically curved 1.5-D phased array for the treatment of localized prostatic cancer. The device is designed to conform to the Ablatherm machine (EDAP-Technomed, France), a commercially available machine in which high intensity focused ultrasound (HIFU) treatment for prostate cancer is administered transrectally. It uses high intensity electronically focused ultrasound to steer a beam along two axes, allowing enough depth to be reached to treat large prostates and eliminating two degrees of mechanical movement. Through computer simulation, it was determined that a curved 1.5-D configuration offered the optimal design. Two configurations were then proposed, and their ability to steer a beam within a target volume centered on the geometric focus of the transducer was simulated. An eight-element prototype was constructed to test the piezo-composite material and its electro-acoustical efficiency. Then, an array was constructed, and a multi-channel amplifier and control system were added, to permit remote operation. Acoustical and electrical measurements were made to verify performance. Finally, the 1.5-D array was tested in vitro on samples of pig liver to confirm the ability to induce lesions.

Modeling of high-intensity focused ultrasound-induced lesions in the presence of cavitation bubbles

The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into account the effects of oscillating microbubbles that occur naturally in the tissue during high-intensity focused ultrasound (HIFU) treatment. First, the Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by microbubbles submitted to HIFU. Because this scattered pressure is not monochromatic, the concept of harmonic attenuation is introduced and a global attenuation coefficient is estimated for bubble-filled tissues. The first results show that this global attenuation coefficient varies significantly with respect to several parameters such as the frequency and the density of microbubbles in the medium, but also with respect to the incident acoustic pressure which thus becomes a transcendental function. Under these conditions, a layer-by-layer modeling, in the direction of propagation, is proposed to calculate the ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are estimated by the calculation of the thermal dose. Using this model, it can be observed first that, when the firing power increases, the lesion develops clearly in the direction of the transducer, with a shape agreeing with in vivo experimentation. Next, it is observed that the lesion can be significantly modified in size and position, if an interface (skin or inner wall) is simulated as a zone with multiple cavitation nuclei. With a firing power increase, it is also shown how a secondary lesion can appear at the interface and how, beyond a certain threshold, this lesion develops at the main lesion expense. Finally, a better in-depth homogeneity of lesions is observed when the acoustic frequency of HIFU is increased.

Theoretical comparison of two interstitial ultrasound applicators designed to induce cylindrical zones of tissue ablation.

Although interstitial techniques are invasive, they are still the first-line therapeutic modalities for certain types of tumour. They are mainly relevant to tumours that are either inoperable or located so deep that access is complicated. Of the various types of radiation that can be delivered by the interstitial route, ultrasound is the most suitable for deep heating. The study compares the efficacy of two types of applicator with respect to their ability to induce cylindrical zones of coagulation necrosis. The transducer of the first applicator is tubular, whereas the second is plane and can rotate around its axis. Both have an external diameter of 4 mm, are fitted with surface cooling systems and operate at 10.7 MHz and 14 W.cm-2. Comparison involves mathematical modelling of ablated tissue in the targeted area by resolving the bioheat transfer equation (BHTE) using an algorithm based on finite differences. The BHTE gives a temperature value from which the thermal dose can be determined. It is shown that tissue ablation by tubular transducers is slow, and, in consequence, perfusion disturbs the heating pattern: in vivo, irradiation with a tubular transducer lasting 1081 s would be required to ablate a tissue mass with a radius of 8 mm. The corresponding period using a rotating plane transducer with 20 firing angles is only 618 s. The mean exposure time of each shot lasts 31 +/- 7 s. Therefore perfusion would have much less impact in the case of therapy administered using a plane transducer than that using a tubular one.

Motorised resection device for transurethral resection of the prostate: a laboratory evaluation.

Transurethral resection of the prostate is the most common method of relieving urinary outflow obstruction secondary to prostatic enlargement. However, this procedure can be responsible for various complications, including irrigant-fluid absorption and blood loss, both of which are strongly dependent on operation duration time. To reduce the latter, a new resection device has been designed for transurethral prostatectomy. The device basically consists of a rotating cutting loop controlled externally, with three degrees of freedom, to fit the adenoma shape. Its performance is assessed in vitro by drilling conical and semi-ellipsoidal cavities in agar gel models. The mean difference between the calculated and obtained cavity volumes is 3% (SD = 0.9%). The volume cutting rate, found to be independent of the type of cavity drilled, is equal to 2.9 +/- 0.3 cm3 min-1. The advantages of this motorised resection device prototype are reduction in operation duration and accuracy of the resected volume. In vivo resection of a 20 cm3 adenoma in less than 15 min can be expected.

[Histologic and immunologic study of the testis after ligation of the vas deferens in dogs]. / Etude histologique wt immunologique du testicule aprés ligature des déférents chez le chien

We wanted to study the effect of bilateral ligature and section of the deferentia of 12 dogs from the histological and immunological aspects. We looked for circulating anti-sperm antibodies and anti-basal membrane of the testes antibodies at the same time as histological study to find out what happened to these lesions after epididymo-deferential anastomosis had been carried out 16 weeks later. The histological lesions (disappearance of exfoliation of the germ cells and of necrobiosis of these cells) disapperared after anastomosis. Anti-basal membrane antibodies were never found. Anti-testicular circulating auto-antibodies were never found. Anti-sperm antibodies appeared between 1 and 5 months after ligature and then disappeared a few months later. Failures to fertilise after epiddidymo-deferential anastomoses therefore do not seem to be due to these two factors.