Intra-operative fluorescence-based detection of positive surgical margins during radical prostatectomy: Lessons learned from a pilot ex vivo translational study.

OBJECTIVES: Nerve-sparing techniques during radical prostatectomy have been associated with an increased risk of positive surgical margins. The intra-operative detection of residual prostatic tissue could help mitigate this risk. The objectives of the present study were to assess the feasibility of using an anti-prostate-specific membrane antigen (anti-PSMA) antibody conjugated with a fluorophore to characterize fresh prostate tissue as prostatic or non-prostatic for intra-operative surgical margin detection. METHODS: Fresh prostatic tissue samples were collected from transurethral resections of the prostate (TURP) or prostate biopsies, and either immunolabelled with anti-PSMA antibody conjugated with Alexa Fluor 488 or used as controls. A dedicated, laparoscopy-compliant fluorescence device was developed for real-time fluorescence detection. Confocal microscopy was used as the gold standard for comparison. Spectral unmixing was used to distinguish specific, Alexa Fluor 488 fluorescence from nonspecific autofluorescence. RESULTS: The average peak wavelength of the immuno-labeled TURP samples (n = 4) was 541.7 ± 0.9 nm and of the control samples (n = 4) was 540.8 ± 2.2 nm. Spectral unmixing revealed that these similar measures were explained by significant autofluorescence, linked to electrocautery. Three biopsy samples were then obtained from seven patients and also displayed significant nonspecific fluorescence, raising questions regarding the reproducibility of the fixation of the anti-PSMA antibodies on the samples. Comparing the fluorescence results with final pathology proved challenging due to the small sample size and tissue alterations. CONCLUSIONS: This study showed similar fluorescence of immuno-labeled prostate tissue samples and controls, failing to demonstrate the feasibility of intra-operative margin detection using PSMA immuno-labeling, due to marked tissue autofluorescence. We successfully developed a fluorescence device that could be used intraoperatively in a laparoscopic setting. Use of the infrared range as well as newly available antibodies could prove interesting options for future research.

A drug free solution for improving the quality of life of fibromyalgia patients (Fibrepik): study protocol of a multicenter, randomized, controlled effectiveness trial.

BACKGROUND: Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient's adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life. METHODS: This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage. DISCUSSION: The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058092.

Detection of pulmonary nodules: a clinical study protocol to compare ultra-low dose chest CT and standard low-dose CT using ASIR-V.

INTRODUCTION: Lung cancer screening in individuals at risk has been recommended by various scientific institutions. One of the main concerns for CT screening is repeated radiation exposure, with the risk of inducing malignancies in healthy individuals. Therefore, lowering the radiation dose is one of the main objectives for radiologists. The aim of this study is to demonstrate that an ultra-low dose (ULD) chest CT protocol, using recently introduced hybrid iterative reconstruction (ASiR-V, GE medical Healthcare, Milwaukee, Wisconsin, USA), is as performant as a standard 'low dose' (LD) CT to detect non-calcified lung nodules ≥4 mm. METHODS AND ANALYSIS: The total number of patients to include is 150. Those are referred for non-enhanced chest CT for detection or follow-up of lung nodule and will undergo an additional unenhanced ULD CT acquisition, the dose of which is on average 10 times lower than the conventional LD acquisition. Total dose of the entire exam (LD+ULD) is lower than the French diagnostic reference level for a chest CT (6.65 millisievert). ULD CT images will be reconstructed with 50% and 100% ASiR-V and LD CT with 50%. The three sets of images will be read in random order by two pair of radiologists, in a blind test, where patient identification and study outcomes are concealed. Detection rate (sensitivity) is the primary outcome. Secondary outcomes will include concordance of nodule characteristics; interobserver reproducibility; influence of subjects' characteristics, nodule location and nodule size; and concordance of emphysema, coronary calcifications evaluated by visual scoring and bronchial alterations between LD and ULD CT. In case of discordance, a third radiologist will arbitrate. ETHICS AND DISSEMINATION: The study was approved by the relevant ethical committee. Each study participant will sign an informed consent form. TRIAL REGISTRATION NUMBER: NCT03305978; Pre-results.

Evaluation of the Needle Positioning Accuracy of a Light Puncture Robot Under MRI Guidance: Results of a Clinical Trial on Healthy Volunteers.

PURPOSE: To assess the accuracy of Light Puncture Robot (LPR) as a patient-mounted robot, in positioning a sham needle under MRI guidance for abdominal percutaneous interventions. MATERIALS AND METHODS: This monocentric, prospective and non-controlled study was approved by the ethics review board. The study evaluated the accuracy of LPR V3 to achieve a virtual puncture in 20 healthy volunteers. Three trajectories were tried on each volunteer, under 3-T MRI guidance. RESULTS: Accuracy under 5 mm in attaining a 10 cm-deep target was reached in 72% of attempts after 2 robot motions with a median error of 4.1 mm [2.1; 5.1]. Median procedure time for one trajectory was 12.9 min [10.2; 18.0] and median installation time was 9.0 min [6.0; 13.0]. CONCLUSION: LPR accuracy in the deployment of a sham needle inside the MRI tunnel and its setup time are promising. Further studies need to be conducted to confirm these results before clinical trials.

Computer assisted electromagnetic navigation improves accuracy in computed tomography guided interventions: A prospective randomized clinical trial.

PURPOSE: To assess the accuracy and usability of an electromagnetic navigation system designed to assist Computed Tomography (CT) guided interventions. MATERIALS AND METHODS: 120 patients requiring a percutaneous CT intervention (drainage, biopsy, tumor ablation, infiltration, sympathicolysis) were included in this prospective randomized trial. Nineteen radiologists participated. Conventional procedures (CT group) were compared with procedures assisted by a navigation system prototype using an electromagnetic localizer to track the position and orientation of a needle holder (NAV group). The navigation system displays the needle path in real-time on 2D reconstructed CT images extracted from the 3D CT volume. The regional ethics committee approved this study and all patients gave written informed consent. The main outcome was the distance between the planned trajectory and the achieved needle trajectory calculated from the initial needle placement. RESULTS: 120 patients were analyzable in intention-to-treat (NAV: 60; CT: 60). Accuracy improved when the navigation system was used: distance error (in millimeters: median[P25%; P75%]) with NAV = 4.1[2.7; 9.1], vs. with CT = 8.9[4.9; 15.1] (p<0.001). After the initial needle placement and first control CT, fewer subsequent CT acquisitions were necessary to reach the target using the navigation system: NAV = 2[2; 3]; CT = 3[2; 4] (p = 0.01). CONCLUSION: The tested system was usable in a standard clinical setting and provided significant improvement in accuracy; furthermore, with the help of navigation, targets could be reached with fewer CT control acquisitions.

Miniaturized robotic laparoscope-holder for rectopexy: first results of a prospective study.

INTRODUCTION: Thanks to the technical progress in instrumentation, laparoscopic surgery has made considerable advances over the last decade. Various robotic systems have been introduced to assist laparoscopic procedures. A new prototype of miniaturized laparoscope-holder (called the Light Endoscope Robot [LER]) has been developed by the TIMC-IMAG-CNRS Laboratory in Grenoble, France and is now currently marketed by the French company Endocontrol™ (La Tronche, Grenoble). The aim of this pilot study was to assess the LER in clinical practice. SUBJECTS AND METHODS: This was a prospective, single-center study. The LER had already been successfully validated on preclinical laboratory and cadaveric trials. The study was conducted at the Grenoble University Hospital during standardized laparoscopic rectopexies on adult patients. Demographic and operative data and qualitative results were collected prospectively and analyzed retrospectively. All patients provided written informed consent, and the study was approved by the Regional Committee for Medical and Health Research Ethics. RESULTS: Between March 2008 and September 2010, 16 adult patients underwent laparoscopic rectopexy assisted by the LER. All the patients were women with an average age of 63.6 years and an average body mass index of 24 kg/m(2). The procedure was completed in 15 patients. No conversion to open surgery was required. The postoperative mortality rate was 0%, and a complication occurred in 1 patient. The surgeon graded ease of use as 7 ± 2, global comfort as 8 ± 2, and quality of vision as 8 ± 2. CONCLUSIONS: This pilot study demonstrated the feasibility, safety, and comfort for the surgeon of the laparoscopic rectopexy assisted by the miniaturized light endoscope-holder LER.