5-ALA fluorescence in indeterminate grade gliomas

5-Aminolevulinic acid (5-ALA) is a useful and well-established adjunct for glioblastoma surgery. A growing body of evidence has revealed the potential utility of 5-ALA in grade II and grade III glioma patients as well. However, reliable means of identifying in whom fluorescence will occur have not been established. The authors report the case of such an indeterminate-grade glioma highlighting two pearls of 5-ALA fluorescence in this subgroup of patients. Firstly, 5-ALA–guided tissue sampling helps to ensure that the true grade of the lesion is not underestimated. Secondly, intraoperative fluorescence can serve as a prognostic marker. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21196

OV04 MASSIVE INGUINAL-SCROTAL HERNIA WITH RETROPERITONEAL CONTENTS AND URETER: VIDEO CASE REPORT OF ROBOTIC REPAIR USING INTRAOPERATIVE FLUORESCENCE IMAGING

Aim Inguinal hernias containing the ureter and retroperitoneal contents are uncommon. We present a robotic repair of a large inguinal-scrotal hernia containing the ureter as a video case presentation. Material and Methods A 66 year old male with no previous abdominal surgical history presents with a large left sided inguinal-scrotal hernia, as well as smaller ventral and right inguinal hernias. On CT imaging the patient was found to have an ectopic pelvic location of the left kidney with evidence of the left ureter coursing into the hernia with a significant amount of retroperitoneal fat. The patient was taken to the operating room for a robotic bilateral inguinal hernia repair and ventral hernia repair. Results A ureteral catheter was placed preoperatively and instilled with indocyanine green (ICG). The hernias were successfully repaired, and intraoperative fluorescence imaging was successfully used to visualize the ureter as it was reduced with the hernia sac. The robotic platform significantly aided in dissection of the large volume of retroperitoneal fat, while being able to quickly transition to intraoperative fluorescence to clearly visualize the course of the ureter. The patient did well post operatively with no complications. Conclusions We present a video case report of a large ureter-containing inguinoscrotal hernia that was successfully repaired using a robotic preperitoneal approach. Use of the robotic platform and indocyanine green/intraoperative fluorescence imaging were helpful adjuncts in aiding dissection by improving intraoperative visualization of the ureter.

Detection by fluorescence of pituitary neuroendocrine tumour (PitNET) tissue during endoscopic transsphenoidal surgery using bevacizumab-800CW (DEPARTURE trial): study protocol for a non-randomised, non-blinded, single centre, feasibility and dose-finding trial

IntroductionAchieving gross total resection and endocrine remission in pituitary neuroendocrine tumours (PitNET) can be challenging, especially in PitNETs with cavernous sinus (CS) invasion, defined as a Knosp grade of 3 or 4. A potential target to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A), which expression is known to be significantly higher in PitNETs with CS invasion.Methods and analysisThe aim of this non-randomised, non-blinded, single centre, feasibility and dose-finding phase 1 trial is to determine the feasibility of intraoperative fluorescence imaging detection of PitNET tissue during endoscopic transsphenoidal surgery using the VEGF-A targeting optical agent bevacizumab-800CW (4, 5, 10 or 25 mg). Nine to fifteen patients with a PitNET with a Knosp grade of 3 or 4 will be included. Secondary objectives are: (1) To identify the optimal tracer dose for imaging of PitNET tissue during transsphenoidal surgery for further development in a phase 2 fluorescence molecular endoscopy trial. (2) To quantify fluorescence intensity in vivo and ex vivo with multidiameter single-fibre reflectance, single-fibre fluorescence (MDSFR/SFF) spectroscopy. (3) To correlate and validate both the in vivo and ex vivo measured fluorescence signals with histopathological analysis and immunohistochemical staining. (4) To assess the (sub)cellular location of bevacizumab-800CW by ex vivo fluorescence microscopy. Intraoperative, three imaging moments are defined to detect the fluorescent signal. The tumour-to-background ratios are defined by intraoperative fluorescence in vivo measurements including MDSFR/SFF spectroscopy data and by ex vivo back-table fluorescence imaging. After inclusion of three patients in each dose group, an interim analysis will be performed to define the optimal dose.Ethics and disseminationApproval was obtained from the Medical Ethics Review Board of the University Medical Centre Groningen. Results will be disseminated through national and international journals. The participants and relevant patient support groups will be informed about the results.Trial registration numberNCT04212793

476 ICG FLUORESCENCE IN IDENTIFICATION OF THORACIC DUCT

Not applicable because it is a Video presentation. Methods Not applicable because it is a Video presentation. Results Not applicable because it is a Video presentation. Conclusion Not applicable because it is a Video presentation. Video Video shows visualisation of thoracic duct during esophagectomy by real-time fluorescent imaging. Intraoperative fluorescence lymphangiography was performed by injecting 2.5 mg of ICG into small bowel mesentery at Laparoscopy.At Thoracoscopy, Thoracic duct was visualised after 65 minutes. ICG fluorescence lymphangiography provides a feasible, reliable and real-time imaging of thoracic duct during esophagectomy, thereby potentially reducing thoracic duct injuries. https://drive.google.com/open?id=1ROGQ1K-yWkO-B3oSk8dGbsRu4iCKGfJq.

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial

Background Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. Methods Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. Results In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. Conclusions This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. Trial registration Clinicaltrials.gov identifier NCT01837225. Registered 23 April 2013.

Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.