Davide Volpi

Yeung, Trevor M. MBBChir, MA, MRCS, DPhil; Volpi, Davide PhD; Tullis, Iain D. C. PhD; Nicholson, Gary A. MD; Buchs, Nicolas MD; Cunningham, Chris MD, RCSEd; Guy, Richard MD, FRCS; Lindsey, Ian MBBS, FRACS; George, Bruce MS, FRCS; Jones, Oliver DM, FRCS; Mun Wang, Lai MB, BCh, MRCP, FRCPath; Hompes, Roel MD; Vojnovic, Borivoj PhD; Hamdy, Freddie MD, FRCSEd (Urol), FRCS, FMedSci; Mortensen, Neil J. MD, FRCS (Eng), Hon FRCPS (Glas), Hon FRCS (Ed) Author Information

BACKGROUND: Sentinel Lymph Node (SLN) sampling may significantly reduce surgical morbidity by avoiding needless radical lymphadenectomy. In gynaecological cancers, the current practice in the UK is testing the accuracy of SLN detection using radioactive isotopes within the context of clinical trials. However, radioactive tracers pose significant logistic problems. We, therefore, conducted a pilot, observational study to assess the feasibility of a novel optical imaging device for SLN detection in gynaecological cancers using near infrared (NIR) fluorescence. METHODS: A novel, custom-made, optical imaging system was developed to enable detection of multiple fluorescence dyes and allow simultaneous bright-field imaging during open surgery and laparoscopic procedures. We then evaluated the performance of the system in a prospective study of 49 women with early stage vulval, cervical and endometrial cancer who were scheduled to undergo complete lymphadenectomy. Clinically approved fluorescent contrast agents indocyanine green (ICG) and methylene blue (MB) were used. The main outcomes of the study included SLN mapping detection rates, false negative rates using the NIR fluorescence technique and safety of the procedures. We also examined the association between injection sites and differential lymphatic drainage in women with endometrial cancer by fluorescence imaging of ICG and MB. RESULTS: A total of 64 SLNs were detected during both open surgery and laparoscopy. Following dose optimisation and the learning phase, SLN detection rate approached 100 % for all cancer types with no false negatives detected. Fluorescence from ICG and MB detected para-aortic SLNs in women with endometrial cancer following uterine injection. Percutaneous SLN detection was also achieved in most women with vulval cancer. No adverse reactions associated with the use of either dyes were observed. CONCLUSIONS: This study demonstrated the successful clinical application of a novel NIR fluorescence imaging system for SLN detection across different gynaecological cancers. We showcased the first in human imaging, during the same procedure, of two fluorescence dyes in women with endometrial cancer.

results using a tumor specific molecular probe and a nonspecific NIR dye are presented.

BACKGROUND: The aim of this study was to demonstrate highlighting of the urethra during surgery through the use of two different methods: a new near-infrared fluorophore IRDye800BK, and indocyanine green (ICG) mixed with silicone. METHODS: Male cadavers from the department of anatomy at the University of Oxford were used to visualise the urethra during near-infrared fluorescence excitation. To assess IRDye800BK, a perineal incision was utilised after infiltrating the urethra directly with an IRDye800BK solution mixed with Instillagel. ICG-silicone was assessed when the urethra was purposely exposed as part of a simulated transanal total mesorectal dissection. ICG was previously mixed with ethanol and silicone and left to set in a Foley catheter. Fluorescence was visualised using an in-house manufactured fluorescence-enabled laparoscopic system. RESULTS: IRDye800BK demonstrated excellent penetration and visualisation of the urethra under fluorescence at an estimated tissue depth of 2 cm. An ICG-silicone catheter demonstrated excellent fluorescence without leaving any residual solution behind in the urethra after its removal. CONCLUSIONS: The newly described ICG-silicone method opens up the possibility of new technologies in this area of fluorescence guided surgery. IRDye800BK is a promising alternative to ICG in visualising the urethra using fluorescence imaging. Its greater depth of penetration may allow earlier detection of the urethra during surgery and prevent wrong plane surgery sooner.