Renal clearance of fluorescent agents can compromise image-guided surgery along the urinary tract

Abstract

Objectives: To study the effect of renally cleared fluorescent agents on image-guided surgery along the urinary tract by using the renally cleared, non-tumour-specific, fluorescent dye fluorescein.

Subjects and methods: Sixteen patients who underwent robot-assisted radical prostatectomy (RARP) with lymph node dissection received an intradermal injection of fluorescein. The slow-release of the fluorescein from the skin into the lymph- and bloodstream were used as a pharmacokinetic model for slow release from receptor-targeted agents. The presence of fluorescein in the urine and the surgical dissection planes around the prostate (representative of cancer margins) during RARP were evaluated. Suction, gauze and irrigation were used to try and reduce fluorescent background signals according to standard operating protocol.

Results: Fluorescein was detected in the urine in the bedside catheter bag after a median of 1.3 h after agent administration and in the surgical field after opening the bladder neck as part of RARP (median of 2.4 h after injection). Suction and application of gauze helped to reduce contamination, but suction combined with irrigation with lukewarm NaCl 0.9% was shown to be most effective. Fluorescein accumulation was seen in the tissue surrounding the bladder neck in 80% of patients.

Conclusions: Renally excreted fluorescent agents risk contamination of the surgical field and possible dissection margins along the urinary tract, a feature that, without proper counter measures, could compromise the accuracy of intra-operative imaging by creating false-positive findings. A clear example of this was the observed bladder neck staining with fluorescein.

Keywords: PSMA; PSMA‐targeted surgery; fluorescein; fluorescence guided surgery; image‐guided surgery; prostate cancer; radioguided surgery; surgical margin assessment.

Fig. 1

General pharmacokinetics based on ADME Encyclopedia and Buckle et al. [10, 33]. Intravenous injection facilitates immediate presence of agents in the (early peak). Intradermal injection creates a more stationary agent deposition at the site of injection, followed by slow release from the tissue. As a result, the latter can be used to mimic receptor‐targeted agents, such as PSMA‐targeted agents, that remain available over a prolonged period of time. As fluorescein is renally cleared, it was visible in the urine in the bedside catheter bag using ultraviolet flashlight.

Fig. 2

Identification of agent (fluorescein) contamination within the surgical field. (A) Schematic lateral view of the male pelvis demonstrating the moment of opening the bladder at the bladder neck during robot‐assisted radical prostatectomy. (B) Schematic lateral view of the male pelvis demonstrating the moment of dissecting prostate from the distal urethra. (C) Schematic lateral view of the male pelvis demonstrating the anatomy after anastomosis. (D) Xi Firefly white‐light imaging of the surgical field after opening the bladder. (E) Xi Firefly white‐light image of the prostatic bed after removal of the prostate. (F) Xi Firefly white‐light imaging of fluorescein visible (yellow) in the bladder neck during anastomosis. (G) Fluorescence imaging using a Karl Storz fluorescence endoscope of the surgical field after opening the bladder. (H) Fluorescence imaging using a Karl Storz fluorescence endoscope of the surgical field after opening the bladder showing the catheter tip illuminating. (I) The excitation and emission spectra of fluorescein and the white‐light properties of the Xi Firefly system (based on Meershoek et al. [22]).

Fig. 3

Agent contamination within the surgical field. The agent (fluorescein) contamination is depicted in white light from the Firefly Xi Camera system (top images) and Karl Storz fluorescence endoscope (bottom images). (A) Directly after removal of the prostate without cleaning the surgical field, in white light. (B) After only suction of the visible contamination. (C) After single irrigation with NaCl 0.9% and suction only fluorescein that has been absorbed by the bladder neck remains visible. (D) The bladder neck with the absorbed fluorescein remains visible using white light and fluorescence imaging also at anastomosis.