title: Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment.
abstract: Accurately identifying close or positive margins in real-time permits re-excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence-guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease-specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence-guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab-IRDye800CW. In a preclinical model of luciferase-positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed-field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human-derived tumour tissues, as little as 0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2). When the sensitivity/specificity of fluorescence-guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence-guided surgery, the technique was highly accurate with a sensitivity of 91%, specificity of 85%, PPV of 81%, and NPV of 93% for 90 human-derived samples. This approach can be used as a companion to the pathologist, eliminating confounding factors while impacting surgical intervention and patient management.
authors: Department of Otolaryngology University of Alabama at Birmingham Birmingham AL.
authors: Jason M
authors: JM
authors: Warram
authors: Department of OtolaryngologyUniversity of Alabama at BirminghamBirminghamAL; Department of Surgery, Nuclear Medicine and Molecular Imaging, and Intensive CareUniversity Medical Center Groningen, University of GroningenThe Netherlands.
authors: Esther
authors: E
authors: de Boer
authors: Department of Surgery, Nuclear Medicine and Molecular Imaging, and Intensive Care University Medical Center Groningen, University of Groningen The Netherlands.
authors: Gooitzen M
authors: GM
authors: van Dam
authors: Department of Otolaryngology University of Alabama at Birmingham Birmingham AL.
authors: Lindsay S
authors: LS
authors: Moore
authors: Department of Medicine, School of Medicine University of Alabama at Birmingham Birmingham AL 35233.
authors: Stephanie L
authors: SL
authors: Bevans
authors: Department of Otolaryngology University of Alabama at Birmingham Birmingham AL.
authors: Erika M
authors: EM
authors: Walsh
authors: Department of Pathology, Division of Anatomic Pathology University of Alabama at Birmingham Birmingham AL 35233.
authors: Erik S
authors: ES
authors: Young
authors: Department of Otolaryngology University of Alabama at Birmingham Birmingham AL.
authors: William R
authors: WR
authors: Carroll
authors: Department of Pathology, Division of Anatomic Pathology University of Alabama at Birmingham Birmingham AL 35233.
authors: Todd M
authors: TM
authors: Stevens
authors: Department of Otolaryngology Stanford University Stanford CA 94305.
authors: Eben L
authors: EL
authors: Rosenthal
keywords: fluorescence imaging; frozen section; surgical margins; surgical pathology