Facial Trauma During the COVID-19 Pandemic.

Study Design: Retrospective cohort study. Objective: The purpose of this study is to evaluate the impact of the COVID-19 global pandemic on the regional trends in facial trauma at a tertiary care, level 1 trauma center in Central New York. Methods: The study sample was derived from the population of patients who presented with facial trauma to the emergency department at the Downtown and/or Community Campuses of SUNY Upstate University Hospital between March 1, 2020, and May 15, 2020, and compared to two historical controls in 2018 and 2019. Descriptive and bivariate statistics were calculated for study variables in each cohort. Poisson regression was used to compare incident rate ratios (IRR) with 95% confidence intervals with significance set at P < .05. Results: Sixty five patients presented during the COVID-19 pandemic, while 83 presented in 2019 and 95 in 2018. For the study period, the most common mechanism was assault in 47.7%. IRR was significantly lower than in 2018 (IRR = 1.46, P = .018), but not significantly different from 2019 (IRR = 1.28, P = .14). During lockdown, IRR was significantly decreased compared to 2019 (IRR = 1.84, P = .0029) and 2018 (IRR = 2.16, P < .001). Conclusions: The volume of facial trauma seen in Central New York appears undeterred in the absence of "shelter in place" orders. Analysis of pandemic and regional trauma variations can offer valuable insight for improved resource allocation to better prepare for potentially high-risk procedures.

Association of Prolonged-Duration Chemoprophylaxis With Venous Thromboembolism in High-risk Patients With Head and Neck Cancer.

Importance: Venous thromboembolism (VTE) is associated with substantial morbidity and is the most common factor associated with preventable death among hospitalized patients. Data from otolaryngologic studies suggest that the risk of VTE may be underestimated among high-risk patients, particularly among those undergoing oncologic procedures. The incorporation of prolonged-duration chemoprophylaxis (PDC) into preventive therapy has been associated with substantial decreases in VTE incidence among patients undergoing oncologic surgery. However, bleeding remains a major concern among otolaryngologists, and substantial variation exists in the use of thromboprophylaxis. Objective: To assess the association between PDC and VTE in high-risk patients with head and neck cancer undergoing oncologic procedures. Design, Setting, and Participants: This retrospective cohort study identified 750 patients with biopsy-confirmed head and neck cancer and a Caprini risk score of 8 or higher who underwent inpatient oncologic surgery at a tertiary care referral center between January 1, 2014, and February 1, 2020. After exclusions, 247 patients were included in the study; patients were divided into 2 cohorts, traditional and PDC, based on the duration of prophylaxis. Univariate and multivariate analyses were performed to examine the development of VTE and bleeding-associated complications during the 30-day postoperative period. Data were analyzed from April 1 to April 30, 2020. Exposures: PDC, defined as 7 or more postoperative days of chemoprophylaxis. Main Outcomes and Measures: VTE and bleeding events during the 30-day postoperative period. Results: Among 247 patients (mean [SD] age, 63.1 [11.1] years; 180 men [72.9%]) included in the study, 106 patients (42.9%) received traditional prophylaxis, and 141 patients (57.1%) received PDC. The incidence of VTE was 5 of 106 patients (4.7%) in the traditional cohort and 1 of 141 patients (0.7%) in the PDC cohort (odds ratio [OR], 0.15; 95% CI, 0.003-1.33). In the multivariate logistic regression analysis, PDC was independently associated with reductions in the risk of VTE (OR, 0.04; 95% CI, 0.001-0.46). The incidence of bleeding events was 1 of 106 patients (0.9%) in the traditional cohort and 6 of 141 patients (4.3%) in the PDC cohort (OR, 4.64; 95% CI, 0.55-217.00). Conclusions and Relevance: The use of chemoprophylaxis for high-risk patients with head and neck cancer remains a high-priority topic. The results of this study suggest that PDC may be associated with reductions in VTE among this patient population. However, the associated increase in nonfatal bleeding events warrants careful consideration and further highlights the need to determine an optimal duration for chemoprophylaxis among this distinct cohort.

Identifying cohort differences in children undergoing partial intracapsular tonsillectomy vs traditional tonsillectomy for sleep disordered breathing.

OBJECTIVE: Partial intracapsular tonsillectomy (PIT) is a well-established technique for reducing post-operative morbidity in pediatric patients with sleep disordered breathing (SDB). Although tonsillar re-growth rates are reported as low, risks of symptom recurrence or need for completion tonsillectomy are clear disadvantages when compared to traditional tonsillectomy (TT). We aim to identify cohort differences to better guide clinical decision making and identify patient-specific factors that may influence this decision. A secondary aim was to evaluate potential risk factors for tonsillar regrowth. METHODS: Retrospective chart review of pediatric patients who underwent TT or PIT for SDB between 2015 and 2019 at a tertiary care academic medical center. Records were reviewed for age, gender, race, body mass index, comorbidities, diagnosis, apnea-hypopnea index, pre-operative Brodsky tonsil size, length of stay, post-operative hemorrhage, tonsillar regrowth, symptom recurrence, and need for completion tonsillectomy. RESULTS: 315 patients were included: 174 underwent TT and 141 underwent PIT. Patients undergoing TT were more likely to have a sleep study showing OSA (OR 3.01, p < 0.0001), asthma (OR 4.28, p = 0.000124), and other comorbidities (OR 4.06, p = 0.0258). The overall complication rate was 4.44% (14/315). Tonsillar regrowth was exclusive to the PIT group, occurring in 7/141 patients (4.96%). Age ≤4 years was significantly associated with increased risk of tonsillar regrowth (≤4 years: 7.69%, >4 years: 0%; p = 0.049). Race and pre-operative tonsil size were not associated with regrowth. CONCLUSIONS: Our study supports the low incidence of tonsillar regrowth in PIT and suggests an association with younger age. Moreover, we found that patients undergoing TT are more likely to be older, have OSA, asthma, and other comorbidities.

Fluorescence Imaging of Nerves During Surgery.

OBJECTIVE: This review details the agents for fluorescence-guided nerve imaging in both preclinical and clinical use to identify factors important in selecting nerve-specific fluorescent agents for surgical procedures. BACKGROUND: Iatrogenic nerve injury remains a significant cause of morbidity in patients undergoing surgical procedures. Current real-time identification of nerves during surgery involves neurophysiologic nerve stimulation, which has practical limitations. Intraoperative fluorescence-guided imaging provides a complimentary means of differentiating tissue types and pathology. Recent advances in fluorescence-guided nerve imaging have shown promise, but the ideal agent remains elusive. METHODS: In February 2018, PubMed was searched for articles investigating peripheral nerve fluorescence. Key terms used in this search include: "intraoperative, nerve, fluorescence, peripheral nerve, visualization, near infrared, and myelin." Limits were set to exclude articles exclusively dealing with central nervous system targets or written in languages other than English. References were cross-checked for articles not otherwise identified. RESULTS: Of the nonspecific agents, tracers that rely on axonal transport showed the greatest tissue specificity; however, neurovascular dyes already enjoy wide clinical use. Fluorophores specific to nerve moieties result in excellent nerve to background ratios. Although noteworthy findings on tissue specificity, toxicity, and route of administration specific to each fluorescent agent were reported, significant data objectively quantifying nerve-specific fluorescence and toxicity are lacking. CONCLUSIONS: Fluorescence-based nerve enhancement has advanced rapidly over the past 10 years with potential for continued utilization and progression in translational research. An ideal agent would be easily administered perioperatively, would not cross the blood-brain barrier, and would fluoresce in the near-infrared spectrum. Agents administered systemically that target nerve-specific moieties have shown the greatest promise. Based on the heterogeneity of published studies and methods for reporting outcomes, it appears that the development of an optimal nerve imaging agent remains challenging.

The Bifurcated Frontal Sinus.

OBJECTIVES: Frontal sinus anatomy is complex, and multiple variations of ethmoid pneumatization have been described that affect the frontal outflow tract. In addition, the lumen proper of the frontal sinus may exist as 2 separate parallel cavities that share an ipsilateral outflow tract. This variant has not been previously described and may have implications for surgical management. STUDY DESIGN: Case series. SETTING: Tertiary rhinology practice. SUBJECTS AND METHODS: Cases with radiographic and intraoperative findings of separate parallel tracts within a unilateral frontal sinus were identified from a consecutive series of 186 patients who underwent endoscopic sinus surgery between May 2015 and July 2016. Data were recorded including sinusitis phenotype, coexisting frontal cells, and extent of surgery. RESULTS: Ten patients (5.4%) were identified with computed tomography scans demonstrating bifurcation of the frontal sinus into distinct medial and lateral lumens. All cases were treated with Draf 2a or 2b frontal sinusotomy with partial removal of the common wall to create a unified ipsilateral frontal ostium. Eleven sides had a coexisting ipsilateral agger nasi cell, 7 had a supra-agger cell, 8 had a suprabullar cell, and 1 had a frontal septal cell. There were no significant complications. CONCLUSION: The bifurcated frontal sinus is an anatomic variant that the surgeon should recognize to optimize surgical outcomes. Failure to do so may result in incomplete clearance of the sinus and residual disease. The bifurcated sinus may occur with other types of frontal sinus cells and may be safely treated with endoscopic techniques.

Total intravenous anesthesia improves intraoperative visualization during surgery for high-grade chronic rhinosinusitis: a double-blind randomized controlled trial.

BACKGROUND: Total intravenous anesthesia (TIVA) has been proposed as a method to reduce blood loss during endoscopic sinus surgery (ESS). Impaired sinonasal visualization due to mucosal bleeding may be burdensome in cases of chronic rhinosinusitis (CRS) with high-grade inflammatory disease, suggesting a role for TIVA in that disease subgroup. METHODS: A double-blind, randomized controlled trial was conducted of adults undergoing ESS at a tertiary medical center. Patients considered for inclusion had high-grade CRS defined as either sinonasal polyposis or a preoperative Lund-Mackay score of ≥12. Subjects were randomized to receive either TIVA or inhaled anesthesia (IA) during ESS. The primary outcome measure was intraoperative visibility as rated by 3 blinded reviewers utilizing the 10-point Wormald Surgical Field Grading Scale. Secondary outcomes included operative blood loss, complications, and change in quality of life evaluated by the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: A total of 72 patients were randomized into TIVA (n = 37) and IA (n = 35) study arms. Aggregate median (interquartile range) Wormald scores across all reviewers demonstrated a more favorable visual field with TIVA compared to IA (3.5 [2.4-3.9] vs IA 4.1[3.0-5.8], p = 0.0089). There was significantly less blood loss in the TIVA group compared to the IA group (200 mL [100-450] vs 300 mL [200-500], p = 0.046). Baseline patient characteristics were comparable between cohorts with no significant postoperative complications. No significant changes were detected between postoperative SNOT-22 scores at 3 months (p = 0.278) and at 6 months (p = 0.396) following ESS. CONCLUSION: TIVA contributes to improved intraoperative visualization and decreased blood loss in patients undergoing ESS for high-grade inflammatory sinus disease.

Evaluation of optical imaging agents in a fluorescence-guided surgical model of head and neck cancer.

BACKGROUND: Tumor proliferation often occurs from pathologic receptor upregulation. These receptors provide unique targets for near-infrared (NIR) probes that have fluorescence-guided surgery (FGS) applications. We demonstrate the use of three smart-targeted probes in a model of head and neck squamous cell carcinoma. METHODS: A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed serially after intravenous injection using commercially available open-field (LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln, NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was performed with IntegriSense750 to demonstrate orthotopic and metastatic disease localization. RESULTS: Disease fluorescence delineation was assessed by tumor-to-background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR: 1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with extended administration-to-resection time (96 h). IntegriSense750 correctly identified all diseased nodes in situ during exploratory surgeries. Ex vivo, whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios (TTR). Agents provided sufficient fluorescence contrast to discriminate disease from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR: 64) while ProSense750EX was superior localizing disease against lung tissue (TBR: 13). CONCLUSION: All three agents appear effective for FGS.

Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS. METHODS: Mucosal explants from patients with and without CRS were submerged in Ringer's solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of Z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plug-in of ImageJ. RESULTS: Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53 ± 0.67 vs controls, 4.86 ± 1.68 pixels/second; p < 0.001). CONCLUSION: This study is the first to report evidence of abnormal mucus strand velocity from submucosal glands in diseased sinonasal mucosa. Future pharmacologic studies targeting this critical component of MCC are warranted.

Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis.

PURPOSE OF REVIEW: The purpose of this review is to provide otolaryngologists with the most up-to-date advancements in both the medical and surgical management of CF-related sinus disease. RECENT FINDINGS: Recent studies have supported more aggressive CRS management, often with a combination of both medical and surgical therapies. Comprehensive treatment strategies have been shown to reduce hospital admissions secondary to pulmonary exacerbations in addition to improving CRS symptoms. Still, current management strategies are lacking in both high-level evidence and standardized guidelines. SUMMARY: The unified airway model describes the bi-directional relationship between the upper and lower airways as a single functional unit and suggests that CRS may play a pivotal role in both the development and progression of lower airway disease. Current strategies for CF CRS focus primarily on amelioration of symptoms with antibiotics, nasal saline and/or topical medicated irrigations, and surgery. However, there are no definitive management guidelines and there remains a persistent need for additional studies. Nevertheless, otolaryngologists have a significant role in the overall management of CF, which requires a multi-disciplinary approach and a combination of both surgical and medical interventions for optimal outcomes of airway disease. Here we present a review of currently available literature and summarize medical and surgical therapies best suited for the management of CF-related sinus disease.

Characterization of primary rat nasal epithelial cultures in CFTR knockout rats as a model for CF sinus disease.

OBJECTIVE: The objectives of the current experiments were to develop and characterize primary rat nasal epithelial cultures and evaluate their usefulness as a model of cystic fibrosis (CF) sinonasal transepithelial transport and CF transmembrane conductance regulator (CFTR) function. STUDY DESIGN: Laboratory in vitro and animal studies. METHODS: CFTR+/+ and CFTR-/- rat nasal septal epithelia (RNSE) were cultured on semipermeable supports at an air-liquid interface to confluence and full differentiation. Monolayers were mounted in Ussing chambers for pharmacologic manipulation of ion transport and compared to similar filters containing murine (MNSE) and human (HSNE) epithelia. Histology and scanning electron microscopy (SEM) were completed. Real-time polymerase chain reaction of CFTR+/+ RNSE, MNSE, and HSNE was performed to evaluate relative CFTR gene expression. RESULTS: Forskolin-stimulated anion transport (ΔIsc in µA/cm2 ) was significantly greater in epithelia derived from CFTR+/+ when compared to CFTR-/- animals (100.9 ± 3.7 vs. 10.5 ± 0.9; P < 0.0001). Amiloride-sensitive ISC was equivalent (-42.3 ± 2.8 vs. -46.1 ± 2.3; P = 0.524). No inhibition of CFTR-mediated chloride (Cl- ) secretion was exhibited in CFTR-/- epithelia with the addition of the specific CFTR inhibitor, CFTRInh -172. However, calcium-activated Cl- secretion (UTP) was significantly increased in CFTR-/- RNSE (CFTR-/- -106.8 ± 1.6 vs. CFTR+/+ -32.2 ± 3.1; P < 0.0001). All responses were larger in RNSE when compared to CFTR+/+ and CFTR-/- (or F508del/F508del) murine and human cells (P < 0.0001). Scanning electron microscopy demonstrated 80% to 90% ciliation in all RNSE cultures. There was no evidence of infection in CFTR-/- rats at 4 months. CFTR expression was similar among species. CONCLUSION: The successful development of the CFTR-/- rat enables improved evaluation of CF sinus disease based on characteristic abnormalities of ion transport. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E384-E391, 2017.

Characterizing the detection threshold for optical imaging in surgical oncology.

BACKGROUND AND OBJECTIVES: Optical imaging to guide cancer resections is rapidly transitioning into the operating room. However, the sensitivity of this technique to detect subclinical disease is yet characterized. The purpose of this study was to determine the minimum range of cancer cells that can be detected by antibody-based fluorescence imaging. METHODS: 2LMP (breast), COLO-205 (colon), MiaPaca-2 (pancreas), and SCC-1 (head and neck) cells incubated in vitro with cetuximab-IRDye800CW (dose range 8.6-86 nM) were implanted subcutaneously in mice (n = 3 mice, 5 tumors/mouse). Following incubation with 8.6 × 10-2 µM of cetuximab-IRDye800CW in vitro, serial dilutions of each cell type (1 × 103 -1 × 106 ) were implanted subcutaneously (n = 3, 5 tumors/mouse). Tumors were imaged with Pearl Impulse and Xenogen IVIS 100 imaging systems. Scatchard analysis was performed to determine receptor density and kinetics for each cell line. RESULTS: Under conditions of minimal cetuximab-IRDye800CW exposure to low cellular quantity, closed-field fluorescence imaging theoretically detected a minimum of 4.2 × 104 -9.5 × 104 2LMP cells, 1.9 × 105 -4.5 × 105 MiaPaca-2 cells, and 2.4 × 104 -6.7 × 104 SCC-1 cells; COLO-205 cells could not be identified. Higher EGFR-mediated uptake of cetuximab correlated with sensitivity of detection. CONCLUSION: This study supports the clinical utility of cetuximab-IRDye800CW to sensitively localize subclinical disease in the surgical setting.

Assessment of acquired mucociliary clearance defects using micro-optical coherence tomography.

BACKGROUND: Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl- ) transport is one such mechanism that contributes to this disorder and can be acquired secondary to environmental perturbations, such as hypoxia at the tissue surface. The objective of this study was to assess the technological feasibility of the novel micro-optical coherence tomography (µOCT) imaging technique for investigating acquired MCC defects in cultured human sinonasal epithelial (HSNE) cells. METHODS: Primary HSNE cell cultures were subjected to a 1% oxygen environment for 12 hours to induce acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Ion transport characteristics were assessed with pharmacologic manipulation in Ussing chambers. ASL, periciliary fluid (PCL), and ciliary beat frequency (CBF) were evaluated using µOCT. RESULTS: Amiloride-sensitive transport (ΔISC ) was greater in cultures exposed to hypoxia (hypoxia: -13.2 ± 0.6 µA/cm2 ; control: -6.5 ± 0.1 µA/cm2 ; p < 0.01), whereas CFTR-mediated anion transport was significantly diminished (hypoxia: 28.6 ± 0.3 µA/cm2 ; control: 36.2 ± 1.6 µA/cm2 ; p < 0.01), consistent with acquired CFTR dysfunction and sodium hyperabsorption. Hypoxia diminished all markers of airway surface function microanatomy as observed with µOCT, including ASL (hypoxia: 5.0 ± 0.4 µm; control: 9.0 ± 0.9 µm; p < 0.01) and PCL depth (hypoxia: 2.5 ± 0.1 µm; control: 4.8 ± 0.3 µm; p < 0.01), and CBF (hypoxia: 8.7 ± 0.3 Hz; control: 10.2 ± 0.3 Hz; p < 0.01). CONCLUSION: Hypoxia-induced defects in epithelial anion transport in HSNE led to predictable effects on markers of MCC measured with novel µOCT imaging. This imaging method represents a technological leap forward and is feasible for assessing acquired defects impacting the airway surface.

Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.

BACKGROUND: Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model. METHODS: Sinus development was evaluated in CFTR-/- and CFTR+/+ rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified. RESULTS: At birth, sinus volumes were decreased in CFTR-/- rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm3 vs 14.5 ± 0.73 mm3 ; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR+/+ animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection. CONCLUSION: CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection.

Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection.

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. Cancer Res; 77(9); 2197-206. ©2017 AACR.

Oncologic Procedures Amenable to Fluorescence-guided Surgery.

OBJECTIVE: Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type. BACKGROUND: For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye. METHODS: We performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016. INCLUSION CRITERIA: fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases. EXCLUSION CRITERIA: fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence. RESULTS: Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision. CONCLUSIONS: The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.