Pharyngeal Mucosal Margin Vessel Counts Predict Pharyngocutaneous Fistula in Salvage Laryngectomy.

OBJECTIVE: We evaluated vessel counts in the pharyngeal mucosal margins of patients who underwent salvage laryngectomy to establish whether mucosal vascularity might predict fistula risk. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary Medical Center. METHODS: Patients who underwent salvage total laryngectomy at our institution between 1999 and 2015 were identified. Pharyngeal mucosal margins from laryngectomy specimens were evaluated histologically for each patient, and vessel counts were performed on 5 ×10 images. The primary outcome measure was fistula within 30 days of surgery and mean vessel counts were assessed as the principle explanatory variable. RESULTS: Seventy patients were included and 40% developed a postoperative fistula. There was a large difference in the mean vessel count in patients who did develop fistula (48.6 vessels/×10 field) compared to those who did not (34.7 vessels/×10 field). A receiver operative characteristic curve found that a cutoff value of 33.9 vessels/×10 field provided a sensitivity of 75% and specificity of 62% to predict the likelihood of fistula occurrence (area under the curve = 0.71, 95% confidence interval [CI]: 0.59-0.83). In a binary logistic regression, patients with vessel counts greater than 33.9 had a 5-fold increased risk of developing fistula (95% CI: 1.8-16.45). Histologically, vessels in the pharyngeal mucosa of patients who developed fistulas were more disorganized. CONCLUSION: After salvage laryngectomy, patients with higher mean mucosal margin vessel counts are at increased risk of fistula. The mechanism is unknown, but the disorganization of the vasculature may contribute to poor wound healing. Vessel counting may allow for fistula risk stratification and guide postoperative care.

Pediatric Robotic Laryngeal Cleft Repair.

OBJECTIVE: Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. METHODS: Pediatric patients who underwent robotic or traditional (open or endoscopic) LC repair between 2010 and 2021 were identified. Patient characteristics, operative times, adverse events, hospital length of stay (LOS), and modified barium swallow study (MBSS) results were compared. RESULTS: Eighteen robotic and thirty traditional LC repairs were identified. Mean surgical (149 vs 111 min, P < .05) and OR times (207 vs 139 min, P < .002) were increased for robotic type I LC repairs, but were similar for type II and III LC. Mean hospital LOS was increased for robotic type I LC repairs (2.6 vs 1.2 days, P < .006), but was decreased for type II (4 vs 12.2 days) and type III (4.3 vs 94.5 days) LC. Postoperative MBSS results were improved for robotic type I LC repairs at 12 months (82% vs 43%, P = .05), and trended toward improvement at 6 months for type II (75% vs 22%), and type III (67% vs 50%) LC repairs, although significance was limited for type II and III LC due to the number of subjects. A robotic approach was used successfully to revise all recurrent LC that failed traditional repairs. CONCLUSION: Robotic type 1 LC repairs demonstrated increased operative times and hospital LOS but improved postoperative swallow outcomes compared to traditional approaches may be particularly useful in cases of recurrent clefts.

Role of the otologist/neurotologist in managing auricular and periauricular cutaneous malignancies: A 10-year otologic oncology experience.

Objective: Auricular/periauricular cutaneous malignancies can be challenging to manage surgically due to the complex anatomy of the region. Otologists/neurotologists have unique skillsets that are well-suited to surgically treat these patients. We aim to highlight the role of otologists and neurotologists in providing surgical care of patients with auricular and periauricular malignancies by describing the experience of a single fellowship-trained neurotologist over a 10-year period. Methods: Retrospective chart review of 387 patients with auricular and periauricular malignancy treated by a single neurotologist between 2012 and 2022 was completed. Tumor histology and procedures performed for each patient were extracted. Additional data was collected for a subset of 84 patients with complex cases requiring selective neck dissection, parotidectomy, lateral temporal bone resection, regional advancement or rotational flap reconstruction, and/or free tissue transfer reconstruction. Results: Within the series of 387 patients, squamous cell carcinoma was the most common histology (42.6%, n = 165), followed by basal cell carcinoma (40.8%, n = 158), and melanoma (9.8%, n = 38). Common surgical procedures included wide local excision (61.8%, n = 239), partial/sub-total auriculectomy 18.3% (n = 71), or total auriculectomy 5.2% (n = 20). Within the 84-patient subset, median age at diagnosis was 71.9 years. Dermatologists provided most patient referrals (50.0%, n = 42). Most common tumor locations included: auricular (58.3%, n = 49), pre-auricular (21.4%, n = 18), and parotid (27.4%, n = 23). Revision surgery occurred in 22.6% of cases (n = 19), of which 26.3% (n = 5) for positive margins and 31.6% (n = 6) for recurrence. Mean follow-up was 22.8 months. Disease-specific 5-year survival was 91%. Conclusions: We demonstrate the feasibility of an otologist/neurotologist incorporating the surgical management of auricular and periauricular malignancies into their practice. Level of Evidence: 4.

Readiness of Medical Students to Care for Diverse Patients: A Validated Assessment of Cross-Cultural Preparedness, Skills, and Curriculum.

Introduction: Effective cross-cultural care is foundational for mitigating health inequities and providing high-quality care to diverse populations. However, medical school teaching practices vary widely, and learners have limited opportunities to develop these critical skills. To understand the current state of cross-cultural education and to identify potential opportunities for improvement, we disseminated a validated survey instrument among medical students at a single institution. Methods: Learners across 4 years of medical school participated in the cross-cultural care assessment, using a tool previously validated with resident physicians and modified for medical students. The survey assessed medical student perspectives on (1) preparedness, (2) skillfulness, and (3) educational curriculum and learning environment. Cross-sectional data were analyzed by class year, comparing trends between school years. Results: Of 700 possible survey responses, we received 260 (37% response rate). Fourth-year students had significantly higher scores than first-year students (p<0.05) for 7 of 12 preparedness items and 4 of 9 skillfulness items. Less than 50% of students indicated readiness to deliver cross-cultural care by their fourth year in 9 of 12 preparedness items and 6 of 9 skillfulness items. Respondents identified inadequate cross-cultural education as the primary barrier. Discussion: Medical students reported a lack of readiness to provide cross-cultural care, with self-assessed deficiencies persisting through the fourth year of medical school. Medical educators can use data from the cross-cultural care survey to longitudinally assess students and enhance curricular exposures where deficiencies exist. Optimizing cross-cultural education has the potential to improve the learning environment and overall patient care.

Verrucous Carcinoma of the Foot: A Retrospective Study of 19 Cases and Analysis of Prognostic Factors Influencing Recurrence.

This study sought to evaluate a cohort of patients with verrucous carcinoma of the foot with special focus on 5 cases of locally recurrent tumors despite negative margins. Nineteen cases of verrucous carcinoma of the foot were identified through the University of Michigan (Ann Arbor, Michigan) pathology database from 1995 to 2019 and were included in demographic and clinical presentation analyses. Sixteen cases were treated at the University of Michigan and are included in the treatment analyses. A review of medical records was conducted to characterize clinical, surgical, and pathologic features. Recurrent cases were found to have a predilection for nonglabrous skin of the foot and great toe. Otherwise, there was little to differentiate outcomes between recurrent and nonrecurrent groups based on demographic, clinical, surgical, or histopathologic data. Recurrent tumors regrew locally and were not associated with histologic progression to conventional squamous cell carcinoma. Verrucous carcinoma of the nonglabrous surface of the foot should have a higher suspicion for possible local recurrence. Recurrence occurs within months of treatment, deserves early biopsy, and warrants aggressive re-treatment. Future directions should include greater examination of pathologic features and genetic markers to improve management of verrucous carcinoma of the foot.

NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.

Evolving understanding of head and neck squamous cell carcinoma (HNSCC) is leading to more specific diagnostic disease classifications. Among HNSCC caused by the human papilloma virus (HPV), tumors harboring defects in TRAF3 or CYLD are associated with improved clinical outcomes and maintenance of episomal HPV. TRAF3 and CYLD are negative regulators of NF-κB and inactivating mutations of either leads to NF-κB overactivity. Here, we developed and validated a gene expression classifier separating HPV+ HNSCCs based on NF-κB activity. As expected, the novel classifier is strongly enriched in NF-κB targets leading us to name it the NF-κB Activity Classifier (NAC). High NF-κB activity correlated with improved survival in two independent cohorts. Using NAC, tumors with high NF-κB activity but lacking defects in TRAF3 or CYLD were identified; thus, while TRAF3 or CYLD gene defects identify the majority of tumors with NF-κB activation, unknown mechanisms leading to NF-kB activity also exist. The NAC correctly classified the functional consequences of two novel CYLD missense mutations. Using a reporter assay, we tested these CYLD mutations revealing that their activity to inhibit NF-kB was equivalent to the wild-type protein. Future applications of the NF-κB Activity Classifier may be to identify HPV+ HNSCC patients with better or worse survival with implications for treatment strategies.

Effects of Moringa Extract on Aminoglycoside-Induced Hair Cell Death and Organ of Corti Damage.

HYPOTHESIS: Moringa extract, a naturally occurring anti-oxidant, protects against aminoglycoside-induced hair cell death and hearing loss within the organ of Corti. BACKGROUND: Reactive oxygen species (ROS) arise primarily in the mitochondria and have been implicated in aminoglycoside-induced ototoxicity. Mitochondrial dysfunction results in loss of membrane potential, release of caspases, and cell apoptosis. Moringa extract has not previously been examined as a protective agent for aminoglycoside-induced ototoxicity. METHODS: Putative otoprotective effects of moringa extract were investigated in an organotypic model using murine organ of Corti explants subjected to gentamicin-induced ototoxicity. Assays evaluated hair cell loss, cytochrome oxidase expression, mitochondrial membrane potential integrity, and caspase activity. RESULTS: In vitro application of moringa conferred significant protection from gentamicin-induced hair cell loss at dosages from 25 to 300 µg/mL, with dosages above 100 µg/mL conferring near complete protection. Assays demonstrated moringa extract suppression of ROS, preservation of cytochrome oxidase activity, and reduction in caspase production. CONCLUSION: Moringa extract demonstrated potent antioxidant properties with significant protection against gentamicin ototoxicity in cochlear explants.

The Clarion Call of the COVID-19 Pandemic: How Medical Education Can Mitigate Racial and Ethnic Disparities.

Public health crises palpably demonstrate how social determinants of health have led to disparate health outcomes. The staggering mortality rates among African Americans, Native Americans, and Latinx Americans during the COVID-19 pandemic have revealed how recalcitrant structural inequities can exacerbate disparities and render not just individuals but whole communities acutely vulnerable. While medical curricula that educate students about disparities are vital in rousing awareness, it is experience that is most likely to instill passion for change. The authors first consider the roots of health care disparities in relation to the current pandemic. Then, they examine the importance of salient learning experiences that may inspire a commitment to championing social justice. Experiences in diverse communities can imbue medical students with a desire for lifelong learning and advocacy. The authors introduce a 3-pillar framework that consists of trust building, structural competency, and cultural humility. They discuss how these pillars should underpin educational efforts to improve social determinants of health. Effecting systemic change requires passion and resolve; therefore, perseverance in such efforts is predicated on learners caring about the structural inequities in housing, education, economic stability, and neighborhoods-all of which influence the health of individuals and communities.

Sudden Sensorineural Hearing Loss: A Diagnostic and Therapeutic Emergency.

The family physician's role in recognizing and managing sudden sensorineural hearing loss (SSNHL) is crucial. A recently updated otolaryngologic clinical practice guideline has been released for this emergency syndrome, but dissemination is limited to a specialty journal. As a result, the guidelines may not be widely available in the primary care setting where patients often present. We provide this focused review to clarify and disseminate SSNHL guidelines for the frontline family physician.

Long-Term Academic Outcomes of Triological Society Research Career Development Award Recipients.

OBJECTIVES/HYPOTHESIS: Each year, the Triological Society awards several Research Career Development Awards (CDAs) to support early-career otolaryngologists. The objective of this study was to evaluate academic outcomes of CDA recipients including National Institutes of Health (NIH) funding acquisition and h-index. A secondary objective was to appraise gender differences in outcomes among awardees. STUDY DESIGN: Cross-sectional study. METHODS: Recipients' practice setting, degree type, academic rank, and leadership titles were determined through review of academic and private practice profiles in October 2019. NIH funding was assessed using the NIH Research Portfolio Online Reporting Tool and the h-index was calculated using the Scopus database. RESULTS: Between 2004 and 2019, 70 investigators received a CDA. Of the 65 awardees prior to 2019, 26 (40.0%) obtained NIH grants after the CDA. Having an MD/PhD or MD/master's was not associated with NIH funding attainment (P = .891) nor with higher funding total (P = .109). However, funding total was significantly higher for full professors compared to assistant professors (P = .022). The median h-index among awardees was 16 (interquartile range = 11-21) and differed significantly by academic rank (P < .001). Moreover, 23 CDAs (32.9%) were awarded to women. However, fewer female recipients obtain NIH funding after the CDA compared to men (10.5% vs. 52.2%, P = .002), and they had significantly lower h-indices than men (10 vs. 17, P < .001). CONCLUSIONS: As a cohort, CDA awardees achieve higher academic success than academic otolaryngologists in general. However, female CDA recipients lag behind their male colleagues, highlighting the need for more research to uncover contributors to gender differences and ways to foster equity in research. LEVEL OF EVIDENCE: NA Laryngoscope, 131:288-293, 2021.

Head and Neck Reconstruction in the Vessel Depleted Neck.

Microvascular free tissue transfer has revolutionized reconstruction and subsequently functional outcomes in the head and neck, but requires suitable recipient vessels for successful results. Recipient vessels can be significantly compromised by prior surgery, radiation therapy, or existing and/or underlying vascular disease in the neck. When further microvascular reconstruction is required in the vessel-depleted neck, identification of appropriate vessels for anastomosis can be difficult and can present complex decisions for the surgeon as well as the patient. In this article, we review the available literature on the vessel depleted neck and the possible vessel options. We present critical strategies for preoperative treatment planning and vessel selection in these patients. We also discuss the benefits and limitations of arterial and venous options while commenting on our unique institution's experiences. The external carotid branches as well as the available subclavian artery branches are presented in detail. The venous anatomy is also described, with particular focus on the accompanying veins and cephalic vein. We provide guidance on the selection and modification of free flaps to achieve the greatest function and cosmetic outcomes in the vessel depleted neck. Our collection of advanced management techniques will provide surgeons with more options to manage the complexity of the vessel depleted neck, and to further help patients understand the risk and benefits of these selections.

Airway Management for Endoscopic Laryngotracheal Stenosis Surgery During COVID-19.

The novel coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for surgical management of laryngotracheal stenosis. High viral concentrations in the upper aerodigestive tract, the ability of the virus to be transmitted by asymptomatic carriers and through aerosols, and the need for open airway access during laryngotracheal surgery create a high-risk situation for airway surgeons, anesthesiologists, and operating room personnel. While some surgical cases of laryngotracheal stenosis may be deferred, patients with significant airway obstruction or progressing symptoms often require urgent surgical intervention. We present best practices from our institutional experience for surgical management of laryngotracheal stenosis during this pandemic, including preoperative triage, intraoperative airway management, and personal protective measures.

Wire bristle foreign body: Never in the same place twice.

Foreign body ingestion is a common reason for visiting the emergency room. Foreign bodies can lodge anywhere in the upper aerodigestive tract and can sometimes be difficult to extract. Wire bristles that dislodge from grill-cleaning wire brushes and which are then accidentally swallowed can be particularly challenging to remove due to their small size, propensity to become embedded, and their ability to migrate through tissues. This case reveals the speed with which wire bristle foreign bodies can migrate through tissues and exemplifies the need to obtain computerized tomography evaluations in close proximity to any planned attempt to remove them.

Infection of Primary Human Alveolar Macrophages Alters Staphylococcus aureus Toxin Production and Activity.

Pulmonary pathogens encounter numerous insults, including phagocytic cells designed to degrade bacteria, while establishing infection in the human lung. Staphylococcus aureus is a versatile, opportunistic pathogen that can cause severe pneumonia, and methicillin-resistant isolates are of particular concern. Recent reports present conflicting data regarding the ability of S. aureus to survive and replicate within macrophages. However, due to use of multiple strains and macrophage sources, making comparisons between reports remains difficult. Here, we established a disease-relevant platform to study innate interactions between S. aureus and human lungs. Human precision-cut lung slices (hPCLS) were subjected to infection by S. aureus LAC (methicillin-resistant) or UAMS-1 (methicillin-sensitive) isolates. Additionally, primary human alveolar macrophages (hAMs) were infected with S. aureus, and antibacterial activity was assessed. Although both S. aureus isolates survived within hAM phagosomes, neither strain replicated efficiently in these cells. S. aureus was prevalent within the epithelial and interstitial regions of hPCLS, with limited numbers present in a subset of hAMs, suggesting that the pathogen may not target phagocytic cells for intracellular growth during natural pulmonary infection. S. aureus-infected hAMs mounted a robust inflammatory response that reflected natural human disease. S. aureus LAC was significantly more cytotoxic to hAMs than UAMS-1, potentially due to isolate-specific virulence factors. The bicomponent toxin Panton-Valentine leukocidin was not produced during intracellular infection, while alpha-hemolysin was produced but was not hemolytic, suggesting that hAMs alter toxin activity. Overall, this study defined a new disease-relevant infection platform to study S. aureus interaction with human lungs and to define virulence factors that incapacitate pulmonary cells.

Adjuvant anti-angiogenic therapy enhances chemotherapeutic uptake in a murine model of head and neck cancer.

Intratumoural metabolic demands result in excessive angiogenic cytokine release leading to unorganised vasculature. Resultant fluid dynamics oppose blood flow and drug penetration due to a marked increase in interstitial fluid hydrostatic pressure. It is hypothesised that anti-angiogenic therapy may function to 'prune' vasculature and lead to improved chemotherapeutic penetration. Subcutaneous, OSC19 tumour bearing mice (n = 5/dose/agent) were administered varying doses of an anti-mouse VEGFR2 (DC101) or an anti-mouse VEGFR3 (31C1) -3 d, -1 d, 0 d, +1 d and +3 d prior to 200 µg of cetuximab fluorescently labelled with IRDye800CW. Fluorescence imaging of tumours was performed 10 d post cetuximab-IRDye800CW dose to monitor therapeutic uptake. Co-administration of dual anti-angiogenic agents at 50-50%, 75-25% and 25-75% using optimal dose and time (-1 d 10 mg/kg anti-VEGFR2 and -1 d 40 mg/kg anti-VEGFR3) was also evaluated. In order to establish vessel normalisation, NG2 (pericyte marker) and CD31 (endothelial cells) ratios were assessed during immunohistochemical staining of tumour sections. Twenty-mg/kg anti-VEGFR3 + 5 mg/kg anti-VEGFR2 significantly (p < .0005) reduced tumour size (-73%) compared to control (59%). The 20 mg/kg anti-VEGFR3 + 5 mg/kg anti-VEGFR2 and 30 mg/kg anti-VEGFR3 + 2.5 mg/kg anti-VEGFR2 significantly (p < .0004) improved percent-injected cetuximab-IRDye800CW dose/gram tumour tissue compared to other groups. Adjuvant, dual anti-angiogenic therapy targeting VEGFR2 and VEGFR3 significantly enhances tumour chemotherapeutic uptake compared to control.

Utility of the Surgical Apgar Score in Head and Neck Squamous Cell Carcinoma.

Objectives To recognize the utility of the surgical Apgar score (SAS) in a noncutaneous head and neck squamous cell carcinoma (HNSCC) population. Study Design Retrospective case series with chart review. Setting Academic tertiary medical center. Subjects and Methods Patients (n = 563) undergoing noncutaneous HNSCC resection between April 2012 and March 2015 were included. Demographics, medical history, intraoperative data, and postoperative hospital summaries were collected. SASs were calculated following the published schema. The primary outcome was 30-day postoperative morbidity. A 2-sample t test, analysis of variance, and χ2 (or Fisher exact) test were used for statistical comparisons. A multivariable logistic regression analysis was conducted to identify independent predictors of 30-day morbidity. Results Mean SAS was 6.2 ± 1.5. SAS groups did not differ in age, sex, or race. Sixty-five patients (11.6%) had a SAS between 0 and 4, with 40 incidences of morbidity (61.5%), while 31 (5.5%) patients with SAS from 9 to 10 had 3 morbidity occurrences (9.7%). Results show that 30-day postoperative morbidity is inversely related to increasing SAS ( P < .0001). Furthermore, lower SAS was associated with significantly increased operative time (SAS 0-4: 9.3 ± 2.6 hours vs SAS 9-10: 3.0 ± 1.1 hours) and lengths of stay (SAS 0-4: 10.0 ± 7.3 days vs SAS 9-10: 1.6 ± 1.0 days), P < .0001. SAS remained highly significant after adjusting for potential confounding variables in the multivariable analysis ( P < .0001). Conclusions An increasing SAS is associated with significantly lower rates of 30-day postoperative morbidities in a noncutaneous HNSCC patient population.

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.

Utility of the Modified Surgical Apgar Score in a Head and Neck Cancer Population.

Objective The Surgical Apgar Score (SAS) is a validated postoperative complication prediction model. The purpose of this study was to investigate the utility of the SAS in a diverse head and neck cancer population and to compare it with a recently developed modified SAS (mSAS) that accounts for intraoperative transfusion. Study Design Case series with chart review. Setting Academic tertiary care medical center. Subjects and Methods This study comprised 713 patients undergoing surgery for head and neck cancer from April 2012 to March 2015. SAS values were calculated according to intraoperative data obtained from anesthesia records. The mSAS was computed by assigning an estimated blood loss score of zero for patients receiving intraoperative transfusions. Primary outcome was 30-day postoperative morbidity. Results Mean SAS and mSAS were 6.3 ± 1.5 and 6.2 ± 1.7, respectively. SAS and mSAS were significantly associated with 30-day postoperative morbidity, length of stay, operative time, American Society of Anesthesiologists status, race, and body mass index ( P < .05); however, no significant association was detected for age, sex, and smoking status. Multivariable analysis identified SAS and mSAS as independent predictors of postoperative morbidity, with the mSAS ( P = .03) being a more robust predictor than the SAS ( P = .15). Strong inverse relationships were demonstrated for the SAS and mSAS with length of stay and operative time ( P < .0001). Conclusion The SAS serves as a useful metric for risk stratification of patients with head and neck cancer. With the inclusion of intraoperative transfusion, the mSAS demonstrates superior utility in predicting those at risk for postoperative complications.

Evaluation of fluorescence-guided surgery agents in a murine model of soft tissue fibrosarcoma.

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence-guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection-associated morbidity while improving local tumor control. METHODS: We evaluate the tumor-targeting specificity and utility of fluorescence-imaging agents to provide disease-specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab-IRDye800CW (anti-EGFR), DC101-IRDye800CW (anti-VEGFR-2), IgG-IRDye800CW, the cathepsin-activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open- and closed-field fluorescence imaging systems. Tumor-to-background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically. RESULTS: At peak, closed-field imaging TBR of cetuximab-IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101-IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post-resection bed; cetuximab-IRDye800CW generated the greatest contrast (2.5). Cetuximab-IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border. CONCLUSION: This study demonstrates cetuximab-IRDye800CW superiority. FGS has the potential to improve post-resection morbidity and mortality by improving disease detection.