EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial.

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

Microvascular Reconstruction of Osteonecrosis: Assessment of Long-term Quality of Life.

OBJECTIVE: Review long-term clinical and quality-of-life outcomes following free flap reconstruction for osteonecrosis. STUDY DESIGN: Retrospective multi-institutional review. SETTING: Tertiary care centers. METHODS: Patients included those undergoing free flap reconstructions for osteonecrosis of the head and neck (N = 232). Data included demographics, defect, donor site, radiation history, perioperative management, diet status, recurrence rates, and long-term quality-of-life outcomes. Quality-of-life outcomes were measured using the University of Washington Quality of Life (UW-QOL) survey. RESULTS: Overall flap success rate was 91% (n = 212). Relative to preoperative diet, 15% reported improved diet function at 3 months following reconstruction and 26% at 5 years. Osteonecrosis recurred in 14% of patients (32/232); median time to onset was 11 months. Cancer recurrence occurred in 13% of patients (29/232); median time to onset was 34 months. Results from the UW-QOL questionnaire were as follows: no pain (45%), minor or no change in appearance (69%), return to baseline endurance level (37%), no limitations in recreation (40%), no changes in swallowing following reconstruction (28%), minor or no limitations in mastication (29%), minor or no speech difficulties (93%), no changes in shoulder function (84%), normal taste function (19%), normal saliva production (27%), generally excellent mood (44%), and no or minimal anxiety about cancer (94%). CONCLUSION: The majority of patients maintained or had advancement in diet following reconstruction, with low rates of osteonecrosis or cancer recurrence and above-average scores on UW-QOL survey suggesting good return of function and quality of life.

Probe-based fluorescence dosimetry of an antibody-dye conjugate to identify head and neck cancer as a first step to fluorescence-guided tissue preselection for pathological assessment.

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

Intraoperative Tumor Assessment Using Real-Time Molecular Imaging in Head and Neck Cancer Patients.

BACKGROUND: In head and neck cancer, surgical resection using primarily visual and tactile feedback is considered the gold standard for solid tumors. Due to high numbers of tumor-involved surgical margins, which are directly correlated to poor clinical outcomes, intraoperative optical imaging trials have rapidly proliferated over the past 5 years. However, few studies report on intraoperative in situ imaging data that could support surgical resection. To demonstrate the clinical application of in situ surgical imaging, we report on the imaging data that are directly (ie in real-time) available to the surgeon. STUDY DESIGN: Fluorescence intensities and tumor-to-background ratios (TBRs) were determined from the intraoperative imaging data-the view as seen by the surgeon during tumor resection-of 20 patients, and correlated to patient and tumor characteristics including age, sex, tumor site, tumor size, histologic differentiation, and epidermal growth factor receptor (EGFR) expression. Furthermore, different lighting conditions in regard to surgical workflow were evaluated. RESULTS: Under these circumstances, intraoperative TBRs of the primary tumors averaged 2.2 ± 0.4 (range 1.5 to 2.9). Age, sex, tumor site, and tumor size did not have a significant effect on open-field intraoperative molecular imaging of the primary tumors (p > 0.05). In addition, variation in EGFR expression levels or the presence of ambient light did not seem to alter TBRs. CONCLUSIONS: We present the results of successful in situ intraoperative imaging of primary tumors alongside the optimal conditions with respect to both molecular image acquisition and surgical workflow. This study illuminates the potentials of open-field molecular imaging to assist the surgeon in achieving successful cancer removal.

End-of-Life Costs and Hospice Utilization in Patients with Head and Neck Cancer.

The Quality Oncology Practice Initiative has several metrics related to end-of life (EOL) care, including hospice enrollment ≤3 days, with lower scores signaling better performance. Of privately insured patients with head and neck cancer, 3.5% were enrolled in hospice prior to death and 21.3% spent ≤3 days in hospice, indicating aggressive EOL care. Patients with late hospice enrollment had higher spending in the last 30 days of life (DOL). Patients in hospice ≤3 days spent $37,426, while those in hospice >3 days spent $24,418 (P = .002). The largest portion of this difference was attributable to inpatient services. Patients in hospice ≤3 days spent $22,089 on inpatient services in the last 30 DOL, while those in hospice >3 days spent $8361 (P < .001). Further research is needed to determine if more high-value care can be provided with earlier hospice enrollment and to ensure that goal concordance is included in defining high-value care.

Outcomes and cost implications of microvascular reconstructions of the head and neck.

BACKGROUND: Critical review of current head and neck reconstructive practices as related to free flap donor sites and their impact on clinical outcomes and cost. METHODS: Retrospective multicenter review of free tissue transfer reconstruction of head and neck defects (n = 1315). Variables reviewed: defect, indication, T classification, operative duration, and complications. A convenience sample was selected for analysis of overall (operative and inpatient admission) charges per hospitalization (n = 400). RESULTS: Mean charges of hospitalization by donor tissue: radial forearm free flap (RFFF) $127 636 (n = 183), osteocutaneous RFFF (OCRFFF) $125 456 (n = 70), anterior lateral thigh $133 781 (n = 54), fibula $140 747 (n = 42), latissimus $208 890 (n = 24), rectus $169 637 (n = 18), scapula $128 712 (n = 4), and ulna $110 716 (n = 5; P = .16). Mean operative times for malignant lesions stratified by T classification: 6.9 hours (±25 minutes) for T1, 7.0 hours (±16 minutes) for T2, 7.3 hours (±17 minutes) for T3, and 7.8 hours (±11 minutes) for T4 (P < .0001). Complications correlated with differences in mean charges: minor surgical ($123 720), medical ($216 387), and major surgical ($169 821; P < .001). Operations for advanced malignant lesions had higher mean charges: T1 lesions ($106 506) compared to T2/T3 lesions ($133 080; P = .03) and T4 lesions ($142 183; P = .02). On multivariate analysis, the length of stay, operative duration, and type a postoperative complication were factors affecting overall charges for the hospitalization (P < .018). CONCLUSION: Conclusion: The RFFF and OCRFFF had the lowest complication rates, length of hospitalization, duration of operation, and mean charges of hospitalization. Advanced stage malignant disease correlated with increased hospitalization length, operative time, and complication rates resulting in higher hospitalization charges.

Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma.

OBJECTIVE: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (<5 mm) are found in 15-30% of head and neck cancer patients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. MATERIALS AND METHODS: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. RESULTS: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. CONCLUSION: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.

Intraoperative Molecular Imaging for ex vivo Assessment of Peripheral Margins in Oral Squamous Cell Carcinoma.

Objective: Complete surgical resection is the standard of care for treatment of oral cancer although the positive margin rate remains 15-30%. Tissue sampling from the resected specimen and from the wound bed for frozen section analysis (FSA) remains the mainstay for intraoperative margin assessment but is subject to sampling error and can require the processing of multiple samples. We sought to understand if an ex vivo imaging strategy using a tumor-targeted fluorescently labeled antibody could accurately identify the closest peripheral margin on the mucosal surface of resected tumor specimen, so that this "sentinel margin" could be used to guide pathological sampling. Materials and Methods: Twenty-nine patients with oral squamous cell carcinoma scheduled for surgical resection were consented for the study and received systemic administration of a tumor-targeted fluorescently labeled antibody (Panitumumab IRDye800CW). After surgical resection, the tumor specimen was imaged using a closed-field fluorescent imaging device. Relevant pathological data was available for five patients on retrospective review. For each of these five patients, two regions of highest fluorescence intensity at the peripheral margin and one region of lowest fluorescence intensity were identified, and results were correlated with histology to determine if the region of highest fluorescence intensity along the mucosal margin (i.e., the sentinel margin) was truly the closest margin. Results: Imaging acquisition of the mucosal surface of the specimen immediately after surgery took 30 s. In all of the specimens, the region of highest fluorescence at the specimen edge had a significantly smaller margin distance than other sampled regions. The average margin distance at the closest, "sentinel," margin was 3.2 mm compared to a margin distance of 8.0 mm at other regions (p < 0.0001). Conclusions: This proof-of-concept study suggests that, when combined with routine FSA, ex vivo fluorescent specimen imaging can be used to identify the closest surgical margin on the specimen. This approach may reduce sampling error of intraoperative evaluation, which should ultimately improve the ability of the surgeon to identify the sentinel margin. This rapid sentinel margin identification improves the surgeon's orientation to areas most likely to be positive in the surgical wound bed and may expedite pathology workflow.

Emerging Intraoperative Imaging Modalities to Improve Surgical Precision.

Intraoperative imaging (IOI) is performed to guide delineation and localization of regions of surgical interest. While oncological surgical planning predominantly utilizes x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), intraoperative guidance mainly remains on surgeon interpretation and pathology for confirmation. Over the past decades however, intraoperative guidance has evolved significantly with the emergence of several novel imaging technologies, including fluorescence-, Raman, photoacoustic-, and radio-guided approaches. These modalities have demonstrated the potential to further optimize precision in surgical resection and improve clinical outcomes for patients. Not only can these technologies enhance our understanding of the disease, they can also yield large imaging datasets intraoperatively that can be analyzed by deep learning approaches for more rapid and accurate pathological diagnosis. Unfortunately, many of these novel technologies are still under preclinical or early clinical evaluation. Organizations like the Intra-Operative Imaging Study Group of the European Society for Molecular Imaging (ESMI) support interdisciplinary interactions with the aim to improve technical capabilities in the field, an approach that can succeed only if scientists, engineers, and physicians work closely together with industry and regulatory bodies to resolve roadblocks to clinical translation. In this review, we provide an overview of a variety of novel IOI technologies, discuss their challenges, and present future perspectives on the enormous potential of IOI for oncological surgical navigation.

Predictors of readmissions after head and neck cancer surgery: A national perspective.

OBJECTIVES: Surgical oncology patients have multiple comorbidities and are at high risk of readmission. Prior studies are limited in their ability to capture readmissions outside of the index hospital that performed the surgery. Our goal is to evaluate risk factors for readmission for head and neck cancer patients on a national scale. MATERIAL AND METHODS: A retrospective cohort study of head and neck cancer patients in the Nationwide Readmissions Database (2013). Our main outcome was 30-day readmission. Statistical analysis included 2-sided t tests, χ2, and multivariate logistic regression analysis. RESULTS: Within 30days, 16.1% of 11,832 patients were readmitted and 20% of readmissions were at non-index hospitals, costing $31million. Hypopharyngeal cancer patients had the highest readmission rate (29.6%), followed by laryngeal (21.8%), oropharyngeal (18.2%), and oral cavity (11.6%) cancers (P<0.001). Half of readmissions occurred within 10days and were often associated with infections (27%) or wound complications (12%). Patients from lower household income areas were more likely to be readmitted (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.16-2.05). Patients with valvular disease (OR, 2.07; 95% CI, 1.16-3.69), rheumatoid arthritis/collagen vascular disease (OR, 2.05; 95% CI, 1.27-3.31), liver disease (OR, 2.02, 95% CI, 1.37-2.99), and hypothyroidism (OR 1.30; 95% CI, 1.02-1.66) were at highest risk of readmission. CONCLUSION: The true rate of 30-day readmissions after head and neck cancer surgery is 16%, capturing non-index hospital readmissions which make up 20% of readmissions. Readmissions after head and neck cancer surgery are most commonly associated with infections and wound complications.

Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment.

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.

Grant-Writing Pearls and Pitfalls: Maximizing Funding Opportunities.

This invited article reviews the grant process to include the following objectives: (1) to provide an understanding of otolaryngology funding mechanisms in the context of career progression; (2) to outline key components of a well-written grant; (3) to highlight vital members of a successful research team, with emphasis on the mentor-mentee relationship; and (4) to clarify grant scoring with emphasis on common pitfalls to avoid. Current otolaryngology funding mechanisms and up-to-date resources are provided. The review is aimed to assist otolaryngology residents, faculty new to the grant process, as well as experienced researchers striving to improve their grant review scores.

Transoral robotic surgery for oropharyngeal and tongue cancer in the United States.

OBJECTIVES/HYPOTHESIS: To compare the clinical and cost outcomes of transoral robotic surgery (TORS) versus open procedures following the U.S. Food and Drug Administration approval in December 2009. STUDY DESIGN: Retrospective analysis of the Nationwide Inpatient Sample from 2008 to 2011. METHODS: Elective partial pharyngectomies and partial glossectomies for neoplasm were identified by International Classification of Diseases, 9th Revision, Clinical Modification code. RESULTS: TORS represented 2.1% in 2010 and 2.2% in 2011 of all transoral ablative procedures. Patients undergoing open partial pharyngectomy for oropharyngeal neoplasms (n = 1426) had more severe illness compared to TORS (n = 641). However, after controlling for minor-to-moderate severity of illness, open partial pharyngectomy was associated with longer hospital stay (5.2 vs. 3.7 days, P < 0.001), higher charge ($98,228 vs. $67,317, P < 0.001), higher cost ($29,365 vs. $20,706, P < 0.001), higher rates of tracheostomy and gastrostomy tube placement, and more wound and bleeding complications. TORS was associated with a higher rate of dysphagia (19.5% vs. 8.0%, P < 0.001). The lower cost of TORS remained significant in the major-to-extreme severity of illness group but was associated with higher complication rates when compared to open cases of the same severity of illness. A similar analysis of TORS partial glossectomy for base of tongue tumors had similar cost and length of stay benefits, whereas TORS partial glossectomy for anterior tongue tumors revealed longer hospital stays and no benefit in charge or cost compared to open. CONCLUSIONS: Early data demonstrate a clinical and cost benefit in TORS partial pharyngectomy and partial glossectomy for the base of tongue but no benefit in partial glossectomy of the anterior tongue. It is likely that anatomic accessibility and extent of surgery factor into the effectiveness of TORS.

A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression.

PURPOSE: Nanoparticle (NP)-enabled near infrared (NIR) photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies. METHODS: Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG)-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm(2). Tumor response was measured for 10-15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed. RESULTS: The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a comparison to the average of all three control groups over time (P<0.01). CONCLUSION: Photothermal nanotherapy, or intratumoral nanorod injections followed by NIR laser irradiation of tumors and tumor margins, demonstrate the potential of NIR photothermal therapy as a viable localized treatment approach for primary and early stage tumors, and prevents NP uptake by the reticuloendothelial system.

Assessment of erlotinib as adjuvant chemoprevention in high-risk head and neck cancer patients.

PURPOSE: To determine the tolerability and efficacy of long-term treatment with erlotinib for head and neck squamous cell carcinoma after salvage surgery. METHODS: An open-label study was conducted of 150 mg of daily erlotinib for 12 months in patients who completed definitive surgical therapy for recurrent head and neck squamous cell carcinoma. The primary outcome measures were tolerability of prolonged erlotinib therapy and disease-free survival and overall survival at 1 and 2 years. RESULTS: Thirty-one patients were enrolled onto this study. Mean duration of erlotinib therapy was 5 months (range 2-374 days), with 8 patients completing the full 12-month course of erlotinib. Of the remaining patients, 8 discontinued therapy as a result of recurrence, 10 for medical or surgical complications deemed unrelated to the study medication, and 3 for drug-related toxicities. There were 25 grade 3 adverse events; 4 were classified as possibly related to study medication. The most common adverse events included acneiform rash (n = 26 patients), fatigue (n = 22), and diarrhea (n = 22). Overall survival was 61 % at 1 year and 56 % at 2 years. Disease-free survival was 54 % at 1 year and 45 % at 2 years. Mean time to recurrence (n = 16) was 8.7 months. CONCLUSIONS: Long-term erlotinib is safe and demonstrates some potential survival benefit compared to historical controls. However, despite the absence of grade 3/4 adverse events attributable to the drug, tolerance of long-term erlotinib was a significant barrier to completion of a 12-month course of therapy.

Microvascular anastomotic coupler assessment in head and neck reconstruction.

OBJECTIVE: To assess the advantages of using mechanical anastomotic systems in head and neck free tissue transfer. STUDY DESIGN: Case series with chart review. SETTING: A university-based tertiary care center. SUBJECTS AND METHODS: A retrospective review of mechanical venous coupler devices in head and neck reconstruction performed between October 2004 and December 2006. A total of 261 venous anastomoses were performed in 234 consecutive patients. Five types of flaps were performed: radial forearm (66%), anterior lateral thigh (12%), fibula (9%), rectus abdominis (8%), and latissimus dorsi (2%). Demographic data were collected, and the outcomes measured were flap survival and microvascular complications. RESULTS: The size of the venous anastomosis ranged from 1.5 to 4.0 mm, with most being 3.0 mm (56%) followed by 3.5 mm (23%). The most common recipient vein used was a stump off the internal jugular vein (76%) followed by the external jugular vein (17%). Microvascular complications occurred in <5% (n = 11) of patients, with >50% of those being arterial insufficiency (n = 7). Total failures occurred in 3% (n = 7) of patients: 1.5% (n = 4) acute failures (<5 days) and 1.5% (n = 3) late failures. Of the acute failures, causes included venous congestion (n = 1) and arterial insufficiencies (n = 3). The venous coupler used in the failures was 3.0 mm in diameter. Free flap failures resulting from arterial insufficiency involved coupling to the external jugular vein, while the remaining free flap failures (n = 4) used the internal jugular vein. CONCLUSION: With an early venous failure rate of 0.38%, mechanical anastomosis is an adequate alternative to hand-sewn techniques.

Assessment and incidence of salivary leak following laryngectomy.

OBJECTIVES/HYPOTHESIS: To determine the incidence and risk factors of pharyngocutaneous fistula formation in patients undergoing either primary or salvage laryngectomies and evaluate the role of barium esophagram in these patients. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of 259 patients who underwent total laryngectomy between 2003 and 2009 at our institution were reviewed. Risk factors for fistula formation were analyzed, including primary treatment modality, comorbidities, and operative details, which included use of a free flap for closure, concurrent neck dissections, margin status, and preoperative tracheostomy. The length of time until leak, postoperative swallow study results, and fistula management strategies were also assessed. RESULTS: Fifty-five patients developed a pharyngocutaneous fistula (overall incidence, 21%) in a median time of 12 days (range, 4-105 days). Twenty of these patients underwent laryngectomy as their initial treatment modality, and 35 had failed previous radiotherapy. Fistula formation was significantly higher in salvage surgery patients (P = .03), particularly those with hypothyroidism (P < .0002). A barium swallow performed at approximately 1 week after laryngectomy demonstrated a sensitivity of 26% with a specificity of 94%. Sixty-two percent of the fistulas healed with conservative measures only. CONCLUSIONS: Our data confirmed that previous radiotherapy and hypothyroidism, particularly in salvage laryngectomy patients, are important significant predictors of postoperative pharyngocutaneous fistula. The use of a postoperative barium swallow in these patients may be useful but was not found to be highly sensitive in predicting who will develop a clinically evident leak and should be used with caution.

Assessment of donor site morbidity for free radial forearm osteocutaneous flaps.

PURPOSE: Assessment of donor site morbidity and recipient site complications following free radial forearm osteocutaneous flap (FRFOCF) harvest and evaluation of patient perceived upper limb disability for free radial forearm osteocutaneous versus fasciocutaneous flaps (FRFF). METHODS: First a case series was undertaken of 218 patients who underwent an FRFOCF at two tertiary referral centers between February 1998 and November 2010. Outcomes included forearm donor site morbidity and recipient site complications. Second, the disability of the arm, shoulder, and hand (DASH) questionnaire assessing patient perceived arm disability was administered by phone to 60 consecutive patients who underwent an FRFOCF or FRFF. RESULTS: Mean patient age was 63 years with male predominance (62.8%). Median bone length harvested was 8 cm (range, 3-12 cm) with prophylactic plating of the radius following harvest. Donor site morbidity included fracture (1 patient, 0.5%) and sensory neuropathy (5 patients, 2.3%). Mean DASH scores were comparative between groups and to established normative values. Mandibular malunion rate was 3.2% and hardware extrusion at the recipient site occurred in 15.6%. CONCLUSION: Reluctance to perform FRFOCF by surgeons usually centers on concerns regarding potential donor site morbidity and adequacy of available bone stock; however, we identified minimal objective or patient perceived donor site morbidity or recipient site complications following harvest of FRFOCFs. Mild wrist weakness and stiffness are common but do not impede ability to perform activities of daily living. Data from this and other reports suggest this flap is particularly useful for midfacial and short segment mandibular reconstruction.

Assessment of tissue autofluorescence and reflectance for oral cavity cancer screening.

OBJECTIVE: Although approved by the US Food and Drug Administration for clinical use, the utility of handheld tissue reflectance and autofluorescence devices for screening head and neck cancer patients is poorly defined. There is limited published evidence regarding the efficacy of these devices. The authors investigated the sensitivity and specificity of these modalities compared with standard examination. STUDY DESIGN: Prospective, cross-sectional analysis. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Patients who were treated previously for head and neck cancer (n = 88) between 2009 and 2010 were included. Patients were screened using white light visualization (standard of care) and compared with tissue reflectance and autofluorescence visualization. Screening results were compared with biopsy or long-term follow-up. RESULTS: Autofluorescence visualization had a specificity of 81% and a sensitivity of 50% for detecting oral cavity cancer, whereas white light visualization had a specificity of 98% and a sensitivity of 50%. Tissue reflectance visualization had low sensitivity (0%) and good specificity (86%). The power of this study was insufficient to compare the positive and negative predictive values of standard white light examination (50% and 98%, respectively) to tissue autofluorescence (11% and 97%) or reflectance (0% and 95%). In addition, stratification by previous radiation therapy found no statistically significant difference in screening results. CONCLUSION: Standard clinical lighting has a higher specificity than tissue reflectance and autofluorescence visualization for detection of disease in patients with a history of head and neck cancer. This study does not support the added costs associated with these devices.

Assessment of indocyanine green-labeled cetuximab to detect xenografted head and neck cancer cell lines.

OBJECTIVE: The aim of this study is to determine the efficacy of indocyanine green (ICG) conjugated to antiepidermal growth factor receptor antibody (cetuximab) to image head and neck cancer. STUDY DESIGN: Mice (n = 3) were injected with unconjugated ICG and imaged at 100-second intervals for a total of 1000 seconds to assess imaging characteristics. Mice (n = 10) xenografted with SCC-1 cells were then systemically injected with cetuximab conjugated to indocyanine green and imaged over a 72-hour period. To assess the sensitivity and specificity, xenografted tumors underwent subtotal resections and then were assessed for residual disease by fluorescence stereomicroscopy and confirmed by histology. RESULTS: Tumors demonstrated excellent fluorescence 24 hours after injection of cetuximab-ICG. There was a direct relationship between fluorescence and the given dose of cetuximab-ICG. Following subtotal resection, we found fluorescence correlated with a sensitivity of 78.4% and specificity of 96%. CONCLUSIONS: This study provides evidence that supports further preclinical investigation of cetuximab in the evaluation of surgical margins, but linkage to ICG lacks the sensitivity for use in a clinical setting.