Investigating Disparities in Hypopharyngeal/Laryngeal Cancer Survival in Florida With Geospatial Mapping Analysis.

OBJECTIVE: Identify predictors of overall survival (OS) after hypopharyngeal/laryngeal cancer in Florida. MATERIAL AND METHODS: We conducted a retrospective cohort study using data from the Florida Cancer Data System (FCDS) on patients diagnosed with hypopharyngeal or laryngeal cancer from 2010-2017. Primary outcome was OS. Hazard ratios (HRs) were estimated from univariable and multivariable Cox regression models for OS. Data was analyzed from November 1, 2022, to June 30, 2023. RESULTS: We analyzed 6771 patients, who were primarily male (81.2%), White non-Hispanic (WNH) (78.2%), publicly insured (70.1%), married (51.8%), and residents of urban counties (73.6%). Black patients were more likely to be younger at diagnosis (38.9%), single (43.4%), to have distant SEER stage disease (25.6%). Median OS were lowest among patients who were uninsured (34 months), with hypopharyngeal site disease (18 months), and a smoking history (current: 34 months, former: 46 months, no smoking: 63 months). Multivariable Cox regression analysis showed worse OS for single/unmarried vs married (HR 1.47 [95%CI: 1.36-1.59], P < .001), history of tobacco use (current: HR 1.62 [95%CI: 1.440-1.817], P < .001; former smokers: (HR 1.28 [95%CI: 1.139-1.437], P < .001) vs no history). Improved OS was observed among White Hispanics (WH) vs WNH (HR .73 [95%CI: .655-.817], P < .001) and women vs men (HR .88 [95%CI: .807-.954], P = .002). Geographical mapping showed that mortality rates were highest in census tracts with low income and education. CONCLUSION: Our findings suggest that sociodemographic and clinical factors impact OS from hypopharyngeal/laryngeal cancer in Florida and vary geographically within the state. These results will help guide future public health interventions.

Practice patterns of virtual surgical planning: Survey of the reconstructive section of the American Head and Neck Society.

PURPOSE: Virtual surgical planning (VSP), with custom made implants and guides represents a recent major advance. Nonetheless, knowledge related to practice patterns is limited. The purpose of this study was to provide data from the AHNS Reconstruction Section related to practice patterns, perceived value of VSP, as well as elucidate specific situations which represent high value for the application of VSP. MATERIALS AND METHODS: A multi-center web-based survey consisting of 30 questions regarding practice patterns related to VSP practices delivered via email to 203 members of the AHNS Reconstructive Surgery Section at institutions across North America. RESULTS: There was a 34% response rate (70/203). A majority of the respondents (96%) used VSP in approximately 50% of their mandibular reconstruction cases, and in 42% of maxillary cases. 46% reported using patient specific implants >75% of cases. Respondents estimated that ~17% of patients received dental implant reconstruction. The majority of respondents (71.0%) did not know the cost of VSP at their institution. The remaining respondents indicated the average cost was $6680 per case. VSP was felt to be necessary as a teaching tool by 55.9%. CONCLUSIONS: Our results demonstrate that a majority of respondents frequently utilize VSP in their practice for head and neck reconstruction. Complex, multi-unit reconstructions were felt to offer the greatest value when utilizing VSP. Future work should focus on increasing the rates of dental implant reconstruction in this population, optimizing value of VSP with careful case selection, and understanding the educational value and costs of these platforms.

Reconstruction of midface defects with the osteocutaneous radial forearm flap: Evaluation of long term outcomes including patient reported quality of life.

BACKGROUND: Maxillectomy defects significantly impair quality of life. Prosthetics can overcome some of these issues, but has limitations. The role of the osteocutaneous radial forearm free flap (OC-RFFF) has been established for reconstruction of smaller maxillectomy defects, but its role in larger defects is not well defined. We aim to evaluate outcomes after midface reconstruction utilizing the OC-RFFF. METHODS: Retrospective review of prospective database collected between 2005 and 2014 of midface reconstruction using OC-RFFF in a tertiary care centre. Donor site complications and acute and long-term recipient site complications were measured. Health related quality of life was assessed using the University of Washington Quality of Life (UW-QOL) Questionnaire. RESULTS: A total of 68 midface defects were reconstructed using the OC-RFFF. Acute recipient site complications included three flap failures (4%), and two additional microvascular revision cases for vascular compromise. Late recipient complications included fistula (n = 10, 14%), ectropion (n = 7, 10%), diplopia (n = 6, 9%) and exposed hardware (n = 5, 7%). Resection of cheek skin or orbital rim correlated with orbital complications. The incidence of fistula was not affected by defect size or prior radiation. There were two donor site infections and no instances of forearm fracture. Patients undergoing OC-RFFF repair had mean scores for UW-QOL outcomes higher than published rates of obturator quality of life. CONCLUSION: The OC-RFFF is suited to a variety of midface defects and can be combined with hardware to reconstruct the orbital floor. Recipient site complications are common, but donor site morbidity is low and outcomes, including HR-QOL, are acceptable.

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

Primary Site Surgery in Distantly Metastatic Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. RESULTS: Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. CONCLUSIONS: Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2243-2251, 2024.

Outcomes of Head and Neck Free Tissue Transfer in Renal Failure Patients.

OBJECTIVE: To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications. METHODS: Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined. RESULTS: Seventy-three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001). CONCLUSIONS: Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre-operatively in this patient population with consideration for regional flaps in the appropriate patient. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:688-694, 2024.

Microvascular reconstruction of midface osteoradionecrosis.

BACKGROUND: Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. METHODS: Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54). RESULTS: The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02). CONCLUSION: In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

Microvascular reconstruction of medication related osteonecrosis of the head and neck.

BACKGROUND: Medication related osteonecrosis of the jaw (MRONJ) requiring free flap (FF) reconstruction is uncommon with limited reported findings. METHODS: Multicenter, retrospective case series of 49 consecutive adult patients presenting with advanced MRONJ requiring FF reconstruction from 2010 to 2022. Perioperative complications and outcomes were analyzed. RESULTS: Eighty-two percent (n = 40) of cases were of the mandible and 18% (n = 9) were of the maxilla. The mean follow-up was 15 months (±19.6). The majority of FF survived (96%, n = 47). FF reconstructions of the maxilla were more likely to require postoperative debridement (56%, 95% CI [27, 81%] vs. 15%, 95% CI [7, 25%], p = 0.008) or develop intraoral bone exposure (56%, 95% CI [27, 81%] vs. 18%, 95% CI [9, 27%], p = 0.02). Most patients (71%, n = 35) received preoperative antibiotics which was associated with a higher rate of FF survival (100% vs. 86%, 95% CI [60, 96%], p = 0.02) and fewer complications. CONCLUSIONS: Patients undergoing FF reconstruction for MRONJ do well with high rates of FF success. MRONJ of the maxilla have a higher rate of some complications. Preoperative antibiotics correlated with higher FF survival and fewer postoperative complications.

Free flap reconstruction following head and neck trauma.

BACKGROUND: Free flap (FF) reconstruction of traumatic injuries to the head and neck is uncommon. METHODS: Multi-institutional retrospective case series of patients undergoing FF reconstruction for a traumatic injury (n = 103). RESULTS: Majority were gunshot wounds (GSW; 85%, n = 88) and motor vehicle accidents (11%, n = 11). Majority underwent osseous reconstruction (82%, n = 84). FF failures (9%, n = 9/103) occurred in GSW patients (100%, n = 9/9) and when multiple subsites were injured (89%, n = 8/9). Preoperative antibiotics correlated with lower rates of a neck washouts (4% vs. 19%) (p = 0.01) and 30-day readmissions (4% vs. 17%) (p = 0.02). CONCLUSIONS: All FF failures occurred in the setting of a GSW and the majority involved multiple subsites. Preoperative antibiotics correlated with lower rates of postoperative washout procedures and 30-day readmission.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma.

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis.

Postoperative analysis of osseous midface reconstructions: The value of imaging and a novel scoring system for complexity and operative success.

BACKGROUND: Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction. METHODS: One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score. RESULTS: Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04). CONCLUSIONS: We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.

Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.

OBJECTIVE: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). RESULTS: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. CONCLUSION: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:95-104, 2023.

Factors Leading to Gastrostomy Tube and Tracheostomy Requirements in Patients Treated Initially With Radiotherapy and Salvaged With Surgery and Free Flap Reconstruction.

OBJECTIVE: Patients with recurrent oropharyngeal cancer can achieve survival benefits from surgical salvage, and often require simultaneous free-flap reconstruction. Resection and reconstruction can impact function, leading to tube dependence. PRIMARY OBJECTIVE: describe rates of tracheostomy and gastrostomy tube dependence after oropharyngeal resection and free flap after prior radiation. SECONDARY OBJECTIVE: evaluate patient, tumor, and treatment factors associated with tube dependence. STUDY DESIGN: Retrospective, multi-institutional cohort study. Patients treated from 2003 to 2020. Average follow-up 21.4 months. SETTING: Five tertiary care centers. METHODS: Consecutive cohort of patients undergoing resection and simultaneous free-flap reconstruction for oropharyngeal squamous cell carcinoma after head and neck radiation. PRIMARY OUTCOMES: gastrostomy tube dependence and tracheostomy or tracheostoma 1 year after surgery. Univariable and multivariable logistic regression were performed to identify factors associated with dependence. RESULTS: 89 patients underwent oropharyngectomy and free-flap reconstruction; 18 (20%) underwent total laryngectomy as part of tumor extirpation. After surgery, 51 patients (57%) lived 12 months. Among patients alive at 12 months, 22 (43%) were at least partially-dependent on gastrostomy tube, and 15 (29%) had either tracheostomy or tracheostoma. On multivariable analysis, extensive glossectomy (OR 16.6, 95% CI 1.83-389, p = 0.026) and total laryngectomy (OR 11.2, 95% CI 1.71-105, p = 0.018) were associated with long-term gastrostomy tube. No factors were associated with long-term tracheostomy on multivariable analysis. CONCLUSION: Even among long-term survivors after salvage resection and free-flap reconstruction, rates of tube dependence are significant. This multi-institutional review is the largest such study to the date and may help inform shared decision-making. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2141-2147, 2023.

Perioperative Hypercoagulability in Free Flap Reconstructions Performed for Intracranial Tumors.

OBJECTIVE(S): Patients with intracranial tumors have a higher risk of thromboembolic events. This risk increases at the time of surgical intervention. We have noted an anecdotal increase in perioperative flap thrombosis in patients undergoing free tissue transfer for intracranial tumor resection. This study aims to formally evaluate this risk. METHODS: A multi-institutional retrospective chart review was performed of patients who underwent free tissue transfer for scalp/cranial reconstruction. Perioperative thrombosis and free flap outcomes were evaluated. RESULTS: The 209 patients who underwent 246 free tissue transfers were included in the study. The 28 free flap scalp reconstructions were associated with intracranial tumors, 19 were performed following composite cranial resections with associated dural resection/reconstruction, and 199 were performed in the absence of intracranial tumors (control group). There was a significantly higher incidence of perioperative flap thrombosis in the intracranial tumor group (11/28, 39%) when compared to controls (38/199, 19%) (p = 0.0287). This was not seen when scalp tumors extended to the dura alone (4/19, 21%, p = 0.83). Therapeutic anticoagulation used for perioperative thrombosis (defined as intraoperative or in the immediate postoperative phase up to 5 days) was associated with a lower risk of flap failure, although this was not statistically significant (p = 0.148). Flap survival rates were equivalent between flaps performed for intracranial pathology (93.3%) and controls (95%). CONCLUSION: There is an increase in perioperative flap thrombosis in patients with intracranial tumors undergoing free tissue scalp reconstruction. Anticoagulation appears to mitigate this risk. LEVEL OF EVIDENCE: This recommendation is based on level 3 evidence (retrospective case-control studies, systematic review of retrospective studies, and case reports) Laryngoscope, 133:1103-1109, 2023.

Clinical outcomes following intraoperative pedicle disruption in fibula free flaps.

OBJECTIVES: Iatrogenic injury of the fibula free flap pedicle is rare. Postoperative flap survival and reconstructive outcomes following intraoperative pedicle severance are unknown. This study assesses free flap outcomes following accidental severance of the peroneal vessels. METHODS: Multi-institutional retrospective chart review from 2000 to 2020. RESULTS: Of 2975 harvested fibula free flaps, 26 had a history of pedicle severance during surgical reconstruction. Reasons for intraoperative pedicle severance included transection during muscular dissection 10/26 (39%), accidental severance with the bone saw 12/26 (46%), and other 4/26 (15.6%). The surgeon responsible for pedicle severance included residents 5/26 (19%), fellows 10/26 (39%), attendings 10/26 (39%), and unknown 1/26 (3.9%). The pedicle artery and vein were severed 10/26 (39%), artery 8/26 (31%), and vein 8/26 (31%). Truncated pedicle vessels were used 3/26 (11.7%), intraoperative anastomoses were performed 23/26 (89%). Postoperative revision in the OR within 7 days of surgery was required 6/26 (23%); 4 flaps were salvaged and 2 flaps failed, both arterial thrombosis. Flap failure was attributed to vascular thrombosis. Long-term flap survival and successful reconstructions were reported 24/26 (92%). CONCLUSION: Accidental severance of fibula free flap pedicle vessels can be corrected with intraoperative repair, without affecting long-term flap survival or reconstructive outcomes. Protecting the flap vessels while using the bone saw and during intramuscular dissection prevents accidental severance.

Use of panitumumab-IRDye800 to image microscopic head and neck cancer in an orthotopic surgical model.

BACKGROUND: Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. METHODS: A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting epidermal growth factor receptor (EGFR; panitumumab) or nonspecific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96 h after systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. RESULTS: Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9 (Pearl) and 2.3 (SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P < 0.05). Tissue biopsy samples (average size 3.7 mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n = 25 of 25). Biopsy samples of nonfluorescent tissue were proven to be negative for malignancy (n = 28 of 28). The SPY was able to detect regional lymph node metastasis (<1.0 mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. CONCLUSIONS: Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology.

CD147 expression in advanced cutaneous squamous cell carcinoma.

BACKGROUND: CD147 is upregulated in multiple cancer types, but its expression in advanced cutaneous squamous cell carcinoma (SCC) is unknown. Our purpose was to evaluate the expression patterns of CD147 and related monocarboxylate transporters (MCT1, MCT4) to determine their correlation with survival. METHODS: This is a retrospective cohort study of patients with advanced stage cutaneous SCC of the head and neck who presented to a tertiary care center between 1998 and 2006 (n=50). CD147, MCT1 and MCT4 expression levels were assessed using immunofluorescence analysis of archived tumor samples and correlated with survival and clinicopathologic characteristics. RESULTS: The majority of patients (92%, n = 46) were diagnosed with stage III disease, with 46% (n = 23) having positive regional lymph node metastasis and 8% (n = 4) with distant metastasis. Primary malignancies had an overexpression of CD147 (78%; n = 35), MCT1 (23%; n = 10) and MCT4 (47%; n = 20). In addition, there was a significant relationship between the overexpression of CD147 and node positive disease (p = 0.048). Two- and five-year survival rates were 69 and 61%, respectively. There was a trend toward decreased survival in patients with overexpression of CD147 (p = 0.17), MCT1 (p = 0.11) and MCT4 (p = 0.15). CONCLUSION: CD147 may represent a biomarker or potential therapeutic target in advanced cutaneous SCC.

Use of recombinant bone morphogenetic protein 2 in free flap reconstruction for osteonecrosis of the mandible.

PURPOSE: Osteoradionecrosis of the mandible is a debilitating consequence of radiation therapy for head-and-neck malignancy. It can result in pain, bone exposure, fistula formation, and pathologic fracture. Recombinant human bone morphogenetic protein 2 (rhBMP-2) has shown promise in reconstruction of bone defects. The purpose of this study is to determine whether the addition of rhBMP-2 at the union of vascularized bone and native bone improves surgical outcomes in patients with osteonecrosis of the mandible. MATERIALS AND METHODS: This study was a retrospective analysis of patients who were treated between 2006 and 2010 for osteonecrosis of the mandible. Patients requiring definitive reconstruction after failure of a course of conservative management were included. Patients were divided into 2 cohorts depending on whether rhBMP-2 was used during the reconstruction. The primary outcome measure was defined as stable mandibular union. RESULTS: Seventeen patients were included. The development of malunion was similar in both groups (13% for rhBMP-2 group vs 11% for non-rhBMP-2 group). Infectious complications were similar between the groups (25% in rhBMP-2 group vs 56% in non-rhBMP-2 group, P = .33). The rates of hardware removal were similar for the 2 groups (33% in non-rhBMP-2 group vs 25% in rhBMP-2 group, P = .10). No cancer recurrences were observed in patients receiving rhBMP-2. CONCLUSIONS: The use of rhBMP-2 is safe in free flap reconstruction of the mandible, but its ability to significantly improve patient outcomes, as measured by rates of malunion, reoperation, or infection, is still unknown.