Publications by authors named "Arnaud Bewley"

38 Publications

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

Cancer 2021 May 6. Epub 2021 May 6.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Background: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear.

Methods: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses.

Results: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59).

Conclusions: With careful selection, surgery alone for AJCC 7th pT0-2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.
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http://dx.doi.org/10.1002/cncr.33611DOI Listing
May 2021

Facial Nerve Sacrifice During Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma.

OTO Open 2021 Jan-Mar;5(1):2473974X21996627. Epub 2021 Feb 25.

Department of Otolaryngology-Head and Neck Surgery, University of California-Davis, Sacramento, California, USA.

Objective: We analyzed the incidence of facial nerve sacrifice during parotidectomy for metastatic cutaneous squamous cell carcinoma (CSCC).

Study Design: We retrospectively reviewed the charts of patients with cutaneous squamous cell carcinoma.

Setting: We used our CSCC institutional database, which includes patients treated at the University of California-Davis from 2001 to 2018.

Methods: We evaluated patients who presented with biopsy-proven head and neck CSCC who underwent parotidectomy as a part of surgical treatment. We assessed the frequency of facial nerve sacrifice required in patients with normal preoperative facial nerve function with metastatic disease to the parotid. We evaluated the association between sacrifice and high-risk tumor variables using multivariate analysis.

Results: We identified 53 patients with parotid metastasis and normal preoperative facial nerve function. Thirteen percent of patients required sacrifice of the main trunk of the facial nerve and 27% required sacrifice of a branch of the facial nerve. All patients who underwent facial nerve sacrifice had extracapsular spread (ECS). Perineural invasion (PNI) in the primary tumor (odds ratio [OR], 9.11; = .041) and location of metastasis within the parotid body (OR, 6.6; = .044) were independently associated with facial nerve sacrifice.

Conclusion: Patients with regionally metastatic CSCC to the parotid gland frequently require sacrifice of all or a component of the facial nerve despite normal preoperative function. The likelihood of nerve sacrifice is highest for tumors with PNI and metastatic disease within the body of the parotid.
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http://dx.doi.org/10.1177/2473974X21996627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917942PMC
February 2021

Thrombocytosis Predicts Surgical Site Infection in Head and Neck Microvascular Surgery- A Pilot Study.

Laryngoscope 2021 07 14;131(7):1542-1547. Epub 2021 Jan 14.

Department of Otolaryngology, University of California, Davis, Sacramento, California, U.S.A.

Objective/hypothesis: Early and objective prediction of complications in head and neck reconstructive surgery could decrease morbidity and prolonged hospital stays but unfortunately most complications are not identified until their effect is fully realized. There are limited data regarding the association of platelet levels and post-operative complications. Post-operative thrombocytosis (POTCT) is proposed as a possible indicator for complications following free-flap reconstruction.

Study Design: Retrospective review.

Methods: A multisite retrospective chart review of patients undergoing free tissue transfer between 2013 and 2018 was undertaken. POTCT was recorded and data normalized between institutions. Data were compared between groups using t-tests and logistic regression (P < .05). A lag-1 difference was used to compare the rate of change in platelet values.

Results: A total of 398 patients were included. POTCT and a rate of change of 30 K between POD5 and POD6 was significantly associated with the presence of post-operative complication (P = .007). Additionally, lag-1 difference demonstrated a significant association of change in daily platelet counts and complication rates.

Conclusions: Isolated POTCT may be an early predictor of complications in HNC patients undergoing free-flap reconstruction.

Level Of Evidence: 4 Laryngoscope, 131:1542-1547, 2021.
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http://dx.doi.org/10.1002/lary.29386DOI Listing
July 2021

Laryngeal Transplantation.

Adv Otorhinolaryngol 2020 9;85:125-132. Epub 2020 Nov 9.

Department of Otolaryngology-Head and Neck Surgery, University of California Davis, Sacramento, California, USA,

Laryngeal transplantation offers the hope of replacing voice and laryngeal function in patients with debilitating laryngeal injuries or loss of the larynx from trauma or oncologic reasons. Our group at UC Davis performed a laryngotracheal transplantation, and our experience is reviewed in this chapter. The indications, challenges, and limitations of this procedure are highlighted, and the world's other published cases are reviewed.
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http://dx.doi.org/10.1159/000456691DOI Listing
November 2020

Characterization and clinical validation of patient-specific three-dimensional printed tissue-equivalent bolus for radiotherapy of head and neck malignancies involving skin.

Phys Med 2020 Sep 20;77:138-145. Epub 2020 Aug 20.

University of California Davis Comprehensive Cancer Center, Department of Radiation Oncology, Sacramento, CA, United States. Electronic address:

Purpose: Megavoltage radiotherapy to irregular superficial targets is challenging due to the skin sparing effect. We developed a three-dimensional bolus (3DB) program to assess the clinical impact on dosimetric and patient outcomes.

Materials And Methods: Planar commercial bolus (PCB) and 3DB density, clarity, and net bolus effect were rigorously evaluated prior to clinical implementation. After IRB approval, patients with cutaneous or locally advanced malignancies deemed to require bolus for radiotherapy treatment were treated with custom 3DB.

Results: The mean density of 3DB and PCB was of 1.07 g/cm 3 and 1.12 g/cm3, respectively. 3DB optic clarity was superior versus PCB at any material thickness. Phantom measurements of superficial dose with 3DB and PCB showed excellent bolus effect for both materials. 3DB reduced air gaps compared with PCB - particularly in irregular areas such as the ear, nose, and orbit. A dosimetric comparison of 3DB and PCB plans showed equivalent superficial homogeneity for 3DB and PCB (3DB median HI 1.249, range 1.111-1.300 and PCB median HI 1.165, range 1.094-1.279), but better conformity with 3DB (3DB median CI 0.993, range 0.962-0.993) versus PCB (PCB median CI 0.977, range 0.601-0.991). Patient dose measurements using 3DB confirm the delivered superficial dose was within 1% of the intended prescription (95% CI 97-102%; P = 0.11).

Conclusions: 3DB improves radiotherapy plan conformity, reduces air gap volume in irregular superficial areas which could affect superficial dose delivery, and provides excellent dose coverage to irregular superficial targets.
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http://dx.doi.org/10.1016/j.ejmp.2020.08.010DOI Listing
September 2020

Nerve grafts in head and neck reconstruction.

Curr Opin Otolaryngol Head Neck Surg 2020 Oct;28(5):346-351

Department of Otolaryngology-Head and Neck Surgery, University of California, Davis, Sacramento, California, USA.

Purpose Of Review: This article reviews recent literature on repair of peripheral nerve injuries in the head and neck with a focus on autografts, allografts, nerve conduits, and technical considerations.

Recent Findings: Contemporary nerve grafting techniques offer the potential to improve peripheral nerve outcomes and reduce donor site morbidity. A variety of donor nerves autografts have been described that offer favorable outcomes for segmental reconstruction of facial nerve defects. Recent studies have demonstrated promising results in repair of inferior alveolar nerve injuries with human allografts. Animal models describe successful reinnervation of small defects with neural conduits. The latest data do not favor protocolled nerve graft polarity or use of a motor versus sensory donor nerves.

Summary: Interposition nerve grafting is the gold standard for repair of peripheral nerve injuries when a tension-free primary neurorrhaphy is not possible. Autografts are the work-horse for the majority of head and neck neural defects, however, can result in some degree of donor site morbidity. Recent developments in allografting and neural conduits have the potential to further diversify the head and neck reconstructive surgeon's armamentarium. It is unclear if nerve graft makeup or polarity affect functional outcome.
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http://dx.doi.org/10.1097/MOO.0000000000000649DOI Listing
October 2020

Intraoperative Margin Assessment in Oral and Oropharyngeal Cancer Using Label-Free Fluorescence Lifetime Imaging and Machine Learning.

IEEE Trans Biomed Eng 2021 03 18;68(3):857-868. Epub 2021 Feb 18.

Objective: To demonstrate the diagnostic ability of label-free, point-scanning, fiber-based Fluorescence Lifetime Imaging (FLIm) as a means of intraoperative guidance during oral and oropharyngeal cancer removal surgery.

Methods: FLIm point-measurements acquired from 53 patients (n = 67893 pre-resection in vivo, n = 89695 post-resection ex vivo) undergoing oral or oropharyngeal cancer removal surgery were used for analysis. Discrimination of healthy tissue and cancer was investigated using various FLIm-derived parameter sets and classifiers (Support Vector Machine, Random Forests, CNN). Classifier output for the acquired set of point-measurements was visualized through an interpolation-based approach to generate a probabilistic heatmap of cancer within the surgical field. Classifier output for dysplasia at the resection margins was also investigated.

Results: Statistically significant change (P 0.01) between healthy and cancer was observed in vivo for the acquired FLIm signal parameters (e.g., average lifetime) linked with metabolic activity. Superior classification was achieved at the tissue region level using the Random Forests method (ROC-AUC: 0.88). Classifier output for dysplasia (% probability of cancer) was observed to lie between that of cancer and healthy tissue, highlighting FLIm's ability to distinguish various conditions.

Conclusion: The developed approach demonstrates the potential of FLIm for fast, reliable intraoperative margin assessment without the need for contrast agents.

Significance: Fiber-based FLIm has the potential to be used as a diagnostic tool during cancer resection surgery, including Transoral Robotic Surgery (TORS), helping ensure complete resections and improve the survival rate of oral and oropharyngeal cancer patients.
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http://dx.doi.org/10.1109/TBME.2020.3010480DOI Listing
March 2021

Fluorescence lifetime imaging for intraoperative cancer delineation in transoral robotic surgery.

Transl Biophotonics 2019 Dec 29;1(1-2). Epub 2019 Oct 29.

Department of Biomedical Engineering, University of California, Davis, California.

This study evaluates the potential for fluorescence lifetime imaging (FLIm) to enhance intraoperative decisionmaking during robotic-assisted surgery of oropharyngeal cancer. Using a custom built FLIm instrument integrated with the da Vinci robotic surgical platform, we first demonstrate that cancer in epithelial tissue diagnosed by histopathology can be differentiated from surrounding healthy epithelial tissue imaged prior to cancer resection and on the excised specimen. Second, we study the fluorescence properties of tissue imaged at surgical resection margins (tumor bed). Fluorescence lifetimes and spectral intensity ratios were calculated for three spectral channels, producing a set of six FLIm parameters. Current results from 10 patients undergoing TORS procedures demonstrate that healthy epithelium can be resolved from cancer ( < .001) for at least one FLIm parameter. We also showed that a multiparameter linear discriminant analysis approach provides superior discrimination to individual FLIm parameters for tissue imaged both and . Overall, this study highlights the potential for FLIm to be developed into a diagnostic tool for clinical cancer applications of the oropharynx. This technique could help to circumvent the issues posed by the lack of tactile feedback associated with robotic surgical platforms to better enable cancer delineation.
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http://dx.doi.org/10.1002/tbio.201900017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351319PMC
December 2019

Endotracheal Tube Bridle Associated With Full-Thickness Facial Necrosis and Parotid Gland Mucormycosis.

Ear Nose Throat J 2020 Jul 5:145561320936489. Epub 2020 Jul 5.

Department of Otolaryngology - Head and Neck Surgery, University of California Davis, Sacramento, CA, USA.

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http://dx.doi.org/10.1177/0145561320936489DOI Listing
July 2020

Advanced head and neck surgery training during the COVID-19 pandemic.

Head Neck 2020 Jul 8;42(7):1411-1417. Epub 2020 May 8.

Department of Otolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: The COVID-19 pandemic has significantly impacted medical training. Here we assess its effect on head and neck surgical education.

Methods: Surveys were sent to current accredited program directors and trainees to assess the impact of COVID-19 on the fellow's experience and employment search. Current fellows' operative logs were compared with those of the 2018 to 2019 graduates.

Results: Despite reduction in operative volume, 82% of current American Head and Neck Society fellows have reached the number of major surgical operations to support certification. When surveyed, 86% of program directors deemed their fellow ready to enter practice. The majority of fellows felt prepared to practice ablative (96%), and microvascular surgery (73%), and 57% have secured employment to follow graduation. Five (10%) had a pending job position put on hold due to the pandemic.

Conclusions: Despite the impact of the COVID-19 pandemic, current accredited trainees remain well-positioned to obtain proficiency and enter the work-force.
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http://dx.doi.org/10.1002/hed.26252DOI Listing
July 2020

Multi-Institutional Regional Otolaryngology Bootcamp.

Ann Otol Rhinol Laryngol 2020 Jun 29;129(6):605-610. Epub 2020 Jan 29.

Department of Otolaryngology, Division of Head and Neck Surgery, University of California, Davis, Sacramento, CA, USA.

Introduction: In order to increase junior resident physician proficiency and improve patient safety, simulation-based procedural training courses, or bootcamps, have been become an emerging educational tool.

Objectives: To compare pre- and post-course confidence levels and to assess station efficacy after completion of our single day bootcamp.

Methods: We developed the University of California (UC) Davis otolaryngology bootcamp, a single day course including six cadaveric task trainer stations and four simulations. The six task trainer stations included (1) Epistaxis, (2) Cricothyrotomy/tracheostomy, (3) Peritonsillar abscess/auricular hematoma, (4) Nasal bone reduction/zygoma reduction/lateral canthotomy/canalicular trauma and probing, (5) Local nerve blocks, and (6) Soft tissue reconstruction. The simulations comprised of airway fire during tracheostomy, pediatric respiratory code during airway evaluation, dislodged pediatric tracheostomy tube in the ICU, and angioedema in the emergency department with inability to intubate or ventilate. Junior residents from multiple locoregional institutions were recruited to participate. Pre- and post-course Likert surveys assessing participant confidence and station efficacy were collected and analyzed.

Results: There was a statistically significant increase in resident confidence levels for all task trainer stations. All stations had a station efficacy Likert score average of 4 "very effective" or 5 "most effective."

Conclusion: A multi-institutional, locoregional, simulation-based bootcamp can be a valuable adjunct to junior resident training. It can promote camaraderie, pool limited resources, and may be cost-effective.
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http://dx.doi.org/10.1177/0003489420903067DOI Listing
June 2020

Prevalence of profound laryngeal sensory neuropathy in head and neck cancer survivors with feeding tube-dependent oropharyngeal dysphagia.

Head Neck 2020 05 27;42(5):898-904. Epub 2019 Dec 27.

Center for Voice and Swallowing, Department of Otolaryngology-Head and Neck Surgery, University of California, Davis, Sacramento.

Background: Laryngopharyngeal sensory neuropathy (LSN) has been observed to be a contributing factor to swallowing dysfunction in head and neck cancer (HNC) survivors.

Methods: Retrospective review of 43 tube-dependent HNC survivors was conducted. LSN was assessed with direct palpation of the aryepiglottic fold and by traversing the true vocal folds without eliciting a cough reflex with a flexible laryngoscope.

Results: The primary tumor sites were oropharynx (51%), larynx (14%), nasopharynx (4.7%), oral cavity (14%), thyroid (4.7%), unknown primary (9.3%), and esophagus (2.3%). The prevalence of profound LSN was 79.1%. Objective fluoroscopic parameters contributing to swallowing dysfunction were diminished laryngohyoid elevation (100%), pharyngeal weakness (67%), and reduced lateral PES opening (37%).

Conclusions: The prevalence of LSN in HNC survivors with feeding tube-dependent dysphagia is high (79.1%). The data suggest that LSN, in addition to fibrosis, pharyngoesophageal stenosis, and cranial nerve motor deficits contributes to swallowing dysfunction in these patients.
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http://dx.doi.org/10.1002/hed.26059DOI Listing
May 2020

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells.

Stem Cells Dev 2020 03 30;29(6):327-335. Epub 2020 Jan 30.

Department of Otolaryngology, University of California, Davis, Sacramento, California.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.
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http://dx.doi.org/10.1089/scd.2019.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081244PMC
March 2020

Malnutrition evaluation in head and neck cancer patients: Practice patterns among otolaryngologists and radiation oncologists.

Head Neck 2019 11 12;41(11):3850-3857. Epub 2019 Aug 12.

Head and Neck Surgery, Indiana University, Indianapolis, Indiana.

Background: Physician practice patterns regarding diagnosis and management of malnutrition in the head and neck cancer patient population are not well studied.

Methods: A 17-question survey was distributed to 1392 members of the American Head and Neck Society (AHNS). The impact of hospital type, fellowship training, experience, and specialty was assessed.

Results: Among AHNS members, there were 124 total respondents (9% response rate), including both otolaryngologists and radiation oncologists. Respondents strongly agreed (90%) that malnutrition negatively impacts patient outcomes. The majority (63%) felt comfortable screening for malnutrition, but 13% reported no routine assessment of malnutrition; 57% were unfamiliar with relevant guidelines. Barriers to screening included lack of familiarity with screening tools/guidelines, lack of time, and lack of access to dietitian.

Conclusion: Although there was a strong consensus among respondents that the identification and management of malnutrition among head and neck cancer patients is critical, familiarity with relevant guidelines was poor.
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http://dx.doi.org/10.1002/hed.25909DOI Listing
November 2019

Use of multiple free flaps in head and neck reconstruction.

Curr Opin Otolaryngol Head Neck Surg 2019 Oct;27(5):392-400

Department of Otolaryngology-Head and Neck Surgery, University of California, Davis, Sacramento, California, USA.

Purpose Of Review: To review the recent literature on the use of multiple flaps in head and neck reconstruction with attention to form, function, outcomes, and complications.

Recent Findings: Multiple free flap reconstructions are technically feasible with high flap survival rates, tolerable complication rates, and overall adequate functional and aesthetic outcomes, given the large extent of the defects and the high surgical complexity of these cases.

Summary: Multiple free flap reconstructions should be considered in cases of large defects involving multiple functional regions and tissue types, which most often arises following resection of advanced malignancies. As there is mortality benefit with clear surgical margins and eradication of malignant lymph nodes, larger resections should be pursued if necessary, followed by a multiple flap reconstruction.
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http://dx.doi.org/10.1097/MOO.0000000000000574DOI Listing
October 2019

HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection.

Hum Vaccin Immunother 2019 7;15(7-8):1920-1928. Epub 2019 May 7.

b Department of Otolaryngology-Head and Neck Surgery, Indiana University , Indianapolis , IN , USA.

The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors present differently than traditional mucosal head and neck cancers, and those affected often lack classic risk factors such as tobacco and alcohol use. Currently, there are no approved approaches for prevention and early detection of disease, thus leading many patients to present with advanced cancers requiring intense surgical or nonsurgical therapies resulting in significant side effects and cost to the health-care system. In this review, we outline the evolving epidemiology of HPV-related OPC. We also summarize the available evidence corresponding to HPV-related OPC prevention, including efficacy and safety of the HPV vaccine in preventing oral HPV infections. Finally, we describe emerging techniques for identifying and screening those who may be at high risk for developing these tumors.
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http://dx.doi.org/10.1080/21645515.2019.1600985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746516PMC
March 2020

Oncologic outcomes after surgery for locally aggressive basal cell carcinoma of the head and neck.

Laryngoscope 2020 01 5;130(1):115-119. Epub 2019 Mar 5.

Division of Otolaryngology-Head and Neck Surgery, The University of California, Davis , Sacramento, California, U.S.A.

Objective: Although basal cell carcinoma (BCC) is the most common skin cancer, locally aggressive BCC of the head and neck is rare and not well studied.

Study Design: Retrospective review of patients who underwent primary surgical resection of locally aggressive head and neck BCC at a single tertiary academic center.

Results: Eighty-seven patients with 98 tumors demonstrated a 5-year Kaplan-Meier estimated recurrence-free survival of 64.5%, overall survival of 83.3%, and disease-specific survival of 98.3%. Intraoperative positive frozen section margin was a strong independent predictor of local recurrence (hazard ratio 6.88, P = 0.038) and was more likely to occur in tumors previously treated with radiation (odds ratio 6.47 = 0.05).

Conclusion: Locally aggressive BCCs of the head and neck have high rates of local recurrence but low disease-specific mortality when treated with primary surgery and selected use of adjuvant therapy. Intraoperative positive frozen section margin is a strong independent predictor of local recurrence and is more likely in tumors that were previously treated with radiation therapy.

Level Of Evidence: 4 Laryngoscope, 130:115-119, 2020.
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http://dx.doi.org/10.1002/lary.27882DOI Listing
January 2020

Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck.

JAMA Otolaryngol Head Neck Surg 2019 02;145(2):153-158

Department of Otolaryngology, University of California, Davis, Sacramento.

Importance: Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors worldwide. There is conflicting evidence regarding the indications for and benefits of adjuvant radiation therapy for advanced CSCC tumors of the head and neck.

Objective: To assess indications for adjuvant radiation therapy in patients with CSCC.

Design, Setting, And Participants: Retrospective analysis of 349 patients with head and neck CSCC treated with primary resection with or without adjuvant radiation therapy at 2 tertiary referral centers from January 1, 2008, to June 30, 2016.

Main Outcomes And Measures: Data were compared between treatment groups with a χ2 analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed using a Kaplan-Meier survival analysis with log-rank test and a Cox proportional hazards multivariate regression.

Results: A total of 349 patients had tumors that met the inclusion criteria (mean [SD] age, 70 [12] years; age range, 32-94 years; 302 [86.5%] male), and 191 (54.7%) received adjuvant radiation therapy. The 5-year Kaplan-Meier estimates were 59.4% for DFS and 47.4% for OS. Patients with larger, regionally metastatic, poorly differentiated tumors with perineural invasion (PNI) and younger immunosuppressed patients were more likely to receive adjuvant radiation therapy. On Cox proportional hazards multivariate regression, patients with periorbital tumors (hazard ratio [HR], 2.48; 95% CI, 1.00-6.16), PNI (HR, 1.90; 95% CI, 1.12-3.19), or N2 or greater nodal disease (HR, 2.16; 95% CI, 1.13-4.16) had lower DFS. Immunosuppressed patients (HR, 2.17; 95% CI, 1.12-4.17) and those with N2 or greater nodal disease (HR, 2.43; 95% CI, 1.42-4.17) had lower OS. Adjuvant radiation therapy was associated with improved OS for the entire cohort (HR, 0.59; 95% CI, 0.38-0.90). In a subset analysis of tumors with PNI, adjuvant radiation therapy was associated with improved DFS (HR, 0.47; 95% CI, 0.23-0.93) and OS (HR, 0.44; 95% CI, 0.24-0.86). Adjuvant radiation therapy was also associated with improved DFS (HR, 0.36; 95% CI, 0.15-0.84) and OS (HR, 0.30; 95% CI, 0.15-0.61) in patients with regional disease.

Conclusions And Relevance: Among patients with advanced CSCC, receipt of adjuvant radiation therapy was associated with improved survival in those with PNI and regional disease.
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http://dx.doi.org/10.1001/jamaoto.2018.3650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439589PMC
February 2019

The anteromedial thigh free flap: a primary reconstructive option or second best?

Curr Opin Otolaryngol Head Neck Surg 2018 Oct;26(5):312-318

Department of Otolaryngology - Head and Neck Surgery, UC Davis Medical Center, California, USA.

Purpose Of Review: This article reviews the recent literature on the anteromedial thigh free flap.

Recent Findings: The anteromedial thigh (AMT) free flap is an excellent reconstructive option for head and neck defects. It is often overshadowed by the anterolateral thigh (ALT) free flap. Lack of familiarity with the anatomy of the AMT likely deters many surgeons from considering it as a reliable option. However, as many as one in 20 patients may not have anatomy suitable for ALT free-flap harvest, and in these cases the AMT provides an ideal alternative as it can be harvested through the same incision without added morbidity. Current areas of research include clinical, anatomic, cadaveric, and radiographic studies evaluating the AMT flap anatomy and utility.

Summary: The AMT flap has been successfully used to reconstruct the same types of soft tissue head and neck defects as the ALT. However, given that approximately 95% of patients appear to have anatomy favorable to harvest an ALT, the utility of the AMT should be reserved for patients with unfavorable lateral thigh anatomy or when when a chimeric flap is indicated and anatomy permits.
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http://dx.doi.org/10.1097/MOO.0000000000000475DOI Listing
October 2018

Head and Neck Cancer and the Elderly Patient.

Otolaryngol Clin North Am 2018 Aug 23;51(4):741-751. Epub 2018 May 23.

Department of Otolaryngology, Division of Head and Neck Surgery, University of California, Davis, 2521 Stockton Boulevard, Sacramento, CA 95817, USA.

Management of head and neck cancer in the elderly patient is particularly challenging given the high morbidity associated with treatment. Surgery, radiotherapy, and chemotherapy have all been demonstrated as effective in older patients; however, older patients are more susceptible to treatment-induced toxicity, which can limit the survival benefits of certain interventions. This susceptibility is better associated with the presence of multiple comorbidities and decreasing functional status than with age alone. Screening tools allow for risk stratification, treatment deintensification, and even treatment avoidance in patients who are deemed at high-risk of being harmed by standard therapy.
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http://dx.doi.org/10.1016/j.otc.2018.03.004DOI Listing
August 2018

Marginal versus segmental mandibulectomy for pediatric desmoid fibromatosis of the mandible - Two case reports and review of the literature.

Int J Pediatr Otorhinolaryngol 2018 Jun 16;109:21-26. Epub 2018 Mar 16.

University of California Davis, Department of Otolaryngology, United States.

Desmoid fibromatosis (DF) is a rare, benign soft tissue neoplasm with high rate of local recurrence. Surgical management of DF in the head and neck can be challenging given the desire to balance the preservation of form and function with the need to minimize local recurrence by achieving complete resection. We present two contrasting cases which highlight the advantages of marginal mandibulectomy over segmental mandibulectomy in children with DF. We favor marginal mandibulectomy even with limited bone stock given the remarkable ability of children to generate new bone.
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http://dx.doi.org/10.1016/j.ijporl.2018.03.012DOI Listing
June 2018

Feasibility of desorption electrospray ionization mass spectrometry for diagnosis of oral tongue squamous cell carcinoma.

Rapid Commun Mass Spectrom 2018 Jan;32(2):133-141

Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907-2084, USA.

Rationale: Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated utility in differentiating tumor from adjacent normal tissue in both urologic and neurosurgical specimens. We sought to evaluate if this technique had similar accuracy in differentiating oral tongue squamous cell carcinoma (SCC) from adjacent normal epithelium due to current issues with late diagnosis of SCC in advanced stages.

Methods: Fresh frozen samples of SCC and adjacent normal tissue were obtained by surgical resection. Resections were analyzed using DESI-MS sometimes by a blinded technologist. Normative spectra were obtained for separate regions containing SCC or adjacent normal epithelium. Principal Component Analysis and Linear Discriminant Analysis (PCA-LDA) of spectra were used to predict SCC versus normal tongue epithelium. Predictions were compared with pathology to assess accuracy in differentiating oral SCC from adjacent normal tissue.

Results: Initial PCA score and loading plots showed clear separation of SCC and normal epithelial tissue using DESI-MS. PCA-LDA resulted in accuracy rates of 95% for SCC versus normal and 93% for SCC, adjacent normal and normal. Additional samples were blindly analyzed with PCA-LDA pixel-by-pixel predicted classifications as SCC or normal tongue epithelial tissue and compared against histopathology. The m/z 700-900 prediction model showed a 91% accuracy rate.

Conclusions: DESI-MS accurately differentiated oral SCC from adjacent normal epithelium. Classification of all typical tissue types and pixel predictions with additional classifications should increase confidence in the validation model.
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http://dx.doi.org/10.1002/rcm.8019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757369PMC
January 2018

Oral leukoplakia and oral cavity squamous cell carcinoma.

Clin Dermatol 2017 Sep - Oct;35(5):461-467. Epub 2017 Jun 27.

Department of Otolaryngology-Head and Neck Surgery, University of California, Davis School of Medicine, Sacramento, CA.

Oral leukoplakia is defined as a white oral lesion not related to another disease process. These lesions are largely asymptomatic, and the clinical relevance of oral leukoplakia is primarily tied to its association with oral cavity squamous cell carcinoma. Timely workup and effective management of these lesions can reduce the risk of malignant transformation and promote early diagnosis of invasive tumors. A biopsy should be performed promptly of any persistent or suspicious leukoplakia with subsequent management dictated by histologic findings. Benign lesions can be observed or treated with topical therapy, and dysplastic lesions should be excised. Some risk of malignant transformation remains even after treatment, and close follow-up is required. Oral cavity squamous cell carcinoma is an aggressive malignancy that can result from malignant conversion of oral leukoplakia or occur de novo. These tumors are primarily treated with surgical resection and adjuvant radiation or chemoradiation as dictated by histopathologic findings.
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http://dx.doi.org/10.1016/j.clindermatol.2017.06.008DOI Listing
November 2017

Perioperative care of head and neck free flap patients.

Curr Opin Otolaryngol Head Neck Surg 2017 Oct;25(5):405-410

aDepartment of Otolaryngology, University of California Davis bDivision of Head and Neck, Department of Otolaryngology, University of California Davis, Davis, California, USA.

Purpose Of Review: This article reviews the recent literature on the perioperative care of head and neck surgical patients undergoing free tissue transfer.

Recent Findings: As the overall success of head and neck free flaps has plateaued above 95%, recent literature on perioperative flap management has focused on minimizing complications, length of stay, and cost of treatment. Current areas of research include preoperative risk stratification, preoperative and postoperative nutrition, intraoperative fluid management, postoperative level of care, postoperative antibiotic prophylaxis, defining the impact of comorbidities, and developing comprehensive evidence-based perioperative care protocols.

Summary: Rates of complications for head and neck free flap surgery remain stubbornly high. Optimization of perioperative nutrition, antibiotics, fluid management, and the establishment of structured pathways has the potential to decrease these complication rates. However, more research is needed into defining and implementing optimal comprehensive care regimens for this complex patient population.
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http://dx.doi.org/10.1097/MOO.0000000000000384DOI Listing
October 2017

Factors Associated with Recurrence and Regional Adenopathy for Head and Neck Cutaneous Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2017 05 21;156(5):863-869. Epub 2017 Mar 21.

1 Department of Otolaryngology, University of California-Davis, Sacramento, California, USA.

Objective Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignancies worldwide. With advanced CSCC of the head and neck, there is conflicting evidence on what constitutes high-risk disease. Our objective is to evaluate which factors are predictive of recurrence and nodal spread and survival. Study Design Case series with chart review. Setting Tertiary academic institution. Subjects and Methods Patients with advanced head and neck CSCC treated with primary resection identified by chart review. Results A total of 212 patients met inclusion criteria, with a mean age of 70.4 years; 87.3% were men. Mean tumor diameter was 3.65 cm, with an average depth of invasion of 1.38 cm. The mean follow-up time was 35 months (median, 21.5), and over that period 67 recurrences were recorded, 49 of which were local. The 5-year Kaplan-Meier estimate of disease-free survival for the cohort was 53.2%. On Cox multivariate analysis, recurrent disease, perineural invasion (PNI), and poorly differentiated histology were independent predictors of recurrence. On multinomial logistic regression, patients with primary tumors on the ear, cheek, temple, or lip, as well as those with PNI, were more likely to present with nodal metastasis. Conclusion For advanced CSCCs of the head and neck, patients with recurrent disease, PNI, and poorly differentiated tumors are at highest risk for local recurrence. Patients with tumors or the ear, cheek, temple, or lip, as well as those with PNI, are at increased risk of harboring nodal disease.
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http://dx.doi.org/10.1177/0194599817697053DOI Listing
May 2017

Minimizing free flap donor-site morbidity.

Curr Opin Otolaryngol Head Neck Surg 2016 Oct;24(5):447-52

Davis Department of Otolaryngology - Head and Neck Surgery, University of California, Sacramento, California, United States.

Purpose Of Review: Fasciocutaneous and osteocutaneous free flap reconstruction has significantly changed the way surgeons reconstruct defects following ablation of head and neck tumors. Over time, success rates of free flaps have approached 98%, allowing surgeons to shift their focus to minimizing morbidities associated with the donor sites. The radial forearm, anterolateral thigh, and fibula free flaps are the three most commonly used flaps in head and neck reconstruction, and therefore each of their advantages and associated morbidities are of particular interest. The present article aims to review the morbidities associated with each of the commonly used head and neck free flaps and techniques to minimize them that are described in the most recent literature.

Recent Findings: New techniques such as negative-pressure wound therapy, full thickness grafts, and rotational flaps have been developed recently that minimize these morbidities.

Summary: The techniques described in the current review may improve long-term patient outcomes both esthetically and functionally.
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http://dx.doi.org/10.1097/MOO.0000000000000286DOI Listing
October 2016

Feasibility and relevance of level I substation node counts in oropharyngeal carcinoma.

Head Neck 2016 08 29;38(8):1194-200. Epub 2016 Mar 29.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: The inclusion of level I in neck dissections for oropharyngeal carcinoma remains controversial. Our objectives were to evaluate the feasibility and relevance of substation node counts in level I of the neck dissection and to determine the specific substation location of metastases in level I in oropharyngeal carcinoma.

Methods: Sixty specimens were retrospectively analyzed after an orientation using a new paradigm of demarcating level I specimens into 8 substations.

Results: Three of the specimens (5%) in this study showed nodal metastasis in level I, one each in 3 different substations. All positive nodes in level I were associated with N+ disease in level II with 2 being radiographically occult (3.3%). Average total node count for level I was 8.1 (range, 2-19).

Conclusion: In oropharyngeal carcinoma, substation level I node quantification is feasible and relevant. This study shows a 5% risk to level I with metastasis in 3 different substations. © 2016 Wiley Periodicals, Inc. Head Neck 38:1194-1200, 2016.
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http://dx.doi.org/10.1002/hed.24356DOI Listing
August 2016

Primary surgery for advanced-stage laryngeal cancer: A stage and subsite-specific survival analysis.

Head Neck 2016 09 25;38(9):1380-6. Epub 2016 Mar 25.

Department of Otolaryngology, Division of Head and Neck Surgery, University of California Davis, Sacramento, California.

Background: Treatment recommendations for advanced-stage laryngeal squamous cell carcinoma (SCC) have evolved significantly over the last 2 decades.

Methods: We retrospectively analyzed patients in the Surveillance, Epidemiology, and End Results (SEER) database with advanced-stage laryngeal SCC treated between 2004 and 2012.

Results: A total of 6797 patients were identified in the SEER database who met inclusion criteria, with 2051 patients undergoing primary surgery and 4746 patients undergoing primary radiotherapy (RT) or chemoradiotherapy (CRT). Disease-specific survival (DSS) and overall survival (OS) were significantly better for patients treated with primary surgery when compared using Kaplan-Meier curves and a Cox multivariate regression. When survival analysis was repeated for patients stratified by T classification, N classification, and subsite, OS and DSS benefits from primary surgery were observed for patients with T3 and T4a tumors, N0 neck disease, or supraglottic primaries.

Conclusion: Patients with advanced-stage laryngeal SCC with T3 and T4a tumors, N0 neck disease, or supraglottic primaries have the greatest chance of survival when treated with primary surgery. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1380-1386, 2016.
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http://dx.doi.org/10.1002/hed.24443DOI Listing
September 2016

Chondroblastoma of the Clivus: Case Report and Review.

J Neurol Surg Rep 2015 Nov 9;76(2):e258-64. Epub 2015 Oct 9.

Department of Neurological Surgery, UC Davis School of Medicine, Sacramento, California, United States.

Background and Importance Chondroblastoma is a benign primary bone tumor that typically develops in the epiphyses of long bones. Chondroblastoma of the craniofacial skeleton is extremely rare, with most cases occurring in the squamosal portion of the temporal bone. In this report, we describe the first case of chondroblastoma of the clivus presenting with cranial neuropathy that was treated with endoscopic endonasal resection. We review the literature on craniofacial chondroblastomas with particular emphasis on extratemporal lesions. Case Presentation A 27-year-old woman presented with severe headache, left facial dysesthesias, and diplopia. Physical examination revealed hypesthesia in the left maxillary nerve dermatome, and complete left abducens nerve palsy. Imaging demonstrated an expansile intraosseous mass originating in the upper clivus with extension superiorly into the sella turcica and laterally to involve the medial wall of the left cavernous sinus. The tumor was completely resected via an endoscopic endonasal approach, with postoperative improvement in lateral gaze palsy. Histopathology was consistent with chondroblastoma. Conclusion Chondroblastoma is a rare tumor of the craniofacial skeleton that should be included in the differential diagnosis of an osteolytic lesion of the clivus. Complete surgical resection remains the mainstay of treatment.
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http://dx.doi.org/10.1055/s-0035-1564601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648736PMC
November 2015

Free flap monitoring: a review of the recent literature.

Curr Opin Otolaryngol Head Neck Surg 2015 Oct;23(5):393-8

Department of Otolaryngology - Head and Neck Surgery, University of California, Davis, Sacramento, California, USA.

Purpose Of Review: Free flap surgery has revolutionized our ability to perform composite reconstructions following ablative surgery. Although flap failure is rare (∼5%), it results in high patient morbidity if not recognized and corrected early. There are numerous means to assess flap viability. We review the recent literature on flap monitoring, and discuss the difference between techniques in regard to overall flap survival, cost, and ease of use.

Recent Findings: The current literature on implantable Doppler, microdialysis, video-based application (Eulerian), fluorescence angiography, spectroscopy, contrast-enhanced duplex, and activated clotting time is reviewed. Of these methods, implantable Doppler and spectroscopy have the most recent and largest series of data describing efficacy with implantable Doppler, demonstrating comparable flap survival rates to clinical monitoring. Arterial implantable Doppler has the additional benefit of less false-positives than venous Doppler. Spectroscopy demonstrates promise with commensurate flap survival rates and improved salvage rates over clinical monitoring.

Summary: Clinical monitoring alone has proven to be so effective that it is difficult to demonstrate better outcomes with alternative methods. That said, a minimally invasive, reliable method that does not require physician assessment on a frequent basis would prove ideal in many small centers and academic centers limited by resident hours. Venous and, more recently, arterial monitoring have been successfully implemented at many programs. Spectroscopy appears promising, but the data are still limited.
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http://dx.doi.org/10.1097/MOO.0000000000000189DOI Listing
October 2015
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