Publications by authors named "Fred M Baik"

25 Publications

  • Page 1 of 1

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

Department of Otolaryngology-Head and Neck Surgery, Stanford Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305;

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49aCD103 cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.
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http://dx.doi.org/10.1073/pnas.2101169118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285950PMC
July 2021

Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW.

Theranostics 2021 24;11(15):7188-7198. Epub 2021 May 24.

Department of Otolaryngology - Division of Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.

Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.
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http://dx.doi.org/10.7150/thno.55389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210603PMC
July 2021

Effect of Formalin Fixation for Near-Infrared Fluorescence Imaging with an Antibody-Dye Conjugate in Head and Neck Cancer Patients.

Mol Imaging Biol 2021 04 19;23(2):270-276. Epub 2020 Oct 19.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Purpose: This study evaluated the effect of formalin fixation for near-infrared (NIR) fluorescence imaging of an antibody-dye complex (panitumumab-IRDye800CW) that was intravenously administered to patients with head and neck squamous cell carcinoma (HNSCC) scheduled to undergo surgery of curative intent.

Procedures: HNSCC patients were infused with 25 or 50 mg of panitumumab-IRDye800CW followed by surgery 1-5 days later. Following resection, primary tumor specimens were imaged in a closed-field fluorescence imaging device, before and after formalin fixation. The fluorescence images of formalin-fixed specimens were compared with images prior to formalin fixation. Regions of interest were drawn on the primary tumor and on the adjacent normal tissue on the fluorescence images. The mean fluorescence intensity (MFI) and tumor-to-background ratios (TBRs) of the fresh and formalin-fixed tissues were compared.

Results: Of the 30 enrolled patients, 20 tissue specimens were eligible for this study. Formalin fixation led to an average of 10 % shrinkage in tumor specimen size (p < 0.0001). Tumor MFI in formalin-fixed specimens was on average 10.9 % lower than that in the fresh specimens (p = 0.0002). However, no statistical difference was found between the TBRs of the fresh specimens and those of the formalin-fixed specimens (p = 0.85).

Conclusions: Despite the 11 % decrease in MFI between fresh and formalin-fixed tissue specimens, the relative difference between tumor and normal tissue as measured in TBR remained unchanged. This data suggests that evaluation of formalin-fixed tissue for assessing the accuracy of fluorescence-guided surgery approaches could provide a valid, yet more flexible, alternative to fresh tissue analysis.

Trial Registration: NCT02415881.
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http://dx.doi.org/10.1007/s11307-020-01553-1DOI Listing
April 2021

Oral squamous carcinoma: Aggressive tumor pattern of invasion predicts direct mandible invasion.

Head Neck 2020 11 25;42(11):3171-3178. Epub 2020 Jul 25.

THANC (Thyroid, Head and Neck Cancer) Foundation, New York City, New York, USA.

Background: Aggressive histologic worst pattern of invasion (WPOI) in surrounding soft tissue has been shown to be predictive of higher local recurrence and poorer survival in oral cavity squamous cell carcinoma (OCSCC) patients. This study investigates whether aggressive WPOI can predict the mandibular invasion phenotype.

Methods: Patients consecutively diagnosed with OCSCC undergoing a mandibulectomy (marginal or segmental) between 2013 and 2018 were reviewed. Senior physicians re-reviewed radiologic scans and pathologic slides of 44 cases.

Results: Aggressive WPOI (WPOI-4, 5) is significantly associated with infiltrative bone invasion. Non-aggressive WPOI (WPOI-1, 2, 3) is significantly associated with the absence of bone invasion.

Conclusions: WPOI has become a useful tool that further characterizes the biologic behavior of OCSCC. Potentially, planned surgery may escalate from a marginal to segmental mandibulectomy based on aggressive WPOI for patients with radiographically uncertain cortical status. Further studies are needed to validate the relationship between OCSCC WPOI and mandible status.
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http://dx.doi.org/10.1002/hed.26360DOI Listing
November 2020

Multifocal Parotid Oncocytic Cystadenomatosis: A Rare Process that Can Mimic Malignancy.

Head Neck Pathol 2021 Mar 14;15(1):323-327. Epub 2020 May 14.

THANC (Thyroid, Head and Neck Cancer) Foundation, 10 Union Square East, Suite 5B, New York, NY, 10003, USA.

Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.
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http://dx.doi.org/10.1007/s12105-020-01170-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010016PMC
March 2021

Radiographic surveillance of abdominal free fat graft in complex parotid pleomorphic adenomas: A case series.

Heliyon 2020 May 4;6(5):e03894. Epub 2020 May 4.

Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Background: Free abdominal fat transfer is commonly used to restore facial volume and improve cosmesis after parotidectomy for pleomorphic adenomas. We describe the radiographic characteristics of these grafts on follow-up imaging.

Methods: Medical records of four patients who underwent parotidectomy with abdominal fat graft in 2016 and had follow up imaging available were retrospectively analyzed. An otolaryngologist and neuroradiologist reviewed imaging studies, evaluated the fat grafts, and monitored for residual or recurrent disease.

Results: The abdominal fat was successfully grafted in all four patients. Post-operative baseline magnetic resonance imaging and additional surveillance imaging showed fat grafts with minimal volume loss. However, there was development of irregular enhancement consistent with fat necrosis in two of the four patients.

Conclusions: Radiographic surveillance of free fat graft reconstruction after pleomorphic adenoma resection shows minimal contraction in size but development of fat necrosis. Recognition of expected changes should help avoid confusion with residual or recurrent disease, reassuring both patient and treating physician.
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http://dx.doi.org/10.1016/j.heliyon.2020.e03894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210407PMC
May 2020

Positive Lymph Node Counts in American Thyroid Association Low-Risk Papillary Thyroid Carcinoma Patients.

World J Surg 2020 06;44(6):1892-1897

THANC (Thyroid, Head and Neck Cancer) Foundation, 10 Union Square East, New York, NY, 10003, USA.

Background: Current American Thyroid Association (ATA) guidelines state that patients with intermediate-risk papillary thyroid cancer (PTC) may benefit from remnant ablation. One criterion for intermediate-risk classification is >5 positive lymph nodes (LNs). We investigate whether performing step-sectioning of LNs increases the metastatic detection rate, thereby influencing ATA risk of recurrence (ROR) classification.

Methods: A retrospective review was conducted of cases in which ≥ 5 LNs were removed during thyroidectomy and ≤5 LNs were found positive for PTC. Step-sectioning was performed on the original tissue blocks. All slides were re-reviewed by a senior pathologist.

Results: Twenty patients met study criteria. Step-sectioning significantly increased LN yield compared to standard sectioning. In total, we found 12 new positive lymph nodes; seven (58%) were in totally new lymph nodes, while five (42%) were in lymph nodes previously read as negative. All newly discovered metastases were classified as micrometastases (≤2 mm). Of the 15 patients originally classified as low-risk, the step-sectioning protocol impacted two patients (13%), increasing ROR stratification.

Conclusion: Intensive step-sectioning reveals additional micrometastases. More detailed analysis did not identify clinically significant nodal disease likely to impact the clinical course of patients in this study. Our study supports current standards of pathology specimen handling related to LN assessment and the impact on ATA ROR classification. Nonetheless, it is important for clinicians to understand their institution's sectioning protocol utilized to report positive and total LN counts, which could impact ATA risk stratification and denote the comprehensive nature of the LN dissection that was performed.
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http://dx.doi.org/10.1007/s00268-020-05399-0DOI Listing
June 2020

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

Front Oncol 2019 10;9:1476. Epub 2020 Jan 10.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States.

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 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. 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. 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 ( < 0.0001). This proof-of-concept study suggests that, when combined with routine FSA, 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.
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http://dx.doi.org/10.3389/fonc.2019.01476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965069PMC
January 2020

Reconstructive and prosthodontic outcomes after multiple palatomaxillary reconstructions.

Laryngoscope 2020 10 30;130(10):2349-2353. Epub 2019 Dec 30.

THANC (Thyroid, Head and Neck Cancer) Foundation, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, New York.

Objective: A subset of patients who undergo major palatomaxillary reconstruction do not initially achieve their intended oncologic and/or reconstructive goals and require additional surgery. We aim to detail the unique management considerations in this patient population.

Methods: We performed a retrospective review of patients who underwent palatomaxillary reconstruction by the senior author (m.l.u.) between 1998 and 2016.

Results: Twenty-one patients required multiple reconstructions. The median time to second reconstruction was 17 months. The most common reason for a second reconstruction was for recurrent disease (10 of 21), followed by functional/aesthetic reasons (7 of 21) and osteoradionecrosis (4 of 21). Four patients went on to have a third reconstruction, and two underwent a fourth. A total of 27 reconstructions were performed, consisting of 20 soft tissue free flaps, four vascularized bone free flaps, and three locoregional flaps.

Conclusion: This patient cohort represents unique oncologic and reconstructive challenges. With long-term follow-up, multiple reconstructions may be required to optimize oncologic and functional/aesthetic outcomes. This is the first series of its kind that details the reasons for, as well as the outcomes of, patients who required multiple reconstructive procedures following initial palatomaxillary reconstruction.

Level Of Evidence: 2B Laryngoscope, 130:2349-2353, 2020.
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http://dx.doi.org/10.1002/lary.28481DOI Listing
October 2020

Development of proficiency-based knot-tying and suturing curriculum for otolaryngology residents: A pilot study.

Auris Nasus Larynx 2020 Apr 24;47(2):291-298. Epub 2019 Dec 24.

Department of Otolaryngology-Head and Neck Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.

Objective: Basic surgical skills such as knot-tying and suturing are important for all otolaryngologists, regardless of subspecialty. The present study was undertaken in order to assess basic surgical techniques such as knot-tying and suturing required for novice otolaryngology residents with taking the variety of subspecialties into consideration, and evaluate the impact of a proficiency-based training curriculum based on these techniques.

Methods: A prospective study was performed for developing of proficiency-based knot-tying and suturing curriculum for otolaryngology residents in the third post-graduate year (PGY-3). The proficiency-based training curriculum was developed based on the tasks selected by RAND/UCLA method with expert panel, which is an iterative and anonymous survey used to establish consensus among participants. Expert panelists were selected from various divisions to reflect variety of their subspecialties. PGY-3 residents trained with the developed curriculum that included proctored pre-test, self-training to proficiency, and proctored post-test. Visual analogue scale (VAS) of trainees' overall competence in the operating room was self-assessed by each resident, before and after completing the training curriculum.

Results: Nine PGY-3 residents were enrolled as trainees. Eleven experts chosen as panelists had various subspecialty, including 2 from otology, 2 from rhinology, 2 from laryngology, 2 from head and neck surgery, and 3 from general otolaryngology. Seven tasks were selected from RAND/UCLA method and used to develop the curriculum. Trainee scores at pre-test were significantly lower than expert scores for all 7 tasks (p < 0.01) and each coefficient of variation of trainee score was larger than that of expert score (p < 0.05), supporting construct validity. The mean of composite scores between pre-test and post-test had statistical significance (68.6 ± 11.6 vs 95.9 ± 3.6, p < 0.01), documenting substantial improvement after training. Self-assessment VAS was also improved pre- to post-training (1.2 ± 0.9 vs 4.5 ± 1.4, p < 0.01). A follow-up questionnaire showed that trainees felt the educational curriculum to be beneficial.

Conclusion: In the present study, seven basic technical skills were selected using the RAND/UCLA method and used to create a proficiency-based training curriculum. Our results indicate that this curriculum significantly improves proficiency of basic surgical skills of junior otolaryngology residents.
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http://dx.doi.org/10.1016/j.anl.2019.11.005DOI Listing
April 2020

Endoscopic Fluorescence-Guided Surgery for Sinonasal Cancer Using an Antibody-Dye Conjugate.

Laryngoscope 2020 12 19;130(12):2811-2817. Epub 2019 Dec 19.

Department of Otolaryngology, Stanford University School of Medicine, Stanford, California, U.S.A.

Objective: Endoscopic resection of sinonasal squamous cell carcinoma has become the standard of care, but challenges remain in obtaining clear resection margins. The current study evaluated the feasibility of endoscopic fluorescence-guided surgery (FGS) to improve surgical resection in a human sinus surgical model.

Methods: A fluorescence endoscope optimized for near-infrared (NIR) fluorescence detection was evaluated in a phantom study. Various endoscope diameters (4 and 10 mm) and viewing angles (0, 30, and 45 degrees) were evaluated to determine the sensitivity of the system for IRDye800CW detection at various working distances (1-5 cm). Endoscopic FGS was then validated in a three-dimensional human sinus surgical model to which squamous cell tumors derived from mice were inserted. Mice had received intravenous panitumumab-IRDye800CW and upon fluorescence-guided tumor resection, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were calculated in in situ and ex vivo settings.

Results: A significantly higher fluorescence intensity was found when using the 10-mm diameter endoscope compared to the 4mm diameter endoscope (P < .001). No significant difference in MFI was found among the viewing angles of the 4-mm diameter endoscope. Using the human sinus model, the highest MFI and TBR were obtained at a 1-cm working distance compared to longer working distances.

Conclusion: We demonstrate that clinically acceptable TBRs were obtained with several working distances to discriminate tumor tissue from adjacent normal tissue in a human sinus model, and that endoscopic FGS may have great potential in identifying residual tumor tissue regions during surgery. Laryngoscope, 2019.
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http://dx.doi.org/10.1002/lary.28483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754277PMC
December 2020

Management of orbital complications in palatomaxillary reconstruction: A review of preemptive and corrective measures.

Head Neck 2020 03 13;42(3):556-568. Epub 2019 Dec 13.

THANC (Thyroid, Head and Neck Cancer) Foundation, New York, New York.

Background: Reconstruction of orbit-sparing palatomaxillary defects requires consideration of globe dystopia, orbital volume, eyelid position and function, and the nasolacrimal system to preserve and optimize vision, globe protection, and appearance. We describe the fundamentals of orbital and eyelid anatomy, common orbital complications related to palatomaxillary reconstruction, and preemptive and corrective surgical techniques to be utilized during and after globe-sparing palatomaxillary reconstruction.

Methods: We present a review of the literature supplemented by clinical case examples.

Results: We advocate for the use of preemptive and corrective techniques to ensure optimal aesthetic and functional outcomes for patients with orbital defects.

Conclusions: Recognition and anticipation of problems in patients undergoing midface ablative and reconstructive procedures are vital to the implementation of corrective measures. Incision choice, orbital volume restoration, appropriate orbital floor reconstruction, and permanent or temporary lower eyelid suspension during the primary surgery can all significantly impact the development of long-term orbital complications.
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http://dx.doi.org/10.1002/hed.26015DOI Listing
March 2020

Ten patients with high-grade transformation of acinic cell carcinomas: Expression profiling of β-catenin and cyclin D1 is useful.

Pathol Res Pract 2020 Feb 30;216(2):152767. Epub 2019 Nov 30.

THANC (Thyroid, Head and Neck Cancer) Foundation, 10 Union Square East, Suite 5B, New York, NY, 10003, USA; Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai Hospital, Mount Sinai Beth Israel, 10 Union Square East, Suite 5B, New York, NY, 10003, USA.

Conventional acinic cell carcinoma (CACC) represents a prototypical low-grade salivary malignancy. Rarely, acinic cell carcinoma (ACC) can demonstrate aggressive features (zones of necrosis, apoptosis, varying nuclear atypia) warranting classification as "ACC with high-grade transformation" (HGT-ACC) or "dedifferentiated" ACC. This study reports ten new cases of HGT-ACC. There is potential for subtlety in recognizing high-grade transformation and distinguishing discrete nodules of necrosis from cytology aspiration changes. We compared immunohistochemical (IHC) profiles, specifically β-catenin (bCAT) and cyclin D1 expression, which have been touted as potentially helpful in this context. We quantified morphology (primary axis nucleus, nuclear area and perimeter) in HGT-ACC and CACC. Clinical outcome is known for eight HGT-ACC patients; three patients developed locoregional or distant metastases, five remained disease-free. Nine of ten HGT-ACC expressed strong, diffuse, membranous bCAT. CACC demonstrated lower intensity of membranous bCAT expression. Strong, diffuse nuclear cyclin D1 was seen in five of ten HGT-ACC whereas no CACC demonstrated cyclin D1 with distribution greater than 50 %. The quantified nuclear morphologic features of CACC and HGT-ACC demonstrated overlapping means values. Maximum values for nuclear primary axis, area, and perimeter were greater for HGT-ACC versus CACC, corresponding to a subpopulation of larger tumor cells in HGT-ACC. The poor outcome associated with HGT-ACC justifies its recognition, which should alter surgical approach with respect to elective neck dissection or possible facial nerve sacrifice. With respect to ancillary IHC studies, strong, diffuse membranous bCAT expression, with or without strong nuclear cyclin D1 ≥ 50 % distribution or Ki67 index ≥ 25 % supports this diagnosis.
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http://dx.doi.org/10.1016/j.prp.2019.152767DOI Listing
February 2020

Combined mandibular and maxillary reconstruction: Managing sinus secretions and preventing infection.

Laryngoscope 2019 11 22;129(11):2475-2478. Epub 2019 Jan 22.

THANC (Thyroid, Head and Neck Cancer) Foundation, New York, New York, U.S.A.

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http://dx.doi.org/10.1002/lary.27819DOI Listing
November 2019

Osteoradionecrosis of the hyoid bone complicated by pharyngocutaneous fistula: A case report and literature review.

Am J Otolaryngol 2019 Mar - Apr;40(2):314-318. Epub 2018 Dec 7.

THANC (Thyroid, Head and Neck Cancer) Foundation, 10 Union Square East, Suite 5B, New York, NY 10003, USA; Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5B, New York, NY 10003, USA.

Background: Osteoradionecrosis (ORN) is a well-known complication following irradiation of head and neck malignancies. ORN commonly occurs in the mandible but is rarely reported in the hyoid bone.

Case Presentation: A 76-year-old female with a history of oropharyngeal squamous cell carcinoma presented with pharyngocutaneous fistula 14 years after primary chemoradiation. Imaging showed necrosis of the hyoid bone. She underwent excision of the hyoid to rule out malignancy. Pathology was negative for carcinoma, but did show extensive fragmentation and bony necrosis consistent with ORN. The patient's clinical course, surgical treatment, and management considerations are discussed here.

Conclusions: Hyoid ORN should remain in the differential during diagnostic workup of previously irradiated head and neck cancer patients. The presentation of a pharyngocutaneous fistula should prompt workup to rule out malignancy before assigning a diagnosis of ORN.
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http://dx.doi.org/10.1016/j.amjoto.2018.12.006DOI Listing
June 2019

Septic arthritis of the sternoclavicular joint: A unique late complication after tracheostomy.

Am J Otolaryngol 2018 Sep - Oct;39(5):646-648. Epub 2018 May 16.

THANC (Thyroid, Head and Neck Cancer) Foundation, 10 Union Square East, Suite 5B, New York, NY 10003, USA; Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5B, New York, NY 10003, USA.

Background: Septic arthritis of the sternoclavicular joint is a rare infection associated with significant morbidity and mortality. Several risk factors for septic arthritis have been reported in the literature ranging from immunodeficiency to intravenous drug use.

Case Presentation: A 63-year-old male previously treated for synchronous squamous cell carcinomas of the epiglottis and floor of mouth presented with tenderness and swelling of the sternoclavicular joint two months after tracheostomy decannulation. Computed tomography and bone scans confirmed the diagnosis of septic arthritis of the sternoclavicular joint. The patient's clinical course, surgical treatment, and management considerations are discussed here.

Conclusion: Septic arthritis of the SCJ is a rare but serious infection. Once diagnosed, septic arthritis of the SCJ should be promptly treated to prevent further morbidity and mortality.
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http://dx.doi.org/10.1016/j.amjoto.2018.05.005DOI Listing
January 2019

Gorilla endoscopic sinus surgery: a life-saving collaboration between human and veterinary medicine.

Int Forum Allergy Rhinol 2018 07 23;8(7):857-862. Epub 2018 Mar 23.

Woodland Park Zoo, Seattle, WA.

Background: Chronic rhinosinusitis is a common disease process in humans; however, in the primate population of gorillas, it has rarely been described. This case describes lifesaving sinus surgery on a critically ill gorilla performed by a human otolaryngology team in collaboration with the gorilla's veterinary medicine team.

Methods: The 35-year-old western silverback gorilla was treated for 3 months with aggressive medical therapy for a worsening sinus infection. When his condition became severe, a computed tomography (CT) scan was performed showing advanced chronic rhinosinusitis with nasal polyps vs other masses and some bone erosion. As his condition deteriorated further, a tertiary otolaryngology team performed sinus surgery using the latest technology available, including image guidance, steroid-eluting sinus stents, and balloon sinus dilation. The postoperative course was complicated by subcutaneous infection and eventual fistulization. Fortunately, with culture-directed antibiotic therapy his condition gradually improved. One year later he required revision sinus surgery. At that point allergy testing was performed followed by appropriate allergy medical therapy. Now, 3 years out from his initial surgery, he continues to do well and has fathered a young female gorilla.

Results: This case represents a unique collaboration between human physicians and veterinarians. The combined medical approach was critical to heal this ailing gorilla. This case discusses many of the challenges and offers recommendations for physicians who may be involved with similar care of animals in the future.

Conclusion: The success of the surgical and medical treatment of this gorilla's life-threatening sinus infection required many experts, careful planning, and corporate generosity. The interaction between human and animal medicine would not have been successful without the close and trusting collaborations between human and veterinary health providers. We encourage human healthcare providers to seek volunteer opportunities through their local zoos by engaging in discussions with their local veterinarians.
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http://dx.doi.org/10.1002/alr.22117DOI Listing
July 2018

A rare primary leiomyosarcoma of the parotid gland: A case report and literature review.

Am J Otolaryngol 2018 May - Jun;39(3):345-348. Epub 2018 Feb 1.

Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai Hospital, Mount Sinai Beth Israel, 10 Union Square East, Suite 5B, New York, NY 10003, USA.

Background: Leiomyosarcoma of the head and neck region is very rare. Primary parotid leiomyosarcoma has only been reported nine times in the medical literature.

Methods: A 68-year-old female presented with a left facial mass. Physical examination revealed a firm immobile mass at the level of the left parotid tail. No facial nerve dysfunction or palpable adenopathy was noted at the time of presentation. This patient underwent a superficial parotidectomy with a facial nerve dissection and left selective neck dissection.

Results: Pathologic findings revealed a sarcoma of intermediate to high-grade, composed of spindle cells with herringbone pattern, eosinophilic fibrillary cytoplasm, and focal granularity. Immunohistochemistry was positive for vimentin and smooth muscle actin and negative for desmin, S100 and CD34. The findings are consistent with a leiomyosarcoma. Following complete surgical resection, adjuvant radiation therapy was administered.

Conclusion: Primary sarcomas of the parotid gland, specifically parotid leiomyosarcomas, are extremely rare. Based on this patient's tumor size, grade and resectability, this case met the criteria for a primary leiomyosarcoma. We present only the tenth case of a primary parotid leiomyosarcoma to be reported in the English literature.
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http://dx.doi.org/10.1016/j.amjoto.2018.01.010DOI Listing
October 2018

Survival and Gastrostomy Prevalence in Patients With Oropharyngeal Cancer Treated With Transoral Robotic Surgery vs Chemoradiotherapy.

JAMA Otolaryngol Head Neck Surg 2016 07;142(7):691-7

Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle6Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Importance: Treatment of oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and can be associated with significant morbidity. Transoral robotic surgery (TORS) has emerged as a treatment modality for OPSCC, but data comparing outcomes between patients treated with TORS-based therapy and nonsurgical therapy are limited.

Objective: To compare survival and gastrostomy prevalence between patients with OPSCC treated with TORS-based therapy and those treated with nonsurgical therapy.

Design, Setting, And Participants: This retrospective matched-cohort study identified patients with OPSCC treated at the University of Washington and University of Minnesota tertiary care medical centers from January 1, 2005, to December 31, 2013. Each patient treated with TORS-based therapy was matched by stage with as many as 3 patients treated with nonsurgical therapy. Final follow-up was completed on April 1, 2015.

Main Outcomes And Measures: Disease-free survival, overall survival, and gastrostomy tube prevalence.

Results: One hundred twenty-seven patients met the study criteria (113 men [89.0%]; 14 women [11.0%]; median [interquartile range] age, 57 [52-63] years); 39 patients who underwent TORS were matched to 88 patients who underwent nonsurgical therapy. Compared with the nonsurgical group, more patients had p16-positive tumors in the TORS group (30 of 31 [96.8%] vs 30 of 37 [81.1%] among patients with known p16 status). No statistically significant difference in survival between treatment groups was found in multivariable analysis (disease-free survival hazard ratio, 0.22; 95% CI, 0.04-1.36; P = .10). Patients who received TORS-based therapy had lower gastrostomy tube prevalence after treatment (13 of 39 [33.3%] vs 74 of 88 [84.1%]) for a univariable relative risk of 0.43 (95% CI, 0.27-0.67; P < .001) and a multivariable relative risk of 0.43 (95% CI, 0.27-0.68; P < .001). Gastrostomy prevalence decreased by time after treatment for both groups (TORS group: 3 of 34 [9%] at 3 months to 1 of 33 [3%] at 12 months; nonsurgical group: 37 of 82 [45%] at 3 months to 7 of 66 [11%] at 12 months).

Conclusions And Relevance: Patients undergoing TORS for OPSCC have statistically indistinguishable survival but lower gastrostomy prevalence compared with patients undergoing nonsurgical therapy for stage-matched OPSCC. TORS offers promise for improved swallowing function in patients with OPSCC.
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http://dx.doi.org/10.1001/jamaoto.2016.1106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167603PMC
July 2016

Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.

JAMA Otolaryngol Head Neck Surg 2016 Apr;142(4):330-8

Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle4Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Importance: Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC.

Objective: To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia.

Design, Setting, And Participants: This was an observational study (including sensitivity and specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches.

Interventions: Various HNSCC xenografts were established in the tongues of NOD-scid IL2Rgammanull (NSG) mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the cheek pouch of Golden Syrian hamsters for 9 to16 weeks. BLZ-100 was subcutaneously injected, and fluorescence uptake was measured.

Main Outcomes And Measures: The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades.

Results: In HNSCC xenografts, BLZ-100 demonstrated a mean (SD) SBR of 2.51 (0.47). The ROC curve demonstrated an area under the curve (AUC) of 0.89; an SBR of 2.50 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and nontumor interface, the AUC increased to 0.97; an SBR of 2.50 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 [0.71] vs 1.51 [0.34], P = .006).

Conclusions And Relevance: BLZ-100 is a sensitive and specific marker of HNSCC and can distinguish high-risk from low-risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of premalignant lesions.
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http://dx.doi.org/10.1001/jamaoto.2015.3617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972605PMC
April 2016

Upper aerodigestive magnetic foreign bodies in children.

Laryngoscope 2014 Jun 3;124(6):1481-5. Epub 2014 Jan 3.

Seattle Children's Hospital, Seattle, Washington; Department of Pediatrics, Division of Emergency Medicine, University of Washington, Seattle, Washington, U.S.A.

Objectives/hypothesis: Small, powerful magnets are increasingly available in toys and other products, and are responsible for increasing numbers of foreign body injuries in children. Small, spherical, neodymium magnets available since 2008 are of particular concern. We aimed to identify all cases of upper aerodigestive foreign bodies at our institution over 15.5 years of study.

Study Design: Case series including all patients treated at an urban, tertiary care children's hospital who had upper aerodigestive magnetic foreign bodies, from January 1, 1998 through April 30, 2013.

Methods: We manually reviewed 7,049 patient records abstracted from billing data to identify all patients 0 to 20 years of age who had upper aerodigestive magnetic foreign bodies.

Results: We identified four cases of upper aerodigestive magnetic foreign bodies, one involving the hypopharynx, and three involving the upper esophagus. Three occurred in 2010 or later. Two cases involve the ingestion of multiple, spherical, neodymium magnets recently marketed as desktop toys. In both of these cases, there was a rapid development of mucosal injury at the site of attraction between two magnets.

Conclusions: As small, powerful magnets become more ubiquitous, pediatric magnet foreign body injuries are increasing. Although most are gastrointestinal, we identified four recent cases involving the upper aerodigestive tract. Multiple magnets lodged in the hypopharynx or esophagus can rapidly cause pressure necrosis of mucosal tissues, and merit prompt management. Education regarding magnet safety and improved magnet safety standards are needed to reduce the risk of these injuries.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lary.24489DOI Listing
June 2014

A large juvenile xanthogranuloma within the tongue.

Otolaryngol Head Neck Surg 2014 Feb 10;150(2):332-3. Epub 2013 Dec 10.

Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1177/0194599813514534DOI Listing
February 2014

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity.

Integr Biol (Camb) 2012 Jun 26;4(6):595-605. Epub 2012 Apr 26.

Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0647, USA.

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL-ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL-ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL-ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL-ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques.
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http://dx.doi.org/10.1039/c2ib00161fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689578PMC
June 2012

Comparative case series of exostoses and osteomas of the internal auditory canal.

Ann Otol Rhinol Laryngol 2011 Apr;120(4):255-60

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California, USA.

Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.
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http://dx.doi.org/10.1177/000348941112000407DOI Listing
April 2011

Exostoses and osteomas of the internal auditory canal.

Laryngoscope 2010 ;120 Suppl 4:S215

School of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA.

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http://dx.doi.org/10.1002/lary.21682DOI Listing
February 2011
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