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1.
Endocrine ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806891

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy that has consistently shown Wnt/ß-catenin (canonical) signaling activation in various study populations. There are currently no targetable treatments for BRAF-wildtype ATC and a lack of effective treatment for BRAFV600EATC. Our aim is to identify whether Wnt inhibitors could be potential therapeutic agents for ATC patients with limited treatment options. METHODS: In this Institutional Review Board-approved study, we utilize a cohort of 32 ATCs and 20 non-neoplastic multinodular goiters (MNG). We also use 4 ATC spheroid cell lines (THJ-16T, THJ-21T, THJ-29T, and THJ-11T) and two primary patient-derived ATC organoid cultures (VWL-T5 and VWL-T60). Finally, we use a murine xenograft mouse model of ATC for in vivo treatment studies. RESULTS: Using a large patient cohort, we demonstrate that this near-universal Wnt signaling activation is associated with ligand expression- rather than being mutationally-driven. We show that pyrvinium pamoate, a potent Wnt inhibitor, exhibits in vitro efficacy against both ATC cell lines and primary patient-derived ATC organoids VWL-T5 (p < 0.05) and VWL-T60 (p < 0.01) Finally, using a murine xenograft model of ATC, we show that pyrvinium significantly delays the growth of ATC tumors in THJ-16T (p < 0.005) and THJ-21T (p < 0.001). CONCLUSIONS: We tested Wnt inhibitor treatment, both in vitro and in vivo, as a potential novel therapy for this highly lethal disease. Future large-scale studies utilizing multiple Wnt inhibitors will lay the foundation for the development of these novel therapies for patients with ATC.

2.
Laryngoscope ; 134(1): 191-197, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37466329

ABSTRACT

OBJECTIVES: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post-operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. METHODS: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. RESULTS: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist-surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. CONCLUSION: Post-operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:191-197, 2024.


Subject(s)
Carcinoma, Squamous Cell , Humans , Retrospective Studies , Carcinoma, Squamous Cell/pathology
3.
Laryngoscope ; 134(2): 717-724, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37584332

ABSTRACT

OBJECTIVE: To evaluate the rate at which carcinoma is present in the re-resection specimen following initial positive margins during head and neck cancer surgery and its impact on oncologic outcomes. STUDY DESIGN: Retrospective chart review. METHODS: A single institution retrospective chart review of patients that underwent curative-intent surgery for oral cavity cancer was performed. Final pathology reports were reviewed to identify patients with initial positive margins who underwent re-resection during the same operation. Initial positive margin was defined as severe dysplasia, carcinoma in situ (CIS), or carcinoma. Cox proportional hazards and Kaplan-Meier analyses were used to assess for associations with survival outcomes. RESULTS: Among 1873 total patients, 190 patients (10.1%) had initial positive margins and underwent re-resection during the same surgery. Additional carcinoma, CIS, or severe dysplasia was found in 29% of re-resections, and 31% of patients with initial positive margins had final positive margins. Half of the patients with a final positive margin had a positive margin at an anatomic site different than the initial positive margin that was re-resected. The median follow-up was 636 days (range 230-1537). Re-resection with cancer and final positive margin status was associated with worse overall survival (OS; p = 0.044 and p = 0.05, respectively). However, only age, T4 disease, and surgery for recurrent oral cavity cancer were independently associated with OS (p < 0.001, p = 0.005, and p = 0.001, respectively). CONCLUSIONS: Fewer than a third of oral cavity re-resections contain further malignancy, which may suggest that surgeons have difficulty relocating the site of initial positive margin. Final positive margins are often at anatomic sites different than the initial positive margin. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:717-724, 2024.


Subject(s)
Carcinoma in Situ , Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Child, Preschool , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Kaplan-Meier Estimate , Margins of Excision , Hyperplasia
4.
Am J Otolaryngol ; 45(1): 104068, 2024.
Article in English | MEDLINE | ID: mdl-37832328

ABSTRACT

PURPOSE: To examine the relationship between comorbidities and the development of immediate post-operative complications in patients undergoing oral cavity composite resection (OCCR) with free flap (FF) reconstruction. MATERIALS AND METHODS: Retrospective analysis was completed on all consecutive OCCRs with FF reconstruction performed at a single quaternary care facility between 1999 and 2020. Comorbidities, immediate post-operative complications, patient demographics, and tumor characteristics were collected. Odds ratios (OR) with 95 % confidence intervals were calculated for associations between comorbidities and immediate post-operative complications. RESULTS: 320 patients who underwent OCCR with FF reconstruction were included. One hundred twenty-one (37.8 %) patients developed a post-operative complication during their initial hospital admission. The most common complications were non-pneumonia cardiopulmonary events (14.1 %), pneumonia (9.4 %), and wound infection (8.4 %). Other complications included flap compromise, bleeding, and fistula. On multivariate analysis, patients without comorbid conditions were less likely to develop a post-operative complication (OR 0.64; 0.41-0.98). Atrial fibrillation (OR 2.94; 1.17-7.39) and cerebrovascular disease (OR 2.28; 1.08-4.84) were associated with increased odds of developing any complications. Furthermore, cerebrovascular disease (OR: 2.33; 1.04-5.39) and peripheral vascular disease (OR: 2.7; 1.2-6.08) were independently associated with pneumonia. CONCLUSION: In this retrospective review of patients undergoing OCCR with FF reconstruction for oral cavity SCC, lack of identifiable comorbidities appeared to be protective for post-operative complications while atrial fibrillation and cerebrovascular disease were associated with increased odds of any complication. Pre-existing vascular disease was also associated with an increased risk of pneumonia.


Subject(s)
Atrial Fibrillation , Cerebrovascular Disorders , Free Tissue Flaps , Head and Neck Neoplasms , Pneumonia , Humans , Retrospective Studies , Mouth , Postoperative Complications/epidemiology , Pneumonia/epidemiology , Pneumonia/etiology
5.
Cell Genom ; 3(10): 100409, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37868034

ABSTRACT

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

6.
Otolaryngol Head Neck Surg ; 168(6): 1570-1575, 2023 06.
Article in English | MEDLINE | ID: mdl-36939627

ABSTRACT

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.


Subject(s)
Laryngostenosis , Humans , Constriction, Pathologic , Prospective Studies , Retrospective Studies , Laryngostenosis/surgery , Treatment Outcome
7.
Head Neck ; 45(1): 22-31, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36156327

ABSTRACT

BACKGROUND: Numerous challenges exist in determining surgical margin status. Communication between surgeons and pathologists is crucial for specimen orientation and accurate margin assessment. METHODS: A prospective study to determine feasibility of incorporating three-dimensional (3D) scanning into surgical pathology workflow was performed. A structured-light 3D scanner captured the photorealistic surface topography of fresh surgical specimens. Computer-aided design (CAD) software was used to document sites of margin sampling and sectioning. Surveys were distributed among faculty and staff stakeholders to assess feasibility. RESULTS: A series of 40 cases were 3D-scanned. Median image acquisition time was 8 min. The majority of respondents agreed that the experimental 3D system helped achieve clearer communication. 3D specimen maps assisted in the communication of a focally positive or close margin in 4 of 17 cases. CONCLUSIONS: Routine 3D scanning and specimen mapping is feasible and represents an innovative approach to intraoperative and final pathology documentation, margin analysis, and surgeon-pathologist communication.


Subject(s)
Computer-Aided Design , Surgeons , Humans , Prospective Studies , Communication
8.
Laryngoscope Investig Otolaryngol ; 7(5): 1499-1505, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36262464

ABSTRACT

Objective: The purpose of this study was to quantitatively compare the effectiveness of unilateral and bilateral botulinum toxin A (BTX-A) injections for mitigating undesirable weak/breathy voice quality and dysphagia for patients with adductor spasmodic dysphonia and/or essential tremor of voice (ETV). Methods: Data were collected from the medical records of 319 patients, yielding three treatment cohorts: patients who received an equal dose bilateral injection regimen (BL=) throughout their course of treatment at VUMC, patients who switched to a unilateral injection regimen (UL), and patients who switched to an unequal dose bilateral injection regimen (BL≠). Changes in length of improvement, duration of weak/breathy voice, and dysphagia severity were compared. Results: The BL = treatment group reported the longest duration of improved voice. Shorter periods of improved voice were reported at baseline by patients who later switched to UL or BL ≠ injection regimens. Patients receiving UL injections reported significantly reduced weak/breathy voice and dysphagia. Patients receiving BL ≠ injections reported increased length of improved voice; however, dysphagia symptoms increased. Ninety-two percent of patients with ETV switched to a UL regimen, with 61% of patients transitioning within the first three injections. Conclusions: Patients with pronounced dysphagia and extended periods of weak/breathy voice may benefit from a UL injection approach to mitigate side effects from BTX-A without sacrificing improved voice outcomes. For patients seeking to extend their length of improved voice, a BL ≠ injection regimen may be effective provided the adverse side effects from BTX-A are minimal. Patients with ETV may benefit from a UL injection approach at the outset of their course of treatment with BTX-A. Level of evidence: III.

9.
Int J Pediatr Otorhinolaryngol ; 162: 111329, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36198231

ABSTRACT

OBJECTIVE: To identify the prevalence of hearing impairment and associated risk factors in children living with human immunodeficiency virus (HIV) in Haiti. METHODS: A validated smartphone-based platform with pure-tone audiometry was used to screen 341 HIV-infected children for hearing impairment in Port-au-Prince, Haiti from March 2019 to September 2020. If screening was failed, a more comprehensive pure-tone audiometric evaluation was administered. Demographic, otologic, and HIV-related data were obtained through caregiver surveys and medical charts. Statistical analysis included univariate and multivariate logistic regression. RESULTS: Sixty (18%) of 341 HIV-infected children (ages 7-18 years) had hearing impairment. Of those failing their hearing assessment, 17 (28%) had moderate and 5 (8%) had severe or profound hearing loss. Hearing impairment was associated with frequent ear infections (OR 3.37; 95% CI 1.76-6.46; p < 0.001) and family history of hearing loss (OR 5.12; 95% CI 2.14-12.23; p = 0.001) but not viral load (OR 1.00; 95% CI 0.73-1.02; p = 0.28) or antiretroviral therapy duration (OR 0.96; 95% CI 0.79-1.17; p = 0.66). Only 35% of caregivers correctly perceived their child's hearing loss. CONCLUSIONS: Hearing impairment occurs at a higher prevalence in HIV-infected children in Haiti than what is expected for those living without HIV. Frequent ear infections were significantly associated with hearing loss while antiretroviral therapy duration was not. Despite their potential ototoxicity, antiretroviral therapies should be continued and may decrease incidence of otitis media. Low caregiver perception of hearing loss emphasizes the need for routine hearing screening for HIV-infected children.


Subject(s)
Deafness , HIV Infections , Hearing Loss , Otitis , Adolescent , Anti-Retroviral Agents , Audiometry, Pure-Tone , Child , Deafness/complications , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Haiti/epidemiology , Hearing Loss/diagnosis , Hearing Loss/epidemiology , Hearing Loss/etiology , Humans , Otitis/complications
10.
JAMA Oncol ; 8(9): 1323-1327, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35679040

ABSTRACT

Importance: Definitive diagnosis of a thyroid nodule in a child is obtained through diagnostic surgery. This is problematic because pediatric thyroid surgery is associated with higher rates of complications. In adults, preoperative molecular testing improves the management of thyroid nodules, but this has not been validated in children. Objective: To determine whether the molecular landscape of pediatric thyroid nodules is amenable to detection by a multigene genomic classifier (GC) test (ThyroSeq v3; Sonic Healthcare USA). Design, Setting, and Participants: This was a retrospective consecutive case series and GC testing of fine-needle aspiration (FNA) and formalin-fixed paraffin-embedded (FFPE) tissues from sequential pediatric thyroidectomies performed between January 2003 and December 2019 at a single tertiary academic medical center. The study included 95 patients (median [range] age, 16.3 [4.8 to 21.1] years; 75 [79%] female) who underwent surgery for a thyroid nodule. Interventions: A total of 118 thyroid nodule samples (95 FFPE, 23 companion FNAs) yielded informative next-generation sequencing data and multigene GC. Main Outcomes and Measures: The primary outcome was the determination of the pediatric thyroid molecular landscape. The secondary outcome was the diagnostic accuracy of the GC test for pediatric thyroid nodules. Results: Of the 95 patients, 75 (79%) were female, and the median (IQR) age was 16.3 (14.0-17.3) years. Next-generation sequencing confirmed the unique molecular landscape of malignant pediatric thyroid nodules (compared with adults), which is dominated by gene fusions (most commonly RET and NTRK), rare BRAF/RAS alterations, and no TP53 or TERT promoter pathogenic variants. Several poorly differentiated thyroid cancers harbored DICER1 variants. Benign nodules appeared to be almost exclusively associated with TSHR and DICER1 alterations. The test demonstrated a 96% sensitivity (95% CI, 87%-99%) and 78% specificity (95% CI, 64%-88%). The negative predictive value was 95% (95% CI, 88%-98%) and the positive predictive value was 83% (95% CI, 74-89%). The concordance of GC between 23 pairs of matched FFPE and FNA tissues was 96%. Conclusions and Relevance: The study results of this retrospective consecutive case series suggest that the molecular landscape of pediatric nodules is unique but remains amenable to molecular classification. The multigene GC test, with high sensitivity and reasonably high specificity, represents a potential addition to the diagnostic workup of children with thyroid nodules and may decrease the use of diagnostic surgery.


Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Adolescent , Adult , Child , DEAD-box RNA Helicases , Female , Formaldehyde , Genomics , Humans , Male , Proto-Oncogene Proteins B-raf , Retrospective Studies , Ribonuclease III , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/surgery , Thyroid Nodule/diagnosis , Thyroid Nodule/genetics , Thyroid Nodule/surgery
12.
Head Neck ; 44(5): 1079-1085, 2022 05.
Article in English | MEDLINE | ID: mdl-35150023

ABSTRACT

BACKGROUND: Acute oropharyngeal hemorrhage is a serious complication for patients with oropharyngeal squamous cell carcinoma (OPSCC), particularly in patients with a history of radiation therapy (RT). METHODS: Retrospective case series from at a tertiary care center for treated patients with HPV-positive OPSCC presenting with oropharyngeal hemorrhage. RESULTS: Median time from completion of chemoradiation to first hemorrhagic event was 186 days (range 66-1466 days). Seven patients (58%) required intervention to secure their airway. All patients were evaluated for endovascular intervention, six (50%) were embolized. Eight patients (67%) had a second hemorrhagic event; median time to second bleed was 22 days (range 3-90 days). CONCLUSIONS: Acute oropharyngeal hemorrhage is a sequelae following treatment for HPV-positive OPSCC. The majority of bleeds occurred within a year of completion of treatment. While more research is needed to determine optimal treatment paradigms, endovascular intervention should be considered, even if noninvasive imaging does not demonstrate active bleeding.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/complications , Hemorrhage/complications , Hemorrhage/therapy , Humans , Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/radiotherapy , Papillomavirus Infections/complications , Papillomavirus Infections/therapy , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/complications , Squamous Cell Carcinoma of Head and Neck/therapy
13.
Otolaryngol Head Neck Surg ; 166(2): 274-281, 2022 02.
Article in English | MEDLINE | ID: mdl-34030493

ABSTRACT

OBJECTIVE: To evaluate the associations between median household income (MHI) and area deprivation index (ADI) on postoperative outcomes in oral cavity cancer. STUDY DESIGN: Retrospective review (2000-2019). SETTING: Single-institution tertiary medical center. METHODS: MHI and ADI were matched from home zip codes. Main postoperative outcomes of interest were length of tracheostomy use, length of hospital stay, return to oral intake, discharge disposition, and 60-day readmissions. Linear and logistic regression controlled for age, sex, race, body mass index, tobacco and alcohol use history, primary tumor location, disease staging at presentation, and length of surgery. A secondary outcome was clinical disease staging (I-IV) at time of presentation. RESULTS: The cohort (N = 681) was 91.3% White and 38.0% female, and 51.7% presented with stage IV disease. The median age at the time of surgery was 62 years (interquartile range [IQR], 53-71). The median MHI was $47,659 (IQR, $39,324-$58,917), and the median ADI was 67 (IQR, 48-79). ADI and MHI were independently associated with time to return of oral intake (ß = 0.130, P = .022; ß = -0.092, P = .045, respectively). Neither was associated with length of tracheostomy, hospital stay, discharge disposition, or readmissions. MHI quartiles were associated with a lower risk of presenting with more advanced disease (Q3 vs Q1: adjusted odds ratio, 0.56 [95% CI, 0.32-0.97]). CONCLUSION: MHI is associated with oral cavity cancer staging at the time of presentation. MHI and ADI are independently associated with postoperative return to oral intake following intraoral tumor resection and free flap reconstruction.


Subject(s)
Free Tissue Flaps , Income/statistics & numerical data , Mouth Neoplasms/surgery , Oral Surgical Procedures , Plastic Surgery Procedures , Poverty Areas , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies
14.
Am J Otolaryngol ; 43(1): 103263, 2022.
Article in English | MEDLINE | ID: mdl-34653954

ABSTRACT

OBJECTIVES: During the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior. MATERIALS AND METHODS: Retrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic). RESULTS: During the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods. CONCLUSION: Head and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms.


Subject(s)
COVID-19/epidemiology , Squamous Cell Carcinoma of Head and Neck/epidemiology , Squamous Cell Carcinoma of Head and Neck/pathology , Aged , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Pandemics , Retrospective Studies , SARS-CoV-2 , Squamous Cell Carcinoma of Head and Neck/therapy , Tennessee/epidemiology
15.
Clin Cancer Res ; 28(5): 915-927, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34911681

ABSTRACT

PURPOSE: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. RESULTS: Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. CONCLUSIONS: Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil.


Subject(s)
Head and Neck Neoplasms , Neoadjuvant Therapy , Squamous Cell Carcinoma of Head and Neck , Head and Neck Neoplasms/drug therapy , Humans , Neoadjuvant Therapy/adverse effects , Nivolumab/therapeutic use , Papillomavirus Infections/complications , Squamous Cell Carcinoma of Head and Neck/drug therapy , Tadalafil/therapeutic use , Treatment Outcome , Tumor Microenvironment
16.
Article in English | MEDLINE | ID: mdl-34950879

ABSTRACT

INTRODUCTION: Approximately 8.9 million children in Sub-Saharan Africa have disabling hearing loss, accounting for 11% of the global child healthcare hearing costs. For children living in Low- and Middle-Income Countries (LMICs), 75% of hearing loss is preventable. METHODS: We evaluate the overall intervention and expansion costs of a humanitarian, pediatric hearing health and screening program in Malindi, Kilifi County, Kenya. A cost analysis is conducted from the provider perspective, identifying the mean cost incurred for each case of newly identified hearing loss. Estimates were made for 3 different cost scenarios. A one-way sensitivity analysis and probabilistic sensitivity analysis using Monte Carlo simulation determined the impact of variations in individual cost parameters. These results were used to project scale-up costs to achieve sub-county expansion of the program. RESULTS: 155 children ages 5 to 16 years old were screened, of which 5.8% were diagnosed with hearing impairment. The total cost for implementation in four schools was $6,783 USD, thus a mean cost of $212 per diagnosis of hearing loss. The highest proportion of costs were recurrent costs of resident travel (27.9%), capital costs for providing audiometric testing (25.3%), and equipment maintenance (18.7%). Expansion of an exclusively CHW-run program across all 77 primary public schools in Malindi is projected to be $130,573 (range $119,352 to $142,240). CONCLUSION: We provide relevant cost-estimation for an expansion of an intervention which identified higher than average rates of hearing loss. Humanitarian aid plays a key role in the sustainability and feasibility of expanding this program.

17.
Ear Nose Throat J ; : 1455613211037639, 2021 Jul 31.
Article in English | MEDLINE | ID: mdl-34338036

ABSTRACT

Chordomas are rare, malignant bone tumors that arise from embryological remnants of the notochord, typically affecting the skull base, mobile spine, and sacrum with uncommon metastasis to the larynx. Patients with metastasis to the larynx may present with slowly progressive dysphonia and dyspnea. Here, we report an organ-preservation treatment strategy for a patient with widely metastatic extra-axial chordoma presenting with airway compromise who was found to have a new metastasis to the cricoid cartilage.

18.
Am J Otolaryngol ; 42(4): 102992, 2021.
Article in English | MEDLINE | ID: mdl-33640803

ABSTRACT

INTRODUCTION: Neuroendocrine tumors of the head and neck are rare and arise either from epithelial or neuronal origin. Debate continues over the classification systems and appropriate management of these pathologies. OBJECTIVE: By investigating a small set of cases of high grade epithelial-derived neuroendocrine tumors of the head and neck (neuroendocrine carcinomas or NEC) from one institution, we compare survival rates of NEC of the head and neck to pulmonary NEC. METHODS: We identified patients from pathology records with neuroendocrine carcinomas of the head and neck and retrospectively collected clinical data as well as immunohistochemical (IHC) staining data. RESULTS: We identified 14 patients with NEC, arising from the parotid (n = 5), nasal cavity (n = 4), larynx (n = 2), and other regions (n = 2). One additional patient had NEC arising in two sites simultaneously (parotid and nasal). Staining patterns using IHC were relatively consistent across specimens, showing reactivity to chromogranin and synaptophysin in 73% and 100% of specimens, respectively. Treatment courses varied across patients and included combinations of surgery, chemotherapy, and/or radiation. The overall survival rate at 1, 2, and 5 years of these patients was 56%, 56%, and 43% with a mean follow-up time of 2.12 years. CONCLUSION: Compared to NEC arising in the lung, this subset of patients had better survival rates, but worse survival rates than the more common squamous cell carcinoma of the head and neck.


Subject(s)
Carcinoma, Neuroendocrine/mortality , Head and Neck Neoplasms/mortality , Aged , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/therapy , Combined Modality Therapy , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/therapy , Survival Rate
19.
Head Neck ; 43(6): 1780-1787, 2021 06.
Article in English | MEDLINE | ID: mdl-33586258

ABSTRACT

BACKGROUND: Head and neck surgical oncology and reconstruction are uniquely suited to address burdens of disease in underserved areas. Since these efforts are not well known in our specialty, we sought to understand global outreach throughout our society of surgeons. METHODS: Survey distributed to members of the American Head and Neck Surgery involved in international humanitarian head and neck surgical outreach trips. RESULTS: Thirty surgeons reported an average of seven trips to over 70 destinations. Identification of candidates, finances, on-site patient care, complications, long-term post-surgical care, ethics, and educational goals are reported. We report a success rate of 90% on 125 free flaps performed in these settings. CONCLUSIONS: The effort to answer the call for alleviating the global burden of surgical disease is strong within our specialty. There is a shared focus on humanitarian effort and teaching. Ethics of high resource surgeries such as free flap reconstruction remains controversial.


Subject(s)
Free Tissue Flaps , Head and Neck Neoplasms , Plastic Surgery Procedures , Surgeons , Head and Neck Neoplasms/surgery , Humans , Neck/surgery , Retrospective Studies , Surveys and Questionnaires
20.
Ann Otol Rhinol Laryngol ; 130(10): 1116-1124, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33629608

ABSTRACT

OBJECTIVES: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. METHODS: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. RESULTS: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. CONCLUSIONS: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.


Subject(s)
Laryngoscopy/methods , Laryngostenosis/surgery , Social Determinants of Health , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Recurrence , Time Factors , Treatment Outcome , United States
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