Search

A prior history of thyroid and non-thyroid malignancies has traditionally been an exclusion criterion in patients with anaplastic thyroid carcinoma (ATC) seeking to enroll in clinical trials. In this study, we examined the impact of prior malignancies on overall survival in patients diagnosed with ATC.In our retrospective cohort study, we identified 451 patients with ATC treated at MD Anderson between 2000-2019. Clinical and pathological information were obtained through chart review. Survival analyses were conducted using Kaplan-Meier method and multivariable Cox proportional hazard models.A history of clinically documented prior differentiated thyroid carcinoma (DTC) was reported in 14% of patients with ATC (n=62), most commonly papillary thyroid carcinoma (81%, n=50). The median time from diagnosis of prior DTC to ATC diagnosis was 3.5 years (range: 6 months to 35 years). Concomitant DTC was found on pathology in a higher proportion of patients (52%, n=234). A history of non-thyroid cancer was reported in 23% of patients (n=102), where 19% (n=87) had one, 2% (n=10) had two, and 1% (n=5) had three prior cancers. The median time from diagnosis of prior non-thyroid cancer to ATC diagnosis was 8 years (range: 3 months to 53 years). The most common prior non-thyroid cancers were non-melanoma skin (28.4%), prostate (19.6%), and breast cancer (16.7%). In a subgroup analysis performed in patients with available tumor mutation information (n=183), the frequency of detected tumor driver mutations (BRAF, RAS, TP53) was not significantly different between patients with ATC with and without a history of prior non-thyroid cancer. On multivariate analysis after adjusting for age and overall stage, prior DTC, concomitant DTC, and prior non-thyroid cancers all had no significant impact on overall survival.The presence of prior malignancy does not significantly impact overall survival in patients with ATC. Revision of eligibility criteria for enrollment of patients with ATC into clinical trials is warranted.

Background: Neck dissections (ND) are a routine procedure in head and neck oncology. Given the post-operative functional impact that some patients experience, it is imperative to identify and track quality of life (QoL) symptomatology in order to tailor each patient’s therapeutic needs. To date, there is no validated francophone questionnaire for this patient-population. We therefore sought to translate and validate the Neck Dissection Impairment Index (NDII) in French. Methods: A three-phased approach was used. Phase 1: The NDII was translated from English to French using a “forward and backward” translational technique following international guidelines. Phase 2: A cognitive debriefing session was held with ten French-speaking otolaryngology patients to evaluate understandability and acceptability. Phase 3: The final version was administered prospectively to 30 patients with prior history of ND and 30 control patients. These patients were asked to complete the questionnaire 2 weeks after their first response. Test-retest reliability was calculated with Spearman’s correlation. Internal consistency was elicited using Cronbach’s alpha. Results: NDII was successfully translated and validated to French. Cronbach’s alpha revealed high internal consistency (0.92, lower 95% CL 0.89). The correlation for test-retest validity were strong or very-strong (0.61-0.91). Conclusion: NDII is an internationally recognized QoL tool for the identification of ND-related impairments. This validated French version will allow clinicians to adequately assess the surgery-related QoL effect of neck surgery in the French-speaking population, while allowing French institutions to conduct and/or participate in multi-site clinical trials requiring the NDII as an outcome measure.

NA.

Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015.Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One-year overall survival was 84%; 1-year locoregional disease-free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes.Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity.

BackgroundDespite the use of aggressive multimodality treatment, most anaplastic thyroid carcinoma (ATC) patients die within a year of diagnosis. Although the combination of BRAF and MEK inhibitors has recently been approved for use in BRAF-mutated ATC, they remain effective in a minority of patients who are likely to develop drug resistance. There remains a critical clinical need for effective systemic agents for ATC with a reasonable toxicity profile to allow for rapid translational development.Material and MethodsTwelve human thyroid cancer cell lines with comprehensive genomic characterization were used in a high-throughput screening (HTS) of 257 compounds to select agents with maximal growth inhibition. Cell proliferation, colony formation, orthotopic thyroid models, and patient-derived xenograft (PDX) models were used to validate the selected agents.ResultsSeventeen compounds were effective, and docetaxel, LBH-589, and pralatrexate were selected for additional in vitro and in vivo analysis as they have been previously approved by the US Food and Drug Administration for other cancers. Significant tumor growth inhibition (TGI) was detected in all tested models treated with LBH-589; pralatrexate demonstrated significant TGI in the orthotopic papillary thyroid carcinoma model and 2 PDX models; and docetaxel demonstrated significant TGI only in the context of mutant TP53.ConclusionsHTS identified classes of systemic agents that demonstrate preferential effectiveness against aggressive thyroid cancers, particularly those with mutant TP53. Preclinical validation in both orthotopic and PDX models, which are accurate in vivo models mimicking tumor microenvironment, may support initiation of early-phase clinical trials in non-BRAF mutated or refractory to BRAF/MEK inhibition ATC.

Introduction Anaplastic thyroid cancer (ATC) is rare with a poor prognosis. There are no approved treatments for non-BRAF-mutated ATCs, leading to an unmet need. Phase II studies of single-agent lenvatinib or immunotherapy showed minimal benefit (lenvatinib: overall response rate (ORR) 2.9%, progression free survival (PFS) 2.6 months, overall survival (OS) 3.2 months; spartalizumab: ORR 19%, PFS 1.7 months, OS 5.9 months). Synergism between lenvatinib and pembrolizumab (L/P) has been reported. We sought to assess the efficacy and safety of L/P in ATC. Methods Thisis a retrospective, single-center study of ATC patients treated with L/P, between 1/2015-10/2021. L/P had to be started before first restaging. Those with pembrolizumab added at the time of progression on lenvatinib alone were excluded. The endpoints were ORR and PFS (primary) and OS and safety (secondary). Response evaluation was assessed by a single radiologist using RECIST v1.1. Treatment start date was the date of either lenvatinib or pembrolizumab initiation. Results 18 patients were included: 61% men; median age 64; initial stage: IVA (17%), IVB (11%), IVC (72%); common distant metastases: lung (83%), mediastinum (39%), bone (22%). Previous therapies: surgery (78%), chemoradiation (39%), cytotoxic chemotherapy (11%), palliative neck radiation (17%), BRAF-targeted therapy (6%), and immunotherapy (6%). All patients had mutation testing, and the common included TP53 (67%), PTEN (50%), TERTp (39%), NF1 (28%), RAS (22%), PIK3CA (17%), BRAF-V600E (6%). 11/12 tested tumors had a PDL-1 score >1%. Lenvatinib was started at 14-24 mg daily. With respect to lenvatinib, pembrolizumab was started from -14 to +49 days (median +6 days) at a fixed dose of 200 mg every 3 weeks. ORR was evaluable in 12 patients (outside hospital restaging scans unavailable in 6 patients): 1/12 (8%) confirmed complete response, 7/12 (58%) partial response (3 confirmed), 2/12 (17%) stable disease, and 2/12 (17%) progressive disease. The median PFS was 4.1 months (95% CI, 2.2 to NA), with treatment durations ranging from 0.5-33.5 months. The median OS of the 18 patients was 6.2 months (95% CI, 4.6 to NA). Respective 12-month PFS and OS rates were 25% and 22%. Grade III/IV toxicities were fatigue (22%); anorexia, weakness, arthralgia, dry mouth, pneumonitis (6%, each). AEs leading to death were pulmonary hemorrhage (17%), gastrointestinal bleed, pulmonary embolism (6%, each). Lenvatinib dose reduction, interruption, and discontinuation rates were 28%, 6%, and 28%, respectively. Pembrolizumab dose interruption and discontinuation rates were 6% and 11%, respectively. Conclusions The combination L/P had an ORR of 66%. Although most responses were short-lived, a quarter of patients benefited for more than 1 year. The ORR, PFS, and OS were better than lenvatinib alone. The toxicity profile was as expected. Our results represent the largest single-institution experience thus far with L/P in ATC and warrant further investigation (NCT04171622). Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Anaplastic thyroid cancer (ATC) remains one of the most aggressive and deadliest malignancies. Traditionally, treatment consisted of cytotoxic chemotherapy and radiation therapy, with or without surgery, although a large proportion of patients were often directed toward palliative/hospice care. In the past decade, significant advances have been made through the advent of targeted therapies and immunotherapy. For patients with targetable disease and considerable treatment response, surgery and other multidisciplinary adjuvant therapies can now be considered. Overall, the era of untreatable ATC is progressively being replaced by highly personalized multidisciplinary therapies, actively shifting the treatment pendulum of this disease.

BACKGROUND: Lactate dehydrogenase (LDH) is a critical metabolic enzyme. LDH A (LDHA) overexpression is a hallmark of aggressive malignancies and has been linked to tumour initiation, reprogramming and progression in multiple tumour types. However, successful LDHA inhibition strategies have not materialised in the translational and clinical space. We sought to develop a rational strategy for LDHA suppression in the context of solid tumour treatment. METHODS: We utilised a doxycycline-inducible short hairpin RNA (shRNA) system to generate LDHA suppression. Lactate and LDH activity levels were measured biochemically and kinetically using hyperpolarised (13)C-pyruvate nuclear magnetic resonance spectroscopy. We evaluated effects of LDHA suppression on cellular proliferation and clonogenic survival, as well as on tumour growth, in orthotopic models of anaplastic thyroid carcinoma (ATC) and head and neck squamous cell carcinoma (HNSCC), alone or in combination with radiation. RESULTS: shRNA suppression of LDHA generated a time-dependent decrease in LDH activity with transient shifts in intracellular lactate levels, a decrease in carbon flux from pyruvate into lactate and compensatory shifts in metabolic flux in glycolysis and the Krebs cycle. LDHA suppression decreased cellular proliferation and temporarily stunted tumour growth in ATC and HNSCC xenografts but did not by itself result in tumour cure, owing to the maintenance of residual viable cells. Only when chronic LDHA suppression was combined with radiation was a functional cure achieved. CONCLUSIONS: Successful targeting of LDHA requires exquisite dose and temporal control without significant concomitant off-target toxicity. Combinatorial strategies with conventional radiation are feasible as long as the suppression is targeted, prolonged and non-toxic.

Utilization of biologic skin substitutes for the management of soft tissue defects as an alternative to autologous skin grafts has expanded over the past 2 decades. The purpose of this case series study was to report our experience with Integra® bilayer wound matrix for reconstruction of intraoral oncologic defects. Case records of 6 patients with intraoral oncologic defects reconstructed with Integra® bilayer wound matrix were retrospectively reviewed. The surgical defect location, size, and time to removal of surgical splint varied. Clinically, normal oral epithelialization was noted for all patients. One patient demonstrated a small area of dehiscence and bone exposure after adjuvant radiation therapy which resolved with minimal intervention. Integra bilayer wound matrix is a viable and versatile option for reconstruction of intraoral oncologic surgical defects. Further exploration of wound healing with Integra® matrix, surgical techniques, and cost‐effectiveness is advocated., Integra® bilayer wound matrix is a viable and versatile option for reconstruction of small to large intraoral oncologic surgical defects on movable and nonmoveable mucosa.

BACKGROUND Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS). METHODS A double-blind, randomized, placebo-controlled trial was completed in a single tertiary-care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high-volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected. RESULTS A total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4-month post-ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22-item Sino-Nasal Outcome Test score improvements than patients on placebo (18 vs -0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin-exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8). CONCLUSION Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

BACKGROUND The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug. METHODS A total of 48 adults with refractory CRS were enrolled in a double-blind, randomized, placebo-controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High-resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis. RESULTS From initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate [FDR] < 0.05) obtained from the differential abundance analysis. This was not observed in placebo-treated patients. By the end of treatments, azithromycin-treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo. CONCLUSION A 4-month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

Author(s): MD Anderson Head and Neck Surgery Treatment Guidelines Consortium; Consortium members; Maniakas, Anastasios; Jozaghi, Yelda; Zafereo, Mark E; Sturgis, Erich M; Su, Shirley Y; Gillenwater, Ann M; Gidley, Paul W; Lewis, Carol M; Diaz, Eduardo; Goepfert, Ryan P; Kupferman, Michael E; Gross, Neil D; Hessel, Amy C; Pytynia, Kristen B; Nader, Marc-Elie; Wang, Jennifer R; Lango, Miriam N; Kiong, Kimberley L; Guo, Theresa; Zhao, Xiao; Yao, Christopher MKL; Appelbaum, Eric; Alpard, Jennifer; Garcia, Jose A; Terry, Shawn; Flynn, Jill E; Bauer, Sarah; Fournier, Danielle; Burgess, Courtlyn G; Wideman, Cayla; Johnston, Matthew; You, Chenxi; De Luna, Rolando; Joseph, Liza; Diersing, Julia; Prescott, Kaitlin; Heiberger, Katherine; Mugartegui, Lilian; Rodriguez, Jessica; Zendehdel, Sara; Sellers, Justin; Friddell, Rebekah A; Thomas, Ajay; Khanjae, Sonam J; Schwarzlose, Katherine B; Chambers, Mark S; Hofstede, Theresa M; Cardoso, Richard C; Wesson, Ruth Aponte; Won, Alex; Otun, Adegbenga O; Gombos, Dan S; Al-Zubidi, Nagham; Hutcheson, Katherine A; Gunn, G Brandon; Rosenthal, David I; Gillison, Maura L; Ferrarotto, Renata; Weber, Randal S; Hanna, Ehab Y; Myers, Jeffrey N; Lai, Stephen Y | Abstract: BackgroundCOVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel.MethodsThe MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular.RecommendationsEach subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred.ConclusionThese guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

BACKGROUND Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real-time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states. METHODS Twenty-seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis. RESULTS Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described. CONCLUSIONS Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.

Background TMPRSS2, ACE2 and TMPRSS11D are genes coding for proteins necessary for SARS-CoV-2 activation, infection and transmission. Once SARS-CoV-2 enters the host cell, it leads to an exaggerated inflammatory state of the lungs mediated by overexpressed TNF-, IL-6, and IL-1β. We assessed azithromycin's effect on the aforementioned genes and their associated pathways to evaluate its potential use as a possible treatment. Objective Confirm the role azithromycin may play in the regulation of pathways and genes involved in inflammation and SARS-CoV-2 activation and cell-to-cell transmission. Methods Primary airway nasal epithelial cells collected from nasal biopsies of three patients with chronic rhinosinusitis (CRS) were primary cultured and treated or not with 10µg of azithromycin. RNA was extracted from these samples and analyzed using a microarray chip. Differential gene expression profiles and gene set enrichment analysis (GSEA) were obtained between both groups. Results Cell cultures treated with 10µg of azithromycin significantly downregulated receptor-mediated endocytosis canonical pathways involving TMPRSS2 and TMPRSS11D genes. Downregulated inflammation-associated genes included IL-1β and NDST1. Interestingly, numerous genes in the cholesterol biosynthesis pathway were significantly upregulated as part of a potential process named drug-induced phospholipidosis (DLP). Conclusions This proof of concept demonstrates azithromycin downregulates pathways involving serine proteases TMPRSS2 and TMPRSS11D required for SARS-CoV-2 activation and its cell-to-cell transmission while downregulating pro-inflammatory cytokine IL-1β, NDST-1 and their associated pathways. This may help reduce the characteristic excessive respiratory epithelial inflammation, key feature of SARS-CoV-2 infection. Finally, azithromycin may also decrease available cholesterol in lipid rafts which may hinder SARS-CoV-2 infection.

The incidence of thyroid cancer has been increasing over the past few decades, and although the majority of cases are localized to the thyroid, the number of patients with lateral neck disease at first presentation has increased. Although an abundance of literature exists about the patterns of metastasis for thyroid carcinoma, some controversy remains surrounding the extent of neck dissection in patients who have suspicious or confirmed metastasis to the lateral neck. However, there is near universal agreement that lateral neck dissection for metastatic thyroid cancer should follow principles of compartment-based neck dissection with resection of involved and at-risk neck levels, most commonly a level II through VB selective lateral neck dissection. This chapter will address the indications and considerations of a lateral neck dissection for thyroid cancer, followed by the surgical approach for an oncologic resection of lateral neck disease.

IMPORTANCE: Anaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated. OBJECTIVE: To evaluate rates of OS in patients with ATC over the last 2 decades. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019. MAIN OUTCOMES AND MEASURES: Overall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery. RESULTS: Of 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P

Long-term transtympanic tube insertions for chronic middle ear disease are associated with high rates of complications. The objective of this study was to examine the clinical outcomes achieved with an alternate technique, the subannular tube insertion, by determining mean tube lifespan, cumulative incidence of post-operative events and complications, audiometric changes and risk factors associated with earlier tube extrusion in the pediatric population.A retrospective chart review of all patients operated for subannular tube insertion between January 2007 and 2013 was conducted in a single pediatric tertiary care center. Exploratory Cox regression analysis was performed to identify potential risk factors.A total of 1014 tubes from 459 patients were included in the study. Mean subannular tube lifespan was 41.3 months with median time of 35.0 months. Cumulative incidence of post-operative events in decreasing frequency were otorrhea (21.7%), tube blockage (16.0%), tympanic membrane retraction (12.5%), otitis media with effusion (10.0%), acute otitis media (6.4%), perforation (4.6%) and cholesteatoma formation (1.1%). For patients with available pre- and post-operative audiograms, mean air-bone gap improved from 19.5 dB to 7.0 dB after subannular tube insertion (p 0.01). Increasing age and previous subannular tube insertion carried hazard ratios of 1.029 (p 0.01) and 1.749 (p 0.01) for tube extrusion respectively, while craniofacial anomalies and concomitant tympanoplasty at the time of tube insertion had hazard ratios of 0.795 (p 0.01) and 0.680 (p = 0.03).Subannular tube insertion appears to be a safe and effective alternate technique for middle ear ventilation in cases of intractable disease.

Thyroid disease is one of the most common pathologies in the world, with two of the most clinically important subgroups being iodine deficiency and thyroid goiter, and thyroid cancer. This review looks at the current state of thyroid disease in the world and evaluates the future direction in terms of thyroid disease treatment and prevention. Several of the most impactful epidemiologic studies are presented and analyzed, as well as a brief overview of the current socioeconomic burden of disease.

Objective Rhinoliquorrhea is defined as a cerebrospinal fluid leakage from the nose. Our objective in this study is to determine the reduction of rhinoliquorrhea rates by Eustachian tube (ET) obliteration in the context of a translabyrinthine approach performed following vestibular schwannoma (VS) excision. Materials and methods This is a prospective study achieved in a tertiary-care center where the chart review revealed 94 VS operated by the translabyrinthine approach between 2009 and 2015. There were 40 males and 54 females aged from 28-76 years. The only exclusion criterion was a previous history of cranial surgery. ET obliteration was systematically executed when the petrous apex pneumatization level was at least 2 of 4. Our main outcome measure was the development of rhinoliquorrhea. Results Eighty-eight patients underwent ET obliteration and were followed for an average of 2.6±1.2 years. Rhinoliquorrhea was reported in 1.14% of the patients having had an ET obliteration. When compared to our previous sample of patients operated with a translabyrinthine approach, it represents a reduction of 84%. Conclusion Obliteration of the ET is a fast and simple procedure that reduces the rate of rhinoliquorrhea. We therefore recommend its use, specifically in cases of petrous apex pneumatization levels 2-4.

Background Perioperative practices in thyroid surgery vary from one specialty, institution, or country to the next. We evaluated the preoperative, intraoperative, and postoperative practices of thyroid surgeons focusing on preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization duration, among others. Methods A survey was sent to 7 different otolaryngology and endocrine/general surgery associations. Results There were 965 respondents from 52 countries. Surgeon-performed ultrasound is practiced by more than one third of respondents. Otolaryngologists perform preoperative and postoperative vocal cord evaluation more often than endocrine/general surgeons (p < .001). Sixty percent of respondents either never place drains or place drains

Background: Well-differentiated thyroid cancer (DTC) presents at a more advanced stage in men than in women, and the mortality in men is higher than that in women. However, it is not clear whether ...

Precision medicine initiatives for chronic rhinosinusitis (CRS) management suggest tailoring treatment to the patient's individual disease profile; however, serum biomarkers for evaluation of disease activity or predicting response to therapy are lacking in CRS. Epithelial-to-mesenchymal transition (EMT) has been described as a component of barrier dysfunction in CRS. SPARC (secreted protein acidic and rich in cysteine) is a marker of EMT that has previously been identified in sinus epithelium by gene expression profiling. We wished to determine if SPARC could represent a serum biomarker for CRS by verifying (1) if SPARC could be detected in serum, (2) whether levels were sensitive to disease burden reduction following surgery, and (3) if it could predict response to therapy.Prospective.Tertiary care center.Patients with CRS undergoing endoscopic sinus surgery (ESS).Twenty-six patients undergoing ESS for CRS were prospectively recruited. Serum was collected at the time of surgery and 4 months following ESS and SPARC level measured using enzyme-linked immunosorbent assay. Postoperative outcome was characterized as "remission" or "unfavorable" based on symptomatology and endoscopy.SPARC could be detected and measured in serum in all subjects. Following ESS, SPARC levels decreased by 33% ( P = .005) but did not predict evolution at 4 months postsurgery ( P = .94).SPARC may be an interesting serum biomarker of disease activity in CRS, as it can be reliably measured and decreases following successful reduction of disease burden after surgery. However, it does not predict post-ESS evolution, suggesting that the link between EMT and outcome is not linear.

Background Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust pre-clinical models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models are thought to closely resemble patient tumors by preserving the tumor microenvironment, making them excellent pre-clinical models for drug response evaluation. We used two distinct ATC PDX models and evaluated drug response following a high-throughput screening (HTS). Methods A HTS, using NCI's Approved Oncology Set V (n=112) and a custom collection of agents (n=145), was conducted on patient-derived thyroid cancer cell lines. To identify the most effective drugs, we selected individual agents with maximal growth inhibition at each dose level relative to wells examined on the day of treatment (top 25th percentile) and subsequently used non-parametric statistics to compare effect size with other drugs and controls. This allowed us to identify classes of systemic agents which demonstrated preferential effectiveness against ATC cell lines and certain mutations. Following our prior successful work on orthotopic xenograft models, we used two established ATC PDX models, HOSC68 and HOSC199, harboring distinct genetic profiles and expanded each of them into 50 athymic mice. HOSC68 has a BRAFV600E and a TP53 mutation, while HOSC199 is wild-type for both genes, but has an HRAS mutation. Equal pieces of 4 × 4mm of tumor were transplanted subcutaneously at the level of the right flank. Following tumor growth, the mice were separated into four treatment arms. All mice received their treatment intraperitoneally following standard drug administration schedules. Tumor volume was measured on the first day of treatment and every two to three days thereafter until trial completion (14 days). Drug response was analyzed by evaluating percent tumor growth inhibition (TGI). Mouse weight was recorded over time to evaluate treatment toxicity. Following treatment completion, tumors were surgically retrieved and evaluated morphologically and histologically. Results Microtubule inhibitors, antimetabolites, and HDAC inhibitors were some of the most effective drug classes identified against ATC cell lines. Specifically, in this study, mice were treated with control (CTR), Docetaxel (DOC)-microtubule inhibitor, Pralatrexate (PRA)-antimetabolite, and LBH-589 (LBH)-HDAC inhibitor. Forty-four HOSC68 and 43 HOSC199 mice successfully grew tumor and were included in the trial. Compared to CTR, HOSC68 mice treated with DOC showed a 37% TGI (p=0.04), 88% with PRA (p&lt0.001), and 83% with LBH (p&lt0.001), while HOSC199 mice had a 2% TGI with DOC (p=0.56), 76% with PRA (p=0.005), and 83% with LBH (p=0.002). PRA and LBH were significantly more toxic than DOC and CTR (p&lt0.001) in HOSC68 mice, while all three drugs were significantly more toxic than CTR in the HOSC199 mice (p&lt0.001). Conclusion We report the first large-scale evaluation of drugs identified through a HTS analysis on ATC PDX models. This trial demonstrates the feasibility of using this platform for in vivo drug testing, while providing an avenue for future drug testing and resistance evaluation, as well as personalized therapeutics development. Citation Format: Anastasios Maniakas, Abdallah S. Mohamed, Ying C. Henderson, Hu Hei, Shaohua Peng, Diana Bell, Michelle D. Williams, Steve Scherer, David A. Wheeler, Gary L. Clayman, Mark Zafereo, Jennifer R. Wang, Maria E. Cabanillas, Clifford Stephan, Faye M. Johnson, Stephen Y. Lai. In vivo drug response evaluation in anaplastic thyroid cancer patient-derived tumor xenografts following high-throughput screening [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1662.

BACKGROUND: Symptoms of Eustachian tube (ET) dysfunction are seldom assessed in patients with chronic rhinosinusitis (CRS). The Sino-Nasal Outcome Test (SNOT-22) quality-of-life tool includes two questions that specifically screen for symptoms of ET dysfunction (Ear Fullness; Ear Pain). OBJECTIVE: The purpose of this study was to determine the extent to which these ET symptoms were present in patients with CRS, and whether these symptoms respond to endoscopic sinus surgery (ESS). METHODOLOGY: SNOT-22 data collected prospectively at time of recruitment into IRB-approved clinical trials or case-control studies in CRS was pooled to provide a cross section of the frequency and severity of ET dysfunction. When applicable to the trials, the SNOT-22 was repeated at least 3 months following ESS. RESULTS: Five trials rendering 131 patients were available for assessment. The control group comprised of 251 participants from two case-control studies. Ear Fullness of equal/greather than 1 was reported in 80/131 CRS patients compared to 45/251 control patients. Ear Pain of equal/greather than 1 was reported in 39/131 CRS patients compared to 33/251 control patients. Following ESS, mean Ear Fullness and Ear Pain scores decreased to 1.17 and 0.73, respectively. CONCLUSION: Symptoms suggestive of ET dysfunction are frequent in CRS, and for most patients the symptoms will decrease post-ESS to a level comparable with a non-CRS population. Patients whose ET symptoms do not respond to ESS may represent a target population for emerging therapeutic options for ET dysfunction.

Background Superior canal dehiscence (SCD) is a benign condition in which a surgical treatment may be considered depending on the patients’ tolerance of their symptoms. In this study, we aim to identify driving factors behind the patients’ choice of a surgical management over watchful waiting. Methods Sixty-two patients with cochlear and/or vestibular symptoms and a temporal bone high-resolution CT (HRCT) scan showing SCD were included in the study. All patients have been offered either surgical management or watchful waiting. Results Of these, 28 elected surgery and 34 declined it. The operated group showed more cochlear (6.6 vs. 2.4) symptoms than the non-operated group (P < 0.001) except for hypoacousis, but no significant difference (P = 0.059) was found for the number of vestibular symptoms between both groups (3.4 vs. 1.1). Footstep and eating hyperacousis were both present in 57.1% of operated vs. 3% of non-operated patients (P < 0.001). Oscillopsia with effort and with walking was found in 50% and 35.7% of operated patients, respectively, but none in the non-operated group (P < 0.001). Hearing tuning fork at malleolus and Valsalva and pneumatic speculum induced vertigo showed a statistically significant difference between the two groups (P = 0.003, P < 0.001, P = 0.010 respectively). Cervical vestibular-evoked myogenic potential (cVEMP) thresholds, air and bone conduction thresholds, and mean air-bone gap (ABG) were similar in the two populations (P > 0.05). The average dehiscence size was 4.7 mm (2.0 - 8.0 mm) and 3.8 mm (1.3 - 7.7 mm) in the operated and non-operated patients, respectively (P = 0.421). Conclusions The natures of cochleovestibular signs and symptoms were shown to be key factors in patients’ choice of a surgical management whereas paraclinical tests seem to be less significant in the patients’ decision for a surgical treatment.

Review the useful hearing preservation and tumor control outcomes of microsurgery (MS), stereotactic radiation (SR), conservative management (CM), and chemotherapy (ChT) for Neurofibromatosis type 2 vestibular schwannomas.Ovid MEDLINE was used to conduct a thorough search of English-language publications dating from 1948 to February 2013.Patients must have had useful hearing at diagnosis and treated with one of the 4 treatments as their primary therapy. All sporadic vestibular schwannoma cases were excluded.A total of 19 articles were reviewed. Hearing preservation was defined as unchanged or improved useful hearing. Tumor control was defined as no change in size or tumor regression for SR, CM, and ChT-treated cases, and as no recurrence for MS treated cases.Microsurgery seems to have the worse overall results, while SR has very good tumor control with poor useful hearing preservation. If a patient qualifies for CM, he is likely to show the most satisfactory results with the least treatment available. A close follow-up on ChT clinical trials and possible side-effects is warranted as preliminary short-term results are quite favorable. Additional long-term studies are required for a better understanding of this disease.

Radioactive iodine (RAI) remnant ablation in low-risk papillary thyroid cancer (PTC) is controversial. Current patient selection guidelines recommend the use of postoperative stimulated thyroglobulin (stim-Tg), neck dissections, and sonography but fail to include sentinel lymph node biopsy (SLNB). The objective of this study was to evaluate the correlation between SLNB status and postoperative stimulated thyroglobulin as a surrogate marker of clinical outcome.Retrospective chart review of low-risk PTC patients who underwent a total thyroidectomy with SLNB at the McGill Thyroid Cancer Center. SLNBs were obtained using methylene blue dye. Biochemical measurements were acquired between 4 and 12 weeks postoperatively. Statistical analyses were performed using logistic regression models and receiver operating characterisitc (ROC) curves. A P-value.05 was considered significant.Ninety-six patients were included in this study. The positive SLNB rate was 14.6%. The mean postoperative Tg level was 1.41 μg/L. There were no significant correlations between the SLNB and the covariates analyzed (age, gender, histology, tumor size, and thyrotropin levels). Patients with negative SLNB were significantly more likely to have a lower stim-Tg (P.0001). When postoperative Tg was analyzed as a categorical variable, a threshold of1 μg/L was significantly associated with a negative SLNB, with a sensitivity and specificity (determined by ROC curves) of 0.86 and 0.88, respectively.There exists a correlation between SLNB and postoperative Tg. This creates the possibility of a new approach to RAI administration among low-risk PTC patients incorporating SLNB to the current guidelines.

Perioperative practices in thyroid surgery vary from one specialty, institution, or country to the next. We evaluated the preoperative, intraoperative, and postoperative practices of thyroid surgeons focusing on preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization duration, among others.A survey was sent to 7 different otolaryngology and endocrine/general surgery associations.There were 965 respondents from 52 countries. Surgeon-performed ultrasound is practiced by more than one third of respondents. Otolaryngologists perform preoperative and postoperative vocal cord evaluation more often than endocrine/general surgeons (p.001). Sixty percent of respondents either never place drains or place drains50% of the time in thyroid lobectomies (43% for total thyroidectomies). Outpatient thyroid surgery is most frequently performed by surgeons in the United States (63%).This epidemiologic study is the first global thyroid survey of its kind and clearly demonstrates the variability and evolving trends in thyroid surgery. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1296-1305, 2017.

While thyroidectomy is considered a safe surgery, dedicated tools facilitating tissue identification during surgery could improve its outcome. The most common complication following surgery is hypocalcaemia, which results from iatrogenic removal or damage to parathyroid glands. This research project aims at developing and validating an instrument based on optical microscopy modalities to identify tissues in real time during surgery. Our approach is based on a combination of reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) to obtain multi-scale morphological contrast images. The orthogonal field of views provide information to navigate through the sample. To allow simultaneous, synchronized video-rate imaging in both modalities, we designed and built a dual-band wavelength-swept laser which scans a 30 nm band centered at 780 nm and a 90 nm band centered at 1310 nm. We built an imaging setup integrating a custom-made objective lens and a double-clad fibre coupler optimized for confocal microscopy. It features high resolutions in RCM (2µm lateral and 20 µm axial) in a 500 µm x 500 µm field-of-view and a larger field-of-view of 2 mm (lateral) x 5 mm (axial) with 20 µm lateral and axial resolutions in OCT. Imaging of ex vivo animal samples is demonstrated on a bench-top system. Tissues that are visually difficult to distinguish from each other intra-operatively such as parathyroid gland, lymph nodes and adipose tissue are imaged to show the potential of this approach in differentiating neck tissues. We will also provide an update on our ongoing clinical pilot study on patients undergoing thyroidectomy.

The objective of this review is to compare the symptomatological evolution following conservative management (CM) or microsurgery (MS) in patients with intralabyrinthine schwannomas (ILS). A thorough systematic review of the English and French literature from 1948 to February 2014 was performed using Ovid Medline. An ancestor search was also completed. The major inclusion criterion consisted of a diagnosis of ILS with magnetic resonance imaging. Patients with a classic vestibular schwannoma, cases of incidentaloma during surgery or an autopsy were the main exclusion criteria. Thirty-one studies met our selective criteria. Descriptive data were collected from the articles. Clinical outcomes regarding the hearing loss, tinnitus, vertigo, dizziness and aural fullness were stated as improved, unchanged or worse at the last follow-up. All data were then separated into two different groups according to the management option: CM and MS. The data were analyzed using a Pearson χ (2) test and Fisher's exact test. This meta-analysis suggests that MS has a statistically significant favorable outcome regarding symptom relief compared to CM in patients with ILS suffering from tinnitus, vertigo and dizziness. Hearing level was not compared between treatment groups, as MS leads to anacusis. An indicative bias was the main limitation of this study, as patients suffering from intractable vertigo with moderate-to-severe hearing loss were referred to MS. Therefore, in the presence of a serviceable hearing, we suggest that CM should be the treatment of choice.

Human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) have been shown to have a significantly better prognosis and response to current treatment modalities. Current guidelines recommend systematic HPV-DNA and/or p16 testing on HNSCCs, although treatment approach should not be directed by test results. The objectives of this study were to (1) assess whether HPV-DNA and/or p16 status are systematically evaluated across North American otolaryngologists-head and neck surgeons and (2) whether the status is used to direct treatment approach.A 15-question online survey was sent to three associations: the Association of Oto-rhino-laryngology-Head and Neck Surgery of Quebec, the Canadian Society of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society.Sixty-seven percent of respondents systematically test for HPV-DNA and/or p16 on HNSCC sites, while 58.3% report using test results to direct treatment for oropharyngeal cancers. A lack of official guidelines was the primary reason (81.8%) physicians did not use test results to direct treatment. Academic centre physicians (83.3%) and physicians with ⩾50% oncologic practice (87.6%) were more likely to test for HPV-DNA and/or p16 in HNSCC compared to non-academic centre physicians (39.7%) and physicians with50% oncologic practices (51.4%) (p0.001). Cost of the tests (69.2%), lack of relevance (46.1%) and time constraints (30.8%) were the primary reasons HPV-DNA and/or p16 were not tested.The majority of North American respondents in this survey systematically test for HPV-DNA and/or p16 in HNSCC sites, and most indicate that test results influence their treatment approach for oropharyngeal cancers.

Objectives:1) Evaluate systematic testing of human papillomavirus (HPV) and p16 status on head and neck cancer in North America. 2) Assess if HPV or p16 status is used to influence treatment in this population.Methods:An online survey was sent to three professional associations: the American Head & Neck Society, the Canadian Society of Otolaryngology, and the Quebec Association of Otolaryngology. Inclusion criteria were physicians practicing in North America. Incomplete surveys were disregarded. Chi-square analyses were conducted.Results:There was a response rate of 20% with a total of 216 complete responses. Most respondents were otolaryngologists (196; 90.7%), English-speaking (178; 82.4%), and practicing in an academic setting (138; 63.9%). Routine HPV or p16 testing was performed by 146 respondents for the oropharynx, 69 for oral cavity, and 44 for other subsites. Most physicians (113; 77.4%) test for both HPV and p16, while 58.3% indicated that HPV/p16 status influences their treatment approach for o...

The objective of this study is to describe the superior canal dehiscence syndrome (SCDS) and its vestibule-cochlear manifestations, while analyzing dehiscence size, audiogram and vestibular-evoked myogenic potential (VEMP) changes following dehiscence obliteration. We conducted a prospective study in a tertiary referral center. All Patients diagnosed and surgically treated for SCDS were operated through a middle fossa craniotomy (MFC). Clinical and radiological data were collected. The main outcome measures were Air-bone gaps, Pure-tone average (PTA), speech discrimination scores (SDS) and VEMP thresholds and were correlated to dehiscence size. 28 patients were included in this study with a mean dehiscence size of 4.68 mm. Phonophobia and imbalance were the most debilitating cochlear and vestibular symptoms, respectively. At 2 months postoperatively, low-frequency air-bone gaps showed a statistically significant improvement (p < 0.001). SDS and PTA did not show any statistically significant changes 2 months postoperatively (p = 0.282 and p = 0.295, respectively). VEMP threshold differences between operated and contralateral ears were statistically significant preoperatively (p < 0.001) and non-significant 2 months postoperatively (p = 0.173). Dehiscence size only showed a statistically significant correlation with preoperative total cochlear symptoms, while remaining insignificant with all other variables measured. Air-bone gaps, VEMP and computerized tomography remain essential tools in diagnosing and following SCDS. Dehiscence size is an independent factor in the analysis of SCDS, with cochlear symptomatology being associated to dehiscence sizes. Finally, it is shown that overall symptomatology, audiometric results and VEMP thresholds return to normal values post-obliteration, confirming the continuing success of the MFC approach for SCDS obliteration.

Objective: 1) To retrospectively assess the usefulness of preoperative thyroglobulin (Tg) levels in predicting sentinel lymph node (SLN) biopsy (SLNB) status. 2) To evaluate the correlation between preoperative Tg levels and the overall number of positive SLNs. 3) To compare primary tumor (T) classification in patients according to SLNB outcome.Method: Data from patients operated for well-differentiated thyroid carcinoma (WDTC) at the McGill University Thyroid Cancer Center were collected from January 2007 to January 2012. Statistical analyses were performed using a Mann-Whitney-Wilcoxon test, a Pearson correlation coefficient and a Pearson χ2 test.Results: Preoperative Tg levels and SLNB results were available in 74 patients (51 negative and 23 positive SLNBs). Mean preoperative Tg levels for negative and positive SLNB groups were 105.2 and 85.9 ng/mL, respectively, yielding no statistically significant difference (P = .143). Moreover, no statistically significant correlation was found between Tg levels ...

To compare the long-term outcome of hearing and tumor control of small vestibular schwannomas treated with conservative management or radiation therapy.A thorough search for English-language publications and "in-process" articles dating from 1948 to January 2011 was performed using Ovid MEDLINE.The principal criteria were patients with no microsurgical intervention before their treatment, a follow-up of at least 5 years, and a useful hearing level at diagnosis.Fourteen studies met our criteria. Hearing preservation outcome (worse, unchanged, and better) and tumor size outcome (growth, unchanged, and regression) data were collected from the articles, as well as all other significant observations. No studies using fractionated stereotactic radiotherapy met our criteria. Stereotactic radiation was the only radiation therapy analyzed.The data were analyzed using the Pearson χ2 test.Current data on conservative management and stereotactic radiation do not provide enough evidence to make a clear conclusion on the outcome of useful hearing preservation in a long-term manner. In this study, however, stereotactic radiation is shown to have better tumor control rates than conservative management. Additional studies reporting long-term follow-ups of patients are required so as to provide the medical field with a better understanding of vestibular schwannoma treatment therapies.

But de la presentation Comparer l’evolution clinique entre le traitement conservateuret la resection chirurgicale chez les patients atteints d’un schwannome intralabyrinthique (SIL). Materiel et methodes Une revue systematique des articles publies entre 1948 et fevrier 2014 a ete effectuee a l’aide de la base de donnees Ovid Medline. La symptomatologie initiale, le type de traitement et les issues cliniques sur l’audition, l’acouphene, les vertiges et les etourdissements ont ete recueillis. Deux groupes ont ete formes : traitement conservateur (TC) et microchirurgie (MC). La relation entre le type d’intervention et les issues cliniques a ete analysee avec le test de Fisher. Resultats Trente et un articles ont rencontre les criteres de selection, comptabilisant 66 patients. Le groupe TC est compose de 44 patients et le groupe MC comprend 22 patients. Une difference statistiquement significative favorisant la MC a ete demontree concernant l’acouphene ( p p p = 0,001). L’audition n’a pas ete comparee, car la MC induit une anacousie. Conclusion Dans un contexte ou l’incidence des SIL est limitee, les etudes descriptives rapportees ne permettent pas la comparaison entre le TC et la MC. Cette meta-analyse suggere un avantage clinique de la MC par rapport au TC, concernant l’amelioration de l’acouphene, des vertiges et des etourdissements. Toufefois, le biais d’indication est une des principales limitations, car la chirurgie est generalement indiquee lorsque la severite des symptomes est plus importante. Des etudes observationnelles ayant des suivis a plus long terme pourront etablir davantage de liens entre le traitement et les issues cliniques.