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Background: Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20-year cohort., Methods: Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021., Results: Fifty-one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda-4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%., Conclusion: OCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease., (© 2024 Wiley Periodicals LLC.)

Objectives: Neoadjuvant targeted therapy has emerged as a promising treatment strategy for locally aggressive thyroid cancer. Its impact on tumor and adjacent tissues remains a nascent area of study. Here we report on a series of six subjects with locally advanced thyroid cancer and recurrent laryngeal nerve (RLN) paralysis who experienced recovery of RLN function with neoadjuvant treatment and describe the morphologic and electrophysiologic characteristics of these recovered nerves., Methods: This is a multicenter retrospective review. Descriptive analysis was conducted to examine the following parameters for recovered nerves: (1) nerve morphology, characterized as Type A (involving epineurium only) versus Type B (extending beyond epineurium); (2) proximal stimulability (normal vs. abnormal vs. absent); and (3) surgical management (resection vs. preservation)., Results: Six subjects with unilateral VFP were identified. Median time to return of VF mobility was 3 months (range 2-13.5). All nerves (100%) were noted to have Type A morphology at surgery. Proximal stimulability was normal in four subjects (66.7%), abnormal in one (16.7%), and absent in one (16.7%). Nerves that had improvement of function through neoadjuvant therapy were able to be surgically preserved in five subjects (83.3%)., Conclusions: This represents the first characterization of RLNs that have recovered function with neoadjuvant treatment of locally advanced thyroid cancer. Although much remains unknown, our findings indicate carcinomatous neural invasion is a reversible process and recovered nerves may demonstrate normal morphology and electrophysiologic activity., Level of Evidence: 4 Laryngoscope, 134:3415-3419, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance., Observations: Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine., Conclusions and Relevance: The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Introduction  Human papillomavirus-related (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective  The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods  Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results  p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p  < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p  < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p  = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p  = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p  = 0.03). Conclusions  Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Postoperative hypoparathyroidism may cause significant patient morbidity and even mortality. Emerging technologies centered on autofluorescent properties of parathyroid glands when exposed to near-infrared light hold promise to improve surgical parathyroid gland identification and preservation. Two systems (probe-based and camera-based) are commercially available currently; however, neither system alone provides indication of vascular viability or postoperative parathyroid gland function. The administration of indocyanine green, when combined with near-infrared fluorescence imaging, enables subjective assessment of parathyroid gland perfusion. Additional technologies to assess parathyroid gland perfusion are being developed. The impact of these nascent technologies on relevant clinical outcomes is an area of active investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Advanced head and neck cancer (HNC) is functionally and aesthetically destructive, and despite significant advances in therapy, overall survival is poor, financial toxicity is high, and treatment commonly exacerbates tissue damage. Although response and durability concerns remain, antibody-based immunotherapies have heralded a paradigm shift in systemic treatment. To overcome limitations associated with antibody-based immunotherapies, exploration into de novo and repurposed small molecule immunotherapies is expanding at a rapid rate. Small molecule immunotherapies also have the capacity for chelation to biodegradable, bioadherent, electrospun scaffolds. This article focuses on the novel concept of targeted, sustained release immunotherapies and their potential to improve outcomes in poorly accessible and risk for positive margin HNC cases.

Objective: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer., Methods: A clinical review based on current literature was generated by a multidisciplinary author panel., Results: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed., Conclusion: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer., Competing Interests: Disclosure Dr Nikiforov has IP ownership and receives royalties related to Thyroseq from the University of Pittsburgh as well as Consultancy agreement with Sonic Healthcare USA. Dr Randolph has received research grants (no personal fees) from Eisai, Medtronic and Fluoptics. Dr Randolph is the program director of the Mass. Eye & Ear Infirmary Endocrine Surgery Clinical Fellowship, which receives partial funding from Medtronic. Dr Randolph is the President of the International Thyroid Oncology Group (ITOG) and the World Congress on Thyroid Cancer (WCTC), is Chair of the Administrative Division of the American Head and Neck Society (AHNS) and is the American College of Surgeons (ACS) Otolaryngology Governor. All other authors have no conflicts to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery., Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery., Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Introduction: The standard complete evaluation of patients with head and neck squamous cell carcinoma (HNSCC) has included a staging exam under anesthesia (EUA) since the 1970s. The EUA for all sites of HNSCC has historically consisted of panendoscopy for the purpose of diagnostic biopsy, accurate staging of primary disease, and identification of second primary tumors. However, due to the accessibility of the oral cavity, the sole purpose of EUA for tumors of this site is to identify second primary tumors. Since the EUA became the gold standard for evaluation of HNSCC, there have been significant advancements in less invasive technologies such as CT, PET-CT, MRI, and fiberoptic examination. In this study, we sought to determine the value to patient care and cost-effectiveness of EUA in patients with oral cavity squamous cell carcinoma (OCSCC)., Methods: A retrospective chart review identified 77 patients who underwent EUA for OCSCC., Results: The most common subsites were the oral tongue and floor of mouth (59.7% and 24.7% respectively). All underwent direct laryngoscopy, 94.8% underwent esophagoscopy, and 20.8% underwent flexible transnasal examination in clinic prior to EUA. For 90.9% of patients, the EUA did not change initial T-staging based on clinical examination and imaging. The remaining 9.1% of patients were upstaged after EUA, however this change did not impact the treatment plan. Second primary tumors were identified in 3.9% of patients, all were found in either the oral cavity or oropharynx, and were also identified with clinical examination or imaging. Analysis of patient charges determined an average cost of $8,022.93 per patient under the current paradigm involving EUA, however with a new algorithm eliminating mandatory EUA average cost decreases to $1,448.44., Conclusion: Formal EUA has historically been the gold standard for all HNSCC tumors. However, when performed for cases of oral cavity carcinoma, it is safe and cost effective to limit its use to select clinical scenarios., (© 2022 S. Karger AG, Basel.)

Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.

Background: This study aims to identify the strongest predictor of postoperative hypocalcemia following thyroid surgery., Methods: Study of patients who underwent total/completion thyroidectomy. No patients received postoperative calcium supplementation. Demographic and perioperative data were collected including preoperative baseline parathyroid hormone (PTH) levels, PTH levels at 30 min and 6 h post-excision, and 18 h post-excision calcium levels., Results: Of 124 patients studied, 20.2% developed temporary hypocalcemia (Ca <8.5 mg/dL at 18 h post-excision). In multivariate analyses, absolute PTH levels at 30 min and 6 h post-excision as well as change in PTH from baseline at 30 min and 6 h post-excision were statistically significantly associated with postoperative hypocalcemia. Per 10 units decrease in PTH from baseline at 30 min post-excision, the risk of developing temporary hypocalcemia increases by 17%., Conclusion: Absolute PTH levels and change in PTH from baseline at 30 min and 6 h post-excision predict hypocalcemia after total or completion thyroidectomy., (© 2022 Wiley Periodicals LLC.)

Background: The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence-based statement on the definition of advanced thyroid cancer and its targeted systemic treatment., Methods: An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel., Results: A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided., Conclusions: With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted., (© 2022 Wiley Periodicals LLC.)

Background: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies., Methods: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel., Results: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided., Conclusions: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted., (© 2021 Wiley Periodicals LLC.)

Objectives: Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)-related HNSCC to those of older patients., Methods: A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114)., Results: When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, P < .01) and females (40.7% vs 24.6% of older patients, P = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, P = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, P = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients ( P = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, P < .01)., Conclusions: Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.

Background: A prospective, stratified, randomized, double-blind, placebo-controlled study was conducted to observe the impact of preoperative calcitriol supplementation on serum calcium levels following total thyroidectomy., Methods: Subjects were randomized 1:1 to receive 1 μg calcitriol or placebo for 1 week preceding thyroidectomy. The primary outcome measure was change in serum calcium from baseline to 18 h post-thyroidectomy. Subjects were also assessed for incidence of symptomatic hypocalcemia, length of stay, readmission for hypocalcemia, and intravenous calcium supplementation., Results: Forty-seven patients underwent thyroidectomy; 23 received preoperative calcitriol supplementation, and 24 received placebo. Repeated measures regression demonstrated no difference in postoperative serum calcium over time (p = 0.22). There were no occurrences of hypocalcemia, intravenous calcium supplementation, or readmission in either group. No difference was observed in length of stay (p = 0.38). One patient in the calcitriol group developed Grade 3 hypercalcemia., Conclusions: Preoperative calcitriol supplementation had no impact on postoperative serum calcium levels compared to placebo., (© 2021 Wiley Periodicals LLC.)

Background: 2015 American Thyroid Association (ATA) guidelines recommended more conservative treatment in low-risk well-differentiated thyroid cancer (WDTC), stating that lobectomy alone may be sufficient. The guidelines further recommend mild thyroid-stimulating hormone (TSH) level suppression (0.5-2 mU/L) for this population. Our goal is to evaluate the natural history of patients undergoing lobectomy to determine the percentage that would require postoperative levothyroxine supplementation under these guidelines., Methods: Retrospective chart review of 168 patients that underwent lobectomy between 2010 and 2019 was performed. Preoperative and postoperative TSH values and the rate of patients prescribed levothyroxine were analyzed., Results: Thirty-five percent of patients were prescribed levothyroxine postoperatively. At 6 weeks postoperatively, 66% had TSH value of >2; this increased to 76% by 6 to 12 months., Conclusion: To adhere to ATA guidelines for WDTC managed with lobectomy alone, the majority of patients (76%) would require postoperative levothyroxine supplementation. Low preoperative TSH was found to be the most significant predictor for postoperative TSH < 2., (© 2020 Wiley Periodicals LLC.)

Background: Care for patients with thyroid nodules is complex and multidisciplinary, and research demonstrates variation in care. The objective was to develop clinical guidelines and quality metrics to reduce unwarranted variation and improve quality., Methods: Multidisciplinary expert consensus and modified Delphi approach. Source documents were workflow algorithms from Kaiser Permanente Northern California and Cancer Care of Ontario based on the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer., Results: A consensus-based, unified preoperative, perioperative, and postoperative workflow was developed for North American use. Twenty-one panelists achieved consensus on 16 statements about workflow-embedded process and outcomes metrics addressing safety, access, appropriateness, efficiency, effectiveness, and patient centeredness of care., Conclusion: A panel of Canadian and United States experts achieved consensus on workflows and quality metric statements to help reduce unwarranted variation in care, improving overall quality of care for patients diagnosed with thyroid nodules., (© 2018 Wiley Periodicals, Inc.)

Objectives/hypothesis: To compare the effectiveness of massed versus interval training when teaching otolaryngology residents microvascular suturing on a validated microsurgical model., Study Design: Otolaryngology residents were placed into interval (n = 7) or massed (n = 7) training groups. The interval group performed three separate 30-minute practice sessions separated by at least 1 week, and the massed group performed a single 90-minute practice session. Both groups viewed a video demonstration and recorded a pretest prior to the first training session. A post-test was administered following the last practice session., Methods: At an academic medical center, 14 otolaryngology residents were assigned using stratified randomization to interval or massed training. Blinded evaluators graded performance using a validated microvascular Objective Structured Assessment of Technical Skill tool. The tool is comprised of two major components: task-specific score (TSS) and global rating scale (GRS). Participants also received pre- and poststudy surveys to compare subjective confidence in multiple aspects of microvascular skill acquisition., Results: Overall, all residents showed increased TSS and GRS on post- versus pretest. After completion of training, the interval group had a statistically significant increase in both TSS and GRS, whereas the massed group's increase was not significant. Residents in both groups reported significantly increased levels of confidence after completion of the study., Conclusions: Self-directed learning using a chicken thigh artery model may benefit microsurgical skills, competence, and confidence for resident surgeons. Interval training results in significant improvement in early development of microvascular anastomosis skills, whereas massed training does not., Level of Evidence: NA. Laryngoscope, 127:2490-2494, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Several studies have sought to identify predictors of postoperative hypocalcemia after total thyroidectomy; however, there have been conflicting results regarding the impact of preoperative vitamin D deficiency., Methods: The medical records of patients undergoing total thyroidectomy were retrospectively reviewed. The number of parathyroid glands identified or reimplanted at the time of surgery was used as a marker of transient parathyroid gland damage., Results: Sixty-seven patients were included in the study. Vitamin D deficiency was a significant predictor of hypocalcemia in patients in whom ≥3 parathyroid glands were identified, but not in patients in whom 0-2 parathyroid glands were identified intraoperatively (odds ratio [OR] 5.8; P = .036)., Conclusion: Vitamin D deficiency is a significant predictor of postoperative hypocalcemia in patients in whom ≥3 parathyroid glands are identified intraoperatively, but not in patients who sustain minimal transient damage to the parathyroid glands., (© 2017 Wiley Periodicals, Inc.)

Importance: Hypocalcemia is the most common complication after total thyroidectomy and can result in prolonged hospital admissions and increased hospital charges., Objective: To determine the effectiveness of preoperative calcium and calcitriol supplementation in reducing hypocalcemia following total thyroidectomy., Design, Setting, and Participants: A retrospective cohort study was conducted at a tertiary care center in 65 patients undergoing total thyroidectomy by a single surgeon. Patients were divided into 2 groups: those receiving preoperative as well as postoperative supplementation with calcium carbonate, 1000 to 1500 mg, 3 times daily and calcitriol, 0.25 to 0.5 µg, twice daily, and those receiving only postoperative supplementation with those agents at the same dosages. Data on patients who underwent surgery between January 1, 2008, and December 31, 2011, were acquired, and data analyses were conducted from March through June 2012, and from October through December 2016., Interventions: Calcium and calcitriol therapy., Main Outcomes and Measures: Postoperative serum calcium levels and development of postoperative hypocalcemia., Results: Of the 65 patients who underwent total thyroidectomy 27 (42%) were men; mean (SD) age was 49.7 (16.7) years. Thirty-three patients received preoperative calcium and calcitriol supplementation, and 32 patients received only postoperative therapy. In the preoperative supplementation group, 15 of 33 (45%) patients underwent complete central compartment neck dissection and 11 of 33 (33%) had lateral neck dissection, compared with 16 of 32 (50%) and 12 of 32 (38%), respectively, patients without preoperative supplementation. The mean measured serum calcium level in those without preoperative supplementation vs those with supplementation are as follows: preoperative, 9.6 vs 9.4 mg/dL (absolute difference, 0.16; 95% CI, -0.12 to 0.49 mg/dL); 12 hours postoperative, 8.3 vs 8.6 mg/dL (absolute difference, -0.30; 95% CI,  -0.63 to 0.02 mg/dL); and 24 hours postoperative, 8.4 vs 8.5 mg/dL (absolute difference, -0.13; 95% CI, -0.43 to 0.16 mg/dL). In patients not receiving preoperative supplementation, 5 of 32 (16%) individuals became symptomatically hypocalcemic vs 2 of 33 (6%) in the preoperative supplementation group; an absolute difference of 10% (95% CI, -6.6% to 26.3%). Compared with the group not receiving preoperative supplementation, the mean [SD] length of stay was significantly shorter in the preoperative supplementation group (3.8 [1.8] vs 2.9 [1.4] days; absolute difference, -0.9; 95% CI, -1.70 to -0.105 days). Preoperative supplementation resulted in an estimated $2819 savings in charges per patient undergoing total thyroidectomy., Conclusions and Relevance: Preoperative calcium and calcitriol supplementation, in addition to routine postoperative supplementation, was associated with a reduced incidence of symptomatic hypocalcemia, length of hospital stay, and overall charges following total thyroidectomy.

Objective: To determine if suprafascial harvest of the radial forearm free flap improves postoperative donor site outcomes compared to subfascial harvest., Methods: Retrospective chart review., Results: Forty-six patients underwent reconstruction of a head and neck defect with a radial forearm free flap (RFFF). Subfascial harvest of the RFFF was performed in 25 (53%) patients and suprafascial harvest performed in 22 (47%) patients. All donor sites were covered with a split thickness skin graft and a bolster that remained in place for 6 days. Postoperative tendon exposure at the donor site occurred in 5 (20%) of the patients in the subfascial group and in 0 (0%) of the patients in the suprafascial group ( P = .05; Fisher's exact test). Average tourniquet time was 117 minutes in the subfascial group and 102 minutes in the suprafascial group. Hematoma formation occurred at the donor site in 2 (8%) and 1 (5%) patients in the subfascial and suprafascial groups, respectively. There were no complete or partial flap losses in either group., Conclusions: Suprafascial harvest of the RFFF decreases the risk of postoperative tendon exposure. The suprafascial harvest technique does not increase harvest time or donor site complications, nor does it negatively impact flap vascularity.

Objectives/hypothesis: Albumin is an indicator of nutritional status and has been investigated as a predictor of cancer survival and perioperative outcomes. This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC)., Study Design: Retrospective cohort study., Methods: A chart review was performed of patients who underwent HNC resection over a 6-year period at a single institution. Statistical analyses including Cox proportional hazards models, Pearson's correlation, and logistic regression were used to identify relationships between preoperative serum albumin and postoperative outcomes. Albumin was analyzed as a continuous variable., Results: A total of 604 patients were studied representing all cancer types. There was no association between albumin and pneumonia, flap complications, or length of stay. Albumin was found to have statistically significant inverse associations with overall survival (OS) (hazard ratio [HR] = 0.685, P < .001) and postoperative wound infection (HR = 0.455, P = .001). In multivariate analysis of OS, albumin did not achieve significance as an independent predictor (HR = 0.78, P = .064), whereas hemoglobin, age, and cancer stage remained significant. In a subgroup of 280 patients with upper aerodigestive squamous cell carcinoma (SCCA), albumin maintained significance in multivariate analysis of OS (HR = 0.74, P = .046). When controlling for preoperative radiotherapy, salvage surgery, and cancer stage in multivariate analysis, albumin was a significant predictor of wound infection (OR = 0.55, P = .018)., Conclusions: In patients with HNC, lower preoperative serum albumin is associated with an increased rate of wound infection and poorer OS. The effect on OS is most pronounced in patients with upper aerodigestive SCCA., Level of Evidence: 2b Laryngoscope, 126:1567-1571, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Rigid esophagoscopy is performed less frequently by resident trainees. Nonetheless, it remains important for certain indications, including foreign body extraction. This study describes the construction of a simulator and evaluates its utility in training residents., Study Design: Simulator development, fabrication, and procedural evaluation of postgraduate trainees., Methods: A simulator was developed and constructed in collaboration with a biomedical engineering team. Residents with varied experience in upper aerodigestive procedures performed rigid esophagoscopy on the model. Key steps and Accreditation Council for Graduate Medical Education's Objective Structured Assessment of Technical Skills (OSATS) criteria for rigid esophagoscopy were evaluated by a faculty surgeon. Pressure measurements were obtained from force sensors at the tip of the endoscope and incisors., Results: Fourteen trainees were evaluated. Operative rigid esophagoscopy and direct laryngoscopy case numbers were noted for each subject. OSATS scores and key steps of the procedure correlated with resident experience (R(2)  = 0.75, P < .0001 and R(2)  = 0.66, P < .001, respectively). Maximal pressure exerted on the simulator esophagus by the esophagoscope was inversely correlated with case number and was statistically significant (R(2)  = 0.51, P = .02), whereas length of procedure did not correlate (R(2)  = 0.04, P = .49). Maximal pressure on the incisors did not correlate (R(2)  = 0.25, P = .15)., Conclusions: A simulator for training residents to perform rigid esophagoscopy was developed and utilized by a faculty proctor to objectively evaluate trainees. OSATS scores, performance of key procedural steps, and pressure exerted on the simulator tissue correlated with upper aerodigestive cases performed, demonstrating validity of the simulator., Level of Evidence: NA Laryngoscope, 126:616-619, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Rigid esophagoscopy (RE) was once an essential part of the evaluation of patients with head and neck squamous cell carcinoma (HNSCC) due to the high likelihood of identifying a synchronous malignant neoplasm in the esophagus. Given recent advances in imaging and endoscopic techniques and changes in the incidence of esophageal cancer, the current role for RE in HNSCC staging is unclear., Objective: To analyze the current role of RE in evaluating patients with HNSCC, and to determine the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC., Design, Setting, and Participants: In this retrospective study performed at an academic tertiary care center, 582 patients were studied who had undergone RE for HNSCC staging from July 1, 2004, through October 31, 2012. To assess the incidence of synchronous esophageal malignant neoplasms, a literature review was performed, and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data set was queried., Main Outcomes and Measures: The primary outcome measure was the incidence of synchronous esophageal malignant neoplasms, as measured by retrospective review at our institution, SEER data set analysis, and literature review. Secondary outcome measures were RE complications and nonmalignant findings during RE., Results: A total of 601 staging REs were performed in 582 patients. The mean age was 60.2 years and 454 (78.0%) were men. There were 9 complications (1.5%), including 1 esophageal perforation (0.2%). Rigid esophagoscopy was aborted in 50 cases. Of the 551 completed REs, no abnormal findings were noted in 523 patients (94.9%), and nonmalignant pathologic findings were identified in 28 patients (5.1%). No synchronous primary esophageal carcinomas were detected. The incidence of synchronous esophageal malignant neoplasms found on screening endoscopy based on literature review and on SEER data set analysis was very low and has decreased from 1980 to 2010 in North America. The incidence reported in South America and Asia was relatively high., Conclusions and Relevance: Rigid esophagoscopy is safe, but the utility is low for cancer staging and for detection of nonmalignant esophageal disease. Review of the literature and analysis of a large national cancer data set indicate that the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC is low and has been decreasing during the past 3 decades. Thus, screening esophagoscopy should be limited to patients with HNSCC who are at high risk for synchronous esophageal malignant neoplasms.

Objectives/hypothesis: To determine whether blood transfusions are associated with adverse outcomes in patients with head and neck cancer (HNC) undergoing microvascular free tissue transfer., Study Design: Retrospective cohort study., Methods: The records of all patients who underwent free flaps for reconstruction after HNC resection from July 2007 through February 2013 at a single institution were reviewed. Rates of overall survival (OS), recurrence free survival (RFS), and postoperative wound infection were determined. Statistical analyses included Cox proportional hazards models and chi-square tests., Results: Of 167 patients, 90 received 0 to 2 units of blood and 77 received ≥ 3. After controlling for age, preoperative hemoglobin, preoperative albumin, cancer stage, and adverse pathologic features, transfusion of ≥ 3 (versus 0 to 2) units was associated with poorer OS (P = 0.0006; hazard ratio [HR] = 2.96) and RFS (P = 0.003; HR = 2.35). The rates of wound infection in patients who received 0, 1, 2, or ≥ 3 units were 13.3%, 21.2%, 33.3%, and 31.2%, respectively. There was a statistically significant difference in wound infection rates between those patients receiving 0 to 1 versus ≥ 2 units (P = 0.04)., Conclusions: Patients who receive ≥ 3 units of blood after free tissue transfer for HNC had a significantly increased risk of death after controlling for age, preoperative hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased transfusions are also associated with higher wound infection rates. The increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit may have a detrimental impact on survival and wound infections and should be revisited., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Midline mandibulotomy is a common approach for resection of head and neck oral cavity and oropharyngeal tumors; however, there are limited data available on the outcomes of lag screw vs plate fixation., Objective: To compare outcomes for midline mandibulotomy open reduction and internal fixation using plates vs lag screw technique., Design, Setting, and Participants: Retrospective cohort study at a tertiary care academic medical center of patients undergoing midline mandibulotomy for head and neck tumor resection over a 6-year period., Interventions: Mandibular fixation using lag screws or plates., Main Outcomes and Measures: The medical records and computed tomographic (CT) scans of patients undergoing midline mandibulotomy for head and neck tumor resection over a 6-year period were retrospectively reviewed. The postoperative CT scans were reviewed by a neuroradiologist who graded the fusion site on a scale of 0 to 2 using a 2-pass method. The rates and grades of union were compared, as well as several factors that affect healing, for fixations performed with plates vs lag screws., Results: Thirty-seven patients were included. The overall rate of radiologic union was 90% (9 out of 10) for lag screw technique and 41% (11 out of 27) for plates (P = .01). The average grade of radiologic union was 1.3 for lag screws and 0.67 for plates (P = .04). Hardware exposure occurred in 4 (15%) of the plate group and fistulae formed in 3 (11%); neither complication occurred in the lag screw group. In univariate analysis, both presence of dentition (odds ratio [OR], 5.50 [95% CI, 1.33-22.73]; P = .02) and plate technique (OR, 13.09 [95% CI, 1.45-11.62]; P = .02) were significantly associated with nonunion. In multivariate analysis, plate technique had an OR of 8.32 (95% CI, 0.85-81.75) for nonunion (P = .07)., Conclusions and Relevance: Fixation of midline mandibulotomy with lag screws results in a significantly increased rate of radiologic union compared with plates. Lag screws were also significantly better at achieving radiologic union in patients who underwent postoperative radiation, and the rates of fistula formation and hardware exposure were lower. Thus, lag screw fixation of midline mandibulotomy should be considered an excellent option, especially when patients will undergo postoperative adjuvant therapy and in patients at high risk for wound complications.

Importance: The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear., Objectives: To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP., Design, Setting, and Participants: Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months., Interventions: A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus., Main Outcomes and Measures: Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status., Results: Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes., Conclusions and Relevance: p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

Purpose: To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed., Results: Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%)., Conclusions: While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC., (© 2014.)

Objective: To provide a framework for the management of scalp and skull defects., Design: Retrospective chart review., Setting: Two tertiary care hospitals., Patients/intervention: Fifty-six consecutive patients who underwent reconstruction of scalp and/or skull defects with free flaps, rotational skin/fascia flaps, skin grafts, and implants. Defects closed primarily and those of the lateral temporal bone and skull base were excluded., Results: Sixty-two reconstructions were performed. Treatment of skin cancers and intracranial tumors necessitated 31 (50%) and 22 (35%) of the reconstructions, respectively. Defects included partial-thickness soft tissue (9, 15%), full-thickness soft tissue (28, 45%), full-thickness soft tissue and skull (17, 27%), and full-thickness soft tissue, skull, and dura (8, 13%). Radiation or prereconstruction wound breakdown or infection was involved in 33 (53%) and 25 (40%) of cases, respectively. The most common method of reconstruction was free tissue transfer (27, 44%) followed by local skin (15, 24%) or fascia (9, 15%) flaps. There was a 15% (9/62) complication rate; 89% (8/9) of these occurred in radiated tissues and 44% (4/9) occurred in smokers. Seven of the nine patients with complications (78%) were managed with local wound care and/or removal of an implant, whereas 2 (22%) required a second reconstructive procedure. All patients ultimately achieved a safe outcome with no infection and no bone or dural exposure., Conclusions: In addition to defect location and extent, availability of surrounding tissue and wound healing characteristics direct reconstruction. Patients who receive radiation therapy are at increased risk of complications. Use of vascularized tissue is critical for successful management, making local flaps and free tissue transfer the mainstay of reconstruction., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Extubation (cessation of ventilatory support) is often delayed in free flap patients to protect the microvascular anastomosis, presumably by reducing emergence-related agitation. We sought to determine if immediate extubation in the operating room (OR) would improve the postoperative course compared to delayed extubation in the intensive care unit (ICU)., Study Design: Retrospective chart review., Methods: Medical records of all patients undergoing free tissue transfer for head and neck reconstruction between January 2009 and July 2010 were reviewed (n = 52). Patients extubated immediately postoperatively in the OR (immediate group, n = 26) were compared to patients extubated in the ICU (delayed group, n = 26)., Results: Tobacco use, alcohol use, pulmonary history, case length, and free flap type were not significantly different between the two groups. Although the average ICU stay for the immediate group was significantly shorter than the delayed group (2.0 days vs. 3.4 days; P = .008), the reduction in overall hospital stay for the immediate group did not achieve statistical significance (8.2 days vs. 9.5 days; P = .21). Use of treatment for agitation (27% vs. 65%) and physical restraints (8% vs. 69%) were significantly lower in the immediate versus delayed group (P = .01 and P < .001, respectively). Although flap-related, surgical, and medical complication rates were not significantly different between the two groups, the delayed extubation group had a significantly higher incidence of pneumonia (15% vs. 0%; P = .05)., Conclusions: Immediate postoperative extubation in the OR following head and neck microvascular free tissue transfer reduces ICU stay, anxiolytic use, restraint use, and incidence of pneumonia without an increase in flap- or wound-related complications., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

The projection and exposure of the auricle make it particularly susceptible to actinic injury and thus to cutaneous malignancies. Auricular reconstruction is challenging because of its unique surface anatomy and undulating topography. This article organizes auricular defects into different categories based on anatomic location and extent of tissue loss, including skin-only defects, small composite defects, full-thickness defects involving or sparing the upper third of the ear, and total auricular loss. The authors share an algorithm for repair of the array of auricular defects.

Objectives/hypothesis: Measure compliance with the Accreditation Council of Graduate Medical Education (ACGME) residents' work hour regulations and evaluate their impact on patient care and residents' performance on the Otolaryngology Training Examination (OTE)., Study Design: Retrospective review of an otolaryngology residency program's resident duty hours violations and OTE scores, and review of the associated hospital's benchmark patient data., Methods: Residents' duty hour violations were compiled and analyzed for individual violation, postgraduate year (PGY), and service in the program. Annual OTE scores and the department's hospital benchmark measures (inpatient mortality, inpatient length of stay, 30-day readmission rate) were compared before and after the institution of the ACGME duty hours mandate., Results: The 10-hour rule was most frequently violated; residents on the oncology service and PGY-2 year were most commonly in violation. There was no difference before and after institution of the ACGME duty hours mandate in 30-day hospital readmission rates (P = .42), hospital mortality index (P = .55), length of stay (P = .55), OTE scores (P = .11, Student's t test), and graduating resident's operative volume., Conclusions: Institution of the ACGME duty hour regulations did not improve patient care as measured by the 30-day readmission rate, inhospital mortality, and patient's length of stay. Residents' performance on the OTE did not change after implementation of the ACGME rules. Further studies are warranted to assess the impact of the ACGME work hour regulations on patient care and resident-physicians' training.

Objective: To determine the predictive ability of the Jahrsdoerfer grading scale score in congenital aural atresia surgery., Design: Retrospective review of medical records., Setting: Tertiary referral center., Patients: One hundred eight patients with aural atresia., Main Outcome Measures: Demographic data, preoperative Jahrsdoerfer score, and postoperative audiometric outcomes were reviewed. One month postoperative, 4-tone pure-tone averages and speech reception thresholds were compared between ears scoring 6 or lower, 7, and 8 or higher on the Jahrsdoerfer grading scale. The percentage of ears with a speech reception threshold of 30 dB hearing level or lower for each group was calculated and compared between groups. Individual anatomical structures on the Jahrsdoerfer grading scale were evaluated for their ability to predict postoperative audiometric success., Results: Of 116 ears evaluated, postoperative 4-tone pure-tone averages and speech reception thresholds were significantly poorer in ears scoring 6 or less on the Jahrsdoerfer grading scale compared with ears scoring 7 or higher (P < .02, t test). Ears scoring 6 or less had a 45% chance of achieving a postoperative speech reception threshold of 30 dB hearing level or lower, while ears scoring 7 or higher had an 89% chance (P < .01, chi(2) test). Lack of middle ear aeration was the only anatomical factor predictive of poor audiometric outcome., Conclusions: Compared with patients with a Jahrsdoerfer score of 6 or lower, patients with a score of 7 or higher had significantly better hearing postoperatively. Middle ear aeration may be the most important predictor of postoperative hearing outcome. The Jahrsdoerfer grading scale is an invaluable tool in the preoperative evaluation of patients with congenital aural atresia.

Objectives: Transforming growth factor beta-1 (TGF-beta1) is a known fibrogenic factor with immunosuppressive properties. We wanted to determine the effect of stimulation with TGF-beta1 on nasal polyp-derived fibroblasts and assess the role this molecule would have in polyp formation and growth., Study Design: Nasal-polyp derived fibroblasts were cultured with or without TGF-beta1, and proliferation and cytokine secretion were measured., Methods: Fibroblasts were isolated from nasal polyps following endoscopic surgery. Cells were plated and grown until confluent, after which they were split and used in assays. Cells were stimulated with TGF- beta1 and mRNA collected after 16 hours, supernatants after 72 hours, and proliferation measured after 96 hours of culture., Results: TGF-beta1 significantly (P < .02) increased proliferation of nasal-polyp derived fibroblasts. We examined the expression of inflammatory cytokines and found that TGF-beta1 decreased expression of CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), granulocyte-colony stimulating factor (G-CSF), and GM-CSF (P < .05). In contrast, incubation with TGF-beta1 increased fibronectin, procollagen, vascular endothelial growth factor (VEGF), and TGF-beta2 protein production (P < .05). For select samples, we confirmed that the increased protein production was due to increased mRNA expression., Conclusion: These studies suggest that TGF-beta1 expression in polyp tissue can have dual effects. One role is to act as an anti-inflammatory agent shown by the ability to inhibit pro-inflammatory mRNA and protein production. At the same time, TGF-beta1 expression leads to increases in factors involved in fibrosis and angiogenesis, promoting remodeling and cell growth.

Objectives: To analyze risk factors leading to full-thickness (FT) defects, to review methods of repair, and to present guidelines for management of aggressive basal cell carcinomas (BCCs) of the nose., Design: Retrospective medical chart review of patients who underwent nasal reconstruction by the Department of Otolaryngology-Head and Neck Surgery between 1996 and 2003., Results: Two hundred ten patients underwent nasal reconstruction; 183 had complete medical records and were included in this study. There were 53 patients with FT nasal defects, 38 (71.7%) of which were due to BCC. Among all patients presenting with an aggressive histologic subtype of BCC, 30.1% (22/73) developed FT defects. In contrast, 14.5% (16/100) with a nonaggressive subtype had FT involvement (P < .05)., Conclusions: Internal lining defects are more likely to occur from aggressive histologic subtypes of BCC (infiltrative, morpheaform, and micronodular) than nonaggressive subtypes (P < .05). For BCCs 1 to 2 cm2 located on the nasal ala, histologic subtype is a significant risk factor for resulting in a FT defect, which should influence the method of excision (direct vs Mohs micrographic surgery) and the anticipated reconstruction. Large lesions (> 2 cm2) involving the ala have a high rate of internal lining involvement independent of pathologic subtype.