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Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.

IntroductionSurgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.Methods and MaterialsFindings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts—surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)—were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.ResultsForty-nine patients were enrolled in the surgery + Cs-131 prospective study. Grade 1 to 3 adverse events (AEs) occurred in 18 patients (37%), and grade 4 AEs occurred in 2 patients. Postoperative percutaneous endoscopic gastrostomy (PEG) tubes were needed in 10 surgery + Cs-131 patients (20%), and wound and vascular complications were observed in 12 patients (24%). No cases of osteoradionecrosis were reported in the surgery + Cs-131 cohort. We found a 49% 2-year disease-free survival at the site of treatment with a substantial number of patients (31%) developing metastatic disease, which led to a 31% overall survival at 5 years.ConclusionsAmong patients with local/regional recurrent HNSCC status-post radiation, surgery + Cs-131 demonstrated acceptable safety with compelling oncologic outcomes, as compared to historic control cohorts.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT02794675 and NCT02467738.

Objective The coronavirus disease 2019 (COVID-19) pandemic has reduced the demand for, and supply of, head and neck cancer services. This study compares the times to diagnosis, staging, and treatment of head and neck cancers before and during the COVID-19 pandemic. Study Design Retrospective cohort study. Setting Tertiary academic medical center in New York City (NYC). Methods The times to diagnosis, staging, and treatment of head and neck cancer for patients presenting to the clinics of 4 head and neck oncology surgeons with newly diagnosed head and neck cancers were compared between pre–COVID-19 and COVID-19 periods. Results Sixty-eight patients in the pre–COVID-19 period and 26 patients in the COVID-19 period presented with newly diagnosed head and neck cancer. Patients in the COVID-19 group had a significantly longer time to diagnosis than the pre–COVID-19 group after adjustment for age and cancer diagnosis ( P = .02; hazard ratio [HR], 0.54; 95% CI, 0.32-0.92). Patients in the pre–COVID-19 and COVID-19 groups had no statistically significant differences in time to staging ( P > .9; HR, 1.01; 95% CI, 0.58-1.74) or time to treatment ( P = .12; HR, 1.55; 95% CI, 0.89-2.72). Conclusion This study found that time to diagnosis for head and neck cancers was delayed during a COVID-19 period compared to a pre–COVID-19 period. However, there was no evidence of delays in time to staging and time to treatment during the COVID-19 period. Our results prompt further investigations into the factors contributing to diagnostic delays but provide reassurance that despite COVID-19, patients were receiving timely staging and treatment for head and neck cancers.

Background We describe a rare case of high-grade myxofibrosarcoma (MFS) of the maxillary sinus and review the literature on MFS of the paranasal sinuses. Methods A 66-year-old man presented for evaluation of 6–8 weeks of epistaxis and persistent nasal congestion and drainage. Imaging revealed a soft tissue mass extending from the left maxillary sinus into the left nasal cavity. After incomplete resection, the patient elected for post-operative radiotherapy, which was interrupted by rapid local progression. At this point, the patient underwent a total maxillectomy and adjuvant radiotherapy. Results The patient was without evidence of recurrence at a follow-up visit 8 months after diagnosis. Conclusions The recommended treatment of MFS is complete surgical resection. Margin status is the most important predictor of local recurrence. Our case, in which incomplete resection was followed by rapid local progression despite adjuvant radiotherapy, illustrates the unique challenges of treating MFS in the head and neck.

Patients with Fanconi anemia (FA) are at increased risk for head and neck cancers that often necessitate extensive reconstructions. Such patients have multiple comorbidities including anemia and thrombocytopenia frequently requiring bone marrow transplant, and they are at an increased risk of cancer recurrence and need for further extirpation. In the present study, charts from 3 patients with FA who underwent microvascular free tissue transfer by the senior author were retrospectively reviewed for pertinent pre- and peri-operative details in addition to functional and cosmetic outcomes. Two of these patients ultimately required metachronous free flap reconstructions for recurrence. All patients had acceptable functional and cosmetic outcomes following each instance of free flap reconstruction, thereby demonstrating the utility of microvascular free tissue transfer in patients with FA. The authors herein present each patient's clinical history in addition to a discussion of the current literature and an outline of our approach to these challenging cases.

Fanconi anemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink (ICL) repair resulting in chromosome breakage1–3. The FA repair pathway comprises at least 22 FANC proteins including BRCA1 and BRCA24–6, and protects against carcinogenic endogenous and exogenous aldehydes7–10. Individuals with FA are hundreds to thousands-fold more likely to develop head and neck (HNSCC), esophageal and anogenital squamous cell carcinomas (SCCs) with a median onset age of 31 years11. The aggressive nature of these tumors and poor patient tolerance of platinum and radiation-based therapy have been associated with short survival in FA11–16. Molecular studies of SCCs from individuals with FA (FA SCCs) have been limited, and it is unclear how they relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or human papillomavirus (HPV) infection17. Here, by sequencing FA SCCs, we demonstrate that the primary genomic signature of FA-deficiency is the presence of a high number of structural variants (SVs). SVs are enriched for small deletions, unbalanced translocations, and fold-back inversions that arise in the context of TP53 loss. The SV breakpoints preferentially localize to early replicating regions, common fragile sites, tandem repeats, and SINE elements. SVs are often connected forming complex rearrangements. Resultant genomic instability underlies elevated copy number alteration (CNA) rates of key HNSCC-associated genes, including PIK3CA, MYC, CSMD1, PTPRD, YAP1, MXD4, and EGFR. In contrast to sporadic HNSCC, we find no evidence of HPV infection in FA HNSCC, although positive cases were identified in gynecologic tumors. A murine allograft model of FA pathway-deficient SCC was enriched in SVs, exhibited dramatic tumor growth advantage, more rapid epithelial-to-mesenchymal transition (EMT), and enhanced autonomous inflammatory signaling when compared to an FA pathway-proficient model. In light of the protective role of the FA pathway against SV formation uncovered here, and recent findings of FA pathway insufficiency in the setting of increased formaldehyde load resulting in hematopoietic stem cell failure and carcinogenesis18–20, we propose that high copy-number instability in sporadic HNSCC may result from functional overload of the FA pathway by endogenous and exogenous DNA crosslinking agents. Our work lays the foundation for improved FA patient treatment and demonstrates that FA SCC is a powerful model to study tumorigenesis resulting from DNA crosslinking damage.

BACKGROUND: For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality. METHODS: A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts. RESULTS: The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval 13-42), with a median time-to-recurrence of 6 months and time-to-death of 11 months (vs >60 months for each among low-risk patient; p < .001). CONCLUSION: The miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early-stage OSCC.

Objective The main objective of this study was to quantify daily pain and opioid use in patients after hemithyroidectomy and cervical lymph node biopsy (CLNB). The secondary objective was to identify factors associated with decreased pain and opioid use. Study Design Prospective cohort study from June 2017 to February 2019. Patients were given paper surveys to record daily postoperative opioid use and maximal pain on a visual analog scale. Setting Single institution (NewYork-Presbyterian/Weill Cornell Medical Center). Methods All adult patients undergoing hemithyroidectomy and CLNB by a single surgeon were consecutively selected for participation. Patients recorded daily pain and opioid analgesic use over a 2-week postoperative period. Results Of 33 patients enrolled, 29 (87.9%) returned a survey. Thirteen underwent CLNB, and 16 underwent hemithyroidectomy. Pain resolved after both procedures by the end of the 2-week period. CLNB patients used a median (interquartile range) of 15.0 (0-41.2) morphine milligram equivalents (MME), and 95% used 70 or fewer MME. Hemithyroidectomy patients used a median of 8.2 (4.5-13.9) MME, and 95% used 30 or fewer MME. Use of nonopioid analgesics was associated with a statistically significant decrease in pain (56.1 vs 171 visual analog scale, 95% confidence interval [CI] of Δ = [12.0 to 217.8]) and opioid use (12.2 vs 48.8 MME, 95% CI of Δ = [5.0 to 68.1 MME]) in CLNB but not in hemithyroidectomy. Conclusion Patients have low pain and opioid requirements after hemithyroidectomy and CLNB. Head and neck surgeons should evaluate their opioid-prescribing patterns for opportunities to safely decrease postoperative prescriptions.

The COVID-19 health crisis abruptly disrupted the practice of otolaryngology. This article aims to define the changes needed to operate an academic otolaryngology practice safely and efficiently from within the epicenter of the pandemic. We define the areas of normal patient workflow that have been affected by COVID-19, and we offer mitigation strategies with attention paid to the specific needs of subspecialties.The article includes data specific to the office practice metrics of the Weill Cornell Medicine Department of Otolaryngology-Head and Neck Surgery, as well as publically available data from New York Presbyterian Hospital system and theExpert opinion.Through careful planning and execution, it is possible to reestablish safe otolaryngologic patient care during the COVID-19 pandemic. It will require a significant change from prior practice models for successful implementation. Additionally, telemedicine can be positively integrated into the treatment of otolaryngology diseases for new and established patients.The information conveyed in this review can be used as a guide by large and small otolaryngology groups to identify aspects of the patient visit that are "at risk" due to COVID-19, and it suggests sensible responses that can be made without a significant disruption to normal practice. The methods used to identify vulnerabilities with the patient visit process can be applied to future unforeseen crises, such as a resurgence of COVID-19 or a novel pandemic.

To quantify pain and opioid use after otorhinolaryngologic surgery. To determine the effect of patient and surgical factors on primary outcomes.Prospective cohort.Tertiary academic hospital.Patients undergoing elective otorhinolaryngologic surgery were prospectively enrolled. Patients completed demographic surveys and psychometric questionnaires assessing attitudes toward pain and baseline anxiety and depression before surgery. After surgery, patients documented peak pain levels (0-100 mm, visual analog scale) and daily prescription and nonprescription analgesic requirements over a 2-week period. Average daily and cumulative pain and opioid use were calculated and compared among patient cohorts stratified by procedure and preoperative factors.A total of 134 patients were enrolled. Total tonsillectomy was associated with significantly higher pain scores and opioid consumption, as compared to all other procedures. There was moderate correlation between average cumulative pain and opioid use. Older patients required significantly fewer doses of opioids. There was no effect of sex, marital status, or education level on postoperative pain or opioid use. Psychometric instrument scores and chronic pain or analgesic use were not associated with significant differences in pain or opioid requirements. Most patients were prescribed substantially more opioids than they actually required.Postoperative pain following elective otorhinolaryngologic surgery decreases dramatically within the first week and requires only few days of opioid analgesia, with the exception of tonsillectomy. Almost all patients required fewer than 15 doses of opioids.

We have developed and validated a novel microRNA (miRNA)-based prognostic model to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into ‘early-stage’ by the TNM system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high and low mortality risk categories. Within the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% (p

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( p < 0.0005 ). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

Purpose To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC.

Background and Objectives Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. Methods Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. Results Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37–0.51, P

Objective: To assess the characteristics and quality of cost utility analyses (CUA) related to otolaryngology within the CEA registry and to summarize their collective results. Methods: All cost-utility analyses published between 1976 and 2011 contained in the Cost-Effectiveness Analysis Registry (CEA Registry) were evaluated. Topics that fall within the care of an otolaryngologist were included in the review regardless of the presence of an otolaryngologist author. Potential associations between various study characteristics and CEA registry quality scores were evaluated using the Pearson product moment correlation coefficient. Results: Sixty-one of 2913 (2.1%) total CUA publications screened were related to otolaryngology. Eighteen of 61 (29.5%) publications included an otolaryngologist as an author. Fourteen studies agreed on the cost effectiveness of at least unilateral cochlear implantation and six of seven (85.7%) studies demonstrated the cost effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). Forty-six percent (28 of 61) of all manuscripts were published between 2008 and 2011. A more recent publication year was associated with a higher CEA registry quality score while the presence of an otolaryngologist author and journal impact factor had no significant correlation with the quality of the CUA. Conclusion: Based on current evidence in the CEA registry, unilateral cochlear implantation for hearing loss and CPAP for OSA are both cost-effective therapeutic interventions. Although CUAs in otolaryngology have increased in quantity and improved in quality in more recent years, there is a relative lack of CUAs in otolaryngology in comparison to other subspecialties. Keyword: Cost-utility analysis

Background The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. Methods We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. Results The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. Conclusion Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Introduction: Fanconi anemia (FA) patients have a high predilection for developing aggressive head and neck squamous cell carcinoma (HNSCC) at an early age. Because of their aggressive HNSCC, these patients frequently require multiple modality treatment, including radiation therapy. However, their underlying chromosomal instability makes giving radiation to these patients difficult because of increased radiation-induced complications. In order to better understand this problem, we evaluated a large population of FA patients with HNSCC who received radiation therapy for HNSCC. Hypothesis: FA patients who have undergone prior bone marrow transplant (BMT) and present with head and neck squamous cell carcinoma (HNSCC) demonstrate decreased relative risk of radiation-induced complications compared to FA patients who have not received BMT. Study Design: Retrospective Cohort Study Methods: Demographic information, genotypic data, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry (IFAR) who developed HNSCC from 1981-2017 were analyzed. Results: Data were collected from the IFAR registry for n=50 patients. The mean age at time of HNSCC diagnosis was 30.5 + 9.0 years, and 36% of total patients were male. 42% of the patients received adjuvant or neoadjuvant radiotherapy for HNSCC, with the most common subsites involving the oral tongue (n=8), followed by alveolus (n=3) and supraglottis (n=2). The average dose given was 48.8 + 16.9 Gy over a 28- to 70-day period. Among patients receiving radiotherapy, 24% had received a bone marrow transplant. No patients who had a prior BMT were noted to develop pancytopenia as a radiation-related complication, while 68% of those without prior BMT developed pancytopenia from radiation. 6/16 patients who did not undergo transplant completed the full course of radiation, while 4/5 BMT patients were able to complete treatment. Both mucositis and sepsis were secondary complications more common in the non-BMT group (56% vs. 40%, and 12% vs. 0%, respectively). The relative risk of pancytopenia among patients receiving BMT and adjuvant radiation was 0.15 (95% CI 0.01-2.2); however, this was not statistically significant given the small BMT-group sample size (p=0.17). Interestingly, 80% of patients in the BMT group exhibited genetic mutations of the Fanconi complementation group C. Among patients who received a BMT and adjuvant radiotherapy, 5 patients died of XRT-related complications, while only 1 patient died from these complications in the BMT group. Conclusion: While it is well known that FA patients have a high predilection for developing aggressive HNSCC at an early age, among the patients who received preradiation bone marrow transplant the incidence of radiation-induced pancytopenia was reduced. This reduction suggests that FA patients undergoing radiotherapy for HNSCC may exhibit less adverse side effects of radiation treatment if they received a prior BMT. Citation Format: Ade Obayemi, K.R. Patel, O. Rosti, A. Smogorzewska, D. Kutler. The role of bone marrow transplantation in patients with Fanconi anemia and head and neck squamous cell carcinoma receiving radiotherapy: An examination of the International Fanconi Anemia (IFAR) Registry [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B23.

Purpose: The feasibility and efficacy of re-irradiation using contemporary radiation techniques to treat recurrent head and neck cancer has been demonstrated but the role of brachytherapy is unclear. Here we describe the use of 131 Cs brachytherapy with concurrent salvage surgery in 18 patients. Material and methods: Eligible patients underwent maximal gross resection of the tumor with implantation of brachytherapy seeds delivering a minimum dose of 80 Gy to the tumor bed. Rates of overall survival, locoregional progression free survival, disease-free survival, and radiation-induced toxicity were analyzed. Results: Retrospective Kaplan-Meier analysis shows median overall survival was 15 months and disease free survival was 12 months. Two patients developed grade 3 toxicity; all other complications were grade 1-2 with no grade 4 or 5 complications. Conclusions: Compared to prior literature, our study shows comparable rates of survival with a decreased rate of radiation-induced toxicity. J Contemp Brachytherapy 2015; 7, 6: 445-452 DOI: 10.5114/jcb.2015.56764

Pycnodysostosis is an extremely rare autosomal recessive osteosclerotic disorder that stems from inactivation of the cathepsin K gene resulting in a predisposition to multiple fractures. We present the case of a 46-year-old male with a history of pycnodysostosis and over 30 previous fractures, who presented with a pathologic fracture of the right mandibular angle which was successfully reconstructed using a fibula osteocutaneous free flap.

Introduction Ultrasonography-guided fine-needle aspiration (US-FNA) yields diagnostic material more often than palpation-guided FNA does. It is often performed by an interventional radiologist (IR) but rarely by a cytopathologist (CP). Herein we describe our method of performance and growing experience with this technique. Materials and methods Data from US-FNA of head and neck lesions performed over a 33-month period by both a CP and an IR were reviewed. Special attention was paid to cases for which histologic follow-up was available. Association in concordance between cytologic and histologic diagnoses was attempted using Fisher's exact test. Mean size of masses biopsied, number of passes performed, and passes needed to achieve adequacy were compared between groups using the Wilcoxon rank-sum test. Tests were 2-sided with P Results Of the 175 US-FNAs performed, 108 (62%) were done by the CP and 67 (38%) by the IR. Fifty-eight patients had histologic follow-up; 37 (64%) for the CP and 21 (36%) for the IR. Mean mass size was significantly smaller for the IR at 2.11 cm versus 2.9 cm for the CP ( P = 0.021). Adequacy was achieved after 1 pass in 70% of cases (26 of 37) by the CP and 67% (14 of 21) by the IR. Number of passes performed did not vary significantly between groups. A variety of masses were biopsied; however, the small sample size precluded meaningful evaluation of cytologic concordance to final histology. Conclusions CP-performed US-FNA has been successfully delivered to clinicians at our institution.

Objectives/Hypothesis To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma. Study Design Cohort study. Methods Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry who developed head and neck squamous cell carcinoma (HNSCC) were analyzed. Results Thirty-five FA patients were diagnosed with HNSCC at a mean age of 32 years. The most common site of primary cancer was the oral cavity (26 of 35, 74%). Thirty patients underwent surgical resection of the cancer. Sixteen patients received radiation therapy with an average radiation dose of 5,050 cGy. The most common toxicities were high-grade mucositis (9 of 16, 56%), hematologic abnormalities (8 of 16, 50%), and dysphagia (8 of 16, 50%). Three patients received conventional chemotherapy and had significant complications, whereas three patients who received targeted chemotherapy with cetuximab had fewer toxicities. The 5-year overall survival rate was 39%, with a cause-specific survival rate of 47%. Conclusions Fanconi anemia patients have a high risk of developing aggressive HNSCC at an early age. Fanconi anemia patients can tolerate complex ablative and reconstructive surgeries, but careful postoperative care is required to reduce morbidity. The treatment of FA-associated HNSCC is difficult secondary to the poor tolerance of radiation and chemotherapy. However, radiation should be used for high-risk cancers due to the poor survival in these patients. Level of Evidence 4. Laryngoscope, 2015

Objective: To evaluate the Weill Cornell Medical College (WCMC)/New York Presbyterian Hospital (NYPH) experience with intraoperative frozen (IOF) section in the management of thyroid nodules with a fine needle aspiration (FNA) diagnosis of Bethesda IIâVI and to analyze the cost and pathology benefit it provides. Methods: The surgical and cytopathology files at WCMC/NYPH were searched within the time period of January 2008 to May 2013. A total of 435 thyroid specimens were identified for which both an FNA and subsequent IOF section was performed. The FNA was correlated with the locations of the resected nodule and the nodule frozen for intraoperative diagnosis. The results of the FNA were compared to the IOF section diagnosis and final diagnosis (FD). Results: Among 435 cases, the FNA diagnosis was Bethesda II: 149 cases, Bethesda III: 170 cases, Bethesda IV: 91 cases, Bethesda V: 19 cases, and Bethesda VI: 6 cases. There were a total of 83 carcinomas identified on FD, which included 69 papillary thyroid carcinomas (PTCs), 12 follicular carcinomas, and 2 poorly differentiated carcinomas. The preoperative FNA diagnosis for these carcinomas was as follows: Bethesda II, 11/149 (7.4%), Bethesda III, 24/170 (14%), Bethesda IV, 26/91 (29%), Bethesda V, 16/19 (84%), and Bethesda VI, 6/6Â (100%). IOF section contributed to the diagnosis of malignancy in 16/429 (4%) cases: 1/149 (0.7%) Bethesda II, 5/170 (3%) Bethesda III, 2/91 (1.1%) Bethesda IV, and 8/19 (42%) Bethesda V. The diagnosis of malignancy was confirmed in the 6 Bethesda VI cases by IOF section. There were no false positives on IOF section. IOF had a sensitivity and specificity of 26% and 100%, respectively. Conclusion: The role of IOF section is limited in the evaluation of thyroid nodules. IOF section is most useful for nodules with an FNA diagnosis of Bethesda V lesions. The diagnosis of follicular variant of PTC remains difficult on frozen section. Keywords: Thyroid, Nodule, Frozen section, Fine-needle aspiration, Sensitivity, Specificity

To analyze the utility of intraoperative parathyroid hormone (IOPTH) monitoring for patients with primary hyperparathyroidism who had evidence of single-gland disease on preoperative imaging with modified 4-dimensional computed tomography that was done in conjunction with ultrasonography (Mod 4D-CT/US).Case series with chart review.Tertiary care university medical center.Patients were drawn from consecutive directed parathyroidectomies performed between December 2001 and June 2013 by the senior authors. All patients had primary hyperparathyroidism and underwent a Mod 4D-CT/US study that showed findings on both studies that were consistent with a single adenoma. The modified Miami criteria were used for IOPTH monitoring (parathyroid hormone decrease by50% and into the normal range).Of 356 patients who underwent parathyroid surgery, 206 had a single gland localized on the Mod 4D-CT and the US studies. IOPTH monitoring was used in 172 cases, of which 169 had adequate clinical follow-up to assess the surgical outcome. Twenty-one patients (12.4%) had IOPTH values that did not meet modified Miami criteria after removal of one gland, of which 7 were found to have multigland disease (4.1%). Three patients (1.8%) had persistent primary hyperparathyroidism despite an IOPTH that met modified Miami criteria.Although IOPTH monitoring correctly identifies a small percentage of patients with multigland disease, some patients will be subjected to unnecessary neck explorations that can result in difficult intraoperative decisions, such as whether to remove normal or equivocal-sized glands when they are encountered.

Background/Aims: Preoperative identification of malignant parotid lesions remains challenging, and thus, some surgeons use frozen section (FS) to assist them in their decision making. We evaluated the pathologic and cost benefit of FS after fine-needle aspiration (FNA) at our institution. Methods: We assessed medical data for 260 patients undergoing parotidectomy with FS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for radiology, FNA, and FS. Results: The sensitivities, specificities, and accuracies of FNA and FS were 75.0, 96.4, and 93.2%, and 75.0, 100, and 96.8%, respectively. FS detected 0% of FNA false negatives and 80% of false positives. The additional pathology charge for FS alone per correctly identified benign lesion after a positive FNA was USD 1,443. Conclusion: FNA and FS are more reliable in the prognostication of the final pathology than radiology. At our center, FS appears to be of limited clinical use after benign FNAs, but may be more useful after positive, indeterminate, and nondiagnostic FNAs.

To quantify the incidence of postoperative voice, swallowing, and other problems, including time to resolution following anterior transcervical approaches to the cervical spine, and to assess surgical factors associated with outcomes.Historical cohort study.Academic medical center.One hundred eighty-eight consecutive patients with cervical spine disease who underwent an anterior transcervical approach to the spine by a single head and neck surgeon over a 4-year time period. Rather than primary, single-level approaches, all patients in this study had multilevel, high-cervical (above C4), low-cervical (below C6), and/or revision approaches. Postoperative voice, swallowing, and other complaints were measured as well as time to resolution using Kaplan-Meier method. Surgical factors related to outcomes were analyzed using regression analysis.Follow-up was available for 129 patients, with average and median time of 35 months. Seventy-seven patients (60%) had a postoperative issue, including 35 patients (27%) with postoperative voice complaint, 62 patients (48%) with postoperative swallowing complaint, and 16 patients (12%) with other problems. Swallowing and voice complaints persisted beyond 1 year in 28% and 9% of patients, respectively. Approaching spinal levels above C4 and exposing more than 3 spinal levels were 2 factors significantly related to voice and swallowing problems.There is a high incidence of subjective voice and swallowing complaints following transcervical anterior approaches to the spine, and such complaints can persist beyond 1 year in many patients. Exposure of more than 3 spinal levels or above level C4 are 2 factors significantly associated with outcome.

To investigate whether parathyroid gland weight has an impact on the accuracy of preoperative localization of parathyroid adenomas with modified 4 dimensional computed tomography/ultrasound. And to determine if the weight of parathyroid adenomas can be calculated accurately based on the dimensions of the gland on the CT images.Case series with chart review.Tertiary care hospital.One hundred forty-two patients who had a preoperative modified 4-dimensional computed tomography/ultrasound and underwent parathyroidectomy for hyperparathyroidism due to a parathyroid adenoma between 1998 and 2009. Charts were reviewed to identify (1) the sensitivity and specificity for localization of parathyroid adenomas according to gland weight and (2) correlation between preoperative estimate of parathyroid weight and the surgical weight of the parathyroid gland.Modified 4-dimensional computed tomography/ultrasound displayed 92% sensitivity for localizing adenomas weighing150 mg to the correct side of the neck (95% confidence interval [CI], 65%-99%), 100% sensitivity for glands weighing 150 to 500 mg (95%-100%), and 98% sensitivity for glands weighing500 mg (92%-100%). For localization to the correct quadrant of the neck, sensitivity was 75% (95% CI, 47%-91%) for glands weighing150 mg, 89% (79%-95%) for those weighing 150 to 500 mg, and 94% (85%-97%) for glands weighing500 mg. A positive correlation was seen between the preoperative weight estimate based on imaging and the operative weight of the gland, with a Pearson correlation coefficient of 0.96.Modified 4-dimensional computed tomography/ultrasound can closely predict the weight of parathyroid glands preoperatively and has good sensitivity for localization of adenomas, even in glands weighing less than 150 mg.

Objectives: In this article, we report our decade-long experience in using modified 4D-computed tomography in combination with ultrasonography (Mod 4D-CT/US) to localize abnormal parathyroid glands in patients with primary hyperparathyroidism. Study Design: Retrospective medical record review at a university-based academic medical center. Methods: Patients with primary hyperparathyroidism who underwent a Mod 4D-CT/US and parathyroidectomy between January 1998 and May 2009 were included in the study. Results from preoperative localization studies were compared with operative findings, pathologic data, and biochemical measurements to assess the sensitivity and specificity as well as the positive and negative predictive values of Mod 4D-CT/US. Results: Mod 4D-CT/US demonstrated 94% sensitivity and 96% specificity when these imaging studies were used to lateralize the hyperfunctioning parathyroid glands to one side of the neck. In regard to localizing abnormal parathyroid glands to a specific quadrant of the neck (i.e., right-left; superior-inferior), the sensitivity and specificity of Mod 4D-CT/US was 82% and 93%, respectively. Mod 4D-CT/US had a 92% positive predictive value for single-gland disease and 75% for multigland disease. The negative predictive value for single and multigland disease (MGD) were 73% and 92%, respectively. Conclusions: Mod 4D-CT/US provides excellent sensitivity and specificity in terms of localizing abnormal parathyroid glands to the correct side and quadrant in patients with primary hyperparathyroidism, and it correctly identifies many patients with MGD.

Background The role of routine central compartment neck dissection in papillary thyroid cancer is controversial. Methods A retrospective medical record review was conducted of 83 patients with papillary thyroid cancer who received either total or hemithyroidectomy and central compartment lymphadenectomy. Results Positive central compartment node metastases were found in approximately equal rates between older and younger patients (38.9% and 42.6%, respectively; Fisher's exact test; p = .82). The primary tumor was a microcarcinoma (1 cm or less) in 32 patients (38.5%). Positive central compartment node metastases were detected in 31.3% of patients with microcarcinomas, compared with 47.1% of patients with tumors greater than 1 cm. Conclusion Younger and older patients had approximately equal rates of central compartment lymph node metastasis. There was also a similar rate of metastasis between microcarcinomas and larger tumors. Our results document that central compartment lymph node dissection is a safe operation and may decrease the need for further operations. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Objective: Sialoendoscopy is a new technology being used at a limited number of institutions for the diagnosis and management of obstructive sialadenitis. This technique is promising for its superior diagnostic potential as well as its decreased morbidity compared to traditional more invasive techniques for managing obstruction. Our objective is to review the sialoendoscopy experience at our institution to identify successes, areas of improvement, and to provide guidance to other programs that may be interested in sialoendoscopy. Study Design: We did a retrospective review of all diagnostic and interventional sialoendoscopies performed at this institution from 2007 to 2009. Methods: Charts were reviewed for epidemiologic and clinical data, as well as procedural techniques, findings, and outcomes. Results: We attempted 37 parotid and submandibular sialoendoscopies, with successful endoscopic canalization of the duct in 36 of these cases. Twenty of 25 stones were removed from 18 patients. Stones that were larger than 5 mm were more difficult to dislodge and remove without fragmentation. Other abnormal findings included strictures, scars, and mucoid debris. There were two failures of technique, and two patients had postoperative purulent sialadenitis that resolved after antibiotics. Conclusions: As an institution that recently began performing sialoendoscopies, we show similar success rates compared to other programs. Obstacles included the initial cost of acquiring equipment and the associated learning curve of using a new technique. Similar to other programs, successful extraction of sialoliths was limited with larger stones. In the future, we hope to use laser lithotripsy for fragmentation, a technique already being trialed at some institutions.

Background It is desirable to detect neoplastic thyroid disease before proceeding with surgical therapy for hyperparathyroidism so that both conditions can be treated with a single operation. Methods Between March 1998 and June 2009, 227 patients with primary hyperparathyroidism were treated with surgical therapy. Of these, 217 were evaluated preoperatively with a modified 4-dimensional CT and ultrasonography. The medical records of these patients were reviewed in order to document the incidence and significance of thyroid pathology in this cohort of patients. Results Thyroid nodules were identified in 159 of the 217 patients (73.3%). Nine of 217 patients (4.1%) were treated with either a partial or a total thyroidectomy at the time of parathyroidectomy. Three of these patients had papillary thyroid carcinoma, 1 had a Hurthle cell carcinoma, and 1 had an incidental micropapillary thyroid carcinoma. Conclusion The rate of clinically significant thyroid malignancy in patients undergoing surgical treatment of primary hyperparathyroidism was 1.8%. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1763–1765, 2014

Purpose Resection of the posterior mandible for tumor or osteonecrosis may include the mandibular condyle, an integral part of the temporomandibular joint (TMJ). Condylar reconstruction, including use of prostheses, the native condylar head, or part of the fibula, all have associated drawbacks including skull base erosion and the potential for ankylosis and TMJ dysfunction as well as the increased difficulty associated with trying to recapitulate the TMJ with high fidelity. We report our experience leaving a single side of the reconstructed mandible unsecured to the glenoid fossa, allowing the mandible to "hang." We hypothesized that a good functional recovery may be achieved with this simple approach while avoiding the potential for ankylosis and TMJ dysfunction. Methods A retrospective chart review of all patients undergoing free fibula reconstruction of the mandible with condylar removal was performed. Outcomes were determined by maximum interincisal opening, occlusion, and diet after full recovery. Results Six patients were studied. Two had condylar reconstruction with a contoured fibular head secured to the glenoid fossa. One of them had progressive postoperative trismus and ankylosis. One patient was reconstructed with the native condyle rigidly fixed to the fibula flap, complicated by avascular necrosis requiring condylar resection, with good function afterward. Three patients were left to "hang." All 3 had either normal or improved function after surgery. Two had slight ipsilateral deviation on mouth opening. Conclusions Function can reliably be reestablished after segmental mandibulectomy and condylectomy with a vascularized fibula flap whose distal end is not precisely contoured or actively seated in the glenoid fossa, as a valid alternative to condylar reconstruction.

This article reviews major salivary gland anatomy and the differential diagnosis of salivary gland disease. The surgical technique for parotid and submandibular gland excision is described in detail. Possible complications and their management are also discussed, followed by a brief literature review of new surgical techniques.

Purpose of review Functional imaging has increasingly become an important diagnostic tool for head and neck cancer and as its availability increases so will its utilization. Positron-emission tomography using the radiotracer [18F]fluoro-2-deoxy--glucose is the most commonly used functional imaging technology and it has the potential to improve the staging and detection of head and neck tumors compared with conventional imaging techniques such as computed tomography or magnetic resonance imaging. Recent findings The combination of [18F]fluoro-2-deoxy--glucose and positron-emission tomography contributes valuable information in localizing a primary tumor in patients with an unknown primary and neck metastases, in the staging of primary head and neck cancer, in the detection of residual disease following definitive chemoradiation, and in the detection of recurrent disease. New technologies have been recently introduced using the combination of computed tomography and positron-emission tomography that allows exact anatomical correlation with areas of increased tracer uptake. In addition, new tracers may allow quantification of important cellular processes related to tumor proliferation or identification of tumors that may respond to certain targeted therapies. Summary [18F]Fluoro-2-deoxy--glucose and positron-emission tomography are increasingly being used as a clinical imaging modality in the complex management of head and neck cancer. In particular, its clinical value in the evaluation of the unknown primary, and the evaluation of recurrent or residual disease, is well established and has shown to be more accurate than conventional imaging modalities.

Survival analysis encompasses investigation of time to event data. In most clinical studies, estimating the cumulative incidence function (or the probability of experiencing an event by a given time) is of primary interest. When the data consist of patients who experience an event and censored individuals, a nonparametric estimate of the cumulative incidence can be obtained using the Kaplan-Meier method. Under this approach, the censoring mechanism is assumed to be noninformative. In other words, the survival time of an individual (or the time at which a subject experiences an event) is assumed to be independent of a mechanism that would cause the patient to be censored. Often times, a patient may experience an event other than the one of interest which alters the probability of experiencing the event of interest. Such events are known as competing risk events. In this setting, it would often be of interest to calculate the cumulative incidence of a specific event of interest. Any subject who does not experience the event of interest can be treated as censored. However, a patient experiencing a competing risk event is censored in an informative manner. Hence, the Kaplan-Meier estimation procedure may not be directly applicable. The cumulative incidence function for an event of interest must be calculated by appropriately accounting for the presence of competing risk events. In this paper, we illustrate nonparametric estimation of the cumulative incidence function for an event of interest in the presence of competing risk events using two published data sets. We compare the resulting estimates with those obtained using the Kaplan-Meier approach to demonstrate the importance of appropriately estimating the cumulative incidence of an event of interest in the presence of competing risk events.

The breast cancer susceptibility gene BRCA2 has recently been identified as identical to the Fanconi anemia (FA) gene FANCD1. Here we expand the clinical implications of this discovery. Notably, we identified 6 children in 5 kindreds exhibiting the co-occurrence of BRCA2 mutations, FA, and early onset acute leukemia. Leukemia occurred at a median of 2.2 years of age in the BRCA2 patients in contrast to a median onset of 13.4 years in all other FA patients in the International Fanconi Anemia Registry (IFAR; P

Fanconi anemia (FA) should be included among the genetic diseases that occur at high frequency in the Ashkenazi Jewish population. FA exhibits extensive genetic heterogeneity; there are currently 11 complementation groups reported, and 8 (i.e., FANCA, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, and FANCL) genes have been isolated. While patients may be from widely diverse ethnic groups, a single mutation in complementation group FA-C, c.711 + 4AT (commonly known as IVS4 + 4AT prior to current nomenclature rules) is unique to FA patients of Ashkenazi Jewish ancestry, and has a carrier frequency of greater than 1/100 in this population. In addition, a mutation (c.65GA) in FANCA (FA-A is the most common complementation group in non-Jewish patients) and the mutation c.6174delT in FANCD1/BRCA2 are also unique to the Ashkenazi Jewish population. Therefore, the study of Fanconi anemia can lend insight into the types of cancer-predisposing genetic diseases specific to the Ashkenazi.

Objectives/Hypothesis Laser-assisted uvulopalatoplasty (LAUP) is a widely accepted procedure for the management of snoring, but its role in the treatment of obstructive sleep apnea syndrome is currently unclear. The objective of the study was to evaluate the role of LAUP in treating moderate and severe obstructive sleep apnea syndrome. Study Design Retrospective review of a surgical treatment protocol for obstructive sleep apnea syndrome. Methods Between October 1993 and January 1999, 80 patients with moderate or severe obstructive sleep apnea syndrome and a significant component of retropalatal obstruction were treated with surgery at the Department of Otolaryngology at Northwestern University Medical School (Chicago, IL). Surgery consisted of LAUP with tonsillectomy (if tonsils were present) with the patient under general anesthesia or LAUP alone with local anesthesia (if the tonsils were absent). No patients received traditional uvulopalatopharyngoplasty. Sixty-four of the 80 patients underwent both preoperative and postoperative polysomnograms. Surgical “response” was defined as a 50% decrease in the apnea-hypopnea index (AHI) (the total number of apneic and hypopneic events per hour of sleep); surgical “cure” was defined as a 50% decrease in AHI and a final AHI of less than 20. Results The surgical response rate was 59% (38 of 64 patients), and the surgical cure rate was 39% (25 of 64 patients). Twelve patients (18.8%) had a higher AHI after surgery. The AHI (mean ± SD) changed significantly from 51.4 ± 30.9 preoperatively to 26.3 ± 20.8 on postoperative polysomnogram (P = 7.0 × 10−9). Laser-assisted uvulopalatoplasty alone was performed in 33 patients with a response rate of 61% and a cure rate of 42%. Laser-assisted uvulopalatoplasty with tonsillectomy was performed in 31 patients with a response rate of 58% and a cure rate of 35%. The overall incidence of nasopharyngeal insufficiency was 0%. Conclusion The results of the study suggested that LAUP with adjunctive tonsillectomy is an effective treatment for patients with obstructive sleep apnea syndrome and retropalatal obstruction with a lower complication rate than standard surgical therapy (uvulopalatopharyngoplasty).

Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents and cancer predisposition. Recent evidence for the interactions of ataxia-telangiectasia mutated protein ATM and breast cancer susceptibility proteins BRCA1 and BRCA2 (identified as FANCD1) with other known FA proteins suggests that FA proteins have a significant role in DNA repair/recombination and cell cycle control. The International Fanconi Anemia Registry (IFAR), a prospectively collected database of FA patients, allows us the unique opportunity to analyze the natural history of this rare, clinically heterogeneous disorder in a large number of patients. Of the 754 subjects in this study, 601 (80%) experienced the onset of bone marrow failure (BMF), and 173 (23%) had a total of 199 neoplasms. Of these neoplasms, 120 (60%) were hematologic and 79 (40%) were nonhematologic. The risk of developing BMF and hematologic and nonhematologic neoplasms increased with advancing age with a 90%, 33%, and 28% cumulative incidence, respectively, by 40 years of age. Univariate analysis revealed a significantly earlier onset of BMF and poorer survival for complementation group C compared with groups A and G; however, there was no significant difference in the time to hematologic or nonhematologic neoplasm development between these groups. Multivariate analysis of overall survival time shows that FANCCmutations (P = .007) and hematopoietic stem cell transplantation (P =

The feasibility of parathyroid preservation during thyroidectomy has not been well documented for cases in which the thyroid gland extends into the mediastinum.Retrospective chart review.Tertiary academic referral center.In this retrospective cohort study, 70 consecutive patients who had substernal thyroid glands treated with a transcervical thyroidectomy between 1993 and 2013 were compared with 286 thyroidectomies that did not entail substernal extension within that same time period. All localized parathyroid glands were confirmed histologically.Of 160 possible parathyroid glands in the substernal cases, 119 (74%) were histologically confirmed intraoperatively (67 superior and 52 inferior). In nonsubsternal cases, 725 (89%) were histologically confirmed (372 superior and 353 inferior). There was a statistically significant difference between the substernal and nonsubsternal cases in the total number of glands found (P.0001) and the number of superior and inferior glands that were identified (P = .009 and0.0001).Even when the thyroid gland extends into the mediastinum, it is often possible, although with reduced efficiency, to identify and preserve the parathyroid glands.

Partial hypopharyngeal defects are most commonly reconstructed with the pectoralis major myocutaneous flap (PMMF) or free fasciocutaneous (FFC) flap. The purpose of this study is to determine the ideal method for reconstruction of partial hypopharyngeal defects by reviewing our institutional experience and the literature.A retrospective review of partial hypopharyngeal reconstructions since 2009 was performed. A National Library of Medicine search of studies on partial hypopharyngeal reconstruction since 1988 was performed. Data on complications, diet, and speech were extracted and pooled.A total of 18 patients were studied-9 had PMMF reconstruction and 9 had FFC reconstruction. Operative time (8.75 vs. 13.0 hours, p = 0.0003) was shorter in the PMMF group. Pharyngocutaneous fistula developed in one PMMF patient (11.1%) and two FFC patients (22.2%). Late strictures occurred in three PMMF patients. Six patients in each group (66.7%) progressed to a regular diet. Three patients in each group produced tracheoesophageal speech after TEP. Literature review identified 36 relevant studies, with 301 patients reconstructed with PMMF and 605 patients with FFC. Pooled-data analysis revealed that PMMF had higher reported rates of fistula (24.7 vs. 8.9%, p 0.0001) and requirement for second surgery (11.3 vs. 5.5%, p = 0.04). There was no difference in stricture rates or progression to regular diet. Fewer PMMF patients produced tracheoesophageal speech (17.5 vs. 52.1%, p 0.0001).PMMF and FFC flaps are valid approaches to reconstructing partial hypopharyngeal defects, though rates in the literature of fistula, need for revisional surgery, and tracheoesophageal speech after laryngectomy are more favorable after free flap reconstruction.

The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations.In silico mutational tolerance prediction.Academic research hospital.We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants.There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score.Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available.

BACKGROUND Recipient-site infection after oropharyngeal reconstruction is a potentially disastrous complication. Although studies suggest that perioperative antibiotics reduces infection rates in these patients from 87% to 20%, there is no consensus regarding what constitutes the most appropriate antibiotic regimen and duration of treatment. METHODS A retrospective review of perioperative antibiotic administration was performed of all patients who underwent local, pedicled, or free flap oropharyngeal reconstruction after oncologic resection by a single surgeon at a single institution between 2007 and 2013 to assess for recipient-site complications. RESULTS Ninety-seven patients underwent 100 reconstructions (61 free flap reconstructions, 39 pedicled/local flap reconstructions) and all received a combination of intravenous (IV) antibiotic agents designed to cover oral flora. There were 23 (23%) recipient-site complications, which included cellulitis (9%), mucocutaneous fistula (5%), abscess (5%), and wound dehiscence (4%). Duration of antibiotic prophylaxis, defined as less than 48 hours (short-course) or greater than 48 hours (long-course), was not a significant predictor of recipient-site complication. Significant risk factors for recipient-site complications were clindamycin prophylaxis (P < 0.008), increased duration of surgery (P < 0.047), and advanced age (P < 0.034). Recipient-site complication was found to be a significant predictor of both increased length of hospital stay (P < 0.001) and increased time to the resumption of enteral feeds (P < 0.035). CONCLUSIONS These data suggest that extended courses of perioperative antibiotics do not confer additional benefits in patients undergoing oropharyngeal reconstruction. We recommend a limited 48-hour course of prophylactic antibiotics with sufficient aerobic and anaerobic coverage to help minimize the incidence of antibiotic-related morbidities.

BACKGROUND Subsequent to the publication of a report in 1984 entitled "Poorly Differentiated ("Insular") Carcinoma: A Reinterpretation of Langhans "wuchernde Struma," poorly differentiated insular thyroid carcinoma (PDITC) has become recognized as a distinct thyroid neoplasm. It is classified morphologically and biologically as an intermediate entity between well-differentiated (papillary and follicular) and undifferentiated (anaplastic) thyroid carcinomas. Only a few publications have addressed the findings with fine needle aspiration biopsy (FNAB). CASE A 67-year-old female presented for evaluation of a massively enlarged thyroid gland. Fine needle aspiration biopsy of the thyroid with a 22-gauge needle showed many large, multilayered, round to oval nests of tumor cells, 0.2-0.4 mm in diameter. Rosettelike configurations of 8-15 cells, 0.025-0.050 mm in diameter, were also observed. Nests of neoplastic cells in the histologic sections were virtually identical to those in the fine needle aspiration biopsy specimens. When the patient developed metastatic cervical adenopathy one year later, a microfollicular pattern was seen on both the FNAB and histologic sections. CONCLUSION When nests of tumor cells, 0.2-0.4 mm in diameter, are identified in a thyroid FNAB specimen, PDITC should be included in the differential diagnosis. A microfollicular pattern in a metastatic lymph node does not exclude the possibility that the primary tumor is a PDITC.

Resistance to thyroid hormone (RTH) is a syndrome characterized by refractoriness of the pituitary and/or peripheral tissues to the action of thyroid hormone. Mutations in the thyroid hormone receptor β (TRβ) gene result in TRβl mutants that mediate the clinical phenotype by interfering with transcription of thyroid hormone-regulated genes via a dominant negative effect. In this study, we developed transgenic mice harboring PV, a potent dominant negative human mutant TRβl devoid of thyroid hormone binding and transcriptional activation, as an animal model to understand the molecular basis of this human disease. Standard molecular biology approaches were used to obtain a cDNA fragment containing mutant PV which was injected into the pronucleus of fertilized egg. Founders were identified by Southern analysis and the expression of PV in tissues was determined by RNA and immunohistochemistry. Thyroid function was determined by radioimmunoassays of the hormones and the behavior of mice was observed using standard methods. The expression of mutant PV was directed by the β-actin promoter. Mutant PV mRNA was detected in all tissues of transgenic mice, but the levels varied with tissues and with different lines of founders. Thyroid function tests in transgenic mice with high expression of mutant PV showed a significantly (∼1.5-fold) higher mean serum total of L-thyroxine levels (p < 0.01) than those of nontransgenic mice. Moreover, thyroid-stimulating hormone levels were not significantly different from those of nontransgenic mice. In addition, these mice displayed decreased weights and a behavioral phenotype characterized by hyperactivity. These mice have phenotypic features consistent with the commonly observed clinical features of RTH and could be used as a model system to better understand the action of mutant TRβl in a physiological context, which could lead to better treatment for this disease.

Objectives:1) Recognize challenges in managing metastatic squamous cell carcinomas (SCC) to the parotid gland. 2) Describe our 5-year experience of treating metastatic SCC of the parotid gland.Methods:Retrospective case series of 22 consecutive patients undergoing parotidectomies for treatment of metastatic SCC to the parotid gland between August 2006 and December 2011 at Weill Cornell Medical College. Interventions included parotidectomy and radiation therapy (RT). Outcome measures included complications, survival, and locoregional recurrence.Results:Seventy-seven percent of patients were male, with a mean age of 77 years (range 46 - 93 years). Eighteen patients underwent superficial parotidectomy, four received total parotidectomy, and 16 underwent neck dissection. Fifteen patients received post-operative RT, and 1 patient had neoadjuvant radiation 4 months prior to surgery. Median dose of radiation delivered was 6300 cGy at 200 cGy per fraction. Overall 2-year survival was 77.4%, and 2-year disease-fre...