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Objective: To assess the opinion, practices, and challenges of international key opinion leaders about two minimal invasive surgical techniques in supraglottic laryngeal tumours: transoral laser microsurgery (TLM) and the transoral robotic surgery (TORS)., Methods: Design of a questionnaire composed of seven sections and fifty questions covering descriptive data of participants, practitioners experience procedural sequences, considerations related to airways, feeding, and voice, intraoperative haemorrhage, postoperative management, and a comparative analysis of TLM and TORS in treating supraglottic laryngeal cancer., Results: A total of 27 head and neck surgeons replied to the survey. The experts had an average experience in laryngeal surgery of 20.0 ± 9.4 years, ranging from 5 to 36 years. We noted a significantly shorter installation time in TLM compared to TORS (19% of experts estimated the installation time of over 20 min with TLM vs 44% with TORS; p = 0.02). According to complications, the experts considered that bleeding was the major concern with supraglottic laryngeal surgery, especially intraoperative bleeding in TLM (52% in TLM vs 26% in TORS) (p = 0.09) and postoperative bleeding in TORS (56% in TORS vs 44% in TLM)., Conclusion: The experts did not identify a clear superiority of one technology (TLM) over the other (TORS). The two techniques seemed equivalent to the experts, except for the control of intraoperative haemostasis and visualisation of the surgical field, where TORS was perceived as superior to TLM., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interest: The author Jerome R. Lechien was not involved with the peer review process of this article., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Small molecule inhibitors (SMIs) are targeted therapies increasingly used in advanced thyroid carcinomas. This study aimed to evaluate the survival outcomes of thyroid cancer on SMI treatment, including in patients with brain metastases., Methods: This retrospective study included patients with thyroid carcinomas who received at least one SMI between 2008 and 2022 at a tertiary level, academic institution. SMI included lenvatinib, sorafenib, dabrafenib-trametinib, selpercatinib, and cabozantinib. Patients were grouped by the presence of brain metastasis. Kaplan-Meier and log-rank tests modeled the overall survival (OS), defined from detection of first metastasis., Results: In total, 116 patients (49.1% female, median age 61.1 years [IQR, 51.1-71.0]) were included. Thyroid cancer subtypes were: 57 (49.6%) papillary, 23 (19.8%) anaplastic, 23 (19.8%) medullary, and 13 (11.2%) follicular. There were 18 (15.5%) patients with brain metastases, and 98 (84.5%) with visceral metastases. Age, sex, thyroid subtype, SMI, and time to recurrence were not different between cohorts. OS was shorter in the brain metastasis cohort (31.7 vs 42.2 months, P =.44) and was not different after excluding anaplastic thyroid cancer (29.1 vs 62.3 months, P =.21). In the case of papillary thyroid cancer, patients with brain metastases trended toward worse OS (22.0 vs 59.9 months, P =.13). Nonanaplastic histology, total thyroidectomy (OR, 40.0; P <.001), number of unique therapies (OR, 10.9; P =.047), and mutation-directed therapy (OR, 24.7; P =.003) were associated with improved OS., Conclusion: This single-institutional analysis reports survival outcomes of 116 patients with advanced thyroid cancer on targeted therapies, including 18 patients with brain metastases. Mutation-directed therapy for BRAF V600E mutations, RET mutations, RET fusions, and NTRK fusions had superior survival., Competing Interests: Disclosure E.Y. serves in the advisory board for Astellas Pharma. S. A. K. received research support from Merck, Bristol-Myers Squibb, and Castle Biosciences, consulted for Merck, Regeneron, and Castle Biosciences, and received honoraria from UpToDate. J. L. G. received institutional funding from Merck, Alkermes, Debio, Regeneron, and Genentech and consulted or served in the advisory boards for Regeneron, Merck, and Exelixis. The other authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined., Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC., Design, Setting, and Participants: This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023., Main Outcome and Measures: Recurrence-free survival (RFS)., Results: The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases., Conclusions and Relevance: The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Importance: Survival outcomes for anaplastic thyroid cancer (ATC), the most aggressive subtype of thyroid cancers, have remained poor. However, targeted therapies and immunotherapies present new opportunities for treatment of this disease. Evaluations of survival outcomes over time with new multimodal therapies are needed for optimizing treatment plans., Objective: To evaluate the association of treatment strategies and tumor characteristics with overall survival (OS) among patients with ATC., Design, Setting, and Participants: This retrospective case series study evaluated the survival outcomes stratified by treatment strategies and tumor characteristics among patients with ATC treated at a tertiary level academic institution from January 1, 2000, to December 31, 2021. Demographic, tumor, treatment, and outcome characteristics were analyzed. Kaplan-Meier method and log rank test modeled OS by treatment type and tumor characteristics. Data were analyzed in May 2022., Main Outcomes and Measures: Overall survival (OS)., Results: The study cohort comprised 97 patients with biopsy-proven ATC (median [range] age at diagnosis, 70 [38-93] years; 60 (62%) female and 85 [88%] White individuals; 59 [61%] never smokers). At ATC diagnosis, 18 (19%) patients had stage IVA, 19 (20%) had stage IVB, and 53 (55%) had stage IVC disease. BRAF status was assessed in 38 patients; 18 (47%) had BRAF-V600E variations and 20 (53%), BRAF wild type. Treatment during clinical course included surgery for 44 (45%) patients; chemotherapy, 41 (43%); definitive or adjuvant radiation therapy, 34 (RT; 35%); and targeted therapy, 28 (29%). Median OS for the total cohort was 6.5 (95% CI, 4.3-10.0) months. Inferior OS was found in patients who did not receive surgery (hazard ratio [HR], 2.12; 95% CI, 1.35-3.34; reference, received surgery), chemotherapy (HR, 3.28; 95% CI, 1.99-5.39; reference, received chemotherapy), and definitive or adjuvant RT (HR, 2.47; 95% CI, 1.52-4.02; reference, received definitive/adjuvant RT). On multivariable analysis, age at diagnosis (HR, 1.03; 95% CI, 1.01-1.06), tumor stage IVC (HR, 2.65; 95% CI, 1.35-5.18), and absence of definitive or adjuvant RT (HR, 1.90; 95% CI, 1.01-3.59) were associated with worse OS., Conclusions and Relevance: This retrospective single-institution study found that lower tumor stage, younger age, and the ability to receive definitive or adjuvant RT were associated with improved OS in patients with ATC.

Importance: Tall cell morphology (TCM) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that has been associated with poor outcomes; however, the risk factors for worse survival are not well characterized., Objective: To identify prognostic factors associated with cancer recurrence and death in patients with PTC-TCM., Design, Setting, and Participants: All patients treated for PTC-TCM at a single tertiary-level academic health care institution from January 1, 1997, through July 31, 2018, were included. Tall cell variant (TCV) was defined as PTC with TCM of 30% or more; and tall cell features (TCF) was defined as PTC with TCM of less than 30%. Patients with other coexisting histologic findings and/or nonsurgical management were excluded. Clinicopathologic features associated with worse outcomes were identified using Kaplan-Meier and Cox proportional-hazards model. Data were analyzed from March 1, 2018, to August 15, 2018., Main Outcomes and Measures: Locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and overall survival (OS) after surgery., Results: A total of 365 patients (median [range] age, 51.8 [15.9-91.6] years; 242 [66.3%] female) with PTC-TCM (TCV, 32%; TCF, 68%) were evaluable. Total thyroidectomy was performed in 336 (92%) patients; 19 (5.2%) received radiotherapy; and 15 (4.1%) received radioactive iodine. Clinical features were pT3 or T4, 65%; node-positive, 53%; and positive surgical margins, 24%. LRRFS at 1-, 3-, 5-, and 10-year was 95%, 87%, 82%, and 73%, respectively. On multivariable analysis, male sex and age were not independent predictors of inferior 5-year LRRFS, whereas positive surgical margins (HR, 3.5; 95% CI, 2.0-6.3), positive lymph nodes (HR, 2.8; 95% CI, 1.4-5.8), and primary tumor size of 3 cm or more (HR, 3.3; 95% CI, 1.4-7.8) were strongly associated with worse LRRFS. Age 55 years or older (HR, 3.2; 95% CI, 1.5-7.0), male sex (HR 4.5; 95% CI, 2.1-10.0), positive surgical margins (HR, 2.7; 95% CI, 1.2-6.0), nodal positivity (HR, 3.1; 95% CI, 1.3-7.7), tumor diameter of 1.5 cm or more (HR, 20.6; 95% CI, 2.8-152.1), and TCV vs TCF (HR, 3.1; 95% CI, 1.5-6.7) were associated with worse DRFS. Male sex (HR, 3.1; 95% 1.4-6.8) and tumor diameter of 1.5 cm or more (HR, 2.8; 95% CI, 1.0-7.4) were associated with worse OS. A findings-based nomogram was constructed to predict 10-year LRRFS (C index, 0.8)., Conclusions and Relevance: This retrospective cohort study found that in patients with PTC-TCM, positive surgical margins, node positive disease, and tumor size of 3 cm or more were risk factors for worse LRRFS. Intensified locoregional therapy, including adjuvant radiation, may be considered for treating these patients.

Background: Over 450,000 individuals are hospitalized with burns annually and roughly 35% are scald burns. Children younger than 5 years of age are at the greatest risk of scald burn injury. Caregiver burn prevention programs have been found to reduce the prevalence of injuries in young children; however, low-income and underserved populations seldomly have access to these programs. The impact of scald burn prevention programs in underserved populations remains unexplored. The objective of the current study was to evaluate the efficacy of a scald burn prevention program at a Level One Pediatric Trauma Center in a low-income, underserved community., Methods: Our hospital developed a one-hour scald burn prevention program for caregivers with children 5 years of age or younger. The program educated caregivers on ways to prevent scald burns and create safeguards in their home. Caregivers completed a pre-post survey to measure their ability to identify hot or cold objects, as well as respond to items about their perceptions of the program's utility, their willingness to share it with others, and the likelihood that they would use the information in the future. Data was analyzed using a paired t-test., Results: Two-hundred and sixty-nine (N = 269) caregivers participated in the program. Before the program, caregivers could identify potentially hot objects 83.17% of the time, and after the program, they were able to identify these items 92.31% of the time: t (268) = 12.46, p < .001, d = 1.07. Additionally, 95% of caregivers indicated that the program was helpful, 99% stated that they were likely to share this information with others, and 100% indicated that they would use the information from the program., Conclusions: Education is a critical component to prevent scald burns. Results indicate that a hospital-led scald burn prevention program can positively impact a caregiver's ability to identify possible scald-burn risks. Providing education to caregivers who typically do not receive this information could lower the prevalence of scald burns not only institutionally, but in communities that are disproportionately impacted by this mechanism of injury., (© 2021. The Author(s).)

Objectives: The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment., Materials and Methods: We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS)., Results: 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2-7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4-32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2-95.0%) and 80.6% (95% CI 74.5-86.8%), respectively., Conclusion: Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement., Methods: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations., Results: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management., Conclusion: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications., (© 2020 Wiley Periodicals LLC.)

Skin grafting is an essential aspect of burn and wound reconstruction. Split-thickness skin grafts (STSGs) harvested from the scalp are used for wound and burn reconstruction. Skin grafts from the scalp bear hair and hair particles. Residual hair fragments and pieces of hair in the graft have been associated with many complications, including foreign body reaction similar to pseudofolliculitis and chronic inflammation that can lead to infections. It is important to remove the hair and the hair particles from the scalp graft before its application to the donor site. Traditionally, surgeons have employed some techniques including saline agitation and mechanical removal of the hair particles with forceps. These techniques are time consuming and can subject the graft to mechanical damage. There is another technique that has been described using an adhesive tape. This technique uses Ioban™ (3M Healthcare, St. Paul, MN), followed by a saline wash to remove hair from grafts prior to grafting. In this paper, we introduce a novel technique for intraoperative hair depilation prior to graft application to recipient site. We used Dermabond® (Ethicon, Bridgewater, NJ) to remove residual hair particles from the STSG donor. Our technique has several advantages: it is expeditious, it allows minimal mechanical damage to the graft, and can be used for patients with allergies to Ioban. Intraoperative Dermabond depilation of scalp STSGs is safe, easy, and effective., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Opoku-Agyeman et al.)

The etiology of head and neck squamous cell carcinoma (HNSCC) is not fully understood. While risk factors such as positive human papilloma virus (HPV) status, smoking and tobacco use have been identified, they do not account for all cases of the disease. We aimed to characterize the bacteriome, mycobiome and mycobiome-bacteriome interactions of oral wash in HNSCC patients and to determine if they are distinct from those of the oral wash of matched non-HNSCC patients. Oral wash samples were collected from 46 individuals with HNSCC and 46 controls for microbiome analyses. We identified three fungal phyla and eleven bacterial phyla of which Ascomycota (fungi, 72%) and Firmicutes (bacteria, 39%) were the most dominant, respectively. A number of organisms were identified as being differentially abundant between oral wash samples from patients with HNSCC and oral wash samples from those without HNSCC. Of note, strains of Candida albicans and Rothia mucilaginosa were differentially abundant and Schizophyllum commune was depleted in those with HNSCC compared to oral wash from those without HNSCC. Our results suggest that the oral cavity of HNSCC patients harbors unique differences in the mycobiome, bacteriome, and microbiome interactions when compared to those of control patients., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no relevant conflicts of interest., (Copyright: © 2020 Shay et al.)

Background: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0)., Methods: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed., Results: There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC., Conclusions: AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion, status outperformed pT as a predictor of LR and LRR in patients with early OTSCC., (© 2019 American Cancer Society.)

Objectives/hypothesis: Case reports of a painful variant of Hashimoto's thyroiditis exist in the literature; however, these cases have only been documented in adult patients and there are no standard treatment guidelines. The aim of this study was to describe an alternative management for Hashimoto's thyroiditis associated with medically intractable head and neck pain in the pediatric population., Study Design: Case series with chart review., Methods: The study was conducted in the Section of Pediatric Otolaryngology at the Cleveland Clinic. We retrospectively analyzed pediatric patients (ages 0-18 years) with painful thyroiditis and/or headache who underwent total thyroidectomy from 2005 to 2014 with a clinical diagnosis of Hashimoto's thyroiditis. A thorough chart review was performed, including medical and family history, presenting symptoms, laboratory values, medical and surgical treatment strategies, operative reports, and surgical pathology., Results: There were 0.02% of patients (5 of 305) who met the criteria of intractable head and or neck pain. All five underwent total thyroidectomy with confirmation of Hashimoto's thyroiditis on surgical pathology. Surgical treatment resulted in complete cervical pain relief and improved headaches with a minimum follow-up of 36 months., Conclusions: Hashimoto's thyroiditis is a relatively common form of autoimmune thyroiditis in pediatric patients that uncommonly results in intractable neck pain or headache. In this case series, thyroidectomy was an effective alternative treatment in the pediatric population for medical failures in chronic painful Hashimoto's thyroiditis., Level of Evidence: 4. Laryngoscope, 128:2213-2217, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P <0.006). Firmicutes was the most abundant bacterial phylum, which was significantly increased in TT compared to NTT (48% vs. 40%, respectively; P =0.004). Abundance of Bacteroidetes and Fusobacteria were significantly decreased in TT compared to matched NTT ( P ≤0.003 for both). Abundance of 22 bacterial and 7 fungal genera was significantly different between the TT and NTT, including Streptococcus , which was the most abundant and significantly increased in the tumor group (34% vs. 22%, P <0.001). Abundance of fungal genus Aspergillus in TT correlated negatively with bacteria ( Actinomyces, Prevotella , Streptococcus) , but positively with Aggregatibacter . Patients with high T-stage disease had lower mean differences between TT and NTT compared with patients with low T-stage disease (0.07 vs. 0.21, P =0.04). Our results demonstrate differences in bacteriome and mycobiome between OMTC and their matched normal oral epithelium, and their association with T-stage., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no relevant conflicts of interest.

Objective: Identifying prognostic risk factors and determining the efficacy of common surgical treatments is critical to determine optimal treatment strategies for patients with medullary thyroid carcinoma (MTC). The objective of this study was to review a contemporary institutional experience with MTC primary treatment with 2 goals: to identify prognostic factors that impact survival and to study the effect of neck dissection on those outcomes., Methods: This study was a retrospective case series of patients with MTC who underwent at least a total thyroidectomy with curative intent. Clinical parameters including tumor and nodal staging with corresponding pathology findings were identified. Survival endpoints included overall survival, disease-free survival, and biochemical cure., Results: Sixty-seven patients were included. The majority presented with early T-stage disease. Fifty (76%) patients were N0 at presentation. Seventeen (24%) had some evidence of neck disease on clinical examination or imaging. Forty (71%) achieved biochemical cure, and the 5-year biochemical recurrence-free survival for those cases was 86.5%. Among patients who had successful resection of all gross disease, 92% had no evidence of structural disease at 5 years. Overall survival was 91% at 5 years. Increased pre-operative calcitonin (Ct) level, primary tumor size, extrathyroidal extension, and neck metastases decrease the rate of biochemical cure. Larger tumor size increases the risk of structural disease recurrence and biochemical relapse after initial cure. The presence and number of neck metastases correlate with biochemical relapse. The presence of lateral neck nodes (pN1b) does not have different survival implications than centrally confined disease (pN1a)., Conclusion: This study shows increasing tumor size, increased Ct level, and cervical metastases are poor prognostic factors. Patients with large tumors, high Ct level, or unfavorable pathologic findings may warrant more aggressive initial treatment, although limitations of the study prevent any conclusion regarding the effect of neck dissection., Abbreviations: ATA = American Thyroid Association BRFS = biochemical recurrence-free survival CND = central neck dissection Ct = calcitonin DFS = disease-free survival MTC = medullary thyroid carcinoma OR = odds ratio OS = overall survival pCND = prophylactic CND.

Objective: Cigarette lighters are frequent vectors in intentional contact burns. Time and temperature needed to cause thermal injury are considered to differentiate accidental from inflicted burns. This study examines the minimum time needed to heat a cigarette lighter's top to temperatures capable of inflicting any clinically visible skin burn. This information could be useful in child abuse and other forensic cases., Methods: A literature search was performed to establish the time and temperature at which partial/full thickness skin burns are acquired, regardless of vector. Using a thermocouple, the temperature of the top of two common lighters was measured at ten second intervals while sustaining maximal flame held both upright and sideways and during cooling once the flame was extinguished., Results: In the literature, the lowest temperatures documented to cause burns in one second were 69°C-70°C for transepidermal or partial thickness burns. From an ambient temperature prior to flame ignition, it took over 50s for the lighter tops to reach 60°C when held upright. After 180s, the lighters were shut off. It then took less than 60s for the lighters to cool to less than 60°C. The BIC lighter held to the side heated to 60°C in about 15s and needed over 100s to cool to under 60°C., Conclusions: Cigarette lighter burns are often blamed on non-intentional occurrences. At least 50s of sustained flame is needed to heat typical cigarette lighter tops to temperatures capable of inflicting clinically visible skin burns. This time is longer than the time required to light a cigarette. Therefore, for a cigarette lighter to inflict a contact burn injury, there needs to be intent and preparation, making accidental cigarette lighter burns unlikely., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Aims/hypothesis: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function., Methods: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin. Following this, glucose homeostasis and beta cell proliferation were evaluated and underlying molecular mechanisms were investigated., Results: The sustained elevation in circulating GLP-1 levels, caused by treatment of the knockout mice with vildagliptin for 6 weeks, significantly improved glucose tolerance secondary to enhanced insulin secretion and proliferation of beta cells. Treating βIRKO beta cell lines with the GLP-1 analogue, exendin-4, promoted Akt phosphorylation and protein expression of cyclins A, D1 and E two- to threefold, in addition to cyclin D2. Pancreases from the vildagliptin-treated βIRKO mice exhibited increased cyclin D1 expression, while cyclin D2 expression was impaired., Conclusions/interpretation: Activation of GLP-1 signalling compensates for impaired growth factor (insulin) signalling and enhances expression of cyclins to promote beta cell proliferation. Together, these data indicate the potential of GLP-1-related therapies to enhance beta cell proliferation and promote beneficial outcomes in models with dysfunctional beta cells.

Purpose: To determine the patterns of adjuvant chemoradiotherapy use in elderly patients treated with definitive surgical resection for squamous cell carcinoma of the head and neck with extracapsular extension (ECE) or positive margins and determine whether an association with overall survival (OS) exists with adjuvant concurrent chemoradiotherapy (CRT)., Methods and Materials: The National Cancer Database was queried to identify patients with SCC of the oral cavity, oropharynx, larynx, and hypopharynx who were treated with primary definitive surgery and adjuvant radiation therapy between 2004 and 2012. For elderly patients (aged >70 years) with pathology revealing ECE or positive margin, the benefit of concurrent chemotherapy was explored using multivariable Cox proportional hazards modeling., Results: A total of 7349 patients were identified meeting study criteria, of whom 1187 were elderly (aged >70 years) with a median follow-up of 30.6 months. Of these elderly patients, 445 had ECE or positive margin and represent the study population, of whom 187 (42%) received CRT. Delivery of CRT in this cohort increased over the study period, and intensity modulated radiation therapy was associated with increased use of CRT (odds ratio 2.07; P=.004). Increasing age was associated with reduced use of CRT (odds ratio 0.88; P<.001). Chemoradiotherapy was associated with a significant improvement in OS on multivariable analysis (hazard ratio 0.74; P=.04) and a trend toward significance on inverse propensity score analysis (hazard ratio 0.78; P=.051). Three-year OS was 53.8% in the CRT group, compared with 44.6% in the adjuvant radiation therapy-alone patients., Conclusions: The use of adjuvant CRT is increasing among elderly patients with resected squamous cell carcinoma of the head and neck exhibiting ECE or positive margins. Chemoradiotherapy was associated with an improvement in OS on multivariable analysis but not propensity-weighted analysis. Among fit elderly patients with ECE or positive margins after definitive surgical resection, concurrent chemotherapy can be carefully considered., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None

Objective: Traditional burn dressings demonstrate unfavourable tendencies of shrinking when wet and failing to maintain their integrity when manipulated. To overcome these obstacles, gel-forming fibre dressings have emerged as an alternative. Our objective was to observe the clinical properties and healing ability in the setting of burn wounds in a paediatric centre of a chitosan-based dressing containing silver., Methods: A sample of 12 partial-thickness burns in 10 children were identified for treatment with the chitosan-based silver dressing. The dressings were moistened before application, and monitored for any shrinkage on application. Patients were monitored for healing at outpatient follow-up visits and the dressings were allowed to separate as healing occurred., Results: We treated 12 burns in 10 children with an average age of 5.2 years. The burns had an average proportion of total body surface area (TBSA) of 3.6 % and involved the trunk and all extremities. Wounds healed mostly or completely in an average of 8.3 days. Dressings retained their size when wet and integrity when removed. No burns were found to be infected at any point in the study., Conclusions: The chitosan-based dressing offered an optimal environment for moist wound management, and did not demonstrate the shrinkage or disintegration that diminishes the clinical usability of widely used hydrofibre dressings. The burns healed within an expected period of time, and did not undergo any infectious processes. Based on the results of this pilot study, the chitosan-based silver dressing is deserving of further study as an alternative to traditional burn dressings.

Background: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC., Methods: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS)., Results: Among 28 samples obtained from 7 HNSCC cases and 7 controls, 422 metabolites were detected (269 identified and 153 unidentified). Oral washes contained 12 and 23 metabolites in healthy controls and HNSCC patients, respectively, with phosphate and lactate being the most abundant. Small molecules related to energy metabolism were significantly elevated in HNSCC patients compared to controls. Levels of beta-alanine, alpha-hydroxyisovalerate, tryptophan, and hexanoylcarnitine were elevated in HNSCC oral washes compared to healthy controls (range 7.8-12.2-fold). Resection tissues contained 22 metabolites, of which eight were overproduced in tumor by 1.9- to 12-fold compared to controls. TCA cycle analogs 2-hydroxyglutarate ( 2-HG) and 3-GMP were detected exclusively in tumor tissues. Targeted quantification of 2-HG in a representative HNSCC patient showed increase in tumor tissue (14.7 μg/mL), but undetectable in normal tissue. Moreover, high levels of 2-HG were detected in HNSCC cell lines but not in healthy primary oral keratinocyte cultures., Conclusions: Oral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted.

Objective: Nonthyroid metastases to the thyroid gland can cause morbidity, including dysphagia, dysphonia, and airway compromise. Because metastatic malignancies portend a poor prognosis, obtaining equipoise between treatment morbidity and local disease progression is paramount. We reviewed cases of nonthyroid metastases to determine treatment and prognostic recommendations., Study Design: Case series with chart review., Setting: Tertiary care hospital., Subjects and Methods: We searched PubMed for reported cases between 1994 and September 2013 using search terms as follows: any combination of primary tumor locations and thyroid, as well as the terms thyroid and metastasis. Only unique cases of nonthyroid metastases were included. Combined with 17 additional tumors at our own institution, we found 818 unique nonthyroid metastases, of which 384 had management and survival data available., Results: Renal cell carcinoma was most common, presenting in 293 (35.8%) patients, followed by lung and gastrointestinal malignancies. Patients were treated with total thyroidectomy (34.0%), subtotal thyroidectomy including lobectomy (32.6%), and no surgery (33.5%). Surgical management was associated with improved survival duration (P < .01). Locoregional recurrence was less likely in patients treated with total versus partial thyroidectomy (4.8% vs 13%). Extent of surgical management did not have a significant effect on patient survival. Delayed presentation was associated with improved survival duration (P = .01)., Conclusions: Nonthyroid metastases to the thyroid gland are unusual tumors. Surgical intervention is associated with improved survival, but expected morbidity of untreated tumors is difficult to assess. Site of origin, time to diagnosis, and surgical approach are related to survival and recurrence rates., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objectives: To analyze a cohort of patients with HPV positive, oropharyngeal squamous cell carcinoma (OPSCC) treated with lower radiation dose to clinically involved lymph nodes., Materials and Methods: We retrospectively identified patients with HPV positive, OPSCC treated with definitive chemoradiotherapy (70-74.4Gy) to the primary site and, since a post-radiation neck dissection was planned, 54Gy to the involved nodal areas. Neck dissection was ultimately omitted in all cases due to complete response. All patients were treated with a 3 field approach with sequential boost plans. Composite plans were generated retrospectively and primary tumor and lymph node GTVs were contoured and nodes were expanded by 5mm to form a CTV. Mean dose, dose to 95% (D95) and dose to 99% (D99) were determined., Results: Fifty patients treated from 2008 to 2010 with 113 involved nodes were identified. The median age was 57years, and 6%, 46%, and 48% were current, former, and never smokers. Ninety percent of patients received concurrent cisplatin based chemotherapy. Median D95 and D99 to involved nodes were 59.8Gy and 55.9Gy respectively. At a median follow up of 54.1months, two patients developed nodal failure and four developed metastatic disease. Five year loco-regional control, disease free survival and overall survival were 96%, 81% and 86% respectively., Conclusion: In this exploratory analysis, regional lymph node control in HPV positive oropharyngeal cancer was not compromised by dose de-escalated radiotherapy to involved nodes in the setting of concurrent cisplatin based chemotherapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Porcine xenograft (PX) has become a valuable part of the armamentarium of treatment options in a US paediatric burn centre. The use in adult patients has been well described in the burn literature, but there is minimal literature describing its use in children. The objective of this article is to describe a three-years' experience with PX use in paediatric burns., Method: A retrospective medical record review of patients with superficial partial-thickness burns treated with PX admitted to a paediatric burn centre between February 2009 and November 2012., Results: A total of 164 patients met the inclusion criteria. Burn total body surface area (TBSA) ranged from 0.5% to 28%. After the placement of PX, significant decreases were seen in the need for narcotic analgesics and burn dressing changes. Only four of 164 patients (2.4%) developed infections, although only one of these infections was at the site of the xenograft., Conclusion: PX appears to reduce pain and eliminate the need for procedural intravenous sedation in many patients. This can make burn wound care more child-friendly and shorten hospital length of stay. The complication rate is low and manageable. The authors believe that PX is an effective and safe treatment for superficial partial-thickness burns in children., Declaration of Interest: P. M.Glat, is a paid consultant and speaker for Mölnlycke Health Care, the manufacturer of EZ Derm.

Cutaneous ciliated cysts are benign lesions occurring primarily on the lower extremity of girls and young women. We present a case of a cutaneous ciliated Mullerian cyst arising in the lower leg of a 14-year-old girl, with brief discussion of etiology and diagnosis. This is a rare entity with approximately 50 cases in the literature.

Objectives: Hospital readmissions are an important focus of national quality and cost containment efforts. With increased emphasis on the impact of unplanned readmissions, it is critical to evaluate factors contributing to readmission rates and optimize strategies aimed at reducing these rates. The objectives of this study were to discuss quality interventions implemented at our institution and to evaluate their impact on reducing readmissions., Study Design: Case series with chart review., Setting: Academic tertiary care medical center., Methods: Medical records of patients who were admitted to an otolaryngology inpatient service and readmitted within 30 days of discharge between January 2010 and December 2012 were reviewed. A quality care plan (QCP) was developed, and various interventions were implemented during this time to affect these rates., Results: There were 769, 816, and 798 admissions during the years 2010, 2011, and 2012, respectively. The number of readmissions during this time were 50 (6.5%), 51 (6.3%), and 28 (3.5%), respectively. There were no statistically significant differences in case mix index, demographics, and subsequent length of stay for those patients requiring readmission. The reduction in number of readmissions in 2012, after the institution of our QCP, was statistically significant (P < .05)., Conclusion: Readmission within 30 days in a large otolaryngology practice can be multifactorial. To reduce rates of readmission, it is essential to understand the diagnoses, postoperative complications, and comorbidities contributing to readmission. Implementation of a QCP composed of comprehensive discharge planning and close postdischarge follow-up can lead to a reduction in readmissions., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.)

Objective: Despite extensive research into the treatment of partial-thickness burns, to date there has not been the emergence of a preeminent modality. This pilot study, the first such study to be performed in a burn unit in the US, was designed to evaluate the efficacy and outcomes of the application of copolymer dressing (Suprathel; PolyMedics Innovations Corporation, Stuttgart, Germany) for both superficial and deeper partial-thickness burns., Method: The copolymer dressing was used as a primary wound dressing to treat superficial and deep partial-thickness burns (average 5% total body surface area) in paediatric patients. Burns were debrided within 24 hours, at bedside, in the burn unit or in the operating room. The copolymer dressing was then applied directly to the wound and covered with a non-adherent second layer and an absorptive outer dressing. After discharge, patients were seen every 5-7 days until healed. Parameters evaluated included average hospital length of stay, average number of intravenous doses of narcotics administered, pain score at first follow-up visit, average time to complete re epithelialisation, incidence of burn wound infection, and patient/parent satisfaction on a 4-point scale. We also evaluated our experience with the dressing. Data were evaluated retrospectively under an Investigational Review Board approved protocol., Results: Of the 17 patients assessed the average hospital length of stay was 1.4 days during which the average number of intravenous narcotic doses administered before copolymer dressing application was 1.5 and after was 0.1 doses. At the first follow-up visit, average pain score was 1.2 on a 10-point scale and the average time to re epithelialisation was 9.5 days. There was no incidence of burn wound infection. Patient/parent satisfaction was average of 3.66 on a 4-point scale. The staff had found that the self-adherence and elasticity of the dressing made it easy to apply and stay adherent, especially in areas of difficult contour. There were no readmissions for further debridement or skin grafting., Conclusion: Our experience shows that patients may be discharged shortly after the application of the copolymer dressing, with manageable pain scores and ease of use as determined by the caretakers high satisfaction. This new, fully synthetic copolymer dressing is easy to apply, does not require any additional antimicrobial coverage and may be used to successfully manage deeper partial-thickness burns, donor sites or burns in areas of contour, where many other dressings might not be considered or be appropriate., Declaration of Interest: None declared.

The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity., (© 2014 by The Author(s).)

Importance: The present study addresses the survival benefit of aggressive surgical treatment of head and neck cancer involving the carotid artery., Objective: To assess survival outcomes in patients treated for advanced squamous cell carcinoma involving the carotid artery using different treatment strategies., Design, Setting, and Participants: Retrospective study at a tertiary care center of 44 consecutive patients with squamous cell carcinoma involving the carotid artery from 2005 to 2012 with a median follow-up of 12 months. The radiologist was blinded to the outcome of surgical procedures., Interventions: Surgery with or without radiotherapy, and definitive chemoradiation., Main Outcomes and Measures: Overall survival and rates of locoregional and distant failures. The hypothesis was formulated before data collection., Results: Of 44 patients, 35 (80%) were treated with curative intent with surgery with or without adjuvant therapy (n = 27 [61%]) or definitive chemoradiation therapy (n = 8 [18%]), while 9 patients (21%) were treated in a palliative fashion. Patients treated with curative intent had improved overall survival (median survival, 13.5 months) compared with the palliative group (median survival, 3.6 months) (P = .001). Of patients treated with curative intent, those with previously untreated disease (n = 14 [40%]) had an improved outcome relative to patients with recurrent or persistent disease (n = 21 [60%]), with median survival of 38.7 and 9.6 months, respectively (P = .008). Patients were treated with curative intent using 3 different treatment strategies (ie, carotid artery resection with or without reanastamosis) (n = 6 [17%]), curative peeling with or without adjuvant therapy (n = 21 [ 60%]), and definitive chemoradiation therapy (n = 8 [23%]). Survival outcome was not significantly different between subgroups treated with curative intention (P = .47). When reviewed by a head and neck radiologist in a blinded fashion (n = 30), preintervention imaging had a positive predictive value of 72.7% for resectability of cancer involving the carotid artery. In cases with almost circumferential involvement (>270°) and narrowing of the carotid artery, the disease was unresectable (n = 3)., Conclusions and Relevance: Advanced head and neck cancer involving the carotid artery can be treated with curative intent with favorable results in most patients. If disease burden merits, an aggressive approach involving resection with or without reanastamosis of the carotid artery can be used without significant added morbidity.

Objective: To compare the clinical Allen test, preoperative Doppler ultrasonography, and intraoperative surgical Allen test with postoperative clinical findings in reconstruction of complex head and neck defects using radial forearm free flaps., Design, Setting, and Patients: Retrospective review of 143 consecutive patients who underwent radial forearm free flap reconstruction from January 1, 1992, through December 31, 2006, at Vanderbilt University Medical Center., Results: Flap survival rate was 96.4%. No patients experienced digital necrosis or other findings of acute ischemia. Two patients (1.9%) who had normal results of clinical and surgical Allen tests developed hand contracture and palmar nodule formation. Surgical Allen test findings were normal in all patients who underwent reconstruction. Eighty-two arms had documentation of clinical Allen testing and Doppler ultrasonography in the patients' medical records. Agreement between these measures was 92.7%. The clinical Allen test result was 100% sensitive and 75% specific in predicting an abnormal Doppler ultrasonographic finding., Conclusions: The clinical Allen test is an appropriate preoperative evaluation before radial forearm free flap reconstruction. The addition of Doppler ultrasonography should be limited to patients with abnormal clinical Allen test results. The surgical Allen test provides reassurance but does not preclude the possibility of ischemic hand complications.

Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0.01). Furthermore, microbial populations can separate tumors by tobacco status (P < 0.008), but not by alcohol status (P = 0.41). If our subhypothesis regarding a mechanistic link from microorganism to carcinogenesis via inflammation and consequent aberrant DNA methylation is correct, then we should see hypermethylation of relevant genes associate with specific microbiomic profiles. Methylation analysis in four genes (MDR1, IL8, RARB, TGFBR2) previously linked to HNSCC or inflammation shows significantly increased methylation in tumor samples compared with normal oral mucosa. Of these, MDR1 promoter methylation associates with specific microbiomic profiles in tumor over normal mucosa. Additionally, we report that MDR1 methylation correlates with regional nodal metastases in the context of two specific bacterial subpopulations, Enterobacteriaceae and Tenericutes (P < 0.001 for each). These associations may lead to a different, and potentially more comprehensive, perspective on the pathogenesis of HNSCC, and support further exploration of mechanistic linkage and, if so, novel therapeutic strategies such as demethylating agents and probiotic adjuncts, particularly for patients with advanced or refractory disease.

1-[(2-adamantyl)amino]acetyl-2-cyano-(S)-pyrrolidine, monohydrochloride (PKF275-055), a vildagliptin analog, is a novel, selective, potent, orally bioavailable, and long-acting dipeptidyl peptidase IV inhibitor. We studied the effect of PKF275-055 administration on the prevention, protection, and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. PKF275-055 improved body and muscle weight. Oral glucose tolerance tests showed a marked improvement in glucose metabolism under all treatment schedules. When tested in prevention and protection experiments, PKF275-055 completely averted the decrease of Na⁺/K⁺-ATPase activity and partially counteracted the nerve conduction velocity (NCV) deficit observed in untreated diabetic rats but had no effects on abnormal mechanical and thermal sensitivity. When used in a therapeutic setting, PKF275-055 induced a significant correction in the alteration in Na⁺,K⁺-ATPase activity and NCV present in untreated diabetics. Diabetic rats developed mechanical hyperalgesia within 2 weeks after streptozotocin injection and exhibited significantly longer thermal response latencies. It is noteworthy that PKF275-055 treatment restored mechanical sensitivity thresholds by approximately 50% (p < 0.01) and progressively improved the alteration in thermal responsiveness. In conclusion, PKF275-055 showed an anabolic effect, improved oral glucose tolerance, and counteracted the alterations in Na⁺,K⁺-ATPase activity, NCV, and nociceptive thresholds in diabetic rats. The present data support a potential therapeutic effect of PKF275-055 in the treatment of rodent diabetic neuropathy.

Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma subtypes. Dual activation of PPARalpha and -gamma is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 mug/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.

Background: Our previous study has shown that nuclear factor-kappa B (NF-kappaB)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-kappaB inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity., Materials and Methods: Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-kappaB-associated genes., Results: Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-kappaB and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis., Conclusion: Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.

Background: We describe the development and validation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), which was designed to screen for tumor- and treatment-specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation (CCR)., Methods: Using a 2-step card sort method, we identified high-impact and high-frequency toxicities in patients with head and neck cancer treated with CCR. This resulted in a 28-item questionnaire which scores symptoms on a 0 to 10 scale (none to severe). The tool was validated using data collected from 5 supportive care studies comprising a total sample of 332 patients with head and neck cancer., Results: Responses to the VHNSS items demonstrated a very consistent pattern (Cronbach's alpha = 0.943) with each item contributing substantially to the global index. Five symptom subscales were identified including "Nutrition," "Pain," "Voice," "Swallow," and "Mucous/Dry Mouth." Each of the cluster scores demonstrated good internal consistency. The pattern of associations between the VHNSS and established tools indicated appropriate convergence and divergence. Comparison of global and subscale scores and objective measure were also in the expected direction providing further evidence of validity., Conclusions: The findings provide support that the VHNSS is a valid and reliable tool to assess head and neck-specific symptom burden and function loss. Further research to evaluate this screening tool as a part of a systems approach to supportive care is warranted.

Technical skill is only one component of overall surgical competency, but it has been one of the most difficult to measure. Assessment methods are currently subjective and unreliable, and include techniques such as operative logs, end-of-rotation global assessments, and direct observation without criteria. Newer objective methods of technical skill assessment are being developed and undergoing rigorous validation, including methods such as direct observation with criteria, final product analysis, and hand-motion analysis. Following the example set in other fields in which high-stakes assessment is paramount, such as in aviation, virtual reality simulators have been introduced to surgical competency assessment and training. Significant work remains to integrate these assessments into both training programs and practice and to demonstrate a resultant improvement in surgical outcome.

Inhibition of dipeptidyl peptidase-4 (DPP-4) is currently explored as a novel therapy of type 2 diabetes. The strategy has been shown to improve glycemia in most, but not all, rodent forms of glucose intolerance. In this study, we explored the effects of DPP-4 inhibition in mice with beta-cell overexpression of human islet amyloid polypeptide (IAPP). We therefore administered the orally active and highly selective DPP-4 inhibitor, vildagliptin (3 micromol/mouse daily) to female mice with beta-cell overexpression of human IAPP. Controls were given plain water, and a series of untreated wildtype mice was also included. After five weeks, an intravenous glucose tolerance test showed improved glucose disposal and a markedly enhanced insulin response in mice treated with vildagliptin. After eight weeks, a gastric tolerance test showed that vildagliptin improved glucose tolerance and markedly (approximately ten-fold) augmented the insulin response in association with augmented (approximately five-fold) levels of intact glucagon-like peptide-1 (GLP-1). Furthermore, after nine weeks, islets were isolated. Islets from vildagliptin-treated mice showed augmented glucose-stimulated insulin response and a normalization of the islet insulin content, which was reduced by approximately 50% in transgenic controls versus wildtype animals. Double immunostaining of pancreatic islets for insulin and glucagon revealed that transgenic islets displayed severely disturbed intra-islet topography with frequently observed centrally located alpha-cells. Treatment with vildagliptin restored the islet topography. We therefore conclude that DPP-4 inhibition improves islet function and islet topography in mice with beta-cell specific transgenic overexpression of human IAPP.

Objective: To shorten head frame wear time associated with external halo distraction (HD), we have adapted a protocol for maxillary distraction with the halo system that integrates plate fixation., Participants: All patients had a history of cleft lip and/or palate and maxillary retrusion > or = 8 mm. Five patients treated with this protocol and followed for at least 1 year were included in this study., Interventions: The protocol included a 3-day latency period, variable maxillary distraction, and removal of the halo device with simultaneous rigid internal fixation. Two patients had a variable period of maxillomandibular fixation (MMF), which maintained the maxillary advancement and idealized intercuspal position while permitting further callus maturation. Cephalographs were obtained preoperatively, immediately following distractor removal, and 1 year after rigid internal fixation., Results: The mean age at time of surgery was 18.7 years. The maxillary deficiency ranged from 8 to 15 mm (mean = 10.6 mm). All five patients demonstrated excellent occlusion. Cephalometric analysis 1-year post rigid internal fixation revealed minimal (<1 mm) skeletal relapse., Conclusions: Rapid maxillary distraction followed by MMF to maintain maxillary advancement may reduce halo device wear to 1 to 2 weeks. MMF optimizes occlusion by forcing the maxillary teeth into maximal intercuspal position. Rigid fixation is not only associated with less long-term relapse compared to nonrigid forms of fixation, but also minimizes the incidence of nonunion. This treatment protocol provides the advancement possible with distraction osteogenesis and the accuracy of orthognathic surgery, thereby minimizing external head frame wear.

Background: The optimal drug schedule and sequencing of chemotherapy and radiation for organ preservation in head and neck cancer has yet to be determined. We undertook a phase II trial of a taxane-based induction chemotherapy (ICT) followed by a taxane-based concurrent chemoradiation (CCR) regimen in patients with resectable stage III or IV disease to determine the feasibility, toxicity, and overall efficacy., Methods: Forty-four patients with laryngeal or tongue base carcinomas were enrolled. All patients received 3 cycles of chemotherapy with paclitaxel 175 mg/m(2) and carboplatin AUC (area under the curve) 6-7.5 over 30 minutes on days 1, 22, and 43. Responding patients went on to receive radiation (70 Gy/7 weeks) with cisplatin 75 mg/m(2) IV on days 1, 22, and 43 and weekly paclitaxel 30 mg/m(2) IV (n = 22). Because of hematologic toxicity, the concurrent regimen was changed to weekly carboplatin AUC 1 plus weekly paclitaxel 30 mg/m(2) (n = 22)., Results: Twenty-three patients with stage III and 21 patients with stage IV disease were enrolled. Median follow-up was 3.7 years. Acute toxicity of concurrent cisplatin and paclitaxel was excessive, with significant hematologic toxicity and 2 toxic deaths. Acute toxicities of concurrent carboplatin and paclitaxel were tolerable. No patients required permanent percutaneous gastrostomy tubes. The organ preservation rate was 83% (toxic deaths considered failures). Of 42 evaluable patients, 20 patients had complete responses (48%), 17 partial responses (41%), 3 minor responses (11%), 1 stable disease (2%), and 1 progressive disease (2%). Two-year local control, relapse-free survival, and overall survival were 82%, 77%, and 71%, respectively., Conclusion: There were no significant differences in relapse-free survival or organ preservation rates between concurrent regimens. Platinum and paclitaxel-based CCR is feasible after ICT and provides a high rate of organ preservation. Substitution of concurrent cisplatin to weekly carboplatin with paclitaxel and radiation has an improved toxicity profile. The ease of administration and low toxicity make this a regimen that is practical for use in the community setting., ((c) 2006 Wiley Periodicals, Inc.)

Background: African Americans (AAs) have a higher prevalence of obesity and type 2 diabetes than do whites. Higher insulin resistance and hyperinsulinemia have been reported in adult AAs than in whites. Differences in adipose tissue and its distribution may account for these findings., Objective: The objective was to ascertain whether differences between AA and white women in adipose tissue (AT) and skeletal muscle (SM) volumes account for ethnic differences in insulin resistance., Design: We used whole-body magnetic resonance imaging to measure AT and SM volumes and used the intravenous-glucose-tolerance test to measure insulin resistance., Results: AAs (n = 32) were 29-42% more insulin resistant than were whites (n = 28) after adjustment for weight and height or any AT volumes (P < 0.05). After adjustment for SM volume, the difference decreased to 19% and became nonsignificant. AAs had a 163% greater acute insulin response to glucose than did whites; this difference was significant even after adjustment for insulin sensivitity index, weight, height, and any magnetic resonance imaging measures. With respect to regional AT volumes, an association independent of race, weight, height, and SM volume was found only between increased intermuscular AT and lower insulin sensitivity index., Conclusions: Premenopausal AA women had significantly higher insulin resistance and acute insulin response to glucose than did their white counterparts. Whereas the difference in insulin resistance was partially accounted for by a greater SM volume in the AAs than in the whites, the difference in the acute insulin response to glucose was independent of any AT and SM measures and was disproportionately larger than expected according to the difference in insulin resistance. In addition, whole-body intermuscular AT was an important independent correlate of insulin resistance.

Glucagon-like peptide-1 (GLP-1) has long-term effects on pancreatic islets by increasing the insulin secretory capacity and beta cell mass. The islet effects of GLP-1 are glucose dependent and therefore tied to glucose sensing and metabolism. We examined whether prevention of inactivation of GLP-1 by inhibiting dipeptidyl peptidase-4 (DPP-4) is sufficient to promote long-term augmentation of glucose-stimulated insulin secretion. We also explored whether a defective glucose sensing and metabolism could be overcome by DPP-4 inhibition. We administered the orally active and highly selective DPP-4 inhibitor (1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidineP-4; vildagliptin; 3 mumol/mouse daily) to normal, wildtype, mice and to mice with a beta-cell targeted dominant-negative mutant hepatocyte nuclear factor-1alpha (HNF-1alpha); these mice have a defective islet response to glucose. After eight weeks, vildagliptin augmented the insulin response after gastric glucose (75 mg) by 5-fold in male mice (7.3+/-0.8 vs. 1.3+/-0.5 nmol/l, P<0.001) and 30-fold in female mice (26.5+/-5.8 vs. 0.9+/-0.3 nmol/l, P<0.001). Furthermore, glucose-stimulated insulin secretion from isolated islets was markedly enhanced by 9 weeks treatment with vildagliptin. In contrast, in transgenic mice, the severely suppressed insulin response was only marginally improved by vildagliptin in males, and not affected at all in females. We conclude that DPP-4 inhibition improves islet function and increases beta cell secretory responses on a long-term basis and that this is dependent on intact expression of HNF-1alpha.

Objective: To break out subcategories of atypical and suspicious cytologic interpretations of thyroid aspirations and correlate those with final histologic diagnosis., Summary Background Data: Fine-needle aspiration (FNA) of thyroid nodules has become the primary diagnostic tool in the initial evaluation of thyroid nodules. Management of thyroid nodules is based on statistical data correlating a specific cytologic reading with the probability of malignancy. Two particular cytologic readings that frustrate both cytopathologists and surgeons are follicular neoplasms and cells that show atypia. In most reported series, follicular neoplasms and cells showing atypia are included in a broad "suspicious" category, with reported overall malignancy rates generally between 20% and 30%. However, there is interest in determining whether these suspicious lesions can be subcategorized, allowing a more accurate assessment of the risk of malignancy. In addition, there is recent evidence that the incidence of follicular cancer may be declining in this country, possibly decreasing the probability that a "follicular neoplasm" will prove to be a follicular cancer., Methods: From January 1994 through December 2000, 709 thyroid FNAs were performed at a single institution. Those interpreted as suspicious and the subsequent histologic reports were reviewed. From this set, four specific categories were defined, and the clinical records for patients whose cytology matched these categories form the subject of this study. These four categories are follicular neoplasms without atypia, follicular neoplasms with atypia, atypia, and suspicious for malignancy. In addition, lesions with nondiagnostic cytology were reviewed. Only lesions for which there was histologic follow-up were considered., Results: Ninety-eight aspirates were categorized as follicular neoplasms without atypia, follicular neoplasms with atypia, or atypia alone. Of 74 follicular neoplasms without atypia, only 5 (6.8%) were malignant, and none of these were follicular thyroid cancers. Nine of the lesions were follicular neoplasms with atypia, and four (44.4%) of these were malignant, including two that were invasive follicular cancers. Of 15 lesions showing atypia alone, 3 (20%) were malignant, all of which were papillary thyroid cancers. Twenty-five additional patients had lesions highly suspicious for malignancy. Twenty-one (84%) of these lesions were malignant, the majority being papillary thyroid cancers. Only one was a follicular cancer. Fifty patients with nondiagnostic cytology had subsequent action taken. Thirty-one of these lesions were resected, with five (16.1%) proving to be malignant., Conclusions: Thyroid nodules whose FNA is diagnosed as highly suspicious for malignancy should be resected unless there are significant contraindications to a surgical procedure. The extremely low rate (2%) of invasive follicular cancers among all follicular neoplasms may reflect changing histologic criteria for follicular carcinoma, a true change in the disease frequency, or both. For thyroid nodules whose cytology shows a follicular neoplasm without atypia, malignancy rates of 8% or less may allow nonsurgical options, including reevaluation in selected populations. Continued efforts to correlate malignancy rates to specific cytologic criteria will allow patients to make more informed decisions regarding their medical care.

Traditionally, the role of chemotherapy in the treatment of squamous carcinoma of the head and neck has been confined to patients with recurrent or metastatic disease who are deemed incurable with surgery or radiation therapy. Over the past decade, however, the role of chemotherapy has changed dramatically. The use of primary combined chemoradiation to preserve function or to enhance survival in patients with unresectable disease has become a standard approach. As the use of chemotherapy in squamous carcinoma of the head and neck has expanded, investigators have been interested in identifying new active agents. Topoisomerase I inhibitors, a new class of drugs, have been found to be active in a number of solid and hematologic malignancies. Three topoisomerase I inhibitors have been investigated in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: 9-aminocamptothecin (9-AC), topotecan (Hycamtin), and irinotecan (CPT-11, Camptosar). Neither 9-AC nor topotecan has demonstrated clinically significant activity in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. In contrast, irinotecan has demonstrated a modest overall response rate of 21.2% (95% confidence interval [CI] = 9%-38.9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted.

Recurrent or metastatic squamous carcinoma of the head and neck (RMSCHN) is a modestly chemoresponsive tumor; however, currently available agents have failed to improve survival. New active agents are needed for the treatment of this disease. Topotecan is a topoisomerase inhibitor that demonstrated initial promising activity in squamous carcinoma of the head and neck. The Eastern Cooperative Oncology Group conducted a phase II trial of topotecan to determine the efficacy and toxicity of a weekly treatment schedule in patients with RMSCHN. Patients with metastatic or locally recurrent squamous carcinoma of the head and neck were treated with topotecan 1.5 mg/m2 x 24 hours by continuous infusion on days 1, 8, 15, and 22 of each 35-day cycle. Patients were stratified in two cohorts: chemonaive and previously treated. Sixteen chemonaive and 16 previously treated patients were registered on study. Grade III/IV neutropenia and anemia occurred in 16% and 18% of patients, respectively. No responses were observed in either cohort. Median survival for previously untreated patients was 4.6 months and 3.2 months for previously treated patients. Topotecan failed to demonstrate efficacy in patients with RMSCHN. Further evaluation of this agent is not planned.

Objectives: To report our results of a study of 28 patients who underwent sequential reconstructions of the head and neck using the lateral arm flap. To discuss the situations where we have found the procedure useful, report the complication rates, and delineate the advantages and disadvantages of using this flap., Design: A clinical series of patients was followed up prospectively. The swallowing function of a subgroup that underwent oropharyngeal reconstruction was compared with that of a simultaneous control group that underwent reconstruction with the pectoralis major flap., Setting: University medical center., Participants: Patients with malignant neoplasms of the head and neck who underwent resections and reconstruction with the lateral arm flap., Interventions: Twenty-eight patients underwent head and neck reconstruction using lateral arm flaps. In 17 patients, the lateral arm flaps were used for pharyngeal and posterior oral cavity defects. Thirteen of these patients underwent reinnervation. Nine combined palatal and midfacial defects were reconstructed, and 1 lateral facial defect was reconstructed. Most cases were advanced malignant neoplasms and represented a selected minority of similar resections performed at our institutions. Three maxillary reconstructions were performed secondarily. All other reconstructions were performed at the time of tumor ablation., Main Outcome Measures: Data were collected regarding flap survival, return of sensation in flaps, complication rates, and the ability to feed orally., Results: All flaps survived in their entirety. Of 7.5 tested flaps acquired sensation. Of 14 patients with large oropharyngeal defects, 8 resumed early oral feeding and all survivors eventually obtained nutrition orally. The ability to swallow was superior to the results obtained in a retrospective analysis of a group reconstructed using pectoralis major flaps., Conclusions: A unique feature of this flap is that it incorporates both thin skin from the proximal forearm and thicker skin from the upper arm. This is ideal for an oropharyngeal defect, where the thin malleable portion can be used in the posterior oral cavity or pharyngeal wall and the thicker portion in the tongue base. Either portion can be used alone as well. The availability of intermediate tissue bulk can also be advantageous for midfacial reconstruction. Sensation can be reliably reconstituted with this flap. We think that the lateral arm flap is versatile and has particularly low donor-site morbidity.

With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.

Cricothyroidotomy as a method of elective airway management, previously shunned by Jackson, was reintroduced to the medical community in 1976. This article examines available data indicating the utility and complications of elective cricothyroidotomy for long-term airway management and defines its place with respect to tracheotomy.

Pediatric nasopharyngeal tumors are rare, and few clinicians possess more than anecdotal experience. The differential diagnosis includes a diverse group of benign and malignant tumors, but can be narrowed further based on the clinical and radiographic appearance of the mass. Nasopharyngeal angiofibroma has such characteristic angiographic and CT imaging that many authors suggest biopsy is not essential in the evaluation of this lesion. We present a case of a pediatric nasopharyngeal neoplasm with angiographic, CT, and clinical findings consistent with angiofibroma. We then discuss the preoperative evaluation of, operative approach to, and postoperative staging and treatment of the biopsy-proven embryonal rhabdomyosarcoma. A review of the literature pertinent to this case is presented, and recommendations made concerning biopsy of lesions resembling juvenile nasopharyngeal angiofibroma. We believe this report reaffirms the use of histologic study whenever possible, in addition to radiographic imaging, in the diagnosis of pediatric nasopharyngeal masses.