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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.

BACKGROUND: The standard treatment for patients with oral cavity cancer (OCC) with intermediate risk pathologic variables after surgery is adjuvant radiotherapy. Despite this, one-third of patients experience locoregional failure (LRF). Clinicopathologic prognostic models have not been able to identify subsets of patients at higher risk of failure in whom treatment intensification with the addition of systemic chemotherapy should be considered. We posited that gene expression-derived tumor taxonomies can predict treatment failures and therefore guide more nuanced clinical decision making. Herein, we report on a score model based on OCC gene expression characteristics that can be incorporated into risk stratification and treatment decisions. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with intermediate risk OCC treated with surgery followed by radiation alone were subjected to quantitative nuclease protection and next-generation sequencing to measure gene expression (HTG Molecular EdgeSeq™). A subset of samples that had corresponding frozen tumor samples were profiled by RNAseq to validate the FFPE results. Patients were divided into two groups based on LRF. Differentially expressed genes were identified using the R limma package. 98 genes were selected on the basis of unadjusted P values and predicted biological impact, as measured by gene set enrichment results (GSEA) and resultant biological pathway scores. The Cancer Genome Atlas (TCGA) HNSCC dataset (n=521) was used to validate the prognostic performance of our gene set. RESULTS: Of the 78 patients included in the study, 35% of patients had LRF. GSEA of the 98 genes demonstrated a role for DNA repair, oxidative phosphorylation, hypoxia and p53 pathways, indicating radiobiologic plausibility for a significant subset of the genes that constitute the score. The mean composite score was 0.42 for patients with LRF, and -0.19 for patients without LRF (P = 0.0002). The Kaplan-Meier estimates of progression free survival at 3 years for the 1st (high risk) and 4th quartile (low risk) groups were 0.65 (0.47 to 0.89; 95% CI) and 0.93 (0.82 to 1; 95% CI), respectively. On multivariate analysis, the composite score was the strongest predictor of LRF (P = 0.0073). Composite scores also strongly predicted for overall survival in the TCGA HNSCC dataset (P < 0.01) and the Kaplan-Meier estimates of overall survival at 2 years for the 1st and 4th quartile groups were 0.55 (0.45 to 0.68; 95% CI) and 0.73 (0.63 to 1; 84% CI), respectively. Composite scores performed the best in patients with OCC (P = 0.033). CONCLUSIONS: We developed a gene signature that predicts LRF in patients with intermediate risk OCC treated with surgery and adjuvant radiotherapy. Further validation on larger datasets are needed. This biomarker can potentially identify higher risk patients who should be considered for intensification strategies with the addition of systemic therapy. Citation Format: Elif I. Sarihan, Brian B. Burkey, Joseph Scharpf, Robert Lorenz, Eric D. Lamarre, Brandon Prendes, Jessica L. Geiger, David J. Adelstein, Shlomo A. Koyfman, Mohamed E. Abazeed. A biologic basis for locoregional failure in patients with oral cavity cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3681.

Synovial sarcoma is typically an aggressive malignant tumor of the soft tissues, usually in the extremities, that affects young adults. Tumors of the head and neck are rare. Reported head and neck sites have included the hypopharynx (the most common site), the oropharynx, the larynx, and the soft tissues of the neck; only 4 cases of orbital involvement have been previously reported. We describe a case of synovial sarcoma of the medial canthus, which we discovered during a review of a tumor registry. The patient, an 18-year-old woman, underwent conservative excision and postoperative radiation therapy. Long-term follow-up detected no evidence of recurrence. Because there is no established, consistent approach to the treatment of synovial sarcoma of the head and neck, we also present a consensus management plan based on our review of the literature.

e18518Background: Facility volume has been found to predict improved survival for patients with breast and esophageal cancer. However, the role of facility volume in head and neck squamous cell car...

Objectives/Hypothesis: To develop a reliable modeling system for head and neck squamous cell carcinoma (HNSCC). Study Design: Laboratory-based translational study. Methods: HNSCC tissue was obtained from patients at biopsy/resection, cultured, and implanted into mice. In vivo, tumor growth, and survival was monitored by bioluminescence imaging. Histology and immunohistochemistry (IHC) were used to confirm HNSCC and human origin. Results: Short-term culture techniques were optimized allowing survival of primary HNSCC cells more than 7 days in 76% of tumors. The size of the tumor biopsy collected did not correlate with the success of short-term culture or xenograft establishment. Xenograft modeling was attempted in primary HNSCCs from 12 patients with a success rate of 92%. Immunostaining confirmed human origin of epithelial tumor cells within the modeled tumor. Bioluminescence and Ki67 IHC suggested tumor proliferation within the model. Luciferase expression was maintained for as long as 100 days in modeled tumors. Conclusions: The techniques developed for short-term primary tumor culture followed by xenograft modeling provide a low-cost and tractable model for evaluation of HNSCC response to standard and novel therapies. The high success rate of human-in-mouse tumor formation from primary HNSCC suggests that selection pressures for tumor growth in this model may be less than those observed for establishment of cell lines. Bioluminescent imaging provides a useful tool for evaluating tumor growth and could be expanded to measure response of the modeled tumor to therapy. This model could be adapted for xenograft modeled growth of other primary tumor types. Laryngoscope, 2009

Objectives/Hypothesis: We will discuss the transoral surgical approach to excising the submandibular gland, the relevant anatomy, the indications, and the risks and benefits of the procedure. We will present our case series of nine patients. Study Design: A retrospective review of a series of nine patients in which transoral submandibular gland excision was attempted over the past 10 years was performed. Methods: The series of nine patients who underwent transoral submandibular gland excision was examined for age, indication for operation, complications, length of stay, and postoperative pathology. Relevant indications, risks, and benefits are also discussed in conjunction with relevant surgical anatomy and approach utilized. Results: Of nine patients who underwent attempted transoral submandibular gland excision, eight operations were completed transorally. Only one operation was converted to a standard external approach due to severe scarring. Six of nine patients presented with chronic sialadenitis, three of nine having obstructing sialoliths. Three patients presented with other benign cystic lesions consistent with a ranula, an infected mucocele, and a cystic teratoma. There was only one patient with a complication of incision breakdown and delayed healing in an irradiated field. There were no long-term complications involving the lingual or hypoglossal nerves, and there were no hemostatic complications. Conclusions: Transoral excision of the submandibular gland is a viable and safe approach to be utilized. There are no external scars caused, there is minimal risk to the marginal mandibular branch of the facial nerve, and skin incisions through irradiated fields are avoided. Although the surgical anatomy is somewhat novel, the transoral approach has been used effectively and without complication in removing benign submandibular gland pathology in our series. Laryngoscope, 119:502–507, 2009

BACKGROUND. Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. METHODS. Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. RESULTS. Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. CONCLUSIONS. The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. Cancer 2008. © 2008 American Cancer Society.

Carcinogen exposure from tobacco smoking is the major cause of upper aerodigestive tract cancer, yet heavy smokers only have about a 10% life-time risk of developing one of these cancers. Current technologies allow only limited prediction of cancer risk and there are no approved screening methods applicable to the general population. We developed a method to assess somatic mutational load using small-pool PCR (SP-PCR) and analysed mutations in DNA isolated from cells obtained by mouth rinse. Mutation levels in the hypermutable tetranucleotide marker D7S1482 were analysed in specimens from 25 head and neck squamous carcinoma (HNSCC) cases and 31 controls and tested for associations with age, smoking history and cancer status. We found a significant association between mutation frequency and age (P=0.021, Generalized Linear Model (GLM), N=56), but no influence of smoking history. Cases had higher mutation frequencies than controls when corrected for the effects of age, a difference that was statistically significant in the subgroup of 10 HNSCC patients who were treated with surgery only (P=0.017, GLM, N=41). We also present evidence that cancer status is linked to levels of nonunique, and presumably clonally derived, mutations in D7S1482. Insertion mutations were observed in 833 (79%) of 1058 alleles, of which 457 (43%) could be explained by insertion of a single repeat unit; deletion mutations were found in 225 (21%) of tested alleles. In conclusion, we demonstrate that the sensitive detection of single molecule mutations in clinical specimens is feasible by SP-PCR. Our study confirms an earlier report that microsatellite mutations increase with age and is the first to provide evidence that these mutations may be associated with cancer status in individual subjects.

Summary 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 (70–74.4 Gy) to the primary site and, since a post-radiation neck dissection was planned, 54 Gy 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 5 mm 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 57 years, 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 59.8 Gy and 55.9 Gy respectively. At a median follow up of 54.1 months, 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.

Severe late dysphagia is common after chemoradiotherapy for cancers of the larynx and oropharynx. Options for reduction of severe late dysphagia are limited for human papillomavirus (HPV)-negative patients. In this study, the role of feeding tube choice in severe late dysphagia is investigated.Patients disease-free after chemoradiotherapy for HPV-negative cancers of the laryngopharynx who received a feeding tube on-treatment were identified. The incidence of severe late dysphagia after reactive nasogastric (R-NG), proactive or reactive percutaneous gastrostomy (P-PEG or R-PEG) was assessed using log-rank and Cox analyses.Seventy-eight patients received a feeding tube on-treatment and remained disease-free. Median follow-up was 64 months. The 5-year incidence of severe late dysphagia was 30.8% in the R-NG cohort (n = 36), 56.4% in the R-PEG (n = 17; p = .193), and 60.9% in the P-PEG (n = 25; p = .016) cohorts. On multivariate analysis, percutaneous gastrostomy (PEG) feeding was independently associated with an increased rate of severe late dysphagia.R-NG use during chemoradiotherapy is associated with less severe late dysphagia and is preferred over PEG. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1054-E1060, 2016.

Nonsurgical treatment of advanced supraglottic laryngeal cancer is widely used as part of a larynx preservation protocol. However, recent studies have suggested that nonsurgical treatment may be associated with inferior survival. Furthermore, it is not clear whether preservation of the larynx provides superior voice or swallowing function in the long term.To test the hypothesis that surgical treatment of advanced-stage squamous cell carcinoma of the supraglottic larynx is associated with superior overall survival (OS), freedom from recurrence (FFR), and noninferior voice and swallowing function.Retrospective medical record review of patients treated for stage III or IV squamous cell carcinoma of the supraglottic larynx between January 1990 and June 2013 at a tertiary referral center: 97 patients underwent surgical treatment and 138, nonsurgical treatment. Exclusion criteria included prior definitive treatment for laryngeal cancer or evidence of distant metastatic disease at presentation. The median follow-up for all 235 patients was 63 months.Surgical or nonsurgical therapy.Freedom from recurrence (FFR), OS, larynx preservation, voice graded from 1 to 5, and swallowing graded from 1 to 6 using our voice and swallowing function scales.Surgical treatment was associated with superior FFR (5-year FFR: 75% vs 55%; P = .006) but not OS (5-year OS: 52% vs 52%; P = .61). The larynx was preserved in 83% of patients in the nonsurgical group vs 42% of patients in the surgical group (P .001). Voice function was superior in the nonsurgical group at all time points through 5 years after treatment (mean voice score, 3.8 vs 2.6; P .001). Swallowing function was comparable between surgical and nonsurgical groups. Multivariable analysis revealed that advanced age (hazard ratio [HR], 1.43 per 10-year increment; 95% CI, 1.19-1.72) and clinical N stage (HR, 1.17 per 1-level increment; 95% CI, 1.05-1.30) were associated with worse OS, while treatment with chemotherapy was associated with superior OS (HR, 0.61; 95% CI, 0.41-0.92).Compared with surgical treatment, nonsurgical treatment as part of a larynx preservation protocol is associated with a higher likelihood of recurrence but has similar OS and should continue to be viewed as a viable alternative for the treatment of advanced supraglottic laryngeal cancer.

Fewer than five case reports of primary large cell neuroendocrine carcinoma of the nasopharynx are known to the authors. No previous reports have included examples of cytomorphology or have proven association with Epstein-Barr virus. We herein illustrate MRI findings, histopathologic features, immunohistochemical characterization, cytologic details, and in situ hybridization studies from a unique case of primary large cell neuroendocrine carcinoma of the nasopharynx in a 38-year-old Caucasian male patient. Recognition of rare tumor types of the nasopharynx allows for refinements in disease management and prognostication.

Objective: Mepilex Ag, a silver-impregnated foam dressing, was introduced to our institution in 2007 and our outcomes in the treatment of paediatric burns were observed to improve significantly. In order to confirm these observations, we wanted to evaluate the results of using the silver-impregnated foam dressing in partial-thickness paediatric burns. Method: In this retrospective study, the St. Christopher's Hospital burn registry was used to identify subjects, who were otherwise in excellent health at baseline, over an18-month period. Outcomes included length of stay, intravenous narcotic use, and time to healing. No direct comparative studies were performed. This was followed by a non-comparative prospective study involving 22 paediatric patients, aged 1–4 years, with partial-thickness burns. This was a sub-study of a larger randomised controlled trial involving adults with partial-thickness burns, comparing the silver-impregnated foam dressing with Silvadene. Results: In the retrospective part of the study, the silver-impregnated foam dressing was used successfully for the treatment of partial-thickness paediatric burns, with few complications and infections, allowing a shorter hospital stay, fewer dressings, and less pain medication than for historical controls. In the non-comparative prospective study, of 22 paediatric patients 50% healed completely within 1 week of treatment. The mean length of stay was 3.77 days and the mean number of dressings used was 1.64. Although narcotic usage was not assessed, patient surveys showed stinging or burning to be recorded as ‘never’ in 13 patients, ‘rarely’ in 8 patients, and ‘sometimes’ in 1 patient. Conclusion: The silver-impregnated foam dressing is effective and safe for use in partial-thickness paediatric burns, eliminating the need for daily dressings. Declaration of interest: The study was supported by an educational grant from Mölnlycke Health Care.

Importance Important differences exist in the pattern and timing of distant metastases between human papillomavirus–initiated (HPV+) and HPV− oropharyngeal squamous cell carcinoma (OPSCC). However, our understanding of the natural history of distant metastases in HPV+ OPSCC and its implications for surveillance is limited. Objective To investigate the rate, pattern, and timing of distant metastases in advanced-stage OPSCC treated definitively with concomitant chemoradiotherapy. Design, Setting, and Participants In a retrospective review, we identified 291 patients with pathologically diagnosed stages III to IVB OPSCC and known HPV status from a tumor registry at the Cleveland Clinic. Patients were treated from January 1, 1996, through December 31, 2013. Details of treatment failure and the natural history of the disease were retrieved from the electronic medical records. Interventions All patients were treated with definitive concomitant chemoradiotherapy. Main Outcomes and Measures The primary outcome was the rate and timing of distant metastases. Secondary outcomes included the pattern of distant failure and survival after distant metastases. Results Thirty-seven patients developed distant metastatic disease after definitive treatment, including 28 of 252 patients with HPV+ disease and 9 of 39 patients with HPV− disease. The 3-year projected distant control rate was higher in the HPV+ group (88% vs 74%; P = .01). The median time to develop distant metastases was also longer after the completion of treatment for HPV+ disease compared with HPV− disease (16.4 vs 7.2 months; P = .008). We detected a trend in patients with HPV+ disease for more distant metastatic sites involved than in those with HPV− disease (2.04 vs 1.33 sites; P = .09). Although the lung was the most common distant site involved in HPV+ and HPV− disease (HPV+ group, 23 of 28 patients [82%]; HPV− group, 7 of 9 patients [78%]), the HPV+ group had metastases to several subsets atypical for head and neck squamous cell carcinoma, including the brain, kidney, skin, skeletal muscle, and axillary lymph nodes in 2 patients each and in the intra-abdominal lymph nodes in 3 patients. The rate of 3-year overall survival was higher in the HPV+ group (89.9% vs 62.0%; P P Conclusions and Relevance This retrospective review suggests that distant metastases in patients with HPV+ OPSCC occurs significantly later after completion of chemoradiotherapy than in patients with HPV− disease. Human papillomavirus–initiated OPSCC also appears to involve a greater number of subsites and metastatic sites infrequently seen in head and neck squamous cell carcinoma. Distant metastatic disease in HPV+ OPSCC has unique characteristics and a natural history that may require alternative surveillance strategies.

PurposeHigh epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC.Patients and MethodsEGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points.ResultsForty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors.ConclusionHigh EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Oropharyngeal and hypopharyngeal squamous cell carcinomas require an interdisciplinary approach to manage patients appropriately. Tumor stage and histology, functional outcome, and patient comorbidities are important factors to consider. Various surgical approaches as well as chemotherapy and radiation therapy alone or in combination remain the mainstay of therapy.

Background. We sought to examine surgical tech- niques used to remove parapharyngeal space (PPS) masses. Methods. This retrospective search was conducted from 1980 to 2003. Age, sex, diagnosis, surgical approach, compli- cations, and outcome were collected. Results. One hundred sixty-six PPS masses were identi- fied: 21 (12.7%) were malignant, 145 (87.3%) were benign, 76 (45.8%) were vascular, and 69 (41.6 %) involved the skull base. Transcervical techniques were used in all cases. Removing the styloid and its musculature and level II lymphadenectomies enhanced exposure for vascular and skull base tumors. Thirty transcervical - transmastoid dissections (20.4%) facilitated removal of vascular skull base tumors. To identify the facial nerve, 20 transparotid- transcervical approaches (13.6%) were performed. Three mandibulotomies (2.0%) were required for internal carotid artery involvement. Expected neurologic se- quelae resulted from cranial nerve involvement by tumor. Three patients (2.0%), all presenting with recurrent cancer, had local recurrences. Conclusion. Careful patient assessment and surgical tech- niques allow the oncologically safe removal of benign, vascular, and skull base PPS tumors. A 2005 Wiley Periodicals, Inc. Head Neck 27: 669 - 675, 2005

Purpose of review Approximately 25% of all oral cavity carcinomas involve the lips, and the primary management of these lesions is complete surgical resection. The management of the resulting lip defect remains a significant reconstructive challenge, requiring meticulous preoperative planning and surgical technique to optimize the functional and cosmetic outcome. Reviewed here are the accepted techniques of lip reconstruction, as well newer techniques that have been reported. Recent findings There have been no major advances in lip reconstruction; rather, continued improvement on accepted techniques. The main goals of reconstruction remain the restoration of oral competence, maintenance of oral opening, and the restoration of normal anatomic relations such that both the active (smile) and passive (form) cosmetic outcome is acceptable. The reconstruction should be tailored to the individual needs of the patient and should take into account the patient's condition, local tissue characteristics, previous treatment(s), and functional needs (eg, denture use), in addition to the size and location of the defect. Summary The lips play a key role in facial expression, speech, and eating. This requires meticulous attention to preoperative planning and surgical technique to maximize the functional and cosmetic outcome. It is important to assess local tissue characteristics (skin laxity) and previous treatment (surgery and/or irradiation) before the surgical plan is made final. Local tissue should be used whenever possible to provide the least donor site morbidity and the best overall tissue color and texture match. Whenever possible, dynamic reconstruction should be attempted. Careful preoperative assessment and planning will allow the surgeon to reach an acceptable balance between form and function with the reconstruction.

PURPOSE OF REVIEW When the complex structures of the upper aerodigestive tract are disrupted after resection of head and neck tumors, an appropriate reconstructive option should be chosen in an attempt to regain maximum function. Reconstructions using microvascular free tissue transfer offer unparalleled flexibility, both in tissue composition and in placement. This article will examine functional outcomes after free flap reconstruction of the upper aerodigestive tract. RECENT FINDINGS With the maturation of free tissue transfer techniques, functional outcomes are being analyzed with increasing frequency. Recent reports show promising results for free flap reconstruction of oral cavity, oropharyngeal, and hypopharyngeal soft tissue defects, as well as for bony mandibular and maxillary defects. SUMMARY For both soft tissue and bony defects of the upper aerodigestive tract, microvascular free flaps provide good functional outcomes. In the future, randomized studies are needed to compare the functional outcomes of microvascular free flaps with those of other reconstructive options.

Purpose of review The anterolateral thigh free flap has achieved recent popularity in North America for the reconstruction of head and neck defects after ablative surgery. The flap is most often based on either the septocutaneous or musculocutaneous perforators of the descending branch of the lateral circumflex femoral artery. Its versatility allows for a subcutaneous, fasciocutaneous, myocutaneous, or adipofascial flap to be obtained. Recent findings Recent publications have described the utility of the anterolateral thigh flap for reconstruction of head and neck defects. It has been used successfully in the reconstruction of the laryngopharynx, oral cavity, oropharynx, external skin, and maxilla. Furthermore, when a thinner flap is needed, a suprafascial anterolateral thigh flap may be raised or the flap may be thinned after it is obtained. Summary The anterolateral thigh flap is a highly versatile and reliable flap for use in the reconstruction of various soft tissue defects of the head and neck. This flap has gained great popularity in mainland China, Taiwan, and Japan given its versatility, ability for a two-team approach, and minimal donor site morbidity. However, it has not met the same enthusiasm in Europe and North America because of the relative difficulty in perforator dissection, reported variations of the vascular anatomy, and the presumed increased thickness of the anterolateral thigh tissue in the Western population in comparison with the patient population of the Far East. These obstacles may be overcome by increased surgical experience and by the ability to create a thinner suprafascial flap or thinning the flap after it has been obtained.

Most skin cancers involving the head and neck region are easily managed with surgical resection and local flap rotation. Occasional patients present with massive neglected skin cancers or skin cancers that have recurred after multiple treatments. Management of these massive tumors may involve craniofacial resection, maxillectomy, or mandibulectomy to obtain clear margins. Reconstruction requires massive composite soft tissue replacement. We presented our experience with, to our knowledge, the largest series reported to date.A retrospective chart review of 43 patients with massive neglected skin cancer of the head and neck reconstructed by means of free tissue transfer from January 1, 1992, through October 1, 2001.Academic tertiary referral medical center.Seventeen patients with squamous cell carcinoma and 26 patients with basal cell carcinoma were treated. Primary sites included the cheek (n = 15), ear (n = 8), forehead (n = 5), neck (n = 4), scalp (n = 5), and nose (n = 6). Treatment involved a combination of orbital exenteration (n = 16), maxillectomy (n = 12), mandibulectomy (n = 6), auriculectomy (n = 5), craniofacial resection (n = 10), rhinectomy (n = 6), and lateral temporal bone excision (n = 5). Flaps used for reconstruction included the rectus abdominis (n = 22), latissimus dorsi (n = 11), radial forearm (n = 8), and lateral arm (n = 2). Radiotherapeutic exposure included pretreatment in 21 patients and posttreatment in 15. Twelve patients had undergone no previous surgeries; 15 patients, 1 to 5; and 16 patients, more than 5. Follow-up revealed evidence of local recurrence (n = 12), locoregional recurrence (n = 3), distant metastasis (n = 3), and no evidence of disease (n = 25).Massive skin cancers are generally associated with disfiguring, debilitating surgery and high mortality rates. We demonstrate that free tissue transfer yields acceptable survival with functional and cosmetic outcomes.

Objectives/Hypothesis: The management of palatal defects resulting from the extirpation of benign and malignant lesions uses a variety of methods, with the optimal techniques allowing maximal postoperative function with minimal morbidity. The palatal island flap is an effective, reliable technique for reconstructing postablative oral cavity defects. Methods: All patients who underwent palatal resections for benign or malignant lesions at a tertiary care, referral-based head and neck cancer center since 1995 were eligible. Ten patients were identified whose surgical defects were reconstructed with palatal island flaps. The cases were reviewed for the symptomatology, tumor features, defect size, perioperative and postoperative management, complications, and impact on palatal function. Results: Ten patients ranging in age from 18 to 81 years underwent palatal island mucoperiosteal flaps after resection of a variety of benign and malignant tumors, most arising from minor salivary glands. The defects ranged in size from 5 to 15 cm 2 , with extension into the floor of the nose in four cases and to the skull base in two. Nine patients were discharged on a regimen of oral diet, and no patient manifested permanent velopharyngeal insufficiency, speech impairment, or airway compromise. Follow-up ranged from 3 months to 6 years, with an average follow-up of 18.5 months. Delayed donor site re-epithelialization required debridement in one case, and two patients required obturation of small oronasal fistulae. Conclusion: The palatal island mucoperiosteal flap provides an effective means of reconstructing hard and soft palate defects with few complications and low morbidity.

Study Design. The lateral cervical spinal approach is illustrated by a case of neurenteric cyst. Objectives. To present a case of a neurenteric cyst resected via the lateral cervical approach, and to review the approach in detail. Summary of Background Data. Intradural lesions located anterior to the high cervical spinal cord may present a difficult surgical problem. Neurenteric cysts are unusual lesions found in the brain and spinal cord. This report presents a case of cervical neurenteric cyst causing anterior cord compression that was resected using the lateral cervical approach. Methods. A 32-year-old woman presented with chronic headaches and worsening nausea, tinnitus, dizziness, and hyperreflexia and clonus in her lower extremities. Magnetic resonance imaging of the cervical spine showed a mass compressing the anterior spinal cord at C3. Pathology showed that this lesion was a neurenteric cyst. The lesion was resected using the lateral cervical approach. Results. At this writing, 36 months after surgery, the patient has continued resolution of her symptoms, and no cyst recurrence has been shown on repeat MRI imaging. She has no evidence of postlaminectomy kyphosis. Conclusions. The lateral cervical approach is useful for surgeons attempting to resect lateral and anterior intradural lesions of the cervical spine. It also gives excellent cranial-to-caudal access to the thecal sac, spinal cord, and the lesion to be resected. The neck incision preserves cosmesis, and neuromuscular function is maintained. Spinal fusion was avoided in the reported case.

Objectives/Hypothesis: Occult papillary thyroid carcinoma has a reported prevalence of 1% to 35% based on autopsy studies. Cervical lymphatic metastases from papillary thyroid carcinoma have been associated with a higher likelihood of recurrence with a questionable impact on survival. Without clinically evident disease in the thyroid or cervical nodes, management of these patients presents a treatment dilemma. We propose an individualized treatment plan for patients in whom metastatic papillary thyroid carcinoma is incidentally detected during neck exploration for other purposes. Study Design: Retrospective review and discussion of the literature. Methods: The clinical course of two patients with incidentally discovered metastatic papillary thyroid carcinoma to the cervical lymph nodes is described. Both patients had previously received head and neck irradiation in childhood and required free flap reconstruction of extensive skull base defects following extirpation of meningiomas. Results: Neck dissection specimens from levels I and II obtained during exposure of recipient vessels for microvascular tissue transfer revealed papillary thyroid carcinoma in both cases. The patients subsequently underwent total thyroidectomy, neck dissection, and postoperative radioactive iodine ablation of residual thyroid tissue. After 1 year of follow-up, both patients were without evidence of recurrent disease. Conclusions: An individualized approach is justified to treat metastatic papillary thyroid carcinoma incidentally discovered during other procedures. The case reports underscore the importance of pathological analysis of surgical specimens obtained during head and neck reconstruction.

Although the current trend in head and neck reconstruction is the use of free tissue transfer, local and regional flaps can still provide effective donor tissue. The recent literature has focused on the use of locoregional and regional flaps used for oral cavity and oropharynx reconstruction. Additi

6072 Background: Addition of chemotherapy to adjuvant radiation (RT) confers an OS benefit and is recommended in HNSCC patients with nodal extracapsular extension (ECE) and positive surgical margins based on pooled data. The purpose of this study is to retrospectively evaluate a larger patient data set in an attempt to confirm this observation and to assess current patterns of practice. Methods: The National Cancer Data Base (NCDB) was queried to identify patients with HNSCC who were treated with primary definitive surgery followed by adjuvant RT between 2004 and 2012. For patients treated with surgery and post-operative RT with or without chemotherapy, the effect of the systemic therapy on OS was explored using multivariable Cox proportional hazards modeling and stratified by patient and disease factors. Results: 6,351 patients were identified meeting study criteria; 3157 patients (49.7%) received adjuvant RT alone, and 3194 patients (50.3%) received adjuvant chemoradiotherapy (CRT). An increase in chemotherapy usage was observed over time (6% of patients in 2004; 16% in 2012). No difference was seen in OS by use of CRT (median OS 8.3 years in patients without CRT vs. 9.4 years in patients with CRT, p = 0.0893). On multivariate analysis OS was improved in younger patients, patients with less co-morbidity, oropharynx, lower T and lower N. OS was also improved in patients given chemotherapy if either ECE or positive surgical margins were present (HR 1.166, p = 0.0438) but not in those with negative surgical margins and no ECE (HR 1.037, p = 0.5888). Nonetheless, chemotherapy was given to 38% of post-operative patients without these risk factors and not given to 35% of patients with risk factors. Conclusions: This NCDB analysis confirms an OS benefit with addition of chemotherapy to post-operative RT in HNSCC patients with ECE or positive surgical margins but not in patients without these risk factors, consistent with current guidelines. National practice patterns, however, do not mirror these recommendations. These results are subject to limitations of retrospective analysis of a large database and further studies are needed to better elucidate high risk factors benefiting from intensifying adjuvant therapy.

Background Immunosuppressed patients have higher rates of cutaneous squamous cell carcinoma of the head and neck. Objective This study reviews the effect of immune status on disease characteristics and treatment outcomes. Methods Patients with cutaneous squamous cell carcinoma of the head and neck treated with surgery and postoperative radiotherapy between 2000 and 2011 were included. Immunosuppressed patients underwent prior organ transplantation or chemotherapy. Baseline variables were compared using χ 2 and unpaired t tests. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. Results In this study of 59 patients, 38 (64%) were immunocompetent and 21 (36%) were immunosuppressed. Most patients had recurrent tumors (63%) and node-positive disease (61%), which were well balanced between the groups. Poorly differentiated tumors (62% vs 21%; P = .009), lymphovascular invasion (29% vs 11%; P = .08), and extracapsular extension (57% vs 41%; P = .09) were more frequent in the immunosuppressed group. Two-year disease-free survival (45% vs 62%) and 2-year overall survival (36% vs 67%) were inferior for immunosuppressed patients. Limitations Limitations include single institution, retrospective study with small sample size, and potential referral bias. Conclusions Immunosuppressed patients with cutaneous squamous cell carcinoma of the head and neck more frequently present with high-risk pathologic features and inferior outcomes. Early multidisciplinary assessment and alternate management strategies merit prospective investigation.

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.Case series with chart review.Academic tertiary care medical center.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.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).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.

Objectives:(1) Compare outcomes of patients with sinonasal malignancies (SNM) treated with an open resection to patients treated with an exclusively endoscopic or endoscopic-assisted approach. (2) Analyze the differences in surgical complications, length of hospital stay, and margin status between open and endoscopic approaches.Methods:A retrospective review was performed on 102 patients with a pathologically diagnosed T3 or T4 SNM treated definitively at a tertiary care academic center from 1995 to 2012. Oncologic outcomes were determined.Results:Of the 102 patients, 29 presented with T3 disease while 73 presented with T4 disease. The most common histologic subtype was squamous cell carcinoma (56.9%). Fifty-three patients (52.0%) underwent open resection while 26 (25.5%) underwent an endoscopic or endoscopic-assisted resection. The 5- and 10-year disease-specific survival (DSS) for the 2 surgically treated groups was 67.6% and 65.2%, respectively. There was no significant difference between patients trea...

Importance This study helps to elucidate the appropriate surgical treatment for sinonasal melanoma. Objective To compare open resection (OR) and endoscopic resection (ER) as surgical approaches to sinonasal mucosal melanoma (SNM)and evaluate their associations with treatment-related outcomes. Design, Setting, and Participants Retrospective review of the medical records of 25 patients with sinonasal mucosal melanoma (SNM) treated by either OR or ER in an academic tertiary care medical center. Interventions The patients underwent either OR or ER of their SNM tumors. Main Outcomes and Measures Overall survival was the primary outcome measured; secondary outcomes were postoperative complications, lengths of hospital stay, patterns of failure, and disease-free survival. Results Thirteen patients with SNM underwent an OR, while 12 had ER of their tumors. The OR and ER groups did not differ significantly in demographic and tumor characteristics. In the OR vs ER group comparisons, mean age (67.8 vs 65.5 years) ( P = .63), the proportions of patients who received adjuvant radiotherapy (85% [n = 11] vs 92% [n = 11]) ( P > .99), and the proportion who achieved negative surgical margins on resection (54% [n = 7] vs 58% [n = 7]) ( P = .82) were similar. Overall all median survival (12.7 and 1.9 years) ( P = .87) and disease-free survival (1.9 and 1.2 years) ( P = .72) were modest and did not differ between OR and ER groups, respectively. Likewise, the OR and ER groups, respectively, showed comparable mean lengths of hospital stay (3.6 and 3.8 days) ( P = .87), rates of postoperative bleeding (8% [n = 1] and 17% [n = 2]) ( P = .59), and rates of cerebrospinal fluid leak (15% [n = 2] and 25% [n = 3]) ( P = .64). In addition, the OR and ER groups, respectively, had high rates of local (23% [n = 3] and 8% [n = 1]) ( P = .59), distant (15% [n = 2] and 25% [n = 3]) ( P = .64), and multiple failures (15% [n = 2] and 25% [n = 3]) ( P = .64). Conclusions and Relevance This retrospective study of a rare disease suggests that endoscopic resection of sinonasal melanoma offers an attractive, minimally invasive surgical option. In the hands of an experienced surgeon, an endoscopic approach yields survival and morbidity outcomes comparable to those of an open approach.

Background Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is associated with high cure rates and distant metastases are rare. Methods and Results We report a case of a 61-year-old man presenting with acute left-sided weakness. An enhancing dural mass was noted and resected. Histology revealed p16-positive SCC. Further workup revealed a p16-positive right tonsillar primary with ipsilateral nodal disease and was classified as T2N2bM1. The patient underwent whole brain irradiation and definitive chemoradiation with curative intent. Complete clinical response was achieved and the patient continues to be disease-free 6 months posttreatment. Conclusion HPV-associated oligometastatic oropharyngeal SCC is a rare entity that may have a unique natural history and behavior. Given the excellent treatment response and prognosis of HPV-positive disease in general, these patients may be appropriate for definitive treatment approaches. © 2014 Wiley Periodicals, Inc. Head Neck, 36: E103–E105, 2014

Although the tongue is not a vital organ in sustaining life, it may be a vital organ in sustaining the will to live in many people. As carcinoma of the tongue represents the majority of the 30,000 oral cavity cancers diagnosed per year in the United States, many patients face the potential consequences of resection of part or all of the tongue for cure. To date, reconstructive options do not restore optimal tongue function including articulation, swallowing, taste, or sensation. With the ultimate goal of improving tongue reconstruction, we report on a successfully performed autograft transplantation of the tongue in an animal model. Before undertaking allograft transplantation of the tongue, an autograft tongue transplant would be attempted to identify the feasibility of such a procedure and to determine the similarity of an animal model with human techniques. The dog's neck, tongue, and oral anatomy represent an excellent animal model for tongue reconstruction. This procedure can be performed successfully in an animal model. The only previously published replantation of the tongue involved the reattachment of the anterior portion of a human tongue after physical trauma. To our knowledge, the enclosed report represents the first successful total excision and replantation of the tongue in either a human or animal model.

Total or near-total esophageal stricture results from multiple processes. Traditional treatment with wire cannulation followed by serial dilation is often contraindicated due to poor visualization and the risk of perforation. We seek to demonstrate that combined antegrade and retrograde endoscopy are useful for treatment of total or near-total esophageal strictures. The gastrostomy tube is removed and the tract dilated. A standard endoscope is passed retrograde to the stricture. An antegrade endoscope is advanced until transillumination across the stricture is visualized. A biopsy forceps or needle is used to traverse the stricture in an antegrade fashion. The tract is cannulated with a stiff wire that is then brought out through the gastrostomy site. The stricture is serially dilated. The gastrostomy tube is replaced, and a nasogastric tube is left across the stricture for 3 to 4 weeks. The endoscope is withdrawn and an 18 or 20 Fr gastrostomy tube is left in place. A total of three patients with total esophageal strictures were treated using combined antegrade and retrograde esophagoscopy. All three patients regained the ability to swallow secretions. Importantly, there were no instances of esophageal perforation. This technique has broader application, including combination with minilaparotomy for patients without retrograde access. Further research is needed to determine durability of stricture dilation.