A novel, bioactive, fibre-reinforced composite implant is a solution to address the shortcomings in craniofacial bone reconstruction. A longitudinal, clinical investigation with a follow-up time of 4 years, was conducted.

A cranial bone reconstruction with the implant was performed to 12 patients. In these patients, the reasons for craniotomies resulting in craniofacial bone defects, were traumatic and spontaneous intra-cranial bleeding as well as infections to the primary reconstruction material. The implant material consisted of a supporting fibre-reinforced framework, porous inner layers and a bioactive glass (S53P4) filling. The framework and the porous layers were made of a pBisGMA-pTEGDMA resin matrix, which was reinforced with silanized E-glass.

In clinical examinations and skull x-rays, the implants were in original positions providing the expected functional and aesthetic outcome at all time points.

The implants functioned appropriately which would provide a potential solution for craniofacial bone reconstruction in the future. Head Neck, 2013

The survival rates and prognostic factors for salivary duct carcinoma (SDC) are not clear.

Survival estimates and prognostic factors were evaluated for 228 SDC patients identified from the Surveillance, Epidemiology, and End Results database.

Median overall survival duration for SDC patients was 79 months and 5-year disease-specific survival rate (DSS) was 64%. Among SDC patients with lymph node involvement (LNI), larger primary tumor size (>3cm) was associated with twice the risk of death (p<0.03). Factors predictive of improved DSS were age (p=0.01), tumor size (p=0.006), tumor grade (p=0.02) and LNI (p<0.001). Adjuvant radiotherapy did not improve survival when compared to surgery alone for early stage (I-II) disease (p=0.28).

Younger SDC patients (<50 years) showed a better prognosis. Primary tumor size and LNI were independent and additive risk factors for poor prognosis. The role of adjuvant radiotherapy in the treatment of SDC needs to be explored further. Head Neck, 2013

Octreotide, a somatostatin analogue, may be beneficial in the treatment of paragangliomas of the head and neck (HNPGLs).

Non-blinded, prospective intervention study. During one year, patients received a monthly intramuscular injection of 30 mg Sandostatin LAR^®. Pre- and post-treatment tumor volumes were assessed by magnetic resonance imaging, urinary catecholamine secretion was measured and HNPGL-related signs and symptoms were recorded.

In one out of four included HNPGL-patients, a stabilization of tumor growth was observed after octreotide therapy. In one patient, octreotide therapy was discontinued before the end of the study because of potential side-effects.

No improvements in HNPGL-related signs and symptoms were observed.

In one out of four patients, HNPGL tumor growth velocity was reduced after octreotide therapy. Research assessing the effects of somatostatin analogues targeting different sst subtypes or combined with other therapies may offer new possibilities for the treatment of HNPGLs. Head Neck, 2013

There have been few reports of prophylactic thyroidectomy using the MIVAT approach in children with MEN2.

Retrospective review of a prospectively maintained database of patients who underwent MIVAT for total thyroidectomy.

Six children underwent MIVAT; RET codon mutations identified were 634, 620, 611, and 918. Mean operative time was 93 minutes(range 68-105). Five patients were discharged on the first postoperative day; one patient suffered a postoperative haematoma and was discharged 2 days postoperatively. There were no cases of laryngeal nerve palsy or post-operative hypoparathyroidism. High levels of satisfaction with post-operative cosmesis were reported. Calcitonin levels have been undetectable at follow-up, thusfar (mean follow-up 42.8 months).

Whilst our outcomes are similar to those reported using the traditional approach, it is important to note that MIVAT is essentially the same operation, just performed through a smaller incision, with resulting benefits in terms of pain, cosmesis and, perhaps, morbidity. Head Neck, 2013

Sinonasal cancers are rare and associated with a poor prognosis. The aim of this study was to report our experience and analyze the risk factors for oncologic failures.

A retrospective review of 156 consecutive patients treated with curative intent for sinonasal malignancy between 1995 and 2005 at tertiary cancer center was performed. Demographic, clinical, morphological and pathological parameters were correlated with oncologic outcomes.

Complete response was obtained for 134 patients. Sixty-eight patients relapsed among which 51 had local recurrence. Nine of these 51 patients (17.6%) underwent successful salvage therapy. Five years local failure and overall survival rates were 50.0% and 61.1%. Maxillary sinus tumors, intracranial invasion and N>0 stage at initial diagnosis were significantly and independently associated with local failure and survival in multivariant analysis.

Local control following initial treatment is primordial to optimizing outcomes due to the poor results of salvage therapy. Head Neck, 2013

Transoral techniques for oropharyngeal tumors, such as transoral robotic surgery (TORS) and transoral laser microsurgery (TLM), require new reconstructive considerations.

Defects from 92 patients undergoing TORS were classified into 4 classes. A reconstruction algorithm was followed. Perioperative outcomes and complications were assessed. Forty seven patients completed the MD Anderson Dysphagia Inventory (MDADI) swallowing questionnaire and a modified Velopharyngeal Insufficiency Quality of Life questionnaire (VPIQL) post-operatively.

The most common reconstructions involved velopharyngoplasties with local flaps (39%), local flaps alone (25%), or secondary healing (20%). More advanced defects (Class III and IV defects) required regional and free flaps more often. No significant differences were found in MDADI scores or VPIQL scores among the four defect classes. Only adjuvant radiotherapy was a predictor of poor swallowing (p = 0.02).

The classification system for transoral oropharyngeal defects maps defects into four classes and guides the reconstructive thought process. Head Neck, 2013

Gasless transaxillary approach (TA) and bilateral axillo-breast approach (BABA) are two distinctive approaches for endoscopic thyroidectomy. The aim of this study was to evaluate and compare these 2 procedures.

From May 2008 to July 2011, we performed endoscopic hemi-thyroidectomy via gasless TA (83 cases) and BABA (45 cases). The following variables were evaluated: operation time, postoperative pain score, drainage amount, drainage day, postoperative complications, and cosmetic satisfaction score.

There were no significant differences between two approaches in terms of clinicopathologic characteristics and surgical outcomes except postoperative pain and cosmetic satisfaction. As for postoperative pain and cosmetic satisfaction, gasless TA group complained of less pain and BABA group had a better cosmetic outcome.

These findings will contribute to providing guidelines for the choice of surgeons between gasless TA and BABA techniques for endoscopic thyroidectomy. Head Neck, 2013

Frozen section analysis (FSA) is frequently employed in salvage surgery for recurrent or residual nasopharyngeal carcinoma after radiotherapy (rNPC) to ensure adequate tumour removal. However, the diagnostic accuracy of FSA in rNPC has never been clearly established. This was the first study to specifically address these issues.

Patients with rNPC who underwent nasopharyngectomy in Queen Mary Hospital from 2006 to 2011 were identified. Clinical data, FSA results, and permanent histological results were analyzed.

In the tissue-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 70.6%, 100%, 100%, 95.2%, and 95.7% respectively. Only 37% of inconclusive FSA turned out negative on permanent histology. Presence of inconclusive (p=0.000) or positive (p=0.000) FSA results in the same operation significantly lowered the NPV of FSA.

FSA is useful in ensuring clear resection margins for rNPC. Further resection is advisable in cases of inconclusive FSA results. Head Neck, 2013

Treatment of oropharyngeal cancer with Transoral Robotic Surgery (TORS) or definitive (chemo)radiotherapy impacts quality of life. Utility scores are needed for quality of life and economic comparisons.

Fifty healthy subjects and 9 experts reviewed scenarios describing treatment (TORS alone or with adjuvant radiotherapy or chemoradiotherapy, definitive radiotherapy, and chemoradiotherapy), complications, remission, and recurrences. Utilities were assessed using visual analogue scales (VAS) and standard gamble (SG) techniques. Treatments were compared using paired comparisons. Demographic variability was assessed.

TORS had higher SG utilities than radiotherapy (p = 0.001) and chemoradiotherapy (p < 0.001) and was preferred in paired comparisons (p < 0.001 for both) for healthy subjects. Utilities did not vary by demographic group and correlated between experts and subjects (VAS r = 0.95, p < 0.001; SG r = 0.97, p < 0.001).

TORS has higher utility scores than chemoradiotherapy. Utilities can be used for cost-utility analyses. Head Neck, 2013

We aimed to validate bioelectrical impedance analysis (BIA) using the Geneva equation for fat-free mass (FFM) in head and neck cancer (HNC) patients.

In 24 HNC patients, agreement between BIA (FFM_BIA) and dual energy x-ray absorptiometry (FFM_DXA) one week before (T₀), one month (T₁) and four months (T₂) after cancer treatment was analyzed.

FFM_BIA did not differ from FFM_DXA (mean difference 0.71±1.9, 0.30±1.9 and 0.02±2.1 kg) at any time point. Only at T₀, mean FFM correlated to the difference between FFM_DXA and FFM_BIA (r=0.48, P=0.017). Limits of agreement were 3.8, 3.7 and 4.1 kg respectively. Concordance Correlation Coefficients were 0.98 at all time points.

BIA may be used to assess FFM with reasonable validity based on mean-level comparisons, but differences between BIA and DXA may vary by about 4 kg in an individual patient. These results require confirmation in a larger sample of HNC patients. Head Neck, 2013

Laryngotracheal stenosis (LTS) can cause persistent or recurrent airway obstruction. While there is extensive literature on surgical techniques to treat LTS at onset, there are few techniques described for complex adult LTS after failed prior airway surgery. We describe a procedure used successfully in three patients who required structural augmentation for complex LTS.

Patients were treated with staged reconstruction using a prefabricated composite graft consisting of auricular cartilage and a radial forearm free flap.

All patients were reconstructed successfully with good wound healing and are tolerating oral diets. Two patients have been successfully decannulated.

A delayed prefabricated graft using auricular cartilage in a radial forearm free flap is a viable surgical intervention in patients with complex adult LTS who are not candidates for conventional approaches. Head Neck, 2013

Rats were allocated into 4 groups of 11 animals each, representing different treatments: (1) alendronate; (2) alendronate and corticotherapy; (3) alendronate and diabetes; and (4) control. Tooth extractions were performed in all animals, and histological analysis was performed by hematoxylin and eosin staining and immunohistochemistry using anti-bone morphogenetic protein (BMP)-4 and anti-matrix metalloproteinase (MMP)-13 antibodies.

On hematoxylin and eosin analysis, proportions of inflammatory infiltrate, microbial colonies, and osteonecrosis were significantly greater in the diabetes group. BMP-4 expression in connective tissue was higher in the corticosteroid group than the alendronate group. There were no significant differences between the other groups. MMP-13 expression did not differ between the groups analyzed.

Diabetes but not corticotherapy is associated with jaw osteonecrosis in rats undergoing alendronate therapy and subjected to tooth extractions. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

We treated 39 patients with chemodectomas with RT. Patients were treated with either single dose stereotactic radiosurgery, fractionated stereotactic radiotherapy, or intensity modulated radiotherapy (IMRT), depending on the size and anatomy of the lesion. At primary diagnosis, 16 patients were treated with surgical resection (41%), 4 with interventional embolization (10%), and 19 with primary RT (49%). Single doses of 18 Gy/80% isodose were applied. For fractionated treatments delivered as primary RT, a median total dose of 57.6 Gy was delivered. Five patients were treated with re-irradiation, of which 4 were treated with fractionated regimens; total dose was 28.8 Gy, 30 Gy, 40 Gy, and 56 Gy in 1.8 to 2 Gy single fractions.

Clinical symptoms improved in 18 patients (46%), remained unchanged in 10 patients (26%), and worsening of sequelae was observed in only 1 patient, which was associated with tumor progression. Actuarial local control was 97% at 10 years. Overall survival was 89% at 5 years and 87% at 10 years. Deaths were not disease-related except in 3 patients with tumor progression. No secondary malignancies were observed.

RT has been established as a treatment alternative for patients with glomus tumors. Long-term local control is very high, with good clinical response to treatment. Head Neck, 2013

Quality of life was assessed using the Medical Outcomes Study-Short Form-36 (MOS SF-36) and the University of Washington Quality of Life (UW-QOL) questionnaires 12 months after reconstruction.

A total of 121 of 163 questionnaires were returned (74.2%). There were significant differences between the 2 groups in the T classification (p < .005). Patients reconstructed with free anterolateral thigh perforator flaps performed better in the appearance and shoulder domains, and the role emotion and social functioning domains.

Using either radial forearm free flaps or free anterolateral thigh perforator flaps for reconstruction of head and neck defects after cancer resection significantly influences a patient's quality of life. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

A case of repeatedly recurrent ameloblastoma with malignant transformation is presented. The clinical course and managements are described.

The 63-year-old man had a recurrent ameloblastoma in the left mandible. Five years after the first surgical resection, he underwent 8 more rounds of surgical excision of the recurrent tumors. The malignant transformation occurred and the unresectable tumor invaded the masticator space, parapharyngeal space, and skull base. He received 3-dimensional conformal RT, at the dose of 66 Gray (Gy) in 33 fractions. The ulcerative exophytic mass had regressed gradually. After follow-up of 28 months, the tumor was well controlled.

RT seems to be a feasible treatment option for recurrent ameloblastoma with malignant transformation. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The study population consisted of 20 consecutive patients presenting multiple oral neoplastic lesions for a total of 25 paired lesions. The mtDNA D-loop analysis was performed by direct sequencing and phylogenetic clusterization.

Agreement between mtDNA analysis and clinical classification was found in 19 cases. Discrepancies arose in 6 cases in which the clinical criteria based only on the spatial or temporal distance of the second lesion from the index tumor had led to a diagnosis of SPT (2 cases) or local recurrence (4 cases).

The present data highlight the value of mtDNA analysis in establishing the clonal relationship between the index tumor and the second neoplastic lesion. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

We used a mass spectroscopy–based approach (Sequenom) to evaluate 95 hallmark single nucleotide variations (SNVs) within 12 oncogenes or tumor suppressor genes (AKT, BRAF, CDK4, Beta-catenin, epidermal growth factor receptor [EGFR], FBXW7, JAK2, c-KIT, KRAS, PDGFR, PI3K, and vascular endothelial growth factor [VEGF]) in 13 histologically confirmed SNUC cases.

None of the samples demonstrated activating mutations in any of the 95 SNVs.

Select clinically relevant activating genomic mutations were not identified in the 13 patient samples. However, polymorphisms were noted within the promoter region of VEGF. These may merit future studies as predictive biomarkers for treatment response or overall survival. Additionally, future studies focusing on larger tumor sets and utilizing whole genome or exome sequencing may help define genetic aberrations in SNUC that can be clinically targeted with available or emerging biological agents. Head Neck, 2013

Data from the California Cancer Registry and U.S. Census were used to compare incidence rates and trends of OPSCC and other human papillomavirus–related and –unrelated cancer sites by neighborhood SES, race/ethnicity, and sex.

The incidence of OPSCC rose in both higher and lower SES neighborhoods. Absolute rates were greater in the latter. Only non-Hispanic white males with OPSCC demonstrated a significant increase in the incidence rate of squamous cell carcinoma of the head and neck (SCCHN). The incidence rate for this group increased from 4.5/100,000 person-years between 1988 and 1992 to 7.1 between 2003 and 2009. Regression analysis demonstrated an annual percentage change of 1% from 1988 to 1997 and 4% thereafter.

Increases in incidence rates are SES independent. Incidence rates are higher in lower-SES groups. The rise in OPSCC incidence is limited to non-Hispanic white males. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroperoxidase antibody (anti-TPO), and thyroglobulin antibody (anti-TG) levels of 55 patients with NPC were taken before RT and at 3, 6, 12, and 18 months after RT. Patients with hypothyroidism at 18 months after RT and those with normal thyroid function were categorized into the hypo and normal groups, respectively. The thyroid antibody levels were compared between the 2 groups, and the correlations of thyroid antibody and thyroid hormone were evaluated for the hypo group.

The anti-TPO and anti-TG of the hypo group were higher than the normal group. In the hypo group, there was a positive correlation (r = 0.51) between TSH and anti-TG and a negative correlation between fT4 and anti-TPO (r = −0.55).

There were correlations of the thyroid antibody and thyroid hormone levels in patients with radiation-induced hypothyroidism. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Patients with head and neck cancer treated with radiation therapy (RT) from 2004 to 2010 who experienced neck spasms werereviewed. Radiation doses were generated for their sternocleidomastoid (SCM) muscles bilaterally. Unaffected SCMs were used as controls.

Thirty-four patients reported neck spasms. Thirty had received definitive chemoradiation, and 4 had RT alone. Seven also had an ipsilateral neck dissection. Median time to onset was 23 months (range, 6–67 months). There were significantly higher radiation doses to the affected SCMs with a median of the mean dose to the affected and unaffected SCM of 62.3 Gy (range, 29–71 Gy) and 53.7 Gy (range, 27–65 Gy), respectively (p < .0001). Other dosimetric variables were also statistically significant but were highly correlated with the mean SCM dose. Neck dissection did not affect our results.

Neck spasms after chemotherapy intensity-modulated radiation therapy (IMRT) shows a strong dose–response relationship. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

In all, 255 consecutive patients with complete clinicopathologic data were included. Survival was determined using the log-rank test and Kaplan–Meier survival curves were generated. A Cox proportional hazards model was used to adjust for the effect of other significant covariates to determine the independent effect of complication variables for overall survival (OS). A competing risk model was used for disease-specific survival (DSS).

On multivariable analysis, major complications independently prognosticated for reduced OS [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1–3.2, p = .02]. There was no evidence for an association between any complication-variable and DSS or recurrence.

Major postoperative complications are independently associated with decreased OS. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Thirty-two patients with stage III–IV head and neck cancer treated by chemoradiotherapy were invited to evaluate nutritional status (malnutrition, relative weight loss), food intake (food modification; quality), and dysphagia.

At a median follow up of 44 months, 6 of 32 patients were at risk for malnutrition. Women (p = .049) and patients with high body mass index before treatment (p = .024) showed more weight loss. None of the 32 patients could eat a “full diet.” Six patients used nutritional supplements/tube feeding. Low dysphagia-related quality of life scores were significantly correlated to increased food modification (r = 0.405; p = .024).

Nutritional advice in patients with head and neck cancer is still necessary years after chemoradiation and should focus on nutritional status, food modification, and quality, in accord with recommended food groups. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

In all, 114 patients treated with surgery with and without chemoradiotherapy for advanced oral/oropharyngeal cancer were recruited. Clinicopathologic tumor parameters and reconstruction modalities were recorded. Swallow function was determined by oral intake, using the Functional Oral Intake Scale (FOIS) pretreatment and posttreatment.

The median time to first attaining swallow function was 14 days. Patients were less likely to attain tube independence within 1 year of surgery if they received radiotherapy or had a low FOIS score preoperatively. Patients' time to first attaining swallow function postsurgery was inversely related to the FOIS score presurgery.

Swallow function recovery postsurgery is better in patients with higher FOIS presurgery, smaller tumors, and no requirement for radiotherapy. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

To study the diagnostic accuracy of physical examination (PE), ultrasonography (US), contrastenhanced computed tomography (CT) and in preoperative detection of macroscopic nodal metastasis in primary/recurrent papillary thyroid carcinoma (PTC) patients to determine if the routine addition of CT would be beneficial in accurate preoperative lymph-node surgery planning.

In a tertiary center prospective study, 162 PTC patients underwent preoperative lymph-node evaluation by PE, US, and CT. Sensitivity, specificity, positive/negative predictive value (PPV/NPV) of each nodal detection technique were calculated in central/lateral cervical compartments. The gold standard for diagnostic-accuracy was surgical pathology.

In patients undergoing primary (Group I)/revision (Group II) surgical treatment for PTC, combined US/CT yielded significantly higher sensitivity for macroscopic lymph-node detection in both lateral and central neck, most marked in Group I-central compartment.

Combined preoperative US/CT provides reliable, objective, preoperative macroscopic nodal metastasis map to design rational nodal surgery in primary/revision PTC patients. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Patient-related e-mails received between January 2002 and June 2009 were retrospectively analyzed regarding the diagnosis of hemangiomas or vascular malformations. Additionally, the visitors' statistics of the corresponding website ‘‘www.angiome.de” was evaluated.

Five hundred forty-eight e-mails matched the criteria of the study. From 2002 to 2008, the number of messages registered annually increased by a factor of 20 and the average number of e-mails per patient tripled. The number of new patients contacting the center via e-mail increased from 12 to 72 per year. The website ‘‘www.angiome.de” was visited 8490 times in 2008 and 13,291 times in 2009.

The presence of the internet is relevant to get in touch with new patients and to provide information for nonprofessionals and experts especially in diseases with low incidence. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

This retrospective study reviewed asymptomatic patients treated with RT for head and neck cancer from 2000 to 2009 who underwent screening carotid ultrasound.

Two hundred twenty-four patients were included, the majority of whom had stage III to IV disease and received cisplatin-based chemotherapy. Median time from RT completion to last carotid ultrasound was 3 years. Actuarial rate of carotid artery stenosis at 4 years was 14% (95% confidence interval [CI], 4% to 22%). Multivariate analysis revealed that carotid artery stenosis was associated with Framingham risk factors (hazard ratio [HR], 1.6 per factor; 95% CI, 1.2–2.2; p = .003). Among 135 patients treated with intensity-modulated radiation therapy (IMRT), the HR for carotid artery stenosis was 1.4 for every 10 Gy increase in mean RT dose to the carotid bulb plus 2 cm (95% CI, 0.8–2.4; p = .35).

Prevention and screening programs should be considered for head and neck cancer survivors given the high risk of carotid artery stenosis. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010.

Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC.

Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

A literature review was performed using Ovid Medline and Embase databases. A total of 306 abstracts and 78 full-text articles were reviewed. Forty-two articles were eligible for inclusion.

Patients undergoing nerve-sacrifice neck dissections have greater disability and lower quality of life scores than those undergoing neck dissections with the least manipulation (ie, selective neck dissections). Shoulder impairments can still occur in patients undergoing selective neck dissections. Disability typically improves over time in patients undergoing nerve-sparing neck dissections.

There was significant variability in the literature in terms of the prevalence and recovery of shoulder morbidity after neck dissection. This variability may not just be related to surgical technique or rehabilitation, but also to study design, definitions, and the variability in disability questionnaires used. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

This was a retrospective review of 10 patients followed over a 5-year period at a single tertiary academic medical center. Patient, tumor, clinicopathologic, functional, and oncologic outcomes were collected and analyzed.

All cancers treated were either T1 (40%) or T2 (60%). Negative margins were achieved in all patients. Four patients received adjuvant radiation therapy (40%). No patients experienced surgical complications and all had excellent functional outcomes. Mean follow-up was 24 months (range, 2–60 months) with locoregional and distant control achieved in 8 patients (80%) and 9 patients (90%), respectively.

Minor salivary malignancies of the oropharynx are a surgical disease. Short-term follow-up data demonstrate feasibility, low morbidity, good functional, and oncologic results for TORS management of these malignancies. Head Neck, 2013

A PMMC flap size of 1.5 × 4 cm was required for repair of leakage which developed 2 weeks after the primary ablative surgery for hypopharyngeal cancer. The skin paddle was designed in the size of 4.5 × 7 cm and was deepithelized except the original dimension. After the skin edge was sutured to the defect margin, the deepithelized dermal portion covered the repair site to enhance the suture.

The effective dimension of a very small skin paddle can be quite enlarged thus increasing the possibility of capturing perforators. This could decrease the risk of avulsion during flap transfer and provide backing of the repair site. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty-seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control.

Median follow-up was 47.3 months (range, 9.7–139.2 months). The 3-year locoregional control, recurrence-free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty-six patients underwent neck only RT with exclusion of the primary site.

TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Local resection of the mass was reported to treat the condylar osteochodroma in some cases. The purpose of this study was to evaluate the feasibility and the indications of the local resection.

In all, 47 patients with osteochondroma of the mandibular condyle were treated from January 2002 to March 2012. The decision to perform local resection depended on 2 factors: there was a stalk existing between the mass and the condyle, and the condylar surface was involved less than 1/2.

Local resection of the mass was performed in 38 cases (80.1%). These masses were removed by 4 methods: direct removal (18 cases), pushed-out by a screw and steel wire (14 cases), excision in multiple pieces (3 cases), and temporary osteotomy of the zygomatic arch (3 cases). In the follow-up period, there was no recurrence.

Local resection of the mass was a more conservative procedure to treat the solitary osteochondroma with a stalk. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Analysis of the impact of risk factors on survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated by primary intensity-modulated radiotherapy (IMRT).

One hundred forty patients were included with tissue microarray (TMA) construction and immunohistochemical analysis in 124 patients (87%).

Survival analysis of patients classified into 3 risk categories according to an algorithm based on p16, smoking, T classification, and N classification revealed significant differences with a low, intermediate, and high-risk group. There was a significant impact of p53 expression as surrogate marker for smoking on outcome. In multivariate analysis, p16-positivity was a positive predictor and alcohol as well as N classification was a negative predictor for survival. The algorithm was modified based on alcohol instead of smoking with even more significant differences between the groups.

A risk model based on multiple factors instead of p16 as single marker can define different risk groups to select patients for treatment deintensification in future prospective clinical trials. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Metastasis in a tracheostomy site occurs rarely, usually from head and neck primary tumors. Breast cancer relapse to a tracheostomy has not been described to date.

A 71-year-old women presented with symptoms typical of central airway obstruction, 10 years after mastectomy for breast cancer. Fifteen months before admission, when cancer follow-up was negative, she also had surgery for cerebral aneurysm and a tracheostomy. On admission, CT showed a solid mass infiltrating the tracheostomy tract and projecting into the airway. Tracheal obstruction palliation was achieved by laser resection of the endotracheal growth and stenting. Histology documented breast cancer metastasis.

Tracheostomy site metastasis was the presenting sign of late-onset relapse of breast cancer. This case supports the concept of surgery-driven interruption of micrometastatic cancer dormancy, in that the initial recurrence developed in a tracheostomy that was surgically created several years after resection of the primary tumor. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Studies concerning prognostic factors specific for alendronate-related osteonecrosis of the jaws (ONJ) are rare.

We surveyed a cohort of 100 osteoporotic patients with 111 alendronate-related ONJ lesions treated during a 4-year period. Prognostic values of clinical variables and serum markers of bone turnover were assessed by univariate and multivariate analyses.

The cumulative complete response rate at 6 months was 48.65%. Serum bone-specific alkaline phosphatase (BSAP) level >10 μg/L, lesion depth ≦ 10 mm, and lesions in anterior regions denoted a better chance of healing within 6 months and the adjusted hazard ratios were 2.48 (95% confidence interval [CI], 1.41–4.37), 2.71 (95% CI, 1.57–4.70), and 3.94 (95% CI, 1.87–8.30), respectively.

Early discovery of lesions and prevention of their deeper extension are crucial for improving the prognosis of alendronate-related ONJ. A higher pretreatment level of BSAP indicates a better prognosis. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

This study evaluated cervical lymph node metastases at level IIb in cases of hypopharyngeal cancer and analyzed the possibility of preservation of level IIb during neck dissection.

In total, 34 patients (51 neck sides) with hypopharyngeal cancer that underwent neck dissection from April 2008 to April 2011 were retrospectively analyzed. We evaluated the distribution of metastatic lymph nodes at various levels (particularly level IIb) in cases treated with therapeutic neck dissection and elective neck dissection.

The incidence of metastases in level IIb was 13.3% (4 of 30 patients) for therapeutic neck dissection and 0% (0 of 21 patients) for elective neck dissection. All the level IIb metastases were found on the ipsilateral side in the cases treated with therapeutic neck dissection.

The results suggest that preservation of level IIb during neck dissection was possible in N0 cases of hypopharyngeal cancer. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The purpose of this study was to evaluate the use of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the identification of extracapsular spread (ECS) with supporting histologic correlation in hypopharyngeal cancer.

We retrospectively reviewed the medical records of 57 patients who underwent FDG PET/CT for hypopharyngeal cancer.

ECS was present in 79% dissected necks (45 of 57 patients) and in 64% dissected cervical levels (55 of 86). A significant difference in standardized uptake value maximum (SUV_max) values was found between cervical lymph nodes with and without ECS (6.10 ± 3.51 vs 1.75 ± 1.46, respectively; p < .001). The cutoff value of SUV_max for differentiating with and without ECS was 2.65 with a sensitivity of 80% and a specificity of 74%. The presence of ECS and median SUV_max were found to have a significant adverse effect on 5-year disease-specific survival.

Median FDG PET/CT SUV_max cutoff values of 2.65 or greater are associated with a greater risk of ECS in cervical lymph node metastasis from hypopharyngeal squamous cell carcinoma (SCC). © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Neuroendocrine tumors of the thyroid encompass a wide differential diagnosis. The most common is medullary thyroid carcinoma. One must consider other possibilities when a neuroendocrine thyroid tumor is calcitonin negative. We report 2 cases of Ewing sarcoma of the thyroid and discuss the differential diagnosis and workup of a calcitonin-negative neuroendocrine tumor of the thyroid.

This is a retrospective review of 2 patients diagnosed with Ewing sarcoma of the thyroid and a review of the literature.

Ewing sarcoma of the thyroid is an exceedingly rare diagnosis, but should be included in the differential diagnosis for a thyroidal neuroendocrine lesion (especially in the absence of calcitonin). The use and interpretation of immunohistochemistry (IHC) and fluorescent in situ hybridization are essential in making the correct diagnosis. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

We compared clinical outcomes between patients with salivary gland carcinomas preoperatively misdiagnosed as benign lesion and properly diagnosed as malignant lesion.

The outcomes were compared between patients with benign lesion and malignant lesion (44 each) on preoperative fine-needle aspiration cytology diagnosis who underwent conservative or radical surgery.

Five-year lesion-free survival (DFS) rates were 86.8% for benign lesion and 76.3% for malignant lesion (p = .128). Surgical extent did not significantly affect locoregional recurrence and DFS (p = .360). Univariate analysis showed that sublingual gland tumor, positive resection margin, and extraparenchymal extension (EPE) were significantly associated with DFS (p < .05 each). On multivariate analysis, EPE remained an independent variable (p = .047, hazard ratio = 6.621, 95% confidence interval = 1.393–31.474).

The clinical outcomes of patients with salivary gland carcinomas misdiagnosed as benign are relatively favorable. Conservative surgery may be sufficient for patients with low-grade and T1–2 salivary gland carcinomas. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

An earlier stage of primary disease at diagnosis is associated with better survival from laryngeal cancer. It remains unproven whether earlier stage is also associated with improved end-organ function and quality of life after treatment.

Questionnaire packs were posted to 250 patients with laryngeal cancer treated between January 2006 and December 2008 within the West of Scotland. Packs contained the Voice Symptom Scale (VoiSS), MD Anderson Dysphagia Inventory (MDADI), and University of Washington Quality of Life Questionnaire (UW-QOL).

One hundred forty-seven eligible patients provided data for analysis (59% of original cohort). Patients with an earlier stage of primary disease reported significantly better VoiSS, MDADI, and UW-QOL scores (p < .05). No differences were found between scores of patients with T1 laryngeal disease treated with endoscopic laser resection (ELR) and radiotherapy.

An earlier stage at diagnosis is associated with significantly better end-organ function and quality of life after treatment for laryngeal cancer. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The purpose of this study was to investigate the rate of simultaneous second primary tumor (SPT) in patients with oral squamous cell carcinoma. The survival of patients with simultaneous SPT was also compared with patients without.

The presence of SPT was documented along with the patients' demographic data, tumor-related features, and survival status. Kaplan–Meier method was used for survival analysis. Relevant factors influencing the survival were examined by the Cox proportional hazard model.

A total of 897 patients' medical records were obtained. Among them, 43 patients (4.8%) had simultaneous SPT and their prognosis was poorer than that of patients without. The Cox proportional hazard model revealed that patients with simultaneous SPT tended to have a higher probability of death (relative risk [RR], 1.694; p = .015).

Simultaneous SPT is an independent prognostic factor for patients with oral squamous cell carcinoma. Those with simultaneous SPT have poorer survival when compared to those without. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to reduce the incidence of radiation-induced toxicity in patients with early-stage oropharyngeal cancer, using highly conformal radiation techniques.

Between 2000 and 2011, 167 patients with T1-3N0-3 oropharyngeal cancer were treated with 46-Gy intensity-modulated radiation therapy (IMRT) followed by 22-Gy brachytherapy boost. In patients with node-positive disease, neck dissection was performed.

The 5-year Kaplan–Meier estimates of local control, regional control, disease-free survival (DFS), and overall survival (OS) were 94%, 97%, 84%, and 72%, respectively. Feeding tubes were required in 26% of the patients. Grade ≥2 late xerostomia and dysphagia were 11% and 8%, respectively. Chemotherapy, tumor subsite, and bilateral neck irradiation correlate significantly with toxicity. Quality of life (QOL) scores deteriorate during and shortly after treatment but returned in all scales to baseline scores within 6 to 12 months, with the exception of xerostomia.

Brachytherapy boost and neck dissection (in node-positive oropharyngeal cancer) after 46-Gy of IMRT resulted in excellent outcomes with low incidence of late toxicity and good QOL scores. © 2013 Wiley Periodicals, Inc. Head Neck, 2012

Frey's Syndrome is a frequent complication of parotid surgery. The aim of this study was to evaluate the association between skin flap thickness and Frey's Syndrome in patients who underwent superficial parotidectomy.

Thirty adult patients were randomized into 2 groups: subcutaneous and subsuperficial musculoaponeurotic (sub-SMAS) skin elevation. In both groups skin flap thickness was measured by a micrometer at defined points. The patients were queried for subjective Frey's Syndrome and Minor's test was performed for objective Frey's Syndrome.

The thickness of skin flap in the subcutaneous group was significantly less than that in the sub-SMAS group. There was no statistical significance between skin flap thickness and objective Frey's Syndrome, although the dimension of the colored area in the subcutaneous group was larger compared with that of the sub-SMAS group: 7.5 cm² (0–48 cm²) and 0.5 cm² (0–18 cm²), respectively.

In conclusion, sub-SMAS elevation of the skin flap in parotid surgery provides better results regarding Frey's Syndrome. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Because of the significant toxicity of chemoradiation regimens, there has been a resurgence of interest in the primary surgical management of head and neck cancer and, in particular, the use of minimally invasive surgery. One such technique is transoral robotic surgery (TORS). We aim to discuss the potential role of TORS in patients requiring total laryngectomy (TL).

Three patients underwent TORS-assisted narrow-field TL. Relative data on preoperative, intraoperative, and postoperative management were collated including postoperative complications.

We present 3 cases of transoral robotic surgery (TORS)–assisted TL in patients requiring narrow field laryngectomy without requirement for neck dissection. In reviewing these cases we provide a discussion of pertinent preoperative and intraoperative considerations that can assist in facilitating successful completion of the procedure. In particular, appropriate assessment at the pinsertlinePOLA_Del_Blank_PgPOLA_Shift_FramePORT_rem_fpg_underremovelinetabminilanning endoscopy in addition to a methodical surgical approach are vital to the successful use of the robot in TORS-assisted TL. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon neoplasm characterized by local extension and an aggressive course. Treatment often includes a combination of chemotherapy, radiation therapy, and surgery, although the optimal strategy remains unclear. Here, we present the first reported case of leptomeningeal carcinomatosis from SNUC.

A 28-year-old man with rapidly progressive headaches, congestion, and exophthalmos was found to have a nasal mass. Biopsy revealed sinonasal undifferentiated carcinoma. He had a transient response to chemotherapy followed by a sustained response to concurrent chemoradiation. At the completion of radiation, he developed subtle neurologic findings and MRI revealed diffuse, bulky leptomeningeal spread. He was able to receive only a single fraction of external beam radiation to his spinal axis before his disease rapidly progressed, leading to respiratory failure and death.

Sinonasal undifferentiated carcinoma can be associated with leptomeningeal carcinomatosis, which can lead to a fulminant clinical course. Head Neck, 2012

This study compared the efficacy of robotic thyroidectomy via a gasless, axillary approach with conventional cervical and endoscopic techniques by meta-analysis.

Articles were identified from the following keyword searches: robotic/robot-assisted thyroidectomy/thyroid surgery. Outcomes included operative time, hospital stay, complications, and cosmetic satisfaction after surgery. Between-group outcome differences were calculated using random-effects models.

In all, 87 publications were identified and 9 studies met inclusion criteria, totaling 2881 patients, 1122 of whom underwent robotic thyroidectomy. Those who underwent robotic surgery reported greater cosmetic satisfaction, with a pooled net mean difference of −1.35 (95% confidence interval [CI]: −1.69, −1.09). Robotic approach operative time was longer than that of the conventional approach (95% CI: 29.23, 54.87), with a trend to be shorter than the endoscopic approaches. Robotic surgery had similar risks to open and endoscopic approaches.

Our meta-analysis suggests that robotic thyroidectomy is as safe, feasible, and efficacious as conventional cervical and endoscopic thyroidectomy, showing superior cosmetic satisfaction than that of conventional thyroidectomy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to examine endoglin (CD105) expression on microvessel endothelial cells (ECs) in juvenile nasopharyngeal angiofibroma (JNA) and its relationship with recurrence.

Immunohistochemistry was performed to detect CD105 expression in a tissue microarray from 70 patients with JNA. Correlation between CD105 expression on microvessel ECs and clinicopathological features, as well as tumor recurrence, were analyzed.

Immunohistochemistry revealed CD105 expression on ECs but not in stroma of patients with JNA. Chi-square analysis indicated CD105-based microvessel density (MVD) was correlated with JNA recurrence (p = .013). Univariate and multivariate analyses determined that MVD was a significant predictor of time to recurrence (p = .009). The CD105-based MVD was better for predicting disease recurrence (AUROC: 0.673; p = .036) than other clinicopathological features.

MVD is a useful predictor for poor prognosis of patients with JNA after curative resection. Angiogenesis, which may play an important role in the occurrence and development of JNA, is therefore a potential therapeutic target for JNA. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Over the past decade, intensity-modulated radiation therapy (IMRT) has gained widespread use in the treatment of head and neck cancer.

All patients with squamous cell carcinoma of the oropharynx treated with primary IMRT with or without chemotherapy over a 5-year period were reviewed. Outcomes and morbidity were analyzed and compared with previously published data.

In all, 170 patients were included in the analysis. The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 92%, 91%, 80%, and 87%, respectively. Feeding tubes were present in 55% of patients during treatment, but remained in only 1% 2 years following treatment.

This study confirms that IMRT yields excellent treatment outcomes for oropharyngeal carcinoma. Although acute toxicity remains a problem, late toxicity rates are low and long-term feeding tube dependence is rare compared with conventional radiation therapy. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive form of MEN2. MEN2B cases usually carry either an M918T or A883T mutation of the RET, but to date, there are 3 atypical MEN2B caused by tandem mutations.

A 32-year-old woman with no family history of medullary thyroid carcinoma (MTC) presented with a neck tumor and multiple mucosal nodules. She was diagnosed with MEN2B. Genetic analyses of RET revealed that she had 2 mutations, Q781R and V804M. Subclone and genetic analyses revealed that Q781R was on the paternal allele and V804M was a de novo. In silico analysis of the tandem mutations showed a high prediction score.

We describe a novel combination of tandem RET mutations (Q781R/V804M) in a MEN2B-like patient. In silico analysis showed a high prediction score, which was compatible with the clinical phenotype in the present case. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Oncologic resection of the clivus, nasopharynx, craniovertebral junction, and infratemporal fossa is a challenging endeavor because of their complex and protected anatomy. Our goals were to design a cadaveric model and identify advantages and limitations of combining the transoral robotic surgery (TORS) and endoscopic endonasal approach (EEA) techniques.

Cadaveric specimens were dissected using a da Vinci surgical robot and endoscopic endonasal instruments in a fashion that mimicked our operating room environment. We then applied these techniques clinically.

EEA was performed to provide a detailed dissection of the infratemporal fossa, nasopharynx, posterior skull base (clivus), and craniovertebral junction. Using TORS, we dissected the parapharyngeal space, infratemporal fossa, and nasopharynx below the eustachian tube, which represented a transition zone that delineated the most effective resection field of each approach.

TORS and EEA seem to be complementary techniques; thus, their combined use seems advantageous for selected advanced tumors in these complex areas. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The purpose of this study was to evaluate the survival impact and prognostic factors of pulmonary metastasectomy in patients with pulmonary metastasis from head and neck cancer.

A retrospective study of 69 patients was analyzed. Twenty-four patients (35%) underwent pulmonary metastasectomy, and the remaining 45 patients (65%) were treated with chemotherapy or best supportive care.

The 1-year overall survival (OS) of 69 patients was 28%. Pulmonary metastasectomy (p = .01) and histology (p < .001) had a significant impact on the prognosis. One-year OS of patients who underwent metastasectomy and those who did not was 90% and 35%, respectively. In the metastasectomy group, recurrence of primary ahead of lung metastasis (p = .006) and disease-free interval (DFI; ≤21.4 months; p = .046) were significant negative prognostic factors.

Pulmonary metastasectomy has an impact on survival in carefully selected patients, especially for those with a long DFI and with no recurrence of primary cancer ahead of lung metastasis. Head Neck, 2012

Surgical therapy for early oropharyngeal carcinoma leads to excellent oncologic results but often requires adjuvant radiotherapy. The purpose of this study was to identify prognostic factors that worsen the outcome of limited oropharyngeal carcinoma treated with surgery ± adjuvant therapy.

Two hundred sixty-six patients were retrospectively evaluated between 1980 and 2007.

Overall 5-year disease-specific survival (DSS) was 88.7% and local control (LC) was 93.3%. The univariate analysis showed a significant difference in DSS between pT1 and pT2 oropharyngeal carcinoma (DSS, 94.0% vs 81.2%; p = .008) and patients with tumor depth greater than 5 mm (DSS, 94.5% vs 78.9%; p = .031). No difference could be found as to N classification, marginal status, p16 human papillomavirus (HPV) status, type of treatment, and adjuvant radiotherapy.

Primary surgical treatment is an effective therapy of limited oropharyngeal carcinoma. Patients with pT2 status and tumor depth of more than 5 mm show a significantly worse survival rate and should be further investigated in future clinical trials. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The purpose of this study was to analyze the surgical management of recurrent retropharyngeal lymph node metastasis after radiotherapy for nasopharyngeal carcinoma (NPC).

We conducted a prospective analysis of preoperative imaging, surgical approach, and oncological results.

Between 1990 and 2011, 82 patients were included. The mean size of the retropharyngeal lymph node on MRI was 1.6 cm, and the mean standardized uptake value maximum (SUVmax) on positron emission tomography (PET) scan was 6.8. All the retropharyngeal lymph nodes were resected via the maxillary swing approach. Among the resected retropharyngeal lymph nodes, 87.8% contained viable tumor cells. The rate of microscopic extracapsular spread was 30.6%. The mean follow-up duration was 38 months. The 5-year actuarial tumor control and the overall disease-free survival of patients who underwent surgeries for isolated recurrent retropharyngeal lymph node metastasis was 79.6% and 59%, respectively.

A PET scan is potentially useful in diagnosing persistent or recurrent retropharyngeal lymph node after previous radiotherapy for NPC. The maxillary swing approach allows surgical resection with clear margins in order to achieve the best oncological outcome. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Based on our experience of trans-areola single-site endoscopic thyroidectomy and a preclinical study in the porcine model, we attempted to develop a new approach called trans-submental single-port endoscopic thyroidectomy (TSSPET).

Two female patients (43 and 27 years old, respectively) were selected for TSSPET. Both were preoperatively diagnosed with benign thyroid nodule by ultrasonography and fine-needle aspiration cytology (FNAC). Two mini-incisions were made in the submental area. The isthmectomy was performed for 1 patient and a right lobectomy for the other.

This procedure was successfully accomplished in 2 cases. The operative time was 108 minutes and 150 minutes, respectively. No complications occurred. Postoperative hospital stay was 2 days. After 3 months, cosmetic result was satisfactory.

Our initial experience demonstrates that the TSSPET is feasible and safe for selected patients. Nevertheless, large series and comparative studies could be necessary to further confirm its effectiveness. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Frey's syndrome (FS), facial depression, and noticeable scar may have an impact on patient's quality of life after a parotidectomy. The superficial musculoaponeurotic system (SMAS) flap has been used to ameliorate those effects.

Forty-seven consecutive parotidectomies were analyzed; SMAS flap was performed in 26 of them. We investigated clinical FS, subclinical FS, and cosmetic satisfaction, and compared SMAS flap versus cases where this was not done.

By performing the SMAS flap, the occurrence of clinical FS was reduced; however, there was no significant difference. Nonetheless, there was a significant difference in the perspiration intensity in favor of the group with SMAS flaps. In the cases we studied, the cosmetic satisfaction was high, even though facial contour-filling techniques were not used.

Provided that the intensity of sweating is the main factor affecting the quality of life after surgery in patients, performing a SMAS flap renders the intervention worthwhile. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Standard treatment for unresectable advanced head and neck squamous cell carcinoma is chemoradiotherapy, which can be toxic, particularly among patients with coexisting medical conditions. We report our experience with the hypofractionated radiotherapy regimen Irradiation HypoFractionnée 2 Séances Quotidiennes (IHF2SQ).

We retrospectively reviewed 78 patients treated with the IHF2SQ regimen. Radiotherapy was administrated as 2 fractions of 3 Gy per day (days 1 and 3), during the first, third, fifth, and seventh week of treatment with concurrent platinum-based chemotherapy.

Tolerance was excellent. Forty-one patients had complete or partial response. Median overall survival (OS) was 12.9 months and median progression-free survival (PFS) was 10.3 months. One-year OS, specific survival (SS), and PFS were 58%, 71%, 51.5%, respectively. Independent predictive factors increasing the PFS were response to chemoradiotherapy, male sex, and laryngeal tumor location.

This regimen is an alternative to conventional chemoradiotherapy with good response rates and acceptable toxicity for selected patients. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined.

Forty-seven patients presenting with CUP syndrome were analyzed after thorough standard diagnostic staging procedures. All patients were surgically treated with tonsillectomy, neck dissection of the diseased neck, as well as adjuvant chemoradiation. The tissue of lymph node metastases (and, if found, of the primary tumor) was analyzed regarding expression of p16, epidermal growth factor receptor (EGFR), and presence of human papillomavirus (HPV) DNA.

In 39% of all cases (20 of 47), the primary cancer was found during diagnostic workup. If HPV DNA was detected in the neck lymph node metastasis, the primary cancer was significantly more frequently found in the oropharynx (p = .002). Patients with a p16-positive tumor had a significantly higher 5-year overall survival (OS; 33% vs 69%; p = .045, disease-free survival [DSF] 77% vs 89%; p = not significant [NS]). Patients with p16-positive neck metastasis and no detectable primary cancer had a better prognosis. Expression of EGFR in this series did not have a significant effect on prognosis.

In patients presenting with CUP syndrome, p16 immunohistochemistry can serve to locate the primary cancer in the oropharynx. It is a positive prognostic indicator in patients with those heterogeneous cancers. Head Neck, 2013

Tracheo-innominate artery fistula (TIF) is a rare and fatal complication after tracheostomy. The diagnosis, treatment, and possible prevention of this disease are discussed in this study.

From 1976 to 2008, 14 patients with TIF were studied retrospectively.

All patients underwent open surgical tracheostomy. Before TIF, herald events occurred in 10 patients (8 had slight hemoptysis and 2 had innominate artery exposure). When TIF occurred, bedside aid was administered, and 5 patients lived long enough to reach the operating room. Four patients accepted median sternotomy and ligation of innominate arteries. After surgery, mediastinal infection caused the rebleeding and death of 3 patients. In conducting follow-up for 11 months, the last patient was still alive without neurological complications. The survival rate was only 7.1%.

Prompt diagnosis and surgical intervention can save the life of a patient with TIF. Prevention is vital because of the high mortality of this disease. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation-induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration–approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation-induced damage and enhance bone regeneration in a murine mandibular model of DO.

A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 μg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-μm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann–Whitney test. Statistical significance was considered at p ≤ .05.

Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals.

We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

To report a single institutional experience with definitive radiation therapy alone for human papillomavirus (HPV)–positive head and neck cancer.

A total of 67 patients were treated by radiation therapy alone to a median dose of 70 Gy (range, 66–72 Gy) for squamous cell carcinoma of the head and neck. Paraffin-embedded, formalin-fixed pretreatment tumor tissues were used to establish HPV-positivity using standardized techniques of immunohistochemistry for p16 and polymerase chain reaction for HPV.

In all, 23 patients with HPV-positive cancers were identified. With a median follow-up of 28 months (range, 6–85 months), the 3-year actuarial rates of overall survival, locoregional control, and distant metastasis-free survival were 83%, 90%, and 88%, respectively.

These findings attest to the exquisite radiosensitivity of HPV-positive head and neck cancer. The clinical outcomes observed from this selected series compare favorably with historical controls treated by more intensive chemoradiotherapy strategies. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

A variety of tumors arise in or extend to the infratemporal fossa. We investigated the outcome of surgical management of these tumors.

We conducted a retrospective review of a craniofacial approach to resection of infratemporal fossa tumors from 1992 to 2008 in a cancer center.

Forty-three patients underwent resection of a infratemporal fossa tumors (68% men). Median age was 46 years (range, 1–81 years). The most common pathology was sarcoma (13; 30%). Twenty-two tumors (51%) were recurrent. Twenty patients (46%) underwent resection of tumors from the infratemporal fossa, 5 (12%) required resection of the anterior skull base, and 18 (42%) required orbital exenteration, additionally. Thirty-one patients (72%) required reconstruction with free tissue transfer. Twenty-seven patients (62.8%) required further treatment with radiation and/or chemotherapy. Complications occurred in 9 patients (21%). Six patients (14%) underwent salvage operations. Median follow-up was 24 months. Median overall survival and 3-year survival were 40 months and 59.6%.

Tumors involving the infratemporal fossa can be resected with acceptable morbidity and long-term survival. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Head and neck squamous cell carcinomas (HNSCCs) have devastating morbidity rates with mortality mainly because of metastasis.

Multiplex enzyme-linked immunosorbent assay (ELISA) to assay a variety of cytokine levels secreted by a panel of stage-specific and anatomic site-specific primary, and recurrent and metastatic University of Michigan-HNSCC cell lines over a 72-hour time course.

Conditioned medium from metastatic or recurrent HNSCC showed significantly higher amounts of interleukin (IL)-6, IL-6 receptor, tumor growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) than nonmetastatic cells or normal oral keratinocytes. Tumor necrosis factor (TNF) was only secreted by stage IV, metastatic, or recurrence-derived cell lines.

The cytokine profile of cultured HNSCC cells suggests that high levels of IL-6 and IL-6R, TGF-β, and VEGF are significantly related with their metastatogenic potential and provide rationale for determining if serum testing for a combination of these 4 soluble factors could be of predictive value for the HNSCC tumor progression and clinical outcome. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

The indications for elective bilateral central node dissection for patients with unilateral papillary thyroid carcinoma (PTC) who are clinically node negative are still not verified. We investigated the predictive factors of lymph node metastasis and formulated guidelines for surgical extent.

From 2004 to 2009, 325 patients diagnosed with unilateral PTC who had undergone total thyroidectomy with bilateral central lymph node dissection (CLND) were enrolled retrospectively.

Central node metastasis was found in 45.2%, ipsilateral and contralateral lymph node metastasis was found in 40.0% and 16.0%, respectively. Tumor size larger than 1.0 cm and extrathyroidal extension were significant factors in predicting ipsilateral node metastasis (p = .004, < .001, respectively), and extrathyroidal extension and ipsilateral lymph node metastasis predicted contralateral node metastasis in multivariable analysis (p = .039, < .001, respectively).

Elective bilateral central node dissection may be considered in unilateral PTC with extrathyroidal extension or ipsilateral node metastasis. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Placement of gastrostomy tubes (g-tubes) in patients with hypopharyngeal cancers undergoing radiation and chemotherapy is generally empirically determined. We examined our experience to identify predictive factors for g-tube placement and length of dependence.

We performed a retrospective review of all patients with primary hypopharyngeal cancer treated with nonsurgical modalities at a tertiary care center between 2002 and 2008. Rates of g-tube placement and length of dependence on enteral feedings were analyzed in relationship to multiple risk factors.

Forty-three patients with hypopharyngeal primary tumors (77%) who had a complete response at the primary site after treatment were included. Thirteen patients (30%) never required g-tube placement. At 1-year follow-up, 11 patients (28%) maintained a g-tube. No clinical variables were significantly associated with g-tube placement. Duration of g-tube dependence was significantly longer in patients with a posterior hypopharyngeal wall primary tumors (p = .026), current smokers (p = .001), and patients with >40 pack-years (p = .010). The duration of g-tube dependence was significantly shorter in those who maintained oral intake at the end of treatment (p = .05), and those who reported adherence to dysphagia exercise regimens (p = .048).

Approximately one third of patients with hypopharyngeal tumors treated on organ preservation regimens may be able to avoid g-tube placement, but further research is needed to identify clinical factors that predict g-tube placement in this population. A posterior hypopharyngeal wall primary and smoking history correlated with longer gastrostomy tube dependence. Adherence to aggressive targeted swallowing exercise regimens may help to prevent long-term dependence on feeding tubes. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Although many patients require nutritional support during radiotherapy or chemoradiotherapy for oropharyngeal cancer, little is known regarding the risk factors that predispose to gastrostomy tube (g-tube) placement and prolonged dependence, or the therapeutic interventions that may abrogate these effects.

We performed a retrospective medical chart review of patients who were treated for primary oropharyngeal cancer at a tertiary care center from 2003 to 2008. Patients who had a complete response at the primary site at 1-year posttreatment were included. G-tube placement and dependence ≥6 months were evaluated in relationship to site and stage of primary tumor, baseline characteristics, treatment type, smoking status, and swallowing intervention.

We evaluated 474 patients (79%) with oropharyngeal cancer; 215 patients (40%) had concurrent chemotherapy, 73 patients (15%) had induction chemotherapy, and 69 patients (15%) had induction chemotherapy followed by concurrent chemotherapy. Two hundred ninety-three patients (62%) received g-tubes, of which 238 (81%) received the g-tube during radiation. At 1-year follow-up, 41 patients (9%) remained dependent on enteral feedings. Placement of g-tubes and prolonged g-tube dependence were significantly more likely in patients with T3 to 4 tumors (p < .001), baseline self-reported dysphagia (p < .001), odynophagia (p < .001), >10% baseline weight loss (p < .001), and in those treated with concurrent chemoradiotherapy. Patients who reported adherence to exercises had significantly lower rates of g-tube placement (p < .001), and duration of dependence was significantly shorter in those who reported adherence to swallowing exercises (p < .001).

Almost 40% of patients with oropharyngeal cancer treated with nonsurgical organ preservation modalities may avoid feeding tube placement. Factors that predispose to g-tube placement and prolonged dependence include T3 to T4 tumors, concurrent chemotherapy, current smoking status, and baseline swallowing dysfunction or weight loss. Adherence to an aggressive swallowing regimen may reduce long-term dependence on enteral nutrition and limit the rate of g-tube placement overall. © 2013 Wiley Periodicals, Inc. Head Neck, 2013

Patients receiving radiotherapy (RT) for head and neck tumors are at risk of developing sensorineural hearing loss. The objective of this study was to analyze the literature regarding sensorineural hearing loss after RT for head and neck cancer.

Seven databases were searched to identify eligible studies. Eligible articles were independently assessed for quality by 2 authors.

Fourteen articles were evaluated. There was considerable heterogeneity among studies. The reported incidence of sensorineural hearing loss (SNHL) varied from 0% to 85% for the speech frequencies and from 27% to 95% for high frequencies. As the follow-up increased, an increase in the incidence of SNHL was observed. The minimum cochlear dose reported to be a risk factor for SNHL was 45 Gy.

High quality literature in the topic is lacking. Radiation-induced SNHL is progressive, permanent, and dose-dependent. Total dose and follow-up time are important factors affecting incidence rates. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Mantle cell lymphoma (MCL) is a B-cell neoplasm with an aggressive clinical course. Recently, an indolent type of MCL has been described under the term in situ MCL.

We report a case of a 70-year-old woman who presented with nasal obstruction. A mass, located in the nasopharynx, was found. Histologic examination revealed lymphoid hyperplasia characterized by CD5 and cyclin D1–positive mantle zone cells, findings consistent with in situ MCL. Three years later, a new biopsy was performed, which showed the same histologic and immunohistochemical (IHC) findings to those observed in the first biopsy. The diagnosis of in situ MCL was confirmed by fluorescence in situ hybridization (FISH) analysis for t(11;14). Since then, the patient has remained free of an overt lymphoma.

In situ MCL may be observed in the nasopharynx, and it would be appropriate to perform cyclin D1 immunostain in cases with marked follicular hyperplasia accompanied by clinical suspicion of lymphoma. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are significantly reduced with appropriate use of thromboprophylaxis and scarcely evaluated in patients undergoing oncologic head and neck surgery (OHNS).

A retrospective study on 1018 patients who underwent oncologic head and neck surgery. The records of patients with venous thromboembolism (VTE) or postoperative bleeding were reviewed for the cancer grading, management, previous known coagulopathy, anticoagulation, and general demographics.

Of a total of 1018 patients undergoing oncologic head and neck surgery, 450 patients had no chemoprophylaxis and 568 received it. The rate of a VTE event in our cohort was 0%. Twelve patients presented with hematoma or bleeding from the surgical site, 11 in the group that received chemoprophylaxis (p = .006).

Our analysis shows no benefit from chemoprophylaxis in oncologic head and neck surgery patients, with no VTE events. Our analysis shows higher rates of morbid side effects from using chemoprophylaxis, and we therefore conclude that chemoprophylaxis should not be routinely used. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

As a first step toward developing effective strategies to control symptoms associated with head and neck cancer (head and neck cancer) and its treatment, we sought to describe the pattern of symptoms experienced before radiation therapy.

Subjects completed the MD Anderson Symptom Inventory–Head and Neck Module before beginning radiation therapy.

In all, 270 patients participated. Symptom severity and interference varied between treatment-naïve patients and those with prior treatment. Cluster analyses revealed that 33% of patients had high symptom burden. Symptoms most often rated moderate-to-severe were fatigue, sleep disturbance, distress, pain, and problems chewing and swallowing. Poorer performance status, higher T classification, and receipt of previous treatment correlated with higher symptom burden.

A substantial proportion of patients were experiencing high symptom burden. Because few interventions currently exist for several of the most problematic symptoms, research in symptom reduction that targets the pattern of symptoms described here is greatly needed. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Oropharyngeal cancers are increasingly associated with human papillomavirus (HPV). Little is known about the experience of patients receiving this diagnosis.

Semistructured interviews were conducted with ten survivors of HPV-related oropharyngeal cancer. The interviews were transcribed, and recurring themes were identified.

Physicians were a trusted source of information regarding HPV. Framing the diagnosis in terms of prognosis resonated with patients. The uncertainty about transmission, latency, and communicability colored the dialogue about HPV. Despite some understanding of prevalence and transmission, patients worried about their partner's risk. Patients sought information about HPV on the Internet, but it was not easily navigable. Emotional reactions to the diagnosis remained mostly cancer-centric rather than HPV-centric. A patient-education handout was developed in response to patient questions.

Additional educational resources explaining the facts about HPV in HNSCC in a consistent way including content of highest priority to patients may improve understanding of HPV. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Gaining a new voice is one of the major aims after total laryngectomy. The objective of this study was to describe the process and results of speech rehabilitation during the first year after surgery.

Speech intelligibility was measured 6 months (n = 273) and 1 year (n = 225) after total laryngectomy.

Objective (23.4 to 47.5 points, p < .0001) and subjective (51.6 to 64.7 points, p < .0001) speech intelligibility improved between 6 months and 1 year after total laryngectomy. Patients who used tracheoesophageal puncture (TEP) had the best results in speech intelligibility 6 months and 1 year after total laryngectomy. In all, 12% of the patients who used TEP initially no longer used it 1 year later. Patients who had received rehabilitation had better objective speech intelligibility than those who did not.

Speech improves considerably between 6 months and 1 year after total laryngectomy. Nonattendance of rehabilitation is associated with a worse functional outcome in speech rehabilitation. Head Neck, 2012

Conventional intraoperative nerve monitoring, predicated on intermittent stimulation, can predict recurrent laryngeal nerve (RLN) palsy only after the damage has been done.

Fifty-two patients (52 nerves at risk) who underwent continuous intraoperative nerve monitoring (CIONM) for thyroid surgery via vagus nerve stimulation had their electromyographic (EMG) tracings recorded and correlated with surgical maneuvers and postoperative RLN function.

There was 1 imminent loss of signal (LOS) with intraoperative signal recovery and there were 4 losses of signal with corresponding unilateral transient RLN palsy. When EMG amplitude decreased >50% and EMG latency increased >10%, LOS and postoperative RLN palsy were noted in 4 of 8 patients (50%) who had multiple combined events. In 9 of 13 patients (70%) who developed adverse EMG changes, modification of the causative surgical maneuver resulted in recovery of those EMG changes and aversion of impending RLN palsy.

CIONM reliably signaled impending nerve injury, enabling immediate corrective action. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The Self-Evaluation of Communication Experiences after Laryngeal Cancer (SECEL) questionnaire assesses the impact of total laryngectomy on communication-related quality of life (QOL). This study evaluates the Italian version of the SECEL (I-SECEL), including reliability, concurrent validity, and differences in scores between patients who undergo either total laryngectomy or partial laryngectomy.

Eighty patients who underwent either total laryngectomy or partial laryngectomy completed the I-SECEL twice and the Voice Handicap Index (VHI) and Short Form Health Survey (SF-36) questionnaires once. Voice recordings were used for objective and perceptual assessment.

The I-SECEL demonstrated good test–retest reliability and internal consistency for 2 of 3 subscales. Correlations were moderate to strong between most of the I-SECEL scales and the VHI/SF-36 scales. The I-SECEL scales demonstrated moderate associations with most perceptual and objective measures.

Preliminary evidence supports the convergent validity, test-retest reliability, and internal consistency of the I-SECEL, notwithstanding low internal consistency and test–retest reliability for 1 subscale. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The BRAF^V600E mutation can be detected peripherally in the serum of patients with thyroid cancer. The purpose of this study was to establish the value of detecting the peripheral BRAF^V600E mutation as a serum tumor marker in this population.

In this study, we obtained 94 serum samples from patients with papillary thyroid cancer positive for the BRAF^V600E mutation in the tumor itself. The serum samples were analyzed for BRAF^V600E mutation using real-time polymerase chain reaction (PCR).

Sixty-seven patients (71.3%) had papillary thyroid microcarcinoma and 26 patients (27.7%) had underlying lymphocytic thyroiditis. Forty-three patients (45.7%) were found to have stage III or stage IV thyroid cancer. None of the patients had a detectable serum BRAF^V600E mutation.

We were unable to identify peripheral BRAF^V600E mutations in patients with papillary thyroid cancer using real-time PCR. Further studies will be needed to validate our results using various diagnostic methods. © Wiley Periodicals Inc. Head Neck, 2012

The purpose of this study was to describe the impact of clinical ethics consultations among patients with head and neck cancer in order to better anticipate and manage clinical challenges.

A database was queried to identify patients with head and neck cancer for whom ethics consultation was performed at a comprehensive cancer center (n = 14). Information from the database was verified via data abstraction and analyzed qualitatively and quantitatively.

Common requests for ethics consultation involved code status (6 of 14) and withdrawal/withholding life-sustaining treatments (6 of 14). Common contextual features were interpersonal conflicts (6 of 14) and communication barriers (5 of 14). Airway management concerns were frequent (5 of 14). Whereas 21% of patients had do not resuscitate (DNR) orders before ethics consultation, 79% were DNR subsequently.

Ethics consultations among patients with head and neck cancer reflect distinctive complexities inherent to their disease, but are entirely consistent with global clinical ethical themes. Consideration of communication barriers, social isolation/stigma, symptom control, and airway management are critical. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to determine whether the disease-free interval (DFI) between treatment of primary head and neck cutaneous squamous cell carcinoma (SCC) and the development of regional metastases is an independent prognostic factor.

A retrospective analysis of 229 patients with metastatic nodal head and neck cutaneous SCC, treated with curative intent by surgery ± adjuvant radiotherapy was conducted.

After adjusting for the effect of nodal staging, extracapsular spread, involved margins, adjuvant radiotherapy, and immunosuppression, a short DFI (≤9 months vs >9 months) was a significant predictor of disease-related mortality (hazard ratio [HR], 3.0; 95% confidence interval [CI], 1.4–6.5; p = .004) and locoregional relapse (HR, 2.0; 95% CI, 1.1–4.0; p = .044).

The DFI is a potentially powerful independent prognostic factor in patients with regional metastases secondary to head and neck cutaneous SCC. It provides information before definitive treatment that may ultimately assist clinicians in applying a risk-adapted management paradigm. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

For patients who have extensive prior treatment, use of the internal mammary artery/vein (IMA/IMV) or cephalic vein has been shown to be a reliable option. Additionally, for those patients who require vascularized bone and extensive soft tissue reconstruction, the combined latissimus dorsi scapular free flap (mega-flap) is an excellent option.

We reviewed 3 cases in which extensive prior surgery and radiation precluded the use of traditional recipient vessels in the neck.

Three patients with major jaw deformities were reconstructed using a mega-flap. In all cases, saphenous vein grafting succeeded in achieving arterial inflow from the IMA to the subscapular artery. Venous egress was achieved using a vein graft to the IMV in 1 patient and a transposed cephalic vein in the remaining 2 patients.

This approach of restoring large oral cavity defects for patients with extensive prior therapy and comorbid conditions has proven to be reliable and reproducible. © Wiley Periodicals Inc. Head Neck, 2012

Jaw complications, including osteoradionecrosis, are significant sequelae of radiation therapy (RT) for oral cancers. This study identifies the impact of patient, tumor, and treatment characteristics on the development of jaw complications in patients treated with RT.

The Surveillance, Epidemiology, and End Results (SEER)–Medicare database was used to identify patients treated with RT for oral cancers from 1999 to 2007. Jaw complications were identified by International Classification of Diseases 9th revision (ICD-9) diagnosis codes and/or related procedures using Current Procedural Terminology (CPT) and ICD-9 codes.

A total of 1848 patients were identified. With a median follow-up of 2.5 years, 297 patients (16.1%) developed jaw complications: 226 patients had a diagnosis, 41 patients had a procedure, and 30 patients had both. On multivariate analysis, female sex, lack of chemotherapy use, and fewer comorbidities were associated with a statistically significant increase in jaw complications.

Even with modern techniques, jaw complications are a notable and potentially devastating side effect of RT for oral cancers. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Mesenchymal stem cells (MSCs) are multipotent mesenchymal progenitor cells, originally identified in bone-marrow. Little is known about MSCs of the head and neck region. We investigated cell biological properties with a potential impact on wound healing of 2 different tissue-resident MSC populations.

MSCs were isolated from human nasal mucosa (nmMSCs) and parotid gland (pgMSCs). Clonogenic potential, cell surface markers, cytokine secretion, chemokine receptor expression, mobility, and adhesion to extracellular matrix were examined in unstimulated and stimulated MSCs.

NmMSCs had the higher clonogenic potential. PgMSCs showed a broader panel of chemokine receptor expression and displayed higher mobility, especially after challenge with bacterial lipopolysaccharide (LPS). NmMSCs were less mobile and showed increased LPS-induced secretion of the inflammatory cytokine interleukin-8 (IL-8) compared with pgMSCs.

These data highlight functional differences between tissue-resident MSCs of the head and neck region, which may impact functional properties of these cells in response to trauma or infection. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Primary intestinal-like adenocarcinoma of the major salivary glands has not previously been reported.

The clinical and radiological findings of 2 patients with primary submandibular and sublingual tumors are presented. Histopathologic and immunohistochemical examinations of tumor sections were performed. Metastatic workup for distant occult primary was carried out.

The light-optic and the immunomarkers revealed intestinal-like adenocarcinoma consistent with upper respiratory tract origin. Metastatic workup of both patients was negative for primary gastro-intestinal primary.

Primary intestinal-like adenocarcinoma can develop in major salivary glands and should be considered in the differential diagnosis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

This study investigated the use of 3 different established cell-sorting strategies to isolate and characterize stem cells from head and neck cancer cell lines.

Five low-passage cell lines were subjected to cell sorting based on Hoechst side population, Aldefluor, and CD44 expression. Isolated cell populations were studied for gene expression, radiosensitivity, and chemosensitivity to cisplatin and paclitaxel.

Each sorting method identified a different set of genes associated with different gene ontology categories, with mitosis being the only common category. CD44-associated gene changes were almost exclusively associated with cell cycle and in particular mitosis. There were no significant differences in radiosensitivity or cisplatin sensitivity of stem or non–stem cells, but CD44-isolated stem cells were more resistant to paclitaxel.

This study suggested that CD44 may be the most promising cell-sorting strategy to isolate and investigate the impact of stem cells in head and neck squamous cell cancer (HNSCC). © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Human papillomavirus (HPV) positivity (+) has been used to identify oropharyngeal squamous carcinomas (SCCs) presenting as unknown primaries in the neck. p16 overexpression correlates with HPV+ in the oropharynx; however, the use of p16 alone as a surrogate marker of oropharyngeal HPV+ tumors has not been validated.

We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx.

Five of 24 primary tumors (20.8%) and 3 lymph node metastases (12.5%) in levels II, III, and V, and the periparotid region diffusely expressed p16. HPV (high-risk types by in situ hybridization) was negative.

p16 expression is relatively common in lymph node-positive cutaneous head and neck SCCs; thus, p16 expression as an independent biomarker and mechanism to determine the oropharyngeal source of an unknown primary is not advised. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

This study evaluated the capability of optical coherence tomography (OCT) to differentiate premalignant and early malignant lesions of the upper aerodigestive tract (UADT).

An OCT screening was performed in 52 healthy volunteers. Epithelial thicknesses on 38 OCT images and histopathological slides were correlated. One hundred primary lesions were rated via OCT concerning invasiveness by an “unblinded” investigator, then biopsied, and the results correlated. All OCT images were evaluated by 3 “blinded” investigators. Forty-eight images underwent retrospective image analysis.

Screening showed large differences concerning epithelial thicknesses, but good correlation (κ = 0.63) between OCT and histopathological slides. In the unblinded evaluation, noninvasive and invasive lesions could be distinguished with a sensitivity of 88.9% and specificity of 89.0% whereas the blinded evaluations led to sensitivities of 100%, 66.7%, and 77.8% and specificities of 75.8%, 71.4%, and 70.3%. The difference of mean intraepithelial intensity reductions in dysplasias (38.7%) and hyperplasias (18.9%) was statistically significant.

OCT complements visual inspection for differentiating UADT-lesions. Head Neck, 2012

Chordomas are malignant neoplasms of the axial skeleton that have rarely been seen in the cervical area.

A 55-year-old woman presented to our department with a history of a left cervical mass protruding into the throat with the symptoms of dysphagia and hoarseness.

The radiological examination revealed 3 polycyclic masses in the neck, 2 on the left side and 1 small mass on the right side. After the neurosurgical excision of the intraspinal parts of the tumor, we performed the surgical resection of the cervical tumors via a lateral collotomy. The histological examination showed a chordoma. Because of the advanced stage of the tumor, a postoperative radiotherapy was performed.

Meticulous radiological workup is essential in order to identify the exact extension of the tumor and to reveal possible multifocal lesions. The current literature and treatment recommendations for this rare tumor at this localization are discussed. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Immunoglobulin G4 (IgG4)–related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. We present a case of a 69-year-old man with maxillary sinus IgG4 sclerosing disease, with orbital invasion treated with rituximab and dexamethasone pulse therapy. Surgery was used as well to debulk the disease and to obtain tissue for diagnosis.

A PubMed search using the key phrase “IgG4-related Sclerosing Disease” was performed. There were 304 different articles regarding the disease for a multitude of different organ sites. Of the 304 articles, there were 3 articles that reported this disease in the paranasal sinuses.

IgG4-related sclerosing disease is a rare entity in the head and neck. There are documented reports of steroid therapy for this disease, but the patient presented here demonstrated clinical progression of disease with steroids alone. The use of combination therapy of surgery, dexamethasone, and rituximab provided clinical improvement and stable disease determined by radiographic means. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

In patients with recurrent and/or metastatic head and neck squamous cell cancer (HNSCC), there are no data about an every-other-week cetuximab maintenance schedule after chemotherapy plus cetuximab as first-line treatment.

We reviewed the safety and feasibility of every-other-week maintenance cetuximab administered at 3 different European centers.

Thirty-one patients with recurrent or metastatic HNSCC were treated from 2006 to 2010. Mean cetuximab dose intensity in the maintenance phase was 93%. The major toxicities reported during every-other-week maintenance cetuximab were skin rash (grade 3, 16%; grade 2, 23%), fatigue (grade 3, 3%; grade 2, 16%), diarrhea (grade 3, 7%; grade 2, 13%), hypomagnesemia (grade 4, 3%; grade 3, 3%; grade 2, 19%), and mucositis (grade 3, 3%; grade 2, 23%).

Every-other-week maintenance cetuximab schedule was well tolerated and did not worsen toxicity that occurred during chemotherapy. In daily practice, this simplified schedule could improve compliance and possibly improve quality of life in patients with recurrent or metastatic HNSCC that showed no progression during first-line chemotherapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The influence of human papillomavirus (HPV) status on survival for patients with very advanced inoperable oropharyngeal SCC treated with radiochemotherapy (RCT) was studied.

Patients received either 69.2 Gy with concomitant boost (ccb) or 70 Gy conventionally fractionated (cf), weekly paclitaxel 40 mg/m², and carboplatin area under the concentration–time curve (AUC) 1. Tumor was analyzed for the presence of high-risk HPV-DNA using polymerase chain reaction (PCR) and direct DNA sequencing. p16-expression, survivin, and epidermal growth factor receptor (EGFR) expression were evaluated by immunohistochemistry and influence on survival was calculated.

Of 52 patients, 25.0% were HPV positive and 75.0% HPV negative. The 2-year progression-free survival (PFS) was 70.1% for p16-positive patients and 37.1% for p16-negative patients (p = .005). The 3-year overall survival (OS) rate was 43.9% for all patients and did not significantly differ between the groups. Neither survivin nor EGFR expression influenced PFS or OS significantly.

HPV status influences PFS in patients with advanced, nonresectable tumor stages but not OS. Additional risk factors seem to have a stronger influence on survival than HPV status. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Supracricoid partial laryngectomy (SCPL) is an option for laryngeal cancer resection that preserves laryngeal function; however, little information exists regarding factors that are associated with functional outcomes.

A medical chart review was performed on patients that underwent SCPL at our institution between 2006 and 2011. Data were collected on surgical, voice, and swallowing outcomes.

Eighteen patients were identified. Thirteen underwent cricohyoidoepiglottopexy (CHEP) and 5 had a cricohyoidopexy (CHP). Mean follow-up was 737 days. On average, decannulation occurred at 27.4 days and feeding tube removal at 87.9 days postoperatively. Sixty-seven percent of patients tolerated an unrestricted diet at follow-up. Increased age and a CHP procedure were associated with negative outcomes. Age may be a proxy for more extensive disease and prior treatments.

Patients who undergo an SCPL require extensive rehabilitation after surgery. Those who have undergone multiple cancer interventions and have more extensive surgery may be at risk for poorer outcomes. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The aims of this study were to assess the clinicopathologic features of patients with chyle leakage following thyroid cancer surgery without lateral neck dissection and to evaluate the factors associated with chyle leakage.

Of 3137 patients who underwent thyroid surgery between January 2006 and December 2007, 2314 patients (73.8%) satisfied our inclusion criteria. Patients were divided into those with (group I, n = 14) and without (group II, n = 2300) chyle leakage.

There were no significant differences between the 2 groups in clinicopathologic features including age, body mass index, extent of thyroidectomy, pathologic type, tumor size, multiplicity, capsular invasion, and coexisting thyroiditis. In univariate and multivariate analyses, male sex, age >45 years, and number of harvested central nodes were significantly associated with chyle leakage.

If extensive central compartment node dissection is needed, meticulous dissection is required, especially in male patients, and aged >45 years, even without lateral neck dissection. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

We investigated the risk of neck metastases in patients undergoing salvage total laryngectomy in association with previous radiotherapy.

The medical records of 42 patients (51 neck specimens) with clinical N0 classification who underwent salvage total laryngectomy in 2 cancer centers were reviewed. Fourteen patients had previous radiotherapy to the central neck and 28 to the central and lateral neck.

Staging before salvage total laryngectomy was similar in both groups. The risk of neck metastases in the central and central/lateral radiation groups was 12% and 18%, respectively (p = .69). Subgroup analysis revealed that 4 of 8 patients initially presenting with clinically N+ had neck metastases before surgery, versus 2 of 26 for those with clinically N0 (p = .015; relative risk [RR] = 4.67). The risk or metastases in the contralateral neck was 0 of 9.

The risk of neck metastases in patients who undergo either central or central/lateral neck radiotherapy is similar. Elective neck dissection seems appropriate in patients undergoing SLR. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Epithelioid hemangioendotheliomas (EHEs) of the head and neck region are uncommon malignant neoplasms that exhibit various biologic behaviors characteristic of both low- and high-grade malignancy. A subgroup of EHEs identified as “high-risk” EHEs because of their size and mitotic activity is associated with an unfavorable clinical course and poor prognosis.

We describe the treatment of the first and, in terms of size, largest case of high-risk EHE arising from the neck. Despite wide excision, recurrence occurred 9 months after surgery, as had been expected. However, the tumor was found to express both vascular endothelial growth factor (VEGF) and VEGF receptor 2, indicating the potential of anti-VEGF therapy in the treatment of such cases.

The finding that a high-risk EHE arising from the head and neck region is characterized by expression of VEGF and its receptor provides further support for the development of targeted molecular therapies. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in frequency. We reviewed patients with advanced-stage OPSCC treated with chemoradiation to assess the impact of residual neck disease on survival.

We reviewed 202 patients with OPSCC between 1990 and 2010 treated with primary chemoradiation followed by neck dissection. Imaging was analyzed using RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria. Survival was evaluated using both univariate and multivariate analyses.

Overall survival at 5 years was 89%. Forty-two patients (21%) had residual disease in the neck (pN+). pN+ was associated with greater locoregional recurrence (LRR) and distant metastasis (DM) and decreased survival. No clinicopathologic factors were predictive of pN+. Contrasted posttreatment CT had low sensitivity and specificity.

In advanced OPSCC pN+, patients have higher rates of LRR and DM. Neither clinicopathologic factors nor posttreatment imaging was predictive of pN+, although increased use of modern imaging may reduce the rate of negative neck dissections. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Organ-preservation approaches are frequently favored in the treatment of advanced pyriform sinus carcinoma. In selected cases, use of free flaps allows voice-sparing surgery.

Thirteen patients underwent conservative extended laryngopharyngectomy. In 11 patients, the resection included the supraglottic larynx, whereas the whole hemilarynx was resected in 2. Reconstruction was achieved with a radial forearm free flap with the palmaris longus tendon. In hemilarynx resection, a costal graft was also used. Functional results were assessed by nasofibroscopy and swallowing videofluoroscopic tests.

At 12 months, no patient was gastrostomy dependent, whereas 1 patient remained tracheostomy dependent. At 1, 3, and 5 years, the locoregional control was 100%, 100%, and 83%; overall survival was 69.4%, 46.3%, and 30.8%; and disease-specific survival was 81.2%, 54.5%, and 36.4%, respectively.

In selected patients, extended conservative laryngopharyngectomy challenges the oncologic results of organ-preservation protocols and allows a good quality of life. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Bilateral neck treatment in oropharyngeal squamous cell carcinoma (OPSCC) is controversial. This study determined the rate of bilateral neck metastases in OPSCC and formulated a neck treatment algorithrm for OPSCC.

In all, 212 consecutive patients with OPSCC underwent ipsilateral level I–V and contralateral I–III or I–V neck dissections. Pathology results were used to identify factors predicting bilateral neck metastases.

A total of 171 patients (81%) had ipsilateral and 41 patients (24%) bilateral neck metastases. Multivariate logistic regression found cT4 and ≥cN_2a significantly associated with contralateral neck metastases (p < .05). However, tumor site was not predictive (p > .05). High-risk pathology features predicted contralateral neck disease (p < .05). cN0 and cN1 necks were unlikely to harbor disease in level V (<5%). Both 2- and 5-year contralateral neck recurrence rates were 1% and 2%.

Bilateral neck disease in OPSCC is more common than once thought. Patients with OPSCC with cT4 or cN_2a+ would benefit from bilateral neck treatment. Posttreatment high-risk features should guide treatment escalation. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Tumors originating from the cervical sympathetic chain are uncommon but important entities in the differential diagnosis of parapharyngeal space masses.

We conducted a retrospective review of patients presenting with tumors of the cervical sympathetic chain.

Twenty-four patients presented between 1994 and 2010. Presenting symptoms were dysphagia (n = 7.29%), neck mass (n = 7.29%), throat fullness (n = 4.17%), and Horner syndrome (n = 2.8%). Although radiologic images showed classic lateral displacement of the carotid arteries in 10 patients (42%), in 9 patients (38%) the radiologic findings demonstrated splaying of the carotid arteries similar to carotid body tumor, and in 5 patients (20%), the findings were indeterminate. Twenty-one patients underwent surgical removal of the tumors with pathology revealing 10 paragangliomas, 10 schwannomas, and 1 neurofibroma. Horner (57%) and first-bite (33%) syndromes were the most common complications.

Although anterolateral displacement of the carotids is suggestive of a sympathetic tumor, absence of these findings does not rule out this entity. To this end, we have included in this review a guide to preoperative radiologic diagnosis of parapharyngeal space lesions. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare malignancy that presents with advanced disease and poor prognosis.

A 75-year-old woman with a history of Hashimoto thyroiditis presented with 6 months of dysphagia and stridor. Imaging revealed a thyroid mass invading the larynx. Primary SCC of the thyroid was diagnosed by histopathologic and immunohistochemical evaluation. Total thyroidectomy, total laryngectomy, bilateral modified neck dissection, and adjuvant radiotherapy (RT) were performed. Radiologic follow-up at 21 months demonstrated no disease and total length of survival was 31 months.

Despite an aggressive T4aN0M0 tumor, survival in this case was more than double the median survival rate previously reported. Concomitant Hashimoto thyroiditis is rare and histopathologic and immunohistochemical evaluation is imperative for an accurate diagnosis.

The case and literature reported here support that a thorough diagnostic workup of primary SCC of the thyroid with aggressive locoregional surgery and adjuvant RT may improve the length of survival. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Inverted papilloma surgery is currently performed primarily with an endoscopic approach, a technique that has a recurrence rate of 12%. However, a recent study reported a recurrence rate of 5% with a strategy based on subperiosteal dissection of the tumor, with limited indications for using an external approach. The aim of this work was to evaluate whether different teams using the same surgical concepts could reproduce the excellent results that were recently reported.

This study is a retrospective chart review of 71 consecutive patients with inverted papilloma who were treated during the last 10 years.

In all, 80% of the patients were treated using a purely endoscopic approach. The mean follow-up period was 31.6 months. The recurrence rate was 3.3% for cases with at least a 12-month follow-up.

This work confirms the results described in recent literature and further supports transnasal endoscopic surgery to manage inverted papilloma. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Human papillomavirus (HPV) positivity improves prognosis in patients with oropharyngeal squamous cell carcinoma (OPSCC). Combining HPV status with other biomarkers may improve its prognostic power.

The approach was a literature search for longitudinal studies of biomarkers in OPSCC, with systematic review and meta-analysis.

In all, 3130 articles were identified; 32 satisfied the inclusion and exclusion criteria. On meta-analysis, there was a significant overall survival (OS) benefit for patients with HPV positive and p16 positive tumors. There was some evidence of improved OS of OPSCC patients with raised bcl2; amplification of 11q3 and loss of 16q genes; and low c-met, ki67, IMD, PLK, FHIT, nuclear surviving, or nuclear cyclin D1. However, none of these was suitable for meta-analysis.

Survival from OPSCC is associated with several biomarkers, which constitute potential targets for research into improving the prognostic power of HPV in OPSCC. Larger trials are needed, with standardization of cut-points and adherence to consensus reporting guidelines. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Despite numerous studies, the tumor biology of pleomorphic adenomas, the most common salivary gland tumors, is still not completely defined. In order to identify further candidate genes important for tumor biology of pleomorphic adenomas, extended cytogenetic and molecular analysis are mandatory.

We performed a detailed molecular cytogenetic analysis using comparative genomic hybridization (CGH) followed by fluorescence in situ hybridization (FISH) with probes for chromosome X, 16p, 17, and 20 on a large cohort of pleomorphic adenomas (n = 29).

We could confirm previously described deletions in pleomorphic adenomas affecting 16p, 17, 20q, and 22 by FISH and/or CGH analysis. Moreover, our CGH study revealed novel candidate regions on 8p23.1pter, 9p, 10q25.1q25.3, and 11q24qter in the series of analyzed pleomorphic adenomas.

Our present study reveals new insights in novel candidate regions implicated in pleomorphic adenoma tumorigenesis which should be considered in further molecular studies. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

We report an extremely rare case of hypopharyngeal paraganglioma that was accompanied by a paraneoplastic neurologic syndrome (PNS).

The clinical, radiological, and histopathologic findings of the patient are presented.

A 49-year-old woman presented with a history of progressive asthenia of the lower extremities persisting for 2 months. She also experienced numbness and sensory disturbance of the left lower limbs, 2 epileptic seizures, and constipation during the period. Clinical and radiological evaluations suggested the diagnosis of encephalomyelitis in combination with a left hypopharyngeal mass lesion. The patient underwent surgical excision of the lesion, which subsequently resolved her symptoms. Postoperative pathology was consistent with a paraganglioma. There was no evidence of local recurrence or distant metastasis of the tumor on recent follow-up.

To the best of our knowledge, our patient represents the third reported case of hypopharyngeal paraganglioma, and the only one to have a paraneoplastic syndrome. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Single-stage procedures for reconstruction of large cricotracheal defects have been limited in success and malignant immature teratomas in the larynx of an adult have never been reported.

This was a case report and literature review. A 27-year-old man presented with 2 weeks of new-onset stridor and was found to have a mass obstructing 80% of the subglottis and trachea. He underwent a noncircumferential partial cricotracheal resection with a resultant 7-cm luminal defect, followed by osteocutaneous radial forearm flap semi-rigid reconstruction. A novel technique was used to allow a functional and patent airway, which may be applied to other partial luminal reconstructive defects. Postoperatively, the patient was decannulated and has good speech quality and swallowing function. This work was performed at the Henry Ford Health System. This project was reviewed and was granted full approval by the Henry Ford Health System Institutional Review Board.

This is the first reported case of malignant immature teratoma to involve the larynx, trachea, and recurrent laryngeal nerve in an adult patient, and the first single-stage technique described to use free tissue transfer without prefabrication for a 7-cm airway defect. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

We present our experience with the use of an immunocompetent medium-sized animal model of tongue cancer that may be suitable for imaging and surgical studies.

A New Zealand white rabbit model of tongue cancer was created by injecting a VX tumor cell suspension grown in culture into the tongue of our model. The tumor was examined 7 days following implantation by physical examination, photography, and ¹⁸fluoro 2-deoxyglucose–positron emission tomography (FDG-PET). At 12 days postimplantation, the model was again studied as described above prior to euthanization, and then tongue excision and bilateral neck dissections were performed. All tissue was examined by histology.

We confirmed a successful orthotopic tongue cancer model that resulted in cervical nodal metastases.

This model may be a useful model of orthotopic head and neck cancer for future surgical or imaging research. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

We earlier observed altered expression of p53 and Bcl-xL in oral cancer cell lines/tissues and wanted to evaluate these proteins for prediction of radiotherapy response and outcome.

Thirty-nine paraffin-embedded, pretreatment oral cancer biopsies were analyzed for protein expression using immunohistochemistry and correlated with tumor response to radiotherapy and disease-free survival (DFS).

High p53 (p = .040) was observed in female versus male patients. Increased p53 intensity (p = .063) was observed in tobacco habitués (chewers ± smokers) versus patients with no habits. In univariate analysis, nodal positivity (p = .044) and favorable/complete tumor response (p = .002) exhibited a significant correlation with DFS, whereas tumor response emerged as an independent predictor of DFS in multivariate analysis. Significantly high Bcl-xL (p = .048) was observed in the unfavorable versus favorable responders.

Our study suggests that Bcl-xL expression along with clinical parameters may be useful for identifying patients with oral cancer likely to draw maximum benefit from curative radiotherapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Vagal nerve stimulation (VNS) has been recommended as a routine procedure during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN). However, many surgeons have been discouraged from performing VNS because of the need for opening the carotid sheath. The purpose of this study was to investigate the feasibility and reliability of VNS without carotid sheath dissection.

Two hundred twenty patients with 376 nerves at risk were enrolled in this study. VNS without nerve exposure during IONM was applied by simply pressing a ball-tip stimulator on the space between the carotid artery and jugular vein.

VNS without nerve exposure was feasible in all cases and did not result in any morbidity. All VNS signals were successfully obtained within 30 minutes of the start of the operation and all showed a clear and reliable laryngeal electromyography (EMG) response that was similar to that from the conventional method in which nerve exposure for VNS is applied.

VNS without dissecting the carotid sheath is feasible and reliable, rendering it a simple, safe, and surgeon-friendly procedure during IONM. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The correlation between vascular endothelial growth factor (VEGF) overexpression and the clinical outcome of head and neck cancer remains inconclusive. This meta-analysis aimed to evaluate the prognostic value of VEGF in patients with head and neck cancer.

We searched Ovid MEDLINE, EMBASE and 2 Chinese science databases in order to enroll all eligible articles. Forty-seven studies were included in this meta-analysis. All results were evaluated by the random-effects model.

VEGF overexpression is significantly associated with worse overall survival (OS; hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.61–2.22) and progression-free survival (PFS; HR, 1.68; 95% CI, 1.33–2.12). Subgroup analysis reveals that VEGF overexpression is a significant poor predictor for nasopharyngeal cancer (HR, 1.66; 95% CI, 1.30–2.12) and salivary gland cancer (HR, 3.32; 95% CI, 1.61–6.84).

Our meta-analysis supports that VEGF overexpression is an available poor predictor for patients with head and neck cancer. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Oral cancer is the most common subset of head and neck squamous cell carcinomas (HNSCC). These tumors often have an aggressive clinical outcome hallmarked by a propensity for local invasion and regional nodal metastasis. Upregulated genes could be useful as markers for diagnosis, prognosis, and as new drug targets for these tumors.

To identify upregulated genes in oral squamous cell carcinomas (OSSCs), we examined the ORESTES public database and used a quantitative reverse transcription–polymerase chain reaction (qRT-PCR) approach to determine the expression level of selected genes in tumor samples.

The ORESTES data mining analysis indicated 40 upregulated genes in HNSCC. Nine of these candidate genes were selected for further qRT-PCR validation and 3 of them (ALDOA, AHSA1, and POLQ) were frequently found upregulated in OSCC samples, which may indicate an association of these genes with the carcinogenesis process in this tumor site and they can constitute potential new targets for therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The human trophoblastic cell surface antigen 2 (TROP2) gene is associated with the development of malignancies, but its expression in laryngeal squamous cell carcinoma (SCC) and its relationship with clinical characteristics of the disease remain undetermined.

Expression of TROP2 protein was detected by immunohistochemistry with a self-made anti-TROP2 antibody in laryngeal SCC tissue microarrays.

Elevated expression of TROP2 was detected in laryngeal SCC tissues compared with adjacent noncancerous tissues. TROP2 expression in laryngeal SCC was related to tumor differentiation (p = .0001) and lymph node metastasis (p = .0352). Cox regression analyses confirmed that TROP2 expression (p = .015), lymph node metastasis (p = .001), degree of differentiation (p = .002), tumor site (p = .021), and T classification (p = .003) were independent prognostic factors.

TROP2 can be used as an independent prognostic indicator for laryngeal SCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Prognosis and appropriate treatment of head and neck squamous cell carcinoma (HNSCC) depend on the tumor type routinely derived by invasive histopathology. A promising noninvasive alternative is nonlinear optical imaging, which is capable of in vivo tissue visualization for tumor typing and grading.

Thin tissue sections from 3 patients aged 56 to 60 years presenting advanced carcinoma of the hypopharynx, larynx, and left tonsil were investigated by coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and 2 photon excited fluorescence (TPEF) to study the morphochemistry of the tissues. Morphologic alterations of prognostic significance, such as cell density, nuclear to cytoplasm ratio, and keratinization as well as the underlying compositional changes during malignant transformation were determined, such as the distributions of lipids, collagen, and autofluorophors.

Nonlinear imaging provides a noninvasive optical biopsy of the epithelial layer comparable to staining microscopy. By integration into an operational microscope, routine screening of suspicious lesions and surgical guidance can be realized. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

First bite syndrome is an unexpected yet relatively common complication of surgeries involving the parapharyngeal space. It can have a significant effect on both the quality of life and physical health of affected patients. This study presents 3 cases of first bite syndrome treated with botulinum toxin and a review of the current literature on available treatment modalities for first bite syndrome.

Three patients with first bite syndrome were injected with 75 units of botulinum toxin into affected parotid glands, focusing on areas of greatest first bite pain.

Two of 3 patients experienced complete relief of symptoms for 4 to 6 months. The third patient had significant decrease in pain at 4-month follow-up.

Many treatments for first bite syndrome have been attempted including: dietary modification, pharmacological treatments, and surgical treatments. However, few have been successful. Botulinum toxin is a safe and effective treatment for this life altering and difficult to treat first bite syndrome. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to identify associations between study sponsorship and the methodological quality and published outcomes of head and neck cancer randomized controlled trials (RCTs).

We systematically searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials for qualified RCTs, evaluating journal impact factor (IF), Jadad score (measure of study quality), and results favoring or not favoring experimental therapy.

Of 118 RCTs, the most common sponsor was government (38; 32%), followed by nonprofit organizations (30; 25%) and industry (26; 22%). Industry-supported RCTs were associated with publication in journals with higher IF compared with RCTs without industry support (p = .013). Government-supported RCTs were associated with higher mean Jadad score (p = .026) and results favoring experimental therapy (p = .034).

Government-supported, but not industry-supported, RCTs were significantly associated with positive study results. These findings may be confounded by broadly applied definitions of sponsorship. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The aim of this economic analysis was to model different strategies using pre-treatment nodal stage or nodal response assessment with CT or positron emission tomography (PET)/CT to determine the need for neck dissection.

A cost-minimization analysis was developed on the basis of probability data from a prospective study of PET-guided management of the neck in patients achieving a complete response at the primary site. Costs were derived from our institution's activity-based clinical costing system. The effect of uncertainty was tested with sensitivity and scenario analyses including nationally representative cost data.

Strategies incorporating PET had a 7% rate for neck dissection compared with 44% for CT-guided and 90% for planned neck dissection. The cost per patient was A$16,502 for planned neck dissection, A$8014 for CT-guided, and A$2573 for PET-guided. A policy with PET used only for incomplete response on CT was the least-cost strategy (A$2111). Policies incorporating PET remained the most efficient for all sensitivity/scenario analyses.

The incorporation of PET/CT into nodal response assessment significantly reduced the number of unnecessary neck dissections and generated considerable cost savings in our cohort. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Several quality of life (QOL) instruments exist for skull base pathology, however, there have been no attempts to appraise and systematically review these instruments.

We systematically reviewed MEDLINE, EMBASE, Central, AMED, Health and Psychosocial Instruments, and PsychoInfo for anterior or central skull base QOL instruments to January 2010. We queried experts, bibliographies, and meeting proceedings from the North American Skull Base Society from 2005 to 2009. Included instruments were evaluated for instrument characteristics, item generation and reduction, field testing, and measurement properties using predefined criteria.

We identified 9 QOL instruments: 7 measuring QOL for pituitary pathology, 1 for midface pathology, and 1 for anterior skull base pathology. Eight of the 9 instruments have had some psychometric testing. None demonstrated all of the predefined psychometric properties.

There are several QOL instruments for patients with skull base pathology. None of these instruments met all predefined requirements, and further instrument development is needed. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The objective of this study was to evaluate the efficacy and safety of minimally invasive transoral en bloc resection of superficial pharyngeal and laryngeal cancers.

Forty-one superficial lesions (from 35 patients) were resected transorally under a surgical microscope using a monopolar cautery. Quality of life (QOL) was assessed using a questionnaire European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35) 1 year after the surgery.

Twenty-eight hypopharyngeal, 5 oropharyngeal, and 8 laryngeal cancers were operated on using this method. The surgical field was widely exposed with a wide-caliber scope or extending laryngoscope. A bimanual procedure under a surgical microscope enabled us to achieve en bloc resection. The local control rate was 98%. No postoperative dyspnea or dysphagia was observed. Postoperative QOL scores were favorable.

Our transoral en bloc resection technique can be easily adopted, and it effectively maintained QOL after treatment. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The association between expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was studied.

Expression of COX-2, VEGF, and EGFR by immunohistochemical (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS), disease-free survival (DFS), locoregional control, and distant metastasis-free survival rates were compared for different expression levels of each marker. Multivariate analysis was by the Cox regression model.

Median follow-up after radiation therapy ± chemotherapy was 116 months. Univariate and multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage were all independent predictors for OS, DFS, locoregional control, and distant metastasis–free survival rates.

High expression of COX-2, VEGF, and EGFR were independent adverse prognostic factors for long-term outcomes in nonmetastatic NPC independent of clinical stage. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Neck and shoulder complaints can be a direct result of a neck dissection.

Maximal active lateral flexion of the neck, forward flexion and abduction of the shoulder, and self-perceived function were determined in 145 patients treated for oral cancer.

No short-term influence of radiotherapy was found on measured range of motion and self-perceived neck and shoulder function (p > .05). One year after a bilateral neck dissection, patients showed deteriorated lateral flexion of the neck, whereas patients treated with a unilateral modified radical neck dissection still reported pain during neck movements. Maximal forward flexion of the shoulder recovered to the level of healthy controls, but maximal abduction was still reduced in all patients.

Neck dissection, tumor site, and extensive reconstruction are related to deterioration of shoulder function shortly after intervention. Maximal active shoulder abduction was affected most. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to analyze the oncologic and functional outcomes of the preserved eye in malignant sinonasal tumors with orbital involvement.

In a retrospective study of 19 consecutive patients who underwent craniofacial resection or maxillectomy with preservation of orbital contents and adjuvant radiotherapy, the oncological outcome in terms of local recurrence and survival was analyzed. The functional outcome in the preserved eye was analyzed for the cases that did not recur in the orbit.

Nineteen patients were analyzed for their oncologic and functional outcomes. Fifteen patients underwent immediate reconstruction of the orbital support. Eight patients had local recurrences; 11 patients were disease free at the end of the follow-up. Squamous cell carcinoma has a high propensity for local recurrences (ie, 5 of 8 local recurrences were squamous cell carcinoma). Sixteen patients, in whom a satisfactory orbital tumor clearance was obtained, remained recurrence free in the orbit. All the preserved eyes retained adequate function after adjuvant radiotherapy.

Adequate local control with preserved visual function can be obtained with surgery and adjuvant radiation in appropriately selected malignant sinonasal tumors with orbital involvement. The preserved eye, if reconstructed appropriately, maintains good overall function with acceptable morbidity. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Published guidelines recommend written health information be written at or below the sixth-grade level. We evaluate the readability of online materials related to thyroid surgery.

Thyroid surgery materials were evaluated using Flesch Reading Ease Score (FRES), Flesch Kincaid Grade Level (FKGL), Gunning Frequency of Gobbledygook (GFOG), and Simple Measure of Gobbledygook (SMOG).

Thirty-one documents were evaluated. FRES scores ranged from 29.3 to 67.8 (possible range = 0 to 100), and averaged 50.5. FKGL ranged from 6.9 to 14.9 (possible range = 3 to 12), and averaged 10.4. SMOG scores ranged from 11.8 to 14.5 (possible range = 3 to 19), and averaged 13.0. GFOG scores ranged from 10.6 to 18.0 (possible range = 3 to 19), and averaged 13.5.

Readability scores for online thyroid surgery materials are higher (i.e., more difficult) than the recommended levels. However, readability is only one aspect of comprehension. Written information should be designed with that fact in mind. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The totally implantable venous access port (TIVAP) is an important device for patients receiving chemotherapy. We have reported, to our knowledge, the first case of a metastatic tumor over a TIVAP implanted via the Seldinger technique with a subclavian vein puncture.

Our patient, a 48-year-old man with hard palate cancer, had metastasis over the TIVAP. CT studies showed that the tumor had spread along the catheter from the neck to the chest wall.

The cause of death was multiple lung metastases and intractable tumor bleeding over the TIVAP.

We present a novel case of metastasis over the TIVAP implanted by use of the Seldinger technique. This technique is used for patients receiving prolonged cytotoxic therapy for malignancy. Although the Seldinger technique is quick and more effective, we prefer the cephalic vein cut-down technique when an aggressive, advanced cancer of head and neck is involved. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Acute promyelocytic leukemia (APL) is a malignant subtype of acute myeloid leukemia caused by the PML-retinoic acid receptor (RAR)α fusion gene. APL may be discovered in adulthood and diagnosed after spontaneous gingival bleeding or difficulty in hemostasis after oral surgery such as tooth extraction. However, APL is extremely rare in children.

A 1-year-old boy presented with a mass on the mentum of the mandible. The marked periosteal reaction was seen on CT and MRI, leading to strong suspicion of a malignant bone-derived tumor such as a sarcoma. Chromosome banding by fluorescence in situ hybridization (FISH) showed PML-RARα, confirming the diagnosis of APL. Treatment with tretinoin was immediately initiated. No signs of recurrence have been noted 1 year after treatment.

We report herein a rare case involving an infant with APL who presented with an extramedullary tumor of the mandible, whom we treated with good results. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Over the last several decades, reconstruction of the head and neck oncologic defect has been revolutionized by the use of microvascular free tissue transfer. The majority of these defects can be reconstructed with the ability to visually monitor the flap, to intervene as soon as vascular compromise becomes evident. Occasionally, it is necessary to use a flap that has no visual external monitor: a buried free flap. A belief has circulated within the microvascular community that buried free flaps do not do as well as visible flaps. By our review, there are no recent data in the literature to support this position. We present our data on the outcomes of buried free flaps in microvascular reconstruction.

A single institutional retrospective review of 1492 flaps was performed between January 1999 and December 2011. A total of 103 free flaps (7.2%) were identified as meeting the criteria for a buried flap. It should be noted that all flaps with or without an external segment were monitored with an implantable Doppler. The flap failure and complications are defined as those failures or complications occurring within 2 weeks of surgery and related to the operation or to the flap itself.

In all, 5 of the 103 patients (4.9%) had complications requiring reoperative intervention. There were no instances of flap failure within the first 2 weeks of surgery.

In our series, there are no differences in flap failure rates comparing buried flaps to externally monitored flaps. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Accurate preoperative assessment of thyroid nodules with fine-needle aspiration biopsy (FNAB) continues to be a challenge, often resulting in unnecessary diagnostic surgical intervention. The detection of several novel gene mutations in differentiated thyroid cancer (DTC) over the last decade has led to the diagnostic use of these oncogenic alterations to improve FNAB sensitivity and specificity.

Thyroid oncogene mutations including BRAF, RAS, and RET/PTC are reviewed. The potential benefit of using this panel on fine-needle aspiration (FNA) cytology samples will be described.

Our use of ‘‘reflexive’’ molecular testing demonstrates its clinical value in conjunction with FNAB cytology, representing an application of personalized molecular medicine to guide appropriate surgical therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

We report a case of laryngeal leishmaniasis in a United Kingdom (UK) resident who lived in Spain for 5 years.

The patient presented with a history of hoarseness. He had returned to the UK after spending 5 years in Spain as a retiree. His past medical history includes chronic obstructive pulmonary disease (COPD). Histology of a vocal cord biopsy was suggestive of leishmaniasis and polymerase chain reaction (PCR) test was positive for Leishmania donovani. His use of steroid inhaler probably contributed to his acquiring this extremely unusual infection. He was successfully treated with intravenous amphotericin.

Laryngeal leishmaniasis is an extremely rare infection and is rarely reported in the UK. The ease of travel ensures that many tropical infections may present to UK clinicians. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Oral cancer is the most common cancer in Indian males and is the third most common cancer in Indian females. Tobacco, alcohol, areca nut, and human papillomavirus (HPV) are the common etiologic factors. Each of these agents follows a unique model of carcinogenesis that leads to a certain distinct presentation and behavior. For example, HPV is strongly associated with oropharyngeal cancers in younger age and is known to have a better outcome and specific histopathologic characteristics. A high incidence of oral submucous fibrosis (OSMF) is linked to areca nut (group 1 human carcinogen) chewing in the Indian subcontinent.

We prospectively studied 371 consecutive patients with proven squamous cell carcinoma of the oral cavity. Of these, 112 patients had oral cancer with OSMF and 259 had oral cancer without OSMF. All patients underwent standard management and their clinicopathologic findings were recorded.

We found that patients of oral cancer with OSMF are younger males with better prognostic factors such as better grade of tumor differentiation, lesser incidence of nodal metastases, and extracapsular spread. This difference was maintained even after matching for stage. We also report that presence of OSMF is an independent factor influencing nodal metastases.

Based on these findings we propose that oral cancers with OSMF constitute a clinicopathologically distinct disease. Since all patients with OSMF had chewed areca nut with or without smokeless tobacco, we believe that the differences in the 2 groups emanate from differential mechanisms of areca nut carcinogenesis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The “Swallowing and Nutrition Guidelines for Patients with Head and Neck Cancer” were developed to guide early identification and management of dysphagia and nutritional risk before, during, and after cancer treatment. The purpose of this study was to validate these guidelines.

Patients attending a Combined Head and Neck Clinic at a major tertiary hospital in 2007 to 2008 were assessed using the guidelines, with high-risk category patients recommended for proactive gastrostomy. Data were collected on guideline adherence, gastrostomy tube insertion, and weight. Sensitivity, specificity, and positive predictive value were calculated for validation.

Proactive gastrostomy tubes were inserted in 173 of 501 patients (25%). Overall guideline adherence was 87%. High-risk category adherence was 75%. Validation outcomes were sensitivity 54%, specificity 93%, and positive predictive value 82%.

The risk categories in the guidelines are valid to assist early identification of swallowing and nutritional risk and guide decision-making on proactive gastrostomy tube insertion. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to analyze the outcome of Australian patients treated for early lip cancer.

Data on 217 patients with T1 to T2 squamous cell carcinoma (SCC) of the lip and treated with radical intent were analyzed.

The addition of local adjuvant radiotherapy in patients with a close/positive margin was associated with a significant improvement in relapse-free survival (RFS; p = .008). Tumor thickness (≤4 mm vs >4 mm) was also significantly associated with RFS (p = .01). The 5-year RFS was 51% after surgery, 87% after radiotherapy, and 92% after adjuvant radiotherapy.

Patients with a tumor thickness >4 mm experienced an increased risk of recurrence, especially nodal. Compared with patients having any radiotherapy, those undergoing surgery experienced a higher rate of locoregional recurrence. The addition of adjuvant radiotherapy in patients with inadequate excision significantly decreased the risk of recurrence. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Currently, there is no clear consensus on the extent of this lateral neck dissection required in papillary thyroid cancer (PTC) with lateral neck metastasis. The purpose of this study was to review our experience with metastatic PTC, and identify the pattern of lymphatic spread to the lateral neck.

A retrospective medical chart review of PTC patients treated with lateral neck dissection (levels II–Vb) at our institution between January 2004 and 2011. A total of 185 patients underwent 248 selective lateral neck dissections.

Levels II, III, IV, and Vb were respectively involved in 49.3%, 76.6%, 61.6%, and 29.2% of cases.

We advocate for a routine excision of levels II, III, IV, and Vb in PTC with metastasize to any lateral neck level. Although we have routinely dissected level IIb, it may be appropriate to omit its dissection, as well as level Va, when there are no clinical, radiologic, or intraoperative evidence of disease involving these sublevels. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by bone marrow failure and increased risk of cancers including acute myelogenous leukemia and various solid tumors, especially head and neck cancer. Management of head and neck cancer in the setting of FA is complicated by pancytopenia, poor tolerance of chemotherapy, and potentially increased radiosensitivity. There are limited reports on tolerance of radiotherapy (RT) in patients with FA.

We report a case of a patient with FA who presented with a small oral tongue cancer that was excised. He rapidly developed extensive locoregional recurrence and underwent surgical resection followed by postoperative RT with concurrent cetuximab.

Both RT and cetuximab were well tolerated with manageable toxicities. Unfortunately, the patient died of early locoregional disease progression.

RT with concurrent cetuximab was well tolerated and may be an appropriate option in patients with FA. However, many patients have a poor prognosis due to aggressive disease. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Ectopic thyroid tissue very rarely occurs in the buccal region. Even more rarely encountered is the papillary carcinoma arising in the ectopic tissue.

We herein present a 78-year-old female patient admitted with a giant, buccal mass that developed within the previous 2 years. Physical examination revealed a vegetative mass on the left buccal region without any cervical lymphadenopathy. Magnetic resonance imaging scan showed an 8- × 6-cm solid mass with cystic components in the left buccal region and thoracic computed tomography scanning revealed pulmonary metastasis. A successful surgery including lower lip splitting was performed, and the mass was totally excised with its surrounding capsule. Histopathologic examination revealed follicular variant of papillary carcinoma of the ectopic thyroid tissue.

To our knowledge, our case is the first case of papillary carcinoma arising from ectopic thyroid tissue in the buccal region in the literature. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Arming antibody with toxins is a new approach in cancer therapy. We evaluated the efficacy of cetuximab–ZZ-PE38 immunocomplex in killing cancer cells in vitro and inhibiting tumor growth in nude mice.

Several cancer cell lines and human foreskin fibroblasts were tested for epidermal growth factor receptor (EGFR) expression and cetuximab binding using Western blot assay, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Cell survival in vitro was estimated by XTT assay. Tumor size was measured twice a week.

Cetuximab–ZZ-PE38 immunocomplex was significantly more effective in killing head and neck cancer cells than nonspecific IgG-ZZ-PE38 complex or free ZZ-PE38, whereas normal cells were not affected. Tumor treatment with immunocomplex resulted in tumor shrinkage. The immunocomplex was safe to mice at a therapeutic dosage of 0.25 mg/mL, whereas the dosage of 0.50 mg/mL induced liver toxicity.

Cetuximab–ZZ-PE38 immunocomplex is a highly effective agent in killing EGFR-positive cancer cells and in tumor shrinkage. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to compare the major thrombin receptor protease-activated receptor-1 (PAR-1) expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanisms that may lead to induce PAR-1 expression.

Thirty OSF and 10 normal buccal mucosa specimens were examined by immunohistochemistry. Buccal mucosal fibroblasts (BMFs) were challenged with arecoline by using Western blot analysis. N-acetyl-L-cysteine (NAC), LY294002, herbimycin A, NS-398, and PD98059 were added to find the possible regulatory mechanisms.

PAR-1 expression was significantly higher in OSF specimens (p < .05). Arecoline was found to elevate PAR-1 expression in a dose-dependent and time-dependent manner (p < .05). The addition of NAC, LY294002, herbimycin A, NS398, and PD98059 markedly inhibited the arecoline-induced PAR-1 expression (p < .05).

PAR-1 expression is significantly upregulated in areca quid chewing-associated OSF. Arecoline-induced PAR-1 expression was downregulated by NAC, LY294002, herbimycin A, NS398, and PD98059. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Trigeminal schwannomas are uncommon intracranial tumors. Extracranial trigeminal schwannomas in the infratemporal fossa are rare.

We present a case with a clinical history of facial pain. MRI and CT scans showed a mass arising from the infratemporal fossa extending into the intracranial space.

We performed a combined neurosurgical and maxillofacial approach with preoperative endovascular embolization. Complete removal of the parasellar component was achieved with a minimal extracranial neoplastic residual. High microvessel density, reflecting intense neoangiogenesis, was detected through the immunohistochemical staining with endoglin.

Due to the unique development pattern of trigeminal schwannoma involving multiple intracranial fossae and extracranial compartment, we chose a combined neurosurgical and maxillofacial approach with preoperative embolization of the tumor. Immunohistochemical findings suggest that the extensive growth observed may be related to an intense neoangiogenesis, opening the perspective to novel therapeutic options based on the inhibition of neoangiogenesis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been introduced for the treatment of superficial pharyngeal cancer.

Sixty superficial pharyngeal cancers in 45 patients were treated by EMR or ESD. Resectability and curability, complications, and survival were analyzed retrospectively.

The en bloc resection and curative resection rate were higher with ESD (100; 81.6%) than with EMR (59; 50%). In subgroup analysis with regard to tumor size ≤10 mm, both resection rates were comparative. All the patients had preserved larynx and swallowing, speech, and airway function. Two of the 45 patients died of other diseases, local recurrence was observed in 4 of 18 patients with noncurative resection with a median observation period of 38 months. No recurrence was observed in patients with curative resection.

ESD or EMR for superficial pharyngeal cancer is minimally invasive treatment and lesions larger than 10 mm should be referred for ESD. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

There have been few reports on lymph node metastasis between sternocleidomastoid and sternohyoid muscle (originally LNSS) in clinically node positive (cN+) papillary thyroid carcinoma (PTC). Therefore, our objective was to investigate the significance of LNSS metastasis.

A total of 115 patients with cN+ PTC underwent a neck dissection with LNSS, as a separate pathologic specimen to be analyzed for the correlation between LNSS and sex, age, tumor size, tumor site, initial or reoperative treatment, lateral cervical lymph nodes, and central compartment metastasis.

The positive rate of LNSS was 22.6%. LNSS metastasis was correlated with a primary site in the inferior pole, the lateral nodal metastasis, level III and level IV nodal metastasis, but not with other clinical parameters.

In cN+ PTC, especially a primary site in the inferior pole, level III and/or level IV metastasis, attention should be given to excising the nodal tissue in LNSS. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Arterial thromboses following cisplatin-based chemotherapy in head and neck cancers are extremely rare and devastating complication.

A 54-year-old male smoker had an acute history of left lower limb pain and calf claudication 3 days following the first cycle of cisplatin-based chemotherapy given concurrently with radiotherapy for squamous cell carcinoma of the base of tongue. CT angiography showed extensive abdominal aortic thrombus along with involvement of left common iliac, saphenopopliteal, and tibeal arteries as well as moderate stenosis in the proximal segments of left anterior descending and right coronary artery. We suggest that endothelial damage and hypercoaguable state secondary to cisplatin may have induced severe arterial and coronary thrombosis.

This is the first reported case of acute multiple arterial thrombosis following cisplatin in head and neck cancer. It is a dreaded complication and has a dismal prognosis if not promptly recognized and treated. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Patients with parathyroid adenomas (PAs) are commonly encountered in otolaryngology and may present with asymptomatic hypercalcemia. Retropharyngeal hematoma and recurrent laryngeal nerve (RLN) paralysis are less commonly encountered presentations and may be harbingers of a malignant process.

We present 2 patients with rare presentations of parathyroid adenoma. The first is a 57-year-old man with retropharyngeal hemorrhage and progressive airway compromise. The second is a 51-year-old woman presenting with dysphonia who was found to have RLN paralysis. Both of these patients were found to have benign disease.

Although most patients with PA present with asymptomatic hypercalcemia, this disease entity must be considered in patients with other unusual presentations including hemorrhagic neck masses and dysphonia. The importance of a broad differential diagnosis and thorough workup is emphasized. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The role of minimally invasive surgery in Graves' disease is still controversial. The aim of this study was to compare the clinical outcomes of patients undergoing minimal-incision thyroidectomy with those undergoing conventional thyroidectomy for Graves' disease.

A prospective study was performed on 148 patients undergoing total thyroidectomy. Seventy-one patients underwent minimal-incision thyroidectomy and 77 underwent conventional thyroidectomy. Minimal-incision thyroidectomy was proposed if the thyroid volume was ≤50 mL.

There were no significant differences in the operative time between minimal-incision thyroidectomy and conventional thyroidectomy. The length of skin incision was significantly shorter in the minimal-incision thyroidectomy than that in the conventional thyroidectomy group. The incidence of postoperative complications was similar in the 2 groups. Patients undergoing minimal-incision thyroidectomy experienced significantly less postoperative pain and were more satisfied with the cosmetic result than patients who underwent conventional thyroidectomy.

Minimal-incision thyroidectomy is a feasible and safe option for the surgical treatment of selected patients with Graves' disease. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The objective of this study was to identify relevant quality of life (QOL) issues in patients with head and neck cancer receiving multimodal and/or targeted therapies.

The literature was searched for QOL issues reported after multimodal and/or targeted therapies resulting in a list of potentially relevant issues. These were discussed within a multiprofessional expert group, revised, and subsequently rated for relevance by patients and health care providers.

Twenty-seven issues were extracted that are not covered by the current version of the European Organization for Research and Treatment of Cancer (EORTC) questionnaires. Interviews (96 health care providers from 13 countries, 137 patients from 8 countries) revealed that 26 of these issues were relevant for patients with head and neck cancer.

Studies investigating targeted and/or multimodal therapy should consider that some QOL issues specific to these treatments are not covered by the current version of the EORTC instruments. Consequently, the EORTC head and neck cancer module is currently in revision. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to determine if there are differences in biomarker modulation and epidermal growth factor receptor (EGFR) degradation between the tumor and the normal mucosa after treatment with an EGFR inhibitor, erlotinib, in head and neck cancer.

Patients with primary oral cavity squamous cell cancers received a course of erlotinib, 150 mg every day for 7 days before surgical resection. Tumor and normal mucosa biopsies were obtained both pre-erlotinib and post-erlotinib. Changes in known markers of EGFR activity (phospho, AKT, STAT3) were measured by immunoblotting, whereas changes in tissue distribution were analyzed by immunohistochemical analysis.

Twelve patients were enrolled; 7 had evaluable paired tumors and normal mucosa biopsies pretreatment and posttreatment. Expression of EGFR was higher in tumors compared to the normal mucosa (p = .005). Erlotinib administration was associated with marked inhibition of phosphorylated epidermal growth factor receptor (pEGFR) and reduction in total EGFR protein (p = .004, p = .007) in tumors, whereas there was heterogeneity in EGFR inhibition in the normal mucosa (p = .10 [pEGFR], and p = .07 [EGFR]). Reduced levels of pSrc and pSTAT3 and enhanced p27 levels were noted in tumors after erlotinib. Cell culture studies confirmed that EGFR is degraded in tumor cells after prolonged treatment with erlotinib.

Our results show that EGFR inhibition by erlotinib led to a marked reduction in EGFR protein levels in patients. Differential effects of erlotinib on tumors compared to the normal mucosa suggest there may be individual patient heterogeneity. These preliminary data suggest EGFR degradation should be further analyzed as a potential biomarker in selecting patients likely to benefit from EGFR inhibitors. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Nodal metastasis in papillary thyroid cancer (PTC) usually occurs in the central compartment of the ipsilateral neck and spreads laterally. The purpose of this study was to evaluate the diagnostic accuracy of frozen biopsy for quantitative nodal evaluation of central neck metastasis in PTC.

In all, 252 patients with PTC underwent total thyroidectomy with bilateral central neck dissection (CND). All tissues from ipsilateral CND were examined by frozen biopsy.

Among them, 53% of patients had central neck metastasis. The sensitivity and specificity of frozen biopsy for central neck metastasis were 92% and 99%, respectively. The positive predictive value and the negative predictive value were 99% and 84%, respectively. The diagnostic accuracy for the exact number of metastatic nodes was 91% compared to permanent biopsy.

Frozen biopsy for quantitative analysis of central compartment is a useful tool for the precise evaluation of central lymphatic status intraoperatively with a high sensitivity and specificity. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Many studies have recently emphasized the role of tumor angiogenesis and lymphangiogenesis in regional and distant spread of disease. Although early laryngeal cancer has a favorable oncologic outcome after conservative surgery or radiation therapy, we observed few cases with poor prognosis in terms of locoregional relapse, organ preservation, and survival. The aim of our study was to evaluate the immunohistochemical expression of CD31 and podoplanin to define angiogenic and lymphangiogenic patterns and their possible prognostic implications in previously untreated T1–T2 glottic squamous cell carcinoma.

Four hundred twenty-eight patients with previously untreated early-stage laryngeal cancer underwent a laser surgical resection in the period between January 1994 and December 2007. Twenty-seven cases with poor outcome were identified and compared with a selected sample of 28 patients. All specimens were negative for the presence of high-risk human papillomavirus genotypes. Patients were followed up until death or for at least 24 months after treatment. Three-micrometer sections were obtained from formalin-fixed and paraffin-embedded tumoral tissues, and an immunohistochemical evaluation was performed. Monoclonal antibodies against CD31 and podoplanin were used for the detection of blood and lymphatic vessels, respectively. A morphometric measurement was used for the analysis of angiogenesis whereas lymphangiogenesis was studied with a semiquantitative technique. The data were analyzed by use of chi-square and Mann-Whitney tests as appropriate.

An increased tumor angiogenesis correlated with local relapse (p = .01), locoregional relapse (p = .01), and death of disease (p = .03). The presence of lymphatic vessels in peritumoral fields had an impact on local (p = .004) and locoregional recurrence (p = .01).

Evaluation of angiogenesis and lymphangiogenesis in early-stage laryngeal cancer could be useful to identify patients at higher risk of recurrence and consequently to modulate treatment planning and follow-up strategy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to investigate the incidence of retropharyngeal lymph node (RPLN) metastasis and to explore the associated risk factors using CT and MRI, to direct clinical radiotherapy in hypopharyngeal carcinoma (HPC).

The CT and MRI images of 218 patients with pathologically confirmed HPC were analyzed retrospectively. The chi-square test and logistic regression were used for statistical analysis.

The incidence of RPLN metastasis in HPC was 17.0%, and the highest rate of 36.4% was found in pharyngeal wall carcinoma. None of the patients with N0 classification exhibited RPLN metastasis. Univariate and multivariate analyses demonstrated that primary tumor subsites, bilateral cervical lymph node metastasis, the number and size of cervical lymph nodes, and level V metastasis were significantly associated with RPLN metastasis.

Our findings demonstrated that primary carcinoma subsites and multiple metastatic cervical lymph nodes are the principal risk factors for RPLN metastasis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Cancers of the head and neck are associated with detriments in health-related quality of life (HRQOL); however, little is known about different experiences between African Americans and non-Hispanic whites.

HRQOL was measured by the Functional Assessment of Cancer Therapy – Head and Neck (FACT-H&N) approximately 5 months postdiagnosis among 222 patients with cancer from North Carolina. Higher scores represent better HRQOL. Regression models included sociodemographic characteristics and clinical factors.

African Americans reported higher physical well-being than whites (adjusted means, 23.1 vs 20.9). African Americans with incomes <$20,000 reported higher emotional well-being (21.4) and fewer head and neck symptoms (22.0). Non-Hispanic whites making <$20,000 reported the poorest emotional well-being (17.3), whereas African Americans making >$20,000 reported the most head and neck symptoms (18.7).

Further investigation is needed to explore variation in HRQOL experiences among different race and socioeconomic groups that may inform resource allocation to improve cancer care. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

There are 600 million betel quid chewers around the world. betel quid chewing is a major risk factor of oral cancer. Why betel quid components induce oral cancer is not clear.

Cytotoxicity of areca nut extract and arecoline (an areca nut alkaloid) to SAS oral epithelial cell line was evaluated by trypan blue dye exclusion and MTT assays. Cell cycle distribution and apoptosis was analyzed by propidium iodide staining flow cytometry. Chk1 and chk2 activation was analyzed by Pathscan phospho-enzyme-linked immunosorbent assay. Metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase (TIMPs) production was measured by enzyme-linked immunosorbent assay.

Areca nut extract (800 μg/mL) and arecoline (>0.4 mmol/L) caused cell death, apoptosis, and cell cycle arrest of SAS cells. Areca nut extract and arecoline stimulated Chk1 and Chk2 phosphorylation in SAS cells. Areca nut extract stimulated cellular MMP-9 but suppressed TIMP-1 and TIMP-2 production.

Areca nut components activate Chk1/Chk2, alter cell cycle regulation/apoptosis, MMP-9, and TIMPs production, contributing to the pathogenesis of oral carcinogenesis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Maxillectomy defects require complex 3-dimensional reconstructions often best suited to microvascular free tissue transfer. Postoperative airway management during this procedure has little discussion in the literature and is often dictated by surgical dogma. The purpose of this article was to review our experience in order to evaluate the effect of airway management on perioperative outcomes in patients undergoing maxillectomy with free flap reconstruction.

A retrospective chart review was performed on patients receiving maxillectomy with microvascular reconstruction at 2 institutions between 1999 and 2011. Patient's airways were managed with or without elective tracheotomy at the surgical team's discretion and different perioperative outcomes were measured. The primary outcome was incidence of airway complication including pneumonia and need for further airway intervention. Secondary outcome was measured as factors leading to perioperative performance of the tracheotomy.

Seventy-nine of 143 patients received elective tracheotomy perioperatively. The incidence of airway complication was equivalent between groups (10.1% vs 9.4%; p = .89). Patients with cardiopulmonary comorbidities were more likely to receive perioperative tracheotomy (74.1% vs 50.9%; p = .03) without a difference in airway complications. Other patient cofactors did not have an impact on perioperative tracheotomy or airway complication rate.

Elective tracheotomy may safely be avoided in a subset of patients undergoing maxillectomy with microvascular reconstruction. Elective tracheotomy should be considered in patients with cardiopulmonary risk factors. Head Neck, 2012

Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robotic surgery (TORS) supraglottic laryngectomy.

Patients with laryngeal cancer who underwent TORS supraglottic laryngectomy and participated in a prospective TORS study between 2008 and 2011 at an academic medical center are presented.

Thirteen of 126 patients underwent TORS supraglottic laryngectomy for laryngeal cancer. Average robotic operative time and estimated blood loss were 25.3 minutes and 15.4 mL, respectively. Negative surgical margins were achieved in all patients. Eleven patients were started on an oral diet within 24 hours of surgery with no evidence of immediate airway compromise. Two patients (15.4%) received adjuvant radiation therapy based on pathology.

In this preliminary study, TORS supraglottic laryngectomy was a safe procedure with good functional outcomes. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

There is a small subgroup of patients with head and neck cutaneous squamous cell carcinoma (cSCC) in which nodal metastases present concurrently with the primary lesion. There is evidence that these tumors may represent a more aggressive subset of cSCC. The aim of this study was to determine whether alternative clinicopathologic prognostic factors should be applied to this patient cohort.

A retrospective analysis of data from prospective databases of 2 large head and neck cancer units in Sydney, Australia, was performed. Ninety-five patients with concurrent primary and nodal metastatic head and neck cSCC were suitable for inclusion in the study.

Univariable analysis was performed for overall survival (OS) and disease-specific survival (DSS). OS was adversely affected by immunosuppression (p = .011) and nodal extracapsular spread (ECS) (p = .006). Similarly, immunosuppression (p = .005) and ECS (p = .005) indicated a worse outcome for DSS. ECS and immunosuppression remained significant in the multivariable analysis.

This study found that adverse prognostic factors were similar to the current evidence for nonconcurrent metastatic cSCC. In particular, the primary lesion had no significant influence on survival. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to prepare the ultrasonographic diagnostic criteria on parotid tumors for preoperative differentiation of superficial and deep tumors.

We evaluated 154 patients with a benign parotid tumor who underwent surgery. The minimum thickness of normal parotid gland tissue between the parotideomasseteric fascia and tumor (minimum fascia–tumor distance [MFTD]) was measured on preoperative ultrasonography and compared among tumors at different locations, and the optimum cutoff value to differentiate a deep tumor was identified.

The MFTD showed significant differences between superficial and deep tumors and between inferior pole and deep tumors. The sensitivity, specificity, and accuracy of an MFTD ≥3 mm for the differentiation of deep tumors were 85%, 91%, and 89%.

A tumor with an MFTD ≥3 mm on preoperative ultrasonography is very likely to be a deep tumor based on a new differentiation method for deep parotid tumors considering those present at other locations. Head Neck, 2012

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy and childhood. This tumor results in poor prognosis, and therefore, development of a more effective treatment is needed.

We describe an 11-year-old boy presenting with left facial palsy caused by aggressive KHE of the left temporomastoid region. He was treated with paclitaxel-based chemotherapy, because of the difficulty with complete surgical resection for anatomic factor, multiple lung metastases on diagnosis, and no response to conventional treatments. This treatment reduced the volume of primary tumor and lung metastatic lesions, but the efficacy was transitory.

Paclitaxel-based chemotherapy for aggressive KHE may be effective, therefore the multimodality therapy including paclitaxel of aggressive KHE, particularly in the head and neck, needs to be investigated in further studies. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

To investigate the impact of up-front neck dissection on the outcome of patients with node-positive hypopharyngeal cancer (HPC) treated with (chemo)radiation.

Of 135 consecutive patients with node-positive HPC, 32 patients underwent up-front neck dissection followed by (chemo)radiation (group 1), and 103 patients received definitive (chemo)radiation (group 2).

The 3-year regional, local and distant control for groups 1 and 2 were 92% versus 87% (p = .37), 84% versus 72% (p = .15), and 80% versus 62% (p = .08), respectively. High T classification was the only significant predictor for poor overall survival on multivariate analysis (OR = 3.0, p = .02). Acute and late toxicities and the prospectively assessed quality of life were comparable in both groups.

Upfront neck dissection followed by (chemo)radiation did not negatively impact on oncologic outcomes, toxicity, or quality of life and therefore is to be regarded as a safe and effective treatment option for small HPC with bulky nodal disease, especially in busy radiation departments with unacceptably long waiting time for definitive (chemo)radiation. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The superficial branch of the radial nerve is frequently encountered when performing the harvest for a radial forearm free tissue transfer.

We present an abnormal course of this nerve which has not been described in the literature. During a harvest of a radial forearm free flap, we encountered a nerve that was not deep to the brachioradialis muscle in the proximal arm; rather, the superficial branch of the radial nerve was found to be superficial to this muscle through its entire course. An in-depth literature review was performed, and there was no documented abnormality identified resembling the abnormality we encountered.

Knowledge of the normal and abnormal anatomy is essential for the microvascular surgeon to assure the safety of this nerve. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Retromolar trigone tumors are rare and aggressive malignancies. There is lack of quality evidence pertaining to their management due to the heterogeneity in treatment policies adopted. We retrospectively reviewed the patients of locally advanced retromolar trigone tumors treated with a standard and uniform multimodality management.

A retrospective review of patients with locally advanced retromolar trigone tumors was performed and an analysis of clinicopathologic profile, treatment details, and survival outcomes was carried out.

Forty-two patients of locally advanced retromolar trigone tumors underwent the standard multimodality treatment. The majority of them presented with stage IVa disease. Margin negative resection could be achieved in 93% of patients. Histopathologically proven bone and node involvement was seen in 20 patients (47.6%) and 21 patients (50%), respectively. The 3-year disease-free and overall survival rates were 64% and 71%, respectively.

Treatment of patients with locally advanced retromolar trigone tumors is challenging. However, good oncologic outcomes can be achieved by advocating an aggressive surgical approach with postoperative radiation therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Studies have focused on enhancing flap viability using superoxide dismutase (SOD), but only a few used SOD from human origin, and most gave the compound systemically. We evaluated the ability of SOD to improve random skin flap survival using human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) in variable doses, injected intradermally into the flap.

Seventy male Sprague Dawley rats were randomly assigned into 4 groups. Cephalic random pattern flaps were elevated on their backs and intradermal injections of different dosages of Hr-CuZnSOD were given 15 minutes before surgery. Flap survival was evaluated by fluorescein fluorescence. Analysis of variance (ANOVA) and t test statistical analyses were performed.

Flap survival in all treated groups was significantly better than in the controls.

The beneficial effect of HR-CuZnSOD on flap survival is attained when it is given intradermally into the flap tissue. Theoretically, Hr-CuZnSOD delivered with local anesthetics used in flap elevation may be a valuable clinical tool. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Paragangliomas are rare, vascular, and predominantly benign neoplasms of neural crest origin. They typically arise in the head and neck from the carotid body, jugulotympanic, or vagal paraganglia. Rarely, paragangliomas occur in the larynx. Only 2 cases of hypopharyngeal paraganglioma have been reported. We discuss the case of a hypopharyngeal paraganglioma and review the literature concerning laryngopharyngeal paragangliomas.

We present the case of a woman with 2 months of dysphagia and hoarseness that was found to have a hypopharyngeal paraganglioma. The patient underwent embolization and resection of the mass via a lateral thyrotomy approach. Pathologic analysis and selective staining confirmed the presence of a paraganglioma.

Proper histopathologic identification of these tumors is tantamount to guiding treatment. The preferred operative approach is a lateral thyrotomy to minimize patient morbidity. We present the third documented case of a hypopharyngeal paraganglioma and the first in the English-language literature. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Treatment for head and neck cancer can reduce peripheral sensory input and impair oropharyngeal swallow. This study examined the effect of enhanced bolus flavor on liquid swallows in these patients.

Fifty-one patients treated for head and neck cancer with chemoradiation or surgery and 64 healthy adult control subjects served as subjects. All were randomized to receive sour, sweet, or salty bolus flavor. Patients were evaluated at 7–10 days, 1 month, and 3 months after completion of tumor treatment. Control subjects received 1 assessment.

All bolus flavors affected oropharyngeal swallow; sour flavor significantly shortened pharyngeal transit time across all evaluations.

Sour flavor influenced the swallow of patients treated for head and neck cancer, as well as that of control subjects in a manner similar to those with neurologic impairment observed in an earlier study. Sour flavor may improve the speed of pharyngeal transit regardless of whether a patient has suffered peripheral or central sensory damage. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC).

Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray.

The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) (p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR (p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS (p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome.

For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior.

A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure. After the fifth biopsy, 15 months after presentation, the diagnosis of AF was made. The tumor was unresectable, so intensity-modulated radiotherapy was given with curative intent using a total dose of 60 Gy in 30 fractions of 2 Gy. After 16 months, she showed progressive disease, for which tamoxifen 40 mg twice daily was started with a good response for 2 years. After that, she started with sorafinib, on which she has stable disease now.

The often long delay in proper diagnosis and the treatment challenges of a desmoid tumor are illustrated in this case. Furthermore, this article reviews the literature concerning AF, especially of the head and neck region. Head Neck, 2012

Paragangliomas are benign neoplasms of neuroendocrine origin. It is estimated that from 20% to 50% of these tumors are familial. Mutations in the succinate dehydrogenase (SDH) gene family have been found to be responsible for a significant percentage of familial paragangliomas.

A 33-year-old man who was found to have 3 synchronous primary tumors including a catecholamine-secreting intrapericardial paraganglioma is presented.

Genetic workup diagnosed this patient with an underlying germ-line mutation in the succinate dehydrogenase complex subunit C (SDHC) gene; consistent with a diagnosis of hereditary paraganglioma/pheochromocytoma syndrome (PGL/PCC). Current knowledge regarding the clinical implications of an SDHC gene mutation is reviewed.

Modern molecular techniques have identified that a significantly greater proportion of paragangliomas are due to underlying hereditary conditions than was previously thought. Appropriate screening in these individuals and their immediate family members may allow for early tumor diagnosis and improved disease outcomes. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

American Indians/Alaska Natives experience poor overall survival. Data are limited on American Indians/Alaska Natives with head and neck squamous cell carcinoma (HNSCC).

We identified all cases of HNSCC among American Indians/Alaska Natives, and white patients from 1996 to 2007 using the Surveillance, Epidemiology, and End Results (SEER) database. Univariate, multivariate, and Cox models were fit to analyze racial differences in sex, age, stage, treatment, and survival.

American Indians/Alaska Natives experienced decreased survival for oropharyngeal cancer (hazard ratio [HR] = 1.4; p = .008). After adjusting for demographic factors, survival was decreased for oral cavity cancer (HR = 1.3; p = .05) and hypopharyngeal/laryngeal cancer (HR = 1.6; p = .04). These disparities were eliminated after adjusting for treatment for oral cavity cancer (HR = 1.2; p = .17) and stage for hypopharyngeal/laryngeal cancer (HR = 1.4; p = .12). American Indians/Alaska Natives received less surgery for oral cavity cancer (78% vs 85%; p = .02).

Disparities in survival exist among American Indians/Alaska Natives patients with HNSCC. They are related to stage and differential treatment patterns. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

In the period 1990 to 2001, a case-control study on oral cancer and maté consumption was conducted at the Cancer Institute of Uruguay.

The study included 696 newly diagnosed cases with squamous cell carcinoma and 696 controls afflicted with nonneoplastic conditions not related to tobacco smoking and alcohol drinking. The participants were matched on age and residence and the study was restricted to men.

In order to control confounding for tobacco and alcohol, we fitted 2 models. According to model 1, the odds ratio (OR) for maté consumption was 1.15 (95% confidence interval [CI], 0.76–1.73), whereas the results for model 2 showed an OR of 3.47 (95% CI, 1.60–7.52).

The inclusion of a term for the interaction between maté and smoking (or drinking) was rewarding and the ORs were even higher than those observed with the crude estimates. Head Neck, 2012

The purpose of this study was to investigate expression of recepteur d'origine nantais (RON) in human hypopharyngeal squamous cell carcinoma (SCC) and to determine whether RON affects tumor cell behavior in hypopharyngeal SCC cell line and if this would serve as a target for molecular therapy in a preclinical model.

Reverse transcriptase-polymerase chain reaction, immunohistochemistry, Western blotting, cell invasion, migration, proliferation, and apoptosis assays were used to assess alteration of RON expression and its impact to cancer progression in human hypopharyngeal SCC.

Immunoreactivity of RON was observed in hypopharyngeal SCC tissues relative to adjacent normal mucosa in all cases. RON protein expression was significantly increased in metastatic lymph nodes than nonmetastatic lymph nodes by Western blotting. Knockdown of RON resulted in significantly reduced cell invasion, migration, and proliferation in human hypopharyngeal SCC cells. Knockdown of RON enhanced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP-ribose polymerase (PARP).

These results indicate that knockdown of RON expression may be associated with the reversal of invasive phenotype in hypopharyngeal SCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Dynamic contrast-enhanced (DCE) MR perfusion imaging allows assessment of vascular density and integrity of tumors. The purpose of this study was to determine the diagnostic efficacy of time intensity curve analysis on DCE MRI for characterization of head and neck tumors.

Twenty patients underwent T1-weighted fast field echo DCE MRI with temporal resolution of 2.6 seconds. In total, 100 dynamic phases covering 20 slices were obtained in 4.5 minutes. Time to peak (TTP), relative maximum enhancement (RME) ratio, and relative washout ratio (RWO) were calculated.

Malignant tumors had a significantly lower RME (p = .025) and prolonged TTP with lower RWO than benign lesions. Postradiation changes had a significantly longer TTP (p = .024) and lower RWO (p = .007) than did postradiation recurrent tumors. Receiver operating characteristic (ROC) analysis revealed RWO had highest accuracy (area under the curve [AUC] = 1.0).

DCE MR perfusion imaging provides pivotal information regarding microcirculation, potentially improves differentiation of malignant tumor from postradiation changes. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Parsonage–Turner syndrome is a rare and painful peripheral neuropathy that usually presents as brachial plexus neuritis and also has other nerve involvement.

Herein, we report the case of a patient with right recurrent nerve palsy as the first clinically isolated manifestation of underlying Parsonage–Turner syndrome. Idiopathic dysphonia was the only symptom presenting during a week for a patient that later developed a more conventional neurological deficit in her right shoulder.

The case illustrates the need for a careful clinical-neurologic examination beyond the larynx in patients presenting with idiopathic dysphonia. Parsonage–Turner syndrome should be considered as one of the rare causes in the differential diagnosis of isolated and otherwise unexplained dysphonia. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to investigate tissue electrical properties in patients with head and neck cancer.

In the cross-sectional study direct bioimpedance measures (resistance, reactance, and phase angle) determined by bioelectrical impedance analysis (BIA) were performed on 31 patients with head and neck cancer and 31 healthy volunteers matched by age and sex as a control group.

Phase angle at 50 kHz was found to be significantly lower (p = .000006) in patients with head and neck cancer than in the control group (4.69° ± 0.71 vs 5.59° ± 0.70, respectively). Resistance was significantly (p = .0002) greater in patients with head and neck cancer than in the control group (596.24 ± 96.31 ohm vs 513.73 ± 65.79 ohm, respectively).

Presurgical patients diagnosed with head and neck cancer have altered tissue electrical properties. Further observations would be valuable to calculate survival, validate the prognostic significance of phase angle, and monitor nutritional and therapeutic interventions in this patient population. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to update and external validation of a prognostic model that is able to predict the survival probability of newly diagnosed patients with head and neck cancer.

Our original prognostic model is based on historical data of 1371 patients with primary head and neck cancer, diagnosed and treated in the Leiden University Medical Center, between 1981 and 1999. The model contains the predictors age, sex, tumor site, TNM-classification, prior tumors, and comorbidity. We updated the model with follow-up data until January 2010. The updated model was then externally validated in 598 patients with head and neck cancer from the Siteman Cancer Center/Barnes-Jewish Hospital, St. Louis, Missouri.

Median follow-up was 5.5 years (range, 0–25.5). Only 2.5% of patients were lost to follow-up. During follow-up 1099 patients (80.2%) passed away. Discrimination of the updated prognostic model was good, with a C-index of 0.73 after internal validation. The discrimination was slightly lower in the external validation set (C-index, 0.69). The predicted 2-year and 5-year survival rates correlated satisfactorily with some slight deviations from the perfect calibration line.

We used recent follow-up information to update the Leiden prognostic model for newly diagnosed patients with head and neck cancer. The model showed acceptably good calibration and discrimination results in internal and external validation procedures. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to determine the feasibility of a randomized trial of resistance exercise in patients with head and neck cancer receiving radiation.

Fifteen patients with head and neck cancer receiving radiation were randomized to resistance exercise (using resistance bands) or control group. Resistance exercise occurred at the radiation therapy site (weeks 1–6) and home (weeks 7–12).

No serious adverse events occurred related to resistance exercise. Medium to large effect size differences favoring resistance exercise versus control group were noted for perceived fatigue at 6 weeks (smaller increase in fatigue for resistance exercise group; 7.4 vs 15.4, effect size [d] = −0.64), quality of life at 6 weeks (−7.0 vs −14.4, d = 0.52), and chair rise time (seconds) at 6 and 12 weeks (−1.6 vs 0.4, d = −.63 and −1.9 vs 0.1, d = −0.60, respectively).

Resistance exercise is safe and feasible in patients with head and neck cancer receiving radiation; a definitive trial is warranted. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The long-term use of highly active antiretroviral therapy (HAART) in patients with human immunodeficiency virus (HIV) has led to sequelae including lipodystrophy syndrome (LDS). We present the first published case of surgical management of bilateral parotid lipomatosis in a patient with HIV on long-term HAART.

We undertook review of the case notes from the time of diagnosis with HIV and literature review of this topic.

A 45-year-old man with HIV on HAART presented with a 4-year history of increasing bilateral facial swelling. He was asymptomatic apart from the stigmatizing cosmetic deformity. MRI revealed the parotid glands had been replaced by fat. He elected for surgery and parotid lipomatosis was diagnosed on histopathological examination.

Lipohypertrophy in LDS is rare in the literature and this presentation of bilateral parotid lipomatosis secondary to HAART is only the third reported case, and the first to undergo surgical resection. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The purpose of this study was to review our experience with the scapular tip free flap for mandibular reconstruction, describe the surgical approach, and highlight specific clinical applications.

A retrospective review of all patients undergoing oromandibular reconstruction using a scapular tip free flap at the London Health Sciences Centre was undertaken. Patient demographics, surgical data, and early outcomes were collated.

Twenty patients were identified. The majority involved mandibular angle and short segment defects (16 of 20). Average length of the segmental defect was 6.2 cm with the longest measuring 8 cm. A single patient required an osteotomy. Six were revision cases. No vein grafts were required. One complete flap failure occurred.

The natural scapular angle makes the scapular tip flap ideal for mandibular angle reconstruction. Short bone segments can be harvested with little donor-site morbidity. The long pedicle length may obviate vein grafts. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The mechanism of transient recurrent laryngeal nerve (RLN) palsy remains unclear.

Samples were harvested from the RLN adjacent thyroid capsule and perineural fascia during 223 lobectomies and 89 RLNs from cadavers were used for histologic and immunohistologic evaluation. Intraoperative chromoendoscopic features of the RLN were compared with postoperative ear, nose, and throat examinations.

Those nerves that macroscopically seem to be single-branched (35 of 89 = 39.3%), microscopically consist of multiple fascicles in most of the cases (23 of 35 = 65.7%), resembling a plexus more than a single cord. Chronic lymphocytic infiltration of the thyroid capsule adjacent to the RLN was present in 29% (65 of 223) of the cases. The perineural fascia showed lymphocytic (18 of 223 = 8.1%) or granulocytic (7 of 223 = 3.1%) infiltration.

The origin of transient RLN palsy is multifactorial: plexus shaped microscopic nerve structure with or without branches, frame-like adventitial tissue, variable epineurium, inflammatory changes that involve not only the thyroid capsule but the perineural fascia, resultant nerve edema, and diffuse microhemorrhages by injury of fragile capillaries. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Salivary mRNA biomarkers can exhibit significant variation over time. The purpose of this study was to investigate the pattern and magnitude of variation of salivary mRNA biomarkers and to explore the effect of performing replicate assays and multiple sampling on the dispersion of salivary biomarkers.

Salivary interleukin-8 (IL-8) and interleukin-1β (IL-1β) mRNAs, developed as biomarkers for oral cancer detection, were selected and measured from 15 healthy subjects at 4 different time points on the same day.

Salivary IL-8 and IL-1β mRNA levels fluctuated randomly over time without predictable rhythm and showed higher within-subject biological variation than analytical variation. The dispersion of salivary IL-8 and IL-1β mRNAs was more effectively reduced by taking multiple saliva sample measurements than by performing replicative assays.

Taking multiple saliva samples can effectively reduce variation of salivary IL-8 and IL-1β mRNA levels in healthy adults. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Head and neck squamous cell carcinoma (HNSCC) is associated with tobacco use. Still, most smokers do not develop HNSCC. The mechanisms of varying susceptibility to HNSCC are poorly studied to date. Tobacco metabolite research provides insight regarding the innate metabolism and excretion of carcinogens.

Smokers with HNSCC (cases) were compared with smokers without HNSCC (controls) in a matched cohort. The tobacco metabolites studied were: 1-hydroxypyrene (1-HOP), N′-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL).

In 33 subjects, mean 1-HOP was 1.82 pmol/mg creatinine versus 1.08 pmol/mg creatinine (p = .004) and mean NNN was 0.10 pmol/mg creatinine versus 0.04 pmol/mg creatinine (p = .01) in cases and controls, respectively. NNAL did not differ between groups.

Smokers with HNSCC have elevated urinary levels of 1-HOP and total NNN compared with matched controls, suggesting an increased effective exposure to these carcinogens. Tobacco constituent metabolites may be useful in understanding tobacco-related carcinogenesis in HNSCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Constitutive activation of nuclear factor κB (NF-κB) is associated with poor prognosis. Irinotecan demonstrates single-agent activity in head and neck cancer but activates NF-κB, promoting cell survival and resistance. Bortezomib is a proteasome inhibitor that inactivates NF-κB.

We performed a randomized phase II trial of bortezomib on days 1, 4, 8, and 11 and irinotecan on days 1 and 8 of each 21-day cycle or single-agent bortezomib on days 1, 4, 8, and 11 on a 21-day cycle. The addition of irinotecan to bortezomib was allowed in patients who progressed on bortezomib alone.

The response rate of bortezomib and irinotecan was 13%. One patient had a partial response to bortezomib alone (response rate 3%). No responses were seen in patients with addition of irinotecan at time of progression on bortezomib.

The bortezomib-based regimens evaluated in this study have minimal activity in recurrent or metastatic head and neck cancer. Head Neck, 2012

Recent evidence suggests that head and neck squamous cell carcinomas (HNSCCs) harbor a small subpopulation of highly tumorigenic cells, designated cancer stem cells. A limiting factor in cancer stem cell research is the intrinsic difficulty of expanding cells in an undifferentiated state in vitro.

Here, we describe the development of the orosphere assay, a method for the study of putative head and neck cancer stem cells. An orosphere is defined as a nonadherent colony of cells sorted from primary HNSCCs or from HNSCC cell lines and cultured in 3-dimensional soft agar or ultralow attachment plates. Aldehyde dehydrogenase activity and CD44 expression were used here as stem cell markers.

This assay allowed for the propagation of head and neck cancer cells that retained stemness and self-renewal.

The orosphere assay is well suited for studies designed to understand the pathobiology of head and neck cancer stem cells. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The AT-motif binding factor 1 (ATBF1) gene is frequently altered at the genetic level in several types of cancer, but its protein expression and subcellular localization have not been well studied in human cancers, including head and neck squamous cell carcinomas (HNSCCs).

ATBF1 expression and localization were examined in 5 cell lines and 197 clinical specimens of HNSCC, and correlated with pathologic and clinical characteristics.

ATBF1 was predominantly localized in the nucleus of hyperplastic squamous epithelium. Whereas nuclear ATBF1 dramatically decreased in invasive tumors (p = .0012), cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors (p < .0001), and the increase correlated with poor survival. Reduced nuclear ATBF1 level was also detected in HNSCC cell lines.

Nuclear localization of ATBF1 is frequently interrupted in HNSCC, and the interruption is significantly associated with the progression of HNSCC. The cytoplasmic ATBF1 level could be useful for predicting patient survival. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies.

By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas.

We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways.

This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway. Head Neck, 2012

The purpose of this study was to evaluate the learning curve for minimally invasive video-assisted thyroidectomy (MIVAT).

Fifty consecutive patients were prospectively included in groups corresponding to their surgical order (10 patients in each group).

The mean operation times between 2 neighboring groups were 33.9 minutes longer in group 1 than in group 2 (p = .01) and 25.8 minutes longer in group 3 than in group 4 (p = .002). The conversion rate for technical difficulties in group 1 was 6% (3 of 50). The definitive complication rate was 2% (1 of 50).

In terms of operative time, 10 patients represented the early stage of the learning curve, and 30 patients represented the number of procedures required to reach an advanced level of skill. Considering the low conversion and complication rates, improved aesthetic results and postoperative course, MIVAT should become a tool in the repertoire of high-volume thyroid surgeons. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular tumor with some characteristics resembling those of vascular malformations. The significance of different growth and angiogenesis promoting factors for the etiology of JNA remains unsolved.

We analyzed the immunoexpressions of glucose transporter 1 (GLUT-1), tenascin-C (TNC), and syndecan-2 in a series of 27 patients with JNA and compared these with each other and the clinical data to investigate their possible connections and role in the angiogenesis and growth of JNA.

We found that frequent stromal TNC expression had a strong correlation with vessel density and tumor stage and endothelial GLUT-1 expression, when present, correlated with higher tumor stage. Stromal TNC and stromal GLUT-1 expressions were also found to correlate with each other.

The immunoexpression of stromal TNC correlated with vascular density and higher tumors stage, which supports the idea of TNC having a role in the tumorigenesis of JNA putatively by promoting angiogenesis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Lymphedema may disrupt local function and affect quality of life (QOL) in patients with head and neck cancer. The purpose of this study was to examine the associations among severity of internal and external lymphedema, symptoms, functional status, and QOL in patients with head and neck cancer.

The sample included 103 patients who were ≥3 months after head and neck cancer treatment. Variables assessed included severity of internal and external lymphedema, physical/psychological symptoms, functional status, and QOL.

Severity of internal and external lymphedema was associated with physical symptoms and psychological symptoms. Patients with more severe external lymphedema were more likely to have a decrease in neck left/right rotation. The combined effects of external and internal lymphedema severity were associated with hearing impairment and decreased QOL.

Lymphedema severity correlates with symptom burden, functional status, and QOL in patients after head and neck cancer treatment. Head Neck, 2012

Intraoperative 3-dimensional (3D) imaging in head and neck surgery was developed using a prototype mobile C-arm for cone-beam CT (CBCT). This article summarizes its implementation in a prospective pilot and feasibility study.

The CBCT C-arm was used in 12 head and neck surgical oncology cases. Human-factors engineering methods and expert feedback from surgeons, nurses, and anesthetists were used to evaluate the impact of intraoperative imaging on the surgical environment and clinical workflow. Image quality of CBCT and the perceived clinical utility were evaluated.

The CBCT C-arm was successfully incorporated in 12 head and neck cases and streamlined into the surgical environment. Reviewed 3D-CBCT images were qualitatively sufficient for intraoperative-guidance for bony detail. Additional artifact management is required to improve soft-tissue visualization.

Intraoperative CBCT provides high-quality images for visualization of bony detail and is feasible during major head and neck surgery with acceptable workflow interruptions. Operations with significant bone ablation and/or reconstruction involving complex 3D anatomical structures are likely to benefit from the updated imaging. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Temporal bone inverted papilloma (IP) is an extremely rare tumor. Its etiology is unknown and represents a source of debate. Only 2 previous cases of bilateral temporal bone IP have been reported. A case report and review of the literature via PubMed database search are presented.

A 52-year-old African-American man who initially underwent medial maxillectomy for right-sided nasal IP returned with bilateral temporal bone IP 7 months later without evidence of extension through the Eustachian tubes. Despite multiple resections and adjuvant radiation, the tumor transformed into squamous cell carcinoma and progressed to involve the intracranial dura, temporal lobe, and cervical dura.

Multiple origins may exist for temporal IP: direct extension, iatrogenic seeding, or development from ectopic Schneiderian epithelium. Temporal bone IP appears to represent a much more aggressive tumor than its nasal counterpart, necessitating aggressive early surgical intervention to decrease recurrence and transformation risk. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Existing treatment regimens for squamous cell carcinoma (SCC) of the base of tongue (BOT) favor chemoradiation. However, there is a shifting paradigm toward minimally invasive surgery with adjuvant radiatiotherapy for select tumors. The aim was to report our experience in conventional surgical management with particular focus on T1/T2 tumors, which may be candidates for minimally invasive techniques.

Between 1985 and 2005, 128 patients were treated with primary surgery. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were calculated using Kaplan–Meier method, and predictive factors analyzed by univariate and multivariate analyses.

Five-year OS, DSS, and RFS rates were 60%, 70%, and 61%, respectively. Multivariate analysis showed pathologic T classification and extracapsular extension (ECE) were significant predictors for DSS, whereas T classification remained significant for local recurrence. DSS for T1/T2 tumors ranged from 77% (node-positive) to 84% (node-negative).

T classification and ECE are independent predictors of outcome for BOT SCC. Patients with cT1/T2 tumors had excellent outcome and may be suitable for transoral robotic or endoscopic surgical procedures. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

The aims of this study were to evaluate the apoptotic activities and molecular mechanisms of methanol extracts of Dianthus chinensis (MEDC) and Acalypha australis L. (MEAL) in human oral cancer cells.

The apoptotic effects and related molecular mechanisms of MEDC and MEAL on oral cancer cells were evaluated using MTS assay, DAPI staining, immunostaining, Western blotting, and reverse transcriptase–polymerase chain reaction.

Sp1 was overexpressed in oral tumor tissues compared with normal oral mucosa. Downregulation of Sp1 inhibited the growth of SCC-15 and YD-15 oral cancer cells. MEDC and MEAL inhibited cell growth and induced apoptosis in both cell lines by decreasing the expression of Sp1. In addition, treatment of cells with MEDC and MEAL decreased Mcl-1 expression, which is a downstream target of Sp1.

Our results indicate that MEDC and MEAL are bioactive natural products that can potentially induce apoptosis of tumor cells that overexpress the Sp1 protein. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

This study was undertaken to determine the recurrence rate for open and endoscopic surgery and the clinical prognosis of this sinonasal tumor.

A systematic review of individual cases of sinonasal hemangiopericytoma was performed. A total of 97 articles were included in the study and reviewed to extract the relevant information about each case.

In all, 194 cases of sinonasal hemangiopericytoma were identified. There were 53 recurrences (27.3%), 6 tumor-related deaths (3.1%), and 4 cases of metastases (2.1%). There was no significant difference between rate of recurrence for endoscopic or open resection (p = .06). Incomplete excision was the most important predictor of recurrence (odds ratio = 11.50, 95% confidence interval 3.76–36.82, p < .001). Radiotherapy may be advantageous in cases of incomplete surgical resection (p = .03).

Complete excision is essential to minimize tumor recurrence and radiotherapy may decrease the rate of recurrence in the case of incomplete resection. Current evidence does not suggest that open resection is superior to endoscopic resection. © 2012 Wiley Periodicals, Inc. Head Neck, 2012