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Epidermoid cysts are rare benign tumors that are derived from the development of abnormally situated ectodermal tissue. Although they may originate from any part of the body head and neck region is occasionally affected. Epidermoid cyst originating from pterygopalatine fossa has not been reported previously in the literature. We report the first case of epidermoid cyst of pterygomaxillary fossa in this study.

A case of cerebral venous infarction (CVI) as a complication of acute otitis media (AOM) was presented in a 16-month-old male patient. The patient admitted with AOM in the right ear, ipsilateral facial paralysis and contralateral hemiplegia. Computerized tomography of the brain showed low density areas involving both the cortex and subcortical white matter in the right frontoparietal region, and there were patchy and multifocal enhancing areas with intravenous contrast enhancement. These findings disclosed the diagnosis of venous infarctions involving the superficial cortical veins on the right side. Complete recovery was achieved with 2 weeks of sulbactam-ampicilline, amikacin and prednisolone treatment. Although it is rather rare, CVI should also be remembered among the otogenic intracranial complications.

Objective: 1) Present results of cost identification analysis for robotic head and neck surgical procedures. 2) Identify drivers of cost for robotic procedures in the persioperative period including services, materials, and patient characteristics.Method: Retrospective review of 128 robotic surgical procedures of the head and neck at an academic medical center between 2008 and 2011. Cost data for the perioperative period (operating room, recovery, hospital stay) were collected and matched with clinical data for each case to determine drivers of cost.Results: Procedures analyzed included transoral robotic surgery (TORS) for oropharyngeal and supraglottic cancers, transaxillary robotic thyroidectomy, and transoral robot assisted approaches to the skull base. Average total cost was $14,455 with a wide range of $3,567-$55,008. In a subset of 24 patients who underwent TORS alone, without neck dissection, the average cost was $6,450. The cost of the robot for these procedures is analyzed in relation to surgical...

Objective: Report patient characteristics and oncologic results of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC).Method: Retrospective review of 52 patients who underwent TORS with neck dissection and postoperative adjuvant treatment as indicated for OPSCC within a prospective single-arm cohort study at an academic medical center. Tumor stage, human papillomavirus (HPV) status, pathology (margin status, nodal status, extracapsular spread), and survival data were collected.Results: Forty-two patients had HPV testing with 36 patients being HPV positive (85.7%). Most patients presented with advanced stage disease: 40 patients (76.9%) stage IV and 6 patients (11.5%) stage III. Mean length of follow-up was 21 months. Overall survival at 1 and 2 years was 97.9% and 72.7%, respectively, and disease-specific survival at 1 and 2 years was 100% and 84.2%, respectively. There were 2 local recurrences (3.8%), 3 regional recurrences (5.8%), and 2 distant recurrences (3.8%). Subset ...

Background 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. Methods 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. Results 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. Conclusion In this preliminary study, TORS supraglottic laryngectomy was a safe procedure with good functional outcomes. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Currently, transoral robotic surgery (TORS) with the daVinci robot is mainly used for squamous cell carcinoma of the oropharynx and supraglottic larynx. The safety, efficacy, and functional outcomes regarding this approach have previously been described. In addition to transoral resection of squamous cell carcinoma, we have found use for this technique in removing selected tumors of the parapharyngeal space. Three patients with benign or malignant tumors of the parapharyngeal space who underwent successful transoral resection using the daVinci robot were included in the study. In all three cases, complete tumor excision was achieved without any complication. None required conversion to an open procedure. Mean TORS operative time and intraoperative blood loss were 16.3 min and 4.7 mL, respectively. Inadequate oral exposure, involvement of the internal carotid artery, limited cervical spine mobility and large tumor size are the main limitations of this approach. Result indicates that magnified view, 3D visualization with the combination of the transoral robotic experience, allow en bloc resection of selected parapharyngeal space tumors located medial to the carotid sheath.

Neuroendocrine carcinoma (NEC) can be an aggressive disease with locoregional and distant metastasis. We present this article (1) to highlight the typical presentation of NEC in head and neck primary sites such as the parotid gland, paranasal sinuses, and supraglottis and (2) to discuss the prognosis of these tumors based on their histologic subtype and stage. We base our comments on the findings of our retrospective review of the cases of 16 adults—10 men and 6 women, aged 43 to 88 years (mean: 65.8)—who had been diagnosed with pathologically confirmed NEC of the head and neck. Analysis of subtypes revealed that 11 of these patients (68.8%) had presented with poorly differentiated NEC, 4 (25.0%) with moderately differentiated NEC, and 1 (6.3%) with well-differentiated NEC. The most common primary sites were the salivary glands (n = 5; 31.3%), paranasal sinuses (n = 4, 25.0%), and larynx (n = 4). There was no statistically significant difference in survival at 24 months between the patients with moderately differentiated NEC and those with poorly differentiated NEC (37.5 vs. 35.4%; p = 0.86); at the end of the study period, the patient with well-differentiated NEC was still living, 129 months after diagnosis. Taken together, patients with stage I, II, and III disease had a combined survival of 77.8% at 12 months, which was significantly higher (p = 0.023) than the 57.1% survival at 12 months for patients with stage IV disease.

Objectives/Hypothesis: Head and neck solitary fibrous tumors (SFTs) are quite rare, with

Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. Whether EMT is involved in cancer metastasis has a specific, practical impact on the field of circulating tumor cells (CTCs). Since the generally accepted definition of a CTC includes the expression of epithelial surface markers, such as EpCAM, if a cancer cell loses its epithelial surface markers (which is suggested in EMT), it will not be separated and/or identified as a CTC. We have developed, and previously reported on the use of, a purely negative enrichment technology enriching for CTCs in the blood of squamous cell carcinoma of the head and neck (SCCHN). This methodology does not depend on the expression of surface epithelial markers. Using this technology, our initial data on SCCHN patient blood indicates that the presence of CTCs correlates with worse disease-free survival. Since our enrichment is not dependent on epithelial markers, we have initiated investigation of the presence of mesenchymal markers in these CTC cells to include analysis of: vimentin, epidermal growth factor receptor, N-cadherin, and CD44. With the aid of confocal microscopy, we have demonstrated not only presumed CTCs that express and/or contain: a nucleus, cytokeratins, vimentin, and either EGFR, CD44, or N-cadherin, but also cells that contain all of the aforementioned proteins except cytokeratins, suggesting that the cells have undergone the EMT process. We suggest that our negative depletion enrichment methodology provides a more objective approach in identifying and evaluating CTCs, as opposed to positive selection approaches, as it is not subjective to a selection bias and can be tailored to accommodate a variety of cytoplasmic and surface markers which can be evaluated to identify a multitude of phenotypic patterns within CTCs from individual patients, including so-called EMT as presented here.

Malignant triton tumor (MTT) is a relatively rare, aggressive tumor comprised of both malignant schwannoma cells and malignant rhabdomyoblasts. Only three cases of MTT which arose after radiation therapy were reported in the literature. We presented an additional case of MTT arising after radiotherapy and disscussed its clinical and pathological characteristics.

To report long-term, health-related quality-of-life (HRQOL) outcomes in patients treated with transoral robotic surgery (TORS).Prospective, longitudinal, clinical study on functional and HRQOL outcomes in TORS.University tertiary care facility.Patients who underwent TORS were asked to complete a Head and Neck Cancer Inventory before treatment and at 3 weeks and 3, 6, and 12 months postoperatively. Demographic, clinicopathological, and follow-up data were collected.Sixty-four patients who underwent TORS were enrolled. A total of 113 TORS procedures were performed. The mean follow-up time was 16.3 ± 7.49 months. The HRQOL was assessed at 3 weeks and at 3, 6, and 12 months, with a response rate of 78%, 44%, 41%, and 28%, respectively. TORS was performed most frequently for squamous cell carcinoma (88%). There was a decrease from baseline in the speech, eating, aesthetic, social, and overall QOL domains immediately after treatment. At the 1-year follow-up, the HRQOL scores in the aesthetic, social, and overall QOL domains were in the high domain. Patients with malignant lesions had significantly lower postoperative HRQOL scores in the speech, eating, social, and overall QOL domains (P.05). Patients who underwent adjuvant radiation therapy or chemotherapy and radiation therapy had lower postoperative scores in the eating, social, and overall QOL domains (P.05).The preliminary data show that patients who undergo TORS for malignancies and receive adjuvant therapy tend to have lower HRQOL outcomes. TORS is a promising, minimally invasive, endoscopic alternative surgical treatment of laryngopharyngeal tumors.

Background Transoral robotic surgery (TORS) has emerged as a novel, safe, and feasible procedure for the resection of supraglottic laryngeal cancers. The purpose of this study was to demonstrate the surgical technique for TORS supraglottic laryngectomy (SGL). Methods A patient with a T2N0M0 laryngeal cancer limited to the supraglottic larynx was selected for TORS. Results En bloc tumor resection was accomplished with negative surgical margins together with bilateral selective neck dissection. There was no perioperative or early postoperative complication. The patient was extubated immediately after surgery. Oral supraglottic diet was initiated within the first 24 hours. No gastrostomy or tracheostomy tube placement was required. A video demonstration of the surgical technique is included on Head & Neck's website. Conclusion TORS SGL is a safe and feasible procedure for the resection of selected supraglottic tumors. © 2014 Wiley Periodicals, Inc. Head Neck 37: 125–126, 2015

As superselective neck dissection strategy is gaining popularity to minimize postoperative morbidity and better life quality, we investigated the metastatic nodal status of level V neck lymph node group for head and neck squamous cell carcinoma in various primary sites. We have also aimed to display the impact of involvement of other nodal groups on level V.Retrospective review of histopathologic examination of case series at a comprehensive cancer center.The study group was composed of 107 patients who underwent a type of neck dissection including level V among 243 patients. The impact of primary site and metastatic nodal status of other levels on metastasis to level V involvement were evaluated.The most common primary tumor site was oropharynx (n = 43), followed by oral cavity (n = 32), larynx (n = 16), carcinoma of unknown primary (n = 10), and hypopharynx (n = 6). General pathologic N positivity for all levels was 78.3% (76 of 97) when 10 carcinoma of unknown primary patients were excluded. Level V was involved in 13 of 107 (12.1%) patients. Level V was not involved in any patient when the other levels were not involved (0 of 21). Even when considering only N+ patients, the ratio of N positivity for level V is still20% (13 of 86, 15.1%).Because level V was not involved in any patient when the other levels were not involved, it might be reasonable to preserve level V especially in clinically and intraoperatively N0 patients.

To determine factors impacting recurrence and long-term survival of adenoid cystic carcinoma (ACC) of the head and neck after definitive resection.Retrospective cohort study at an academic tertiary care hospital.Patients with ACC of the head and neck treated at our institution were reviewed. Those not receiving surgery, or with metastatic disease were excluded. Clinicopathological data on each patient was collected.Of 113 patients identified with ACC, 99 were studied. The overall median survival for the cohort was 71 months (mean +/- standard deviation, 94 +/- 79 months). American Joint Committee on Cancer (AJCC) tumor stage and N stage were independent predictors of survival on multivariate analysis. Mean overall survival (P = .001) and time to recurrence (P = .006) were lower for patients with cervical lymph node positive disease (N+). Tumors in major salivary glands were associated with longer survival (P = .027). The overall recurrence rate was 53%, with a mean time to recurrence of 63 +/- 64 months. The presence of lymphovascular invasion predicted recurrence on multivariate analysis (P = .002), with advanced tumor stage predicting early (or=36 months) recurrence (P = .013). Among the 57 patients who received adjuvant radiation therapy, there was no difference in survival, rate of recurrence, or time to recurrence, when compared to patients treated with surgery alone.Clinicopathological variables including AJCC tumor stage, tumor site, presence of N+ disease, and lymphovascular invasion may be used as prognostic factors in predicting survival and recurrence after a definitive resection of ACC of the head and neck.

We evaluated the results of endoscopic repair for choanal atresia.Ten patients (2 males, 8 females) underwent transnasal endoscopic repair for choanal atresia. Involvement was unilateral in five cases and bilateral in five cases. Unilateral patients were treated at a mean age of 22.6 years (range 1 to 44 years), while bilateral cases were treated within the first six days of life. Two patients with bilateral involvement had associated polydactyl and tracheoesophageal fistula, respectively. The mean follow-up period was 26 months (range 8 to 56 months).No postoperative complications such as significant hemorrhage, injury to the skull base, cerebrospinal fluid fistula, septal perforation, or granulation tissue formation were encountered. All the patients had choanal patency at the end of six months.Endoscopic repair of choanal atresia is effective in both unilateral and bilateral cases.

Objective To determine the feasibility of, compliance with, and long-term survival with intensification treatment regimens for patients with advanced, resectable, previously untreated head and neck squamous cell carcinoma. Design Prospective phase 2 clinical trial (3 similar, consecutively evolved trials). Setting Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University. Patients One hundred twenty-three patients (median age, 60 years; range, 30-78 years) with previously untreated, resectable, advanced squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx. Interventions Perioperative cisplatin chemoradiotherapy, surgical resection with intraoperative radiotherapy, and postoperative paclitaxel and cisplatin chemoradiotherapy. Main Outcome Measures The feasibility, compliance, and long-term survival associated with the 3 intensification regimens. Results Compliance with all 3 intensification regimens averaged 61% (75/123). Patient-directed noncompliance occurred in 16 patients (13%). The average locoregional (112/123, 91%) and systemic (106/123, 86%) disease control rates were excellent. Overall long-term disease-specific survival was 73%. Median time at risk was 62.5 months (range, 1 day to 100.4 months). Conclusions The intensification regimens result in excellent disease control rates and long-term survival in this particular patient population. Future evolution of these regimens will include some modifications to further decrease toxic effects followed by phase 2 multi-institutional trials to determine whether the single-institutional experience can be duplicated. The results of these studies will determine whether phase 3 trials can be proposed.

Background: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed. Methods: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery. Results: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%. Conclusions: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.

Tuberculosis can affect every organ, most importantly the lungs, and worldwide it is the leading cause of death attributable to a single infectious agent. Tuberculous involvement of the neck is also possible. Patients mostly present with masses or draining fistulas in the neck, which are mostly located in the posterior cervical, submandibular, and supraclavicular regions. We report on a soldier who presented with a tuberculous deep neck infection, followed by miliary tuberculosis. The clinical presentation and diagnostic dilemmas are discussed.

Granular cell tumor (GCT) is an infrequent and usually benign neoplasm which is found predominantly in the head and neck region. More than half of the head and neck GCTs originate from the tongue. It is most frequently seen in the fourth to sixth decades of life. We presented an interesting case of a giant GCT in a 2.5-year-old patient. It was located under the anterior tongue, filled the floor of the mouth and was resected by the transoral route.

The present study was designed to demonstrate the regional distribution prevalence and management differences of certain pediatric neck masses in this region of the country.Fifty-five patients with pediatric neck masses, who were diagnosed and treated surgically were retrospectively analyzed.Analysis of 55 patients showed that congenital neck masses were the most common pathology in pediatric neck masses (47%), followed by infectious and tuberculous lymphadenopathies (24%).It can be concluded from the study that besides the age group and the characteristics of the neck mass, life standards of the region is also an important factor to be considered.

Objective: To assess neurotological status and its ophthalmological correlates in Behçet’s disease. Study design: A cross sectional study in which 17 patients with Behçet’s disease and 13 healthy controls were included. Patients and methods: The patients were divided into two groups: those with and without end stage ocular involvement. Neurotological status was evaluated with audiological tests (pure tone and speech audiometry, tympanometry, short increment sensitivity index, tone decay, and evoked response audiometry), and Dix-Halpike positional testing. Results: The positional test was normal. The audiological test results of the patients with and without end stage ocular involvement were not significantly different (p>0.05). A sloping audiogram with bilateral symmetric and mild sensorineural hearing loss was the main audiogram obtained. There was no relationship between the presence or absence of the end stage ocular involvement and the otological parameters studied excluding I–III interval on evoked response audiometry (p>0.05). Conclusion: Although the main underlying pathogenetic factor in Behçet’s disease is the autoimmune vasculitis, the mechanisms involved in the pathogenesis of neurological and ocular damage may be different. Alternatively, the differential involvement of certain organ systems may not reflect the nature of the disease process itself, but rather the manner in which each organ responds to injury.

In this study, we aimed to assess anatomical relationship between the anterior inferior cerebellar artery (AICA) and cochleovestibular nerve (CNV) in patients with non-specific cochleovestibular symptoms using magnetic resonance imaging (MRI). One-hundred and forty patients with non-specific neuro-otologic symptoms were assessed using cranial and temporal MRI. Classification was performed according to four different types of anatomical relationship observed between the AICA and CVN. In type 1 (point compression), the AICA compresses only a limited portion of the CVN. In type 2 (longitudinal compression), the AICA approaches the CVN as both traverse parallel to each other. In type 3 (loop compression), the vascular loop of the AICA encircles the CVN. In type 4 (indentation), the AICA compresses the CVN so as to make an indentation in the nerve. The anatomical relationship between the CVN and AICA was encountered in 19 out of 140 (13.6%) patients (20 ears). The VCC was unilateral in 18 patients (94.7%) and bilateral in one patient (5.3%). There was no other vascular structure causing VCC to the CVN except for vertebral artery that was seen in 2 out of 140 patients (1.4%). These were unilateral cases. There were tinnitus, vertigo or dizziness, hearing loss, and both hearing loss and vertigo in 5 (25%), 13 (65%), 1 (5%) and 1 (5%) ears of 20 patients, respectively. There was no relationship between the cochleovestibular symptoms and type of compression (p > 0.05). Neurovascular relationship between the CVN and AICA can be imaged properly using MR and MR based classification may help reporting this relationship in a standard way. Although, MR images can show the anatomical relationship accurately, diagnosis of vascular conflict should not be based on imaging findings alone.

Objective: To assess the significance of cyclo-oxygenase 2 (COX-2) in laryngeal squamous cell carcinoma (LSCC). Study Design: An immunohistochemical study in which 39 patients with LSCC were included. Methods: Immunohistochemical staining of the paraffin-embedded tumour tissues was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz, Calif., USA). COX-2 results were compared with the clinical parameters of the patients. Results: COX-2 was detected in all tumour tissues. In the normal laryngeal tissue around the tumour area, which served as control, there was no COX-2 staining. There was no relationship between the COX-2 results and the location of the primary tumour, T stage and N stage, survival, recurrence or pulmonary metastases. Conclusion: The absence of a relation between COX-2 positivity and clinical parameters may suggest an involvement of COX-2 in laryngeal carcinogenesis. Since COX-2 positivity could be detected in all LSCC specimens studied, COX-2 could serve as a therapeutic target in LSCC.

We assessed the mastoid air cell size and variables of the sigmoid sinus in healthy ears and ears with chronic otitis media (COM). Thirty-eight patients with unilateral COM [15 with cholesteatoma (COM/+) and 23 without cholesteatoma (COM/-)], and 20 subjects with healthy ears, were included in the study. Assessment was performed using a quantitative digital image processing computed tomography (CT) program, and the volume of the mastoid bone was measured using the morphometric method of Cavalieri. In both COM/+ and COM/- patients the sigmoid to suprameatal spine distance and mastoid size were greater on the healthy side than on the diseased side ( p0.05). The distance and area were significantly greater in the healthy control subjects than in either the healthy or the diseased ears of the patients with COM ( p0.05). In the healthy ears of COM patients, there was significant correlation between the sigmoid to suprameatal spine distance and air cell size and mastoid volume ( p0.05). In the diseased ears of COM patients, this correlation was absent ( p0.05). The sigmoid sinus shape was of the half-moon type (62%), protrusive type (22%) and saucer type (16%). The digital image processing CT program allowed us to estimate the individual area of the air and soft tissue filled mastoid air cells. The mastoid size in both intact and disease ears of COM patients was smaller than in the healthy controls. The mastoid size may be determined genetically. However, environmental factors such as infection may also affect the mastoid size. Therefore, both genetic and environmental factors may be related to COM as far as the size of the mastoid air cells is concerned.

The major cells involved in cancer cell kill are the T lymphocytes. However, T cells need to be activated upon antigen presentation, which is mediated by the antigen presenting cells, one of which is the Langerhans cell (LC). The purpose of this study was to assess the significance of LC and inflammatory cell infiltration in the laryngeal squamous cell carcinoma (LSCC). Forty-five patients who were operated on for LSCC between 1992 and 1999 were included in the study. The clinical and histopathological features of the patients were reviewed. A semiquantitative estimation of the lymphocyte dominant inflammatory reaction within and around the tumor was performed. Anti S-100 antibodies were used for immunohistochemical detection of LCs. Horseradish peroxidase method was used. LCs were present in almost all of the specimens within and around the tumor tissue. The S-100 results did not associate with grade, T and N stages, tumor stage, laryngeal site of involvement and survival (P>0.05). The S-100 results significantly associated with inflammatory reaction in the tumor tissue (P

Understanding the relationship between the anatomy of the fallopian canal and a variety of ear diseases is necessary. In this study, our purpose was to identify the incidence of facial nerve dehiscence in patients undergoing surgery for a variety of chronic ear diseases.The operative records of 219 patients were reviewed retrospectively for dehiscence of the facial canal. The diagnoses were cholesteatoma (n = 49), tympanosclerosis (n = 51), adhesive otitis media (n = 38), and chronic otitis media (n = 81). Only 17 of 219 who underwent tympanoplasty without mastoidectomy were excluded from the calculations.Dehiscence of the facial canal was encountered in 18 (8.9 per cent) of 202 patients. The dehiscence rate was highest with cholesteatoma, followed by adhesive otis media, chronic otis media and tympanosclerosis (p

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. Herein we report the first case of PNET of the mandible in a 6-year-old female who was admitted to the hospital with a two-months history of painless, progressively enlarging lower jaw mass.

Background: Although brucellosis can lead to multisystem complications, involvement of the ear in brucellosis is rarely reported in the literature. The purpose of this study was to assess the hearing status of patients with brucellosis. Study Design: Thirty-two patients with brucellosis were included in the study. Pure tone and speech audiometry and tympanometry were performed in the patients. Results: The mean pure tone averages of the patients were within normal limits and were similar in both ears ( P > 0.05). The pure tone averages of the patients with or without anti- Brucella treatment were not significantly different ( P > 0.05) and were within the normal limits. When the hearing levels of these patients were compared at the frequencies of 250, 500, 1000, 2000, 4000, and 8000 Hz, there was no significant difference as well ( P > 0.05). Conclusions: Peripheral brucellosis does not appear to be associated with hearing loss. (Otolaryngol Head Neck Surg 2002;127:97-100.)

Background: Consumption of phytochemical-rich fruits and vegetables is associated with a lower risk of oral cancer and protection against oxidative stress-mediated damage from reactive oxygen species (ROS). We proposed that antioxidant components in black raspberries (BRBs) could “scavenge” ROS and diminish oxidative stress burden. We tested the hypothesis that a long-term, low-dose administration of BRBs to a population of disease-free oral cancer survivors is both (i) achievable and (ii) will result in the attenuation of oxidative DNA damage. Methods: Participants were assigned to consume 0, 4, or 8 gms of BRBs daily for 6 months and provided self-report logbooks of adherence. Mass spectrometry (MS) of urine for dimethyl ellagic acid (DMEA) at baseline, 10, and 20 wks was utilized as a biomarker of adherence. ELISA of urine was used to measure 8-hydroxy-2’-deoxyguanosine (8-OHdG). A logistic regression model was used to determine factors associated with willingness to continue on the regimen once enrolled. Results: 112 participants were enrolled and assigned to a BRB regimen. 81 participants (72%) provided self-reported adherence logbooks. Adherence at wks 2, 10 and 20 was 92% (n=77), 85% (n=55), and 86% (n=44) respectively. The regimen was well tolerated with no significant adverse events. MS/MS measurements of DMEA was 10 fold higher (p Conclusions: A food-based prevention strategy utilizing BRBs in oral cancer survivors is safe and feasible. Compliance for those staying on regimen was high and factors identified that influenced continued participation included: having insurance, travel distance, having had adjuvant therapy, and tobacco use. While the number of active participants declined, those completing the intervention maintained outstanding levels of adherence (>85%). Biomarkers of adherence were identified as an objective means of validating self-reported adherence. Moreover, 8-OHdG levels were reduced, providing a potentially useful biomarker of BRB efficacy. Citation Format: Lana K. Uhrig, Thomas J. Knobloch, Bruce C. Casto, Amit Agrawal, David E. Schuller, Theodoros N. Teknos, Enver Ozer, Matthew O. Old, Christine L. Sardo, Jeff Xueliang, Steven K. Clinton, Dennis K. Pearl, Christopher M. Weghorst. Biomarkers of adherence and efficacy: modulation of biomarkers of DNA damage in a Phase 1b trial of post-surgical oral cancer patients on a long-term food-based prevention study with black raspberries. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4680. doi:10.1158/1538-7445.AM2013-4680

To identify specific alcohol-related predictors of postoperative delirium.Inception cohort, logistic regression with step-wise selection.Ohio State University Comprehensive Cancer Center, Columbus.A total of 774 patients undergoing major resection of head and neck squamous cell carcinoma.The correlation of 19 variables with postoperative delirium. One variable was an alcohol-related blood test: mean red blood cell volume (MCV). Eight variables were patient responses to alcohol-related questions.Eighty-nine of 774 surgical procedures (11.5%) were complicated by delirium. Six variables were significantly associated with delirium: age older than 69 years (odds ratio [OR], 2.43; P.01), preexisting cognitive impairment (OR, 3.83; P.01), surgery duration greater than 6 hours (OR, 2.40; P.01), MCV greater than 95.0 femtoliters (OR, 2.23; P.01), ever being advised to cut back on alcohol (OR, 2.25; P = .01), and not abstaining from alcohol for at least 1 continuous week in the preceding year (OR, 2.16; P = .02). The number of variables stratified delirium risk (0 variables: 198 patients, 2.5% incidence of delirium; 1 variable: 278 patients, 6% incidence of delirium; 2 variables: 206 patients, 18% incidence of delirium; and2 variables: 92 patients, 34% incidence of delirium).Three clinical variables not related to alcohol drinking (age, preexisting cognitive impairment, and surgery duration), an alcohol-related laboratory test (MCV), and 2 alcohol-related questions ("At any time in your life, has anyone ever suggested that you should cut back on your drinking?" and "What is the greatest number of days in a row you have gone without an alcoholic drink in the past year?") may help in estimating a patient's risk for postoperative delirium.

In 2009, According to the National Cancer Institute, 48 010 new cases of oral cavity, pharyngeal, and laryngeal cancer were estimated to occur in the United States; approximately 11 260 deaths were attributed to these cases. It has been established that squamous cell carcinomas make up greater than 95% of these cases.1,2 For all stages combined, the 5-year survival rate is approximately 50%,3 and this rate has not changed significantly in the last 3 decades. Treatment failure in patients with squamous cell carcinoma of the head and neck (SCCHN) can include local recurrence, regional recurrence (cervical lymph nodes), distant metastasis, or development of a second primary cancer. Despite intensive therapeutic treatment of the primary lesion, approximately 50% to 60% of patients will later develop locoregional recurrence, and 20% of these patients will go on to develop distant metastasis. Despite surgical resection with negative histopathological margins, approximately 20% of patients will have local recurrence. There are various theories with respect to the cause of local cancer recurrence including field cancerization4 or that clinically relevant micrometastatic spread is not detectable by histopathological margins alone.5 In oral cavity cancer, between 23% and 27% of patients with SCCHN with a clinically negative neck on physical examination will have micrometastatic disease on elective neck dissection.6,7 The presence of lymphatic metastasis is currently the most significant prognostic factor affecting survival; the presence of this alone can reduce survival by 50%.8–10 These current statistics indicate that there is a significant need for a reliable blood marker to determine prognosis in patients with SCCHN, specifically those who may be at higher risk of locoregional or distant recurrence. The concept of the development of metastasis involves a tumor cell or microembolus that dissociates from the primary tumor, circulates within lymphatic or vascular channels, and ultimately resides in a regional or distant site. The ability to detect such cells, known as circulating tumor cells (CTCs), may have an impact on the prognosis and treatment of patients with cancer by providing (1) definitive evidence for early occult spread of the primary cancer, (2) a risk factor for the development of future metastasis, and (3) a peripheral marker for treatment susceptibility and cancer surveillance. Furthermore, genetic analysis of CTCs may lead to targeted treatment strategies.11 Studies have linked circulating/ disseminated tumor cells to poor prognosis in breast,12 lung,13,14 prostate,15 and colorectal cancers.16 It should be noted, however, that the role of CTCs in patients with SCCHN is yet to be conclusively elucidated, and the mechanism between CTCs and cancer recurrence or metastasis is not yet known. Nevertheless, the presence of CTCs could be an independent marker of more aggressive cancers. It is a diagnostic challenge to identify CTCs from a patient’s blood specimen when 1 mL of blood contains an average of 5 billion red blood cells (RBCs), 7 million white blood cells (WBCs), and 295 million platelets.17 A negative depletion method involves removal of normal, unwanted cells, such as RBCs through lysis, and normal lymphocytes through magnetic depletion of CD45+-labeled cells. In contrast, positive selection of tumor cells can be performed by magnetic selection of epithelial cells using antibodies binding to surface markers such as epithelial cell adhesion molecule (EpCAM). At present, there are 3 general types of CTC detection methods: (1) immunocytochemistry, which implies visual observations, (2) flow cytometry and/or image cytometry, and (3) reverse transcriptase–polymerase chain reaction. Prior to the use of 1 of these 3 detection methods, an enrichment method (using negative depletion or positive selection) can greatly increase both the sensitivity and specificity of the test. A majority of the published studies on the detection of CTCs in the blood of patients with cancer uses a combination of a negative depletion step (removal of RBCs) and a positive selection of the CTCs using an antiepithelial antibody bound to a magnetic particle. The most well known of these methods available is the CellSearch System by Veridex LLC, Raritan, New Jersey.18,19 In addition, the “CTC Chip” technology uses a positive selection method to initially isolate cells expressing EpCAM and then allow staining with secondary antibody markers.20 However, the use of a positive selection technique for the CTCs introduces a potential, significant bias into the final detection analysis: the CTCs must express the surface marker to which the antibodies are specific. This bias has been recently experimentally demonstrated by a study from Sieuwerts et al.21 Specifically, these researchers demonstrated that the effectiveness of the CellSearch System varied significantly with respect to its ability to detect subtypes of human breast cancer cells spiked into healthy human blood. As expected, the CellSearch System was able to recover 85% of the breast cancer cells exhibiting the typical epithelial characteristics. However, as the cell types expressed a different phenotype characteristic of tumor-initiating stem cells (CD24 low and CD44 high), the recovery of the spiked cells drops to only 2%.21 EpCAM may be downregulated during epithelial-to-mesenchymal transition, in which cancer cells may acquire a more invasive, migratory phenotype.20 Therefore, using a positive selection technique may not identify CTCs in some patients. In contrast to the positive selection approaches, which introduce significant bias into the type of CTCs detected, we have been developing an enrichment method that is based only on negative depletion of normal cells. We recently demonstrated that this optimized method is able to obtain an average 5.66 log10 enrichment of CTCs in the blood of patients with head and neck cancer.22 In this initial study, we sought to determine the clinical significance of CTCs with regard to disease-free survival in patients with SCCHN and present our prospective clinical follow-up to this point.

Purpose: Cancer chemoprevention is the use of natural or synthetic agents, in combination or alone, to inhibit, delay or reverse the carcinogenic process, and is an active topic of cancer research. Numerous epidemiological studies have shown the strong correlation between the consumption of fresh fruits and vegetables and a decreased cancer risk. With a food-based approach to cancer prevention, emphasis is placed on the potential for complex mixtures of preventive agents in whole food to inhibit multiple process of carcinogenesis. In support of this approach, our laboratory conducted several preclinical animal studies that demonstrate the remarkable chemopreventive activities of black raspberries on chemically-induced oral squamous cell carcinoma (OSCC). We have shown that an extract of lyophilized black raspberries (LBR) dramatically inhibits the in vitro proliferation of cells derived from human OSCC, suggesting that the chemoprevention of oral cancer by LBR components in vivo is possible. Survivin (BIRC5) is a member of the Inhibitor of Apoptosis (IAP) family of caspase inhibitors that direct the negative regulation of apoptosis. BIRC5 is highly expressed in most human tumors, including oral squamous cell carcinoma (OSCC), but nearly undetectable in terminally differentiated normal adult tissues. BIRC5 acts to antagonize apoptosis in tumors and to promote resistance to common apoptotic-inducing therapies such as ionizing radiation. A series of studies examining BIRC5 in OSCC have associated increased BIRC5 expression levels with cancer progression and poor prognosis. The current study reports the LBR-dependent modulation of BIRC5 expression in OSCCs as part of an ongoing Phase I clinical trial. Methods: According to protocols approved by the Internal Review Board (IRB) of The Ohio State University, 24 biopsy-confirmed OSCC patients were administered three LBR troches 4x/day (4.3g cumulative dose) between presurgical enrollment and their normally scheduled surgery. Biopsies were obtained from distant high “at-risk normal” (N1) and tumor (T1) tissues at enrollment and following LBR exposure (N2, T2) acquired during surgical resection [exposure 2.5–34 days (mean exposure = 11.2±7.2 days)]. Pre-validated TaqMan gene expression assays were used to assess apoptosis-related genes for LBR-dependent expression changes. Results: OSCC tumor samples had significantly greater BIRC5 expression compared to the high “at-risk normal” oral samples, both prior to (T1 vs N1, p Conclusions: BIRC5 expression was significantly decreased in OSCC tumor tissues following short-term exposure to LBR as part of an ongoing Phase 1 clinical trial. Consequently, down-regulation of BIRC5 expression following administration of LBR to OSCC patients may provide mechanistic insight for future food-based cancer risk reduction interventions. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A81.

A66 Background Black raspberries represent a food-based chemopreventive agent rich in polyphenolics compounds, including anthocyanins, that have been shown to reduce inflammation. Numerous studies have demonstrated that inflammation plays a prominent role in tumor growth, progression, and metastasis. Common risk factors for oral squamous cell carcinoma (OSCC), such as tobacco use, also contribute to the inflammatory process. Cell culture and animal studies have shown altered gene expression in tumor and diseased tissues following exposure to lyophilized black raspberries (LBR) or their extracts. Consistently, these chemopreventive studies show the ability of LBR to modulate the expression of genes prominently associated with inflammation, including members of the NFκB family. In OSCC cells exposed to LBR extract in culture, we have shown a down-regulation of inflammatory biomarkers, including NFkB1D, NFkB1 and NFkB2. To transition these in vitro findings into an in vivo setting, we have used the hamster cheek pouch (HCP) model of OSCC to demonstrate a striking suppression of oral tumor lesion incidence and multiplicity (Anticancer Res 22, 2002) following dietary LBR treatment. Ultimately, the role of these essential pre-clinical studies is to translate into a human patient-based clinical investigation. Consequently, the aim of our ongoing Phase 1 Clinical Trial is to evaluate the molecular changes in oral cavity tissues following short-term, locoregional, oral exposure to LBR troches. According to protocols approved by the IRB of The Ohio State University, biopsy-confirmed OSCC patients were administered three LBR troches 4x/day (4.3g cumulative dose) between pre-surgical enrollment and their normally scheduled surgery. Tissue biopsies were obtained from tumor and distant normal tissues at enrollment and during surgical resection, after an exposure range of 2.5-34 days. Using a partial interim cohort of patients, NFκB1 was used as a surrogate endpoint biomarker for inflammation in order to assess LBR-dependent gene expression changes. Methods TaqMan real-time PCR assays were used to examine NFkB1 gene expression in a partial interim cohort of 24 patients. Experimental gene expression levels were normalized to GAPDH, RPS18, B2M, HPRT, and ACTB “housekeeping” gene expression levels. The interim patient cohort was stratified into “young” (≤ 45 years of age) and “older” (> 45 years of age) groups for the purpose of this analysis. Results When patients were grouped into young (n = 7) and older (n = 17) populations, statistically significant differences were seen between LBR-modulated NFκB1 expression in tumor tissue compared to pre-treated, patient matched tumor tissue, with regard to age. Patients in the older population showed a significant decrease in NFκB1 expression in tumor tissue following LBR exposure compared to the younger population (p = 0.003). Conclusions These results suggest that inflammation can play a prominent role in the development of OSCC in older patients, and that LBR treatment may help alleviate the pathological effects of the inflammatory process in this population of patients. The lack of significant NFκB1 LBR-dependent modulation in the young OSCC population may signify that NFκB-independent or other functional pathways play an important role in tumorigenesis. Support: NIH/NIDCR R21DE016361, ACS RSGT-06-126-01-CNE Citation Information: Cancer Prev Res 2008;1(7 Suppl):A66.

Objective To determine feasibility, compliance, long-term survival, and disease control rates in the intensification regimen for advanced resectable hypopharyngeal carcinoma. Design Prospective, nonrandomized, controlled phase 2 trial with a median follow-up period of 89 months (range, 3.4-140.0 months). Setting Cancer center at a state university. Patients Thirty-two patients (age range, 44-79 years; median age, 59 years) with advanced (69% stage IV, 31% stage III) resectable hypopharyngeal carcinoma. Interventions Combination of surgery, radiation therapy, and chemotherapy (cisplatin and paclitaxel) along with intraoperative radiation therapy. Main Outcome Measures Compliance, long-term survival, and locoregional and systemic disease control rates and functional outcome. Results The protocol compliance rate was 62% (20 of 32 patients), and the overall 5-year survival rate was 56%. Local recurrence occurred in 3 patients (9%). The systemic disease control rate was 91% (29 of 32 patients). Total laryngectomy was required in 15 patients (47%); preservation of the larynx was possible in 17 patients (53%). Only 3 (13%) of 6 patients were percutaneous endoscopic gastrostomy tube dependent in the long-term follow-up. Conclusions The intensification regimen described in this study accomplished excellent long-term survival and disease control rates in patients with advanced resectable hypopharyngeal carcinoma. The future plan is to proceed with a phase 3 trial if the single-institutional experience at The Ohio State University can be duplicated in a multi-institutional phase 2 study.