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Background T1 and T2 tonsillar squamous cell cancer with limited neck disease can be managed with single-modality radiation or surgery. Over 11 years, 17 patients underwent radical tonsillectomies; and 33 patients underwent radiation-based treatments for T1 and T2 and N0 to N2a tonsil cancer. Patients were intended to receive single-modality treatment based on presentation; however, some ultimately received adjuvant treatments. Methods A retrospective chart review to compare overall survival (OS), disease-specific survival (DSS), and locoregional control (LRC) between the groups was used. Results In surgical group, of 17 patients, 11 underwent surgery alone, 3 underwent surgery and radiation, and 3 underwent surgery with concurrent chemoradiation. Five-year OS for the surgical and radiation groups was 93% and 72%, respectively (no significance achieved). Five-year DSS rates (93% and 80%) and LRC (69% and 89%) similarly did not yield any significant difference. Conclusion Surgery remains a viable option in the management of T1 and T2 tonsillar cancers with comparable LRC, OS, and DSS.

The authors report on the development and use of an impedance probe to measure the volume fraction of air (void-fraction) in bubble plumes generated by breaking waves. The void-fraction gauge described was found to be most useful in the initial period after breaking when large void-fractions prevail. The authors describe the instrumentation at length and report on its use in the laboratory and in the field. The instrument is found to be capable of rendering the space-time evolution of the void-fraction field from controlled laboratory breaking waves. Field results show measurements of void-fractions (up to 24%) which are several orders of magnitude greater than time averaged values previously reported. Preliminary measurements show that the fraction of breaking waves per wave is dependent on significant wave height and wind speed. The dependence on wind speed is compared with data of previous investigators. Underwater video photography from the field shows the formation and evolution of distinct bubble plumes and the presence of large bubbles (at least 6-mm radius) generated by breaking. >

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with more than half a million people being diagnosed with the disease annually. Within the last 2 decades, the human papillomavirus (HPV) has been found to be associated with this malignancy. More recently, HPV-infected HNSCC has been found to exhibit higher levels of global DNA methylation. In a recent study, we identified five tumor suppressive genes (IRX1, EBF3, SLC5A8, SEPT9, and FUSSEL18) as frequently methylated in HNSCC biopsies using a global methylation analysis via restriction landmark genomic scanning. In this study, we verify these genes as valid methylation markers in two separate sets of HNSCC specimens. By using the available clinical information linked to the patient specimens, we found a strong association between promoter methylation of FUSSEL18, IRX1, and EBF3 and prior radiation therapy (P < 0.0001) irrespective of HPV status. Also, promoter methylation of FUSSEL18 and SEPTIN9 was found to correlate significantly with exposure to alcohol and tobacco (P = 0.021). Importantly, in this study, we preliminarily show a trend between HPV16 positivity and specific target gene hypermethylation of IRX1, EBF3, SLC5A8, and SEPT9. If replicated in a larger study, the HPV status may be a patient selection biomarker when determining the most efficacious treatment modality for these different subsets of patients (e.g., inclusion or exclusion of epigenetic therapies). Equally notable and independent of HPV status, hypermethylation of the promoters of a subset of these genes in recurrences especially in the setting of prior radiation or in the setting of alcohol and tobacco use might help guide adjunctive inclusion or exclusion or epigenetic therapy.

1. Case report A 36-year-old man presented to the clinic with a 3-month history of an enlarging right-sided neck mass. He had some associated pain in the region but denied any dysphonia, dysphagia, flushing, palpitations, diarrhea, or previous syncopal episodes. He denied a history of tobacco use, chronic alcohol use, or a family history of paragangliomas. Physical examination demonstrated a right-sided level II neck mass measuring approximately 5 cm in anteriorposterior dimension that was tender to touch. Palpation of the neck did not reveal any additional lymphadenopathy. All cranial nerves were functional with particular attention to cranial nerve X: he had symmetric palatal elevation and normal laryngeal function on fiberoptic nasopharyngolaryngoscopy. The mucosal surface of the entire upper aerodigestive tract was unremarkable. Magnetic resonance imaging (MRI)/magnetic resonance angiography demonstrated a 3.9 × 3.6 × 5.0-cm multilobulated parapharyngeal mass displacing the carotid artery anteromedially and the jugular vein posteromedially with slight compression (Fig. 1), most consistent with a glomus vagale tumor. When compared with a previous MRI performed 3 months earlier, there was interval growth of the mass of approximately 0.5 cm. A whole-body octreotide scan failed to show any additional areas of uptake. The patient was presented at our multidisciplinary tumor board. After extensive discussion of the options in treating vagal paragangliomas along with the functional sequela of surgical resection and the reconstructive options, the patient decided against pursuing a radiation oncology consult but rather opted for a surgical resection. A vascular surgery consult was obtained, and the patient underwent preoperative embolization of the right ascending pharyngeal artery with an Onyx injection (ethylene vinyl alcohol copolymer) less than 24 hours before the procedure. Surgical resection involved a right parapharyngeal space dissection along with a selective neck dissection (levels 2–3) via a modified Blair incision with a cervical extension. External jugular nodes were sent for frozen pathology and were found to be negative. Cranial nerves IX, XI, and XII and the sympathetic chain were identified and preserved, with X being sacrificed. The ansa hypoglossal nerve was significantly attenuated precluding its use for purposes of reinnervation. The stylohyoid and digastric muscles were divided to provide access to the proximal portion of the tumor at the level of the skull base. The tumor was removed en bloc without complication, requiring sacrifice of the superior laryngeal nerve (SLN). Reconstitution of the anticipated defects involved the following: a left ansa cervicalis to right recurrent laryngeal nerve (RLN) neuroplasty; a right greater auricular nerve to right SLN neuroplasty, and a free nerve interposition graft from the left cricothyroid muscle to the right cricothyroid muscle (Fig. 2). The contralateral ansa cervicalis nerve was used because of the attenuation found along the ipsilateral nerve, and a cut branch of the vagus that was found to be histologically normal on frozen section was used for the interposition graft.

Inositol hexakisphosphate kinase 2 (IP6K2), a member of the inositol hexakisphosphate kinase family, functions as a growth suppressive and apoptosis-enhancing kinase during cell stress. We created mice with a targeted deletion of IP6K2; these mice display normal embryogenesis, development, growth and fertility. Chronic exposure to the carcinogen 4-nitroquinoline 1-oxide (4-NQO, a UV-mimetic compound) in drinking water resulted in fourfold increased incidence of invasive squamous cell carcinoma (SCC) formation in the oral cavity and esophagus of the knockout (KO) mice compared to the wild-type (WT) littermates. Paradoxically, KO mice displayed relative resistance to ionizing radiation and exhibit enhanced survival following 8-10 Gy total body irradiation. Primary KO fibroblasts displayed resistance to antiproliferative effects of interferon-beta and increased colony forming units following ionizing radiation. Radioresistance of KO fibroblasts was associated with accelerated DNA repair measured by comet assay. Direct microinjection of 5-PP-Ins(1,2,3,4,6)P(5) (the enzymatic product of IP6K2), but not InsP(6) (the substrate of IP6K2) induced cell death in SCC22A squamous carcinoma cells.

WAVE breaking transfers momentum from the atmosphere (winds) to the ocean (currents)1,2 and entrains air in bubbles which are believed to generate and scatter underwater sound3–5. Wave breaking and the associated entrainment of air in bubbles are also thought to be important in heat and gas transfer across the air–sea interface6–8, but the lack of detailed measurements of air entrainment in bubbles has impeded our understanding of the effect of wave breaking on these processes. Here we present measurements of air entrainment by controlled deep-water breaking waves, which show that the bubble plumes generated by breaking waves contain volume fractions of air that are many orders of magnitude greater than expected. Bubble plumes with such large void fractions may be the source of low-frequency sound in the ocean9. We conclude that the processes of surface-wave evolution and air entrainment are dynamically coupled, and that the contribution of bubbles to air–sea gas transfer and to sound propagation may be seriously underestimated if the existence of these plumes of large bubbles is not taken into account.

ObjectivePET/CT in sinonasal malignancies is largely undefined. The objective of this study was to evaluate PET/CT in the initial staging and oncologic surveillance of paranasal sinus carcinomas.MethodsRetrospective review was performed of patients undergoing PET/CT for sinonasal neoplasms from 2001–2006 at tertiary care referral center. Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of PET/CT were calculated. The gold standard was histology and clinical course when histology was not available. Any uptake in PET was considered a positive study.Results78 PET/CT scans were reviewed from 32 patients. Most common histopathologies included esthesioneuroblastoma (28.1%), sinonasal undifferentiated carcinoma (18.8%), sinonasal melanoma (18.8%), squamous cell carcinoma (18.8%), and adenosquamous carcinoma (9%). Overall sensitivity and specificity of PET/CT was 89% and 90% with PPV of 67% and NPV of 98%. PPV at the primary site, neck, and distant sites was 81%, 47% ...

e17091 Background: The RTOG and EORTC have reported benefit from adding chemotherapy to post-operative radiation therapy (PORT) in high-risk patients (pts) with squamous cell head and neck cancer, ...

6039 Background: Studies have demonstrated better prognosis for patients (pts) with HPV-initiated OPC when compared to OPC caused by smoking. A small subset of pts however experience disease recurr...

Materials/Methods: From August 2001 through May 2012, 183 patients with cancer of the oral cavity were identified. Following exclusion of patients with prior head and neck cancer, non-squamous histology, no surgery, N2c or greater or M1 staging, or PORT plans unavailable or bilateral necks treated, 57 patients remained for analysis. Patient demographics, tumor, treatment, and outcome information were abstracted from the charts. Regional recurrence was estimated via Kaplan-Meier method and groups were compared via log-rank test. Results: Median follow-up from diagnosis was 21 months range. Primary sites included alveolar ridge (17.5%), buccal (8.8%), floor of mouth (21.1%), hard palate (5.3%), retromolar trigone (5.3%), and oral tongue (42.1%). Primary site was staged T1-2 in 59.6% and T3-4 in 40.4%. Of the cohort, 12% did not undergo neck dissection, while 18% underwent bilateral and 70% ipsilateral neck dissection. Concurrent chemotherapy was used in 26.3% of patients. Of the cohort, 34 (59.6%) patients were found to be clinically or pathologically node negative, out of which 22 (38.5%) were treated with PORT only to the primary site and 12 (21.1%) had primary site and ipsilateral neck PORT; actuarial regional control (RC) at 2 years was 78.6% and 80%, respectively. Of the 4 total regional failures in the PORT-primary only group, 1 patient had a regional only relapse, the remainder failed both locally and regionally. Of the 2 total regional failures in the PORT-primary/ipsilateral neck, both were in the treated neck, and one was both local and regional. Of the node positive patients, all 23 were treated with primary and ipsilateral PORT with 2 year RC rate of 94.7%. The one patient with regional failure relapsed in the treated neck. Conclusions: In selected patients with lateralized oral cavity squamous cell carcinoma it may be reasonable to exclude the N0 bilateral neck, or in ipsilateral node positive neck the contralateral neck, from the post-operative radiation therapy volumes. Author Disclosure: J.A. Contreras: None. N.G. Rao: None. A.M. Trotti: None. J.J. Caudell: None.

We review a series of laboratory experiments on the sound production and air entrainment by breaking waves. The acoustic radiation and microwave backscatter from individual breaking events are found to correlate with important kinematic and dynamic properties of the breaking waves. Air entrainment measurements using a conductivity technique show that the bubble plume characteristics evolve as simple functions of time. The void-fraction for time scales of the order of a surface wave period is found to be several orders of magnitude greater than time-averaged values reported from the field. A large fraction (30% to 50%) of the surface wave energy dissipated is found to be expended in entraining air against buoyancy forces. A simple model of the sound generated by breaking is shown to reproduce the sound spectrum from gently breaking waves measured by Medwin & Daniel (1990).

This work reports on a series of laboratory and field experiments on the measurement of air entrainment by breaking waves. The first part of this thesis addresses the measurement of high volumetric concentrations of air (0.3% to 100% void-fraction) found immediately beneath breaking waves. Instrumentation based on the change of electrical impedance of the bubbly mixture is developed. Laboratory and field measurements are conducted. Maps of the evolution of the void-fraction distribution for various size breaking waves yield several bulk characteristics of the air entrainment process. In particular, up to 95% of the initially entrained air volume is lost in the first wave period after breaking and up to 50% of the energy dissipated by breaking is found to be expended in entraining bubbles against their buoyancy. The second part addresses the measurement of very low void-fractions. Instrumentation based on the propagation velocity of low-frequency acoustic pulses is developed. Simultaneous measurements of the sound-speed at several depths are conducted during two field experiments. Time-series of sound-speed and attenuation show dramatic fluctuations over time periods on the order of minutes or less which are attributed to bubble clouds. The time-averaged sound-speed profile is found to have lower velocities and to be shallower than previously reported. (MM)

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with more than half a million people being diagnosed with the disease annually. Therefore, it is critical to identify early detection markers, such as DNA methylation, for more timely diagnosis. In a recent study, we identified five tumor suppressive genes (IRX1, EBF3, SLC5A8, SEPT9, and FUSSEL18) as frequently methylated in HNSCC biopsies using a global methylation analysis via restriction landmark genomic scanning (RLGS). Interestingly, we found these candidates are all potentially involved in the TGF-B signaling pathway, which is often disrupted in HNSCC. Therefore, we sought to determine coordinated epigenetic silencing of these candidate genes in HNSCC as potential key disruptors of TGF-B signaling, which could ultimately result in HNSCC progression. Through immunoprecipitation studies, all five of the investigated candidate genes were found to interact with components of the TGF-B pathway. Also, overexpression of SLC5A8, EBF3, and IRX1 resulted in decreased mitotic activity and increased apoptosis. These findings are significant because they reveal a set of genes that interact with components of the TGF-B pathway, and their silencing via methylation in HNSCC results in coordinated decrease in apoptosis, increased proliferation, and decreased differentiation. We went on to define the methylation of these genes in relationship to HPV16-positivity, radiation therapy, and alcohol and tobacco exposure. By utilizing the available clinical information linked to the patient specimens, we found a strong association between promoter methylation of FUSSEL18, IRX1, and EBF3 and prior radiation therapy (P < 0.0001) irrespective of HPV status. Also, promoter methylation of FUSSEL18 and SEPTIN9 were found to correlate significantly with exposure to alcohol and tobacco (P = 0.021). Importantly, in this study we preliminarily show a trend between HPV16 positivity and specific target gene hypermethylation of IRX1, EBF3, SLC5A8, and SEPT9. Equally notable and independent of HPV status, hypermethylation of the promoters of a subset of these genes in recurrences especially in the setting of prior radiation or in the setting of alcohol and tobacco use might help guide adjunctive inclusion or exclusion or epigenetic therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4911.

We review a series of laboratory experiments on the sound production and air entrainment by breaking waves. The acoustic radiation and microwave backscatter from individual breaking events are found to correlate with the important kinematic and dynamic properties of the breaking waves. Air entrainment measurements show that the bubble plume characteristics evolve as simple functions of time. A large fraction (30% to 50%) of the surface wave energy dissipated is found to be expended in entraining air against buoyancy forces.

It is well known that wave breaking events create a bubbly layer a few meters thick below the water surface. The most important characteristic of this shallow channel is its sound‐speed profile. Results are presented from two recent field experiments in which the sound‐speed profile was directly measured in the first few meters below the surface for frequencies in the range 5–40 kHz. Preliminary results in moderate sea states (wind speeds less than 10 m/s) indicate that significant departures from the sound speed in bubble‐free water occur in a shallow [O(1 m)] layer and are intermittent in time. Two dominant time scales are present. A fast time scale associated with the surface waves, which advect the bubble clouds horizontally with respect to the buoy; and a slow time scale O(100 s). Sound‐speed reductions up to 150 m/s have been observed at 50‐cm depth with 10‐min means well above the 5 to 15 m/s previously cited in the literature. Other results including ambient sound, acoustic attenuation, and upward...

In this presentation, recent progress is reviewed in the understanding of the relationship between the dynamics of breaking and the sound generated by breaking waves. Gently breaking waves entrain a small number of bubbles that may break up, resonate, and relax toward their equilibrium shape. Medwin and Daniel’s (1990) measurements of the sound spectrum under gently spilling waves are shown to be consistent with a simple model of the acoustics based on the resonant relaxation of individual bubbles. More energetic breaking may lead to significant air entrainment with recent laboratory and field measurements showing void fractions of O(10−1 ) or more. At these large void fractions the entrained air becomes dynamically significant and up to 50% of the energy lost from the surface wave field by breaking may be expected by entraining air against buoyancy forces. Bubble clouds of large void fraction may oscillate collectively and radiate sound at frequencies much lower that the resonant frequencies of the indiv...

Recent experiments have confirmed that low‐frequency sound (10 to 300 Hz) is generated under breaking waves. It has been suggested that volume oscillations of the bubble plume generated by breaking is the mechanism responsible for the generation of this sound. Confirmation of this process requires independent measurement of the void fraction, and therefore sound speed, in the bubbly mixture. Detailed measurements of the evolution of the void‐fraction field in bubble plumes generated by 2‐D and large scale 3‐D laboratory breaking waves are presented and compared. Various moments of the bubble plume void‐fraction field give information on the (a) volume of air entrained, (b) cross‐sectional area of the plume, (c) mean void fraction and sound speed, (d) bubble plume resonant frequencies, (e) potential energy of the bubble plume, (f) horizontal and vertical displacement and velocity of the bubble plume. These measurements along with independent measurements of the sound radiated (Loewen and Melville, this meeting) support the hypothesis that low‐frequency sound is generated by the volume oscillation of the bubble plume. The radial dependence of the bubble plume’s void‐fraction (and sound speed) field and its effect on low‐frequency sound generation is investigated and the influence of the void‐fraction instrumentation detection threshold in estimating the above moments is also examined. [Work supported by ONR (Ocean Acoustics) and NSF (Physical Oceanography).]