The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.

Purpose:To determine the accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for nodal staging in patients with head and neck cancer. Materials and Methods:Twenty patients with carcinomas of the upper aerodigestive tract were prospectively enrolled. MRI was performed before and 24 -36 hours after intravenous infusion of an USPIO agent, ferumoxtran-10 (Sinerem; Guerbet, France; and Combidex; Advanced Magnetics) at a dose of 2.6 mg Fe/kg using T2-weighted spin-echo and gradient-echo sequences. Surgery was performed the same day or the day after the ferumoxtran-10 -enhanced MR examination. Based on MRI, selected nodes were surgically removed and directly correlated with pathology using hematoxylin-eosin (H&E) and Perls stainings.Results: A total of 63 nodes were studied; 36 were nonmetastatic, 25 metastatic, and two inflammatory. Ferumoxtran-10 -enhanced MRI allowed diagnosis of 24 metastatic and 30 nonmetastatic nodes, yielding a sensitivity of 96%, a specificity of 78.9%, a positive predictive value of 75%, and a negative predictive value of 96.8%, compared to 64%, 78.9%, 66.6%, and 76.9%, respectively, for nonenhanced MRI. Accuracy of ferumoxtran-10 -enhanced MRI was 85.7%. The gradient-echo T2-weighted sequence was the most accurate to detect signal loss in nonmetastatic nodes.Conclusion: USPIO-enhanced MRI is useful for nodal staging of patients with head and neck cancers. CROSS-SECTIONAL IMAGING plays an important role in the study of patients with head and neck squamous cell carcinomas, allowing detection of lymph nodes (LN) missed by physical examination, or demonstrating invasion of structures such as the skull base or the carotid arteries (1,2). Using these imaging modalities, the criteria for diagnosing metastatic nodes is mainly dimensional. Measurements include the minimum transaxial diameter, the maximum transaxial diameter or a ratio between the maximum longitudinal and the maximum axial diameters (3-7). Other parameters, such as morphological criteria or the pattern of enhancement, are regarded as less important in this setting. Nodal metastases in the head and neck are frequently smaller than 10 mm, sometimes even under 5 mm in diameter, a fact that accounts for the unsatisfactory performance of the current imaging techniques (8,9).MRI can be improved when using contrast agents suited for intravenous MR lymphography, such as the new ultrasmall superparamagnetic iron oxide (USPIO) particles, which are taken up by cells of the reticuloendothelial system of nonmetastatic LN (10 -15). As it has been shown in previous studies, iron oxide deposition leads to a decrease in the signal intensity (SI) in nonmetastatic nodes due to the T2 shortening effects, whereas metastatic nodes, devoid of macrophages, will not undergo SI changes when using T2-weighted sequences (11). The clinical use of this contrast agent is still under evaluation on phase III clinical trials (15)(16)(17)(18)(19)(20). Reports show promising results, with sensitivity and specificity value...

Despite the increased molecular knowledge and the diagnostic and therapeutic improvements, the survival of patients with upper aerodigestive tract carcinoma remains poor. The identification of early diagnostic and prognostic biomarkers and the development of molecular models to distinguish patients that will recur and/or develop metastasis after treatment as well as to benefit with target therapies can be important to decrease mortality, improve survival rates and improve the quality of life of these patients. The current study analyzed 21 upper aerodigestive tract carcinomas through array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification techniques. A number of chromosomal regions and genes were observed with copy number alterations and methylation. A predictive (epi)genomic model that comprises the 3p chromosomal region and WT1, VHL and THBS1 genes was built, highlighting a molecular signature with possible clinical use. The current study may aid in the development of a more individualized patient management and targeted drug design. The power of this genomic and epigenetic model to predict the recurrence and metastasis development should be evaluated and validated in future larger cohort study.

Objectives/Hypothesis: Quinine, a cinchona bark-derived antimalarial alkaloid, is a known ototoxic. Isolated and named in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou, it has since been employed in the treatment of different maladies. Quinine was also recommended as a local anesthetic in surgical procedures in the early 20th century. This article aims to identify early ototoxicity reports regarding quinine and to investigate if quinine was previously used in otology as an anesthetic agent or as an actual therapy. Method: Historical review of medical and pharmaceutical literature from the 19th and 20th centuries in databases (PubMed; Web of Science), as well as medical books on ototoxic drugs, quinine, and therapies in otology. Results: The first identified reference of quinine ototoxicity was from 1824. Quinine also had a therapeutic role in otology and neurotology and was employed for its analgesic properties. It was used in Menière's disease, vertigo, otalgia, purulent otitis media, neuralgia of the plexus tympani, furuncles in the auditory canal, and herpes zoster in the auricle. Conclusion: Quinine was acknowledged as an ototoxic drug in the 19th century. Quinine was used in several otologic disorders, both as an analgesic (for herpes zoster, otalgia) and as a therapeutic agent (Menière's disease, vertigo, purulent otitis media, furuncles in the auditory canal). This research demonstrates that, analogously to gentamicin, quinine was used in Menière's disease specifically due to its ototoxic effects.

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