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Current adjuvant treatment for head and neck cancer includes radiation, chemo­therapy, and immunotherapy. Among the recent advances in this eld are the use of repurposed drugs to overcome drug resistance in common chemotherapies and the development of new immunomodulatory drugs, cancer vaccines, and biomaterial­based delivery systems in the immunotherapy eld.

Mesoporous silica rod (MSR)-based biomaterial vaccines form structures that pro­vide a microenvironment that support and modulate immune cells invivo. MSR­based vaccines have also been shown to confer long-term immunity and protect against tumor rechallenge in multiple preclinical models as previously reviewed [30]. These studies illustrate the potential of MSR-based cancer vaccines to gener­ate a potent anti-tumor effector T-cell response in situ. Dharmaraj etal., in an ortho­topic syngeneic model of OSCC, assessed the efcacy of a mesoporous silica rod (MSR) cancer vaccine targeting HPV-16 E7. While the mEER model that constantly expresses the E7 antigen showed increased efcacy, the MOC2-E6E7 model exhib­ited tumor growth delay and a modest prolonged survival [31]. Synthetic cyclic dinucleotides (CDNs) are a new class of immunotherapeutics that induce strong anti-tumor responses in preclinical models through the Stimulator of Interferon Genes (STING) pathway [32]. In fact, STING-agonist therapy using CDNs have been considered as an “intratumoral in situ vaccine” to convert cold tumors into hot tumors. However, CDN monotherapy has shown poor efcacy in preclinical models of HNSCC, requiring multiple injections and concurrent administration of immune checkpoint antibodies [33]. Leach etal. developed a novel peptide hydrogel-based platform for intratumoral CDN delivery, called “STINGel” based on the ability of biomaterials to allow for controlled release of drugs. MultiDomain Peptide (MDP) is an easily syringe-deliverable carrier hydrogel that self-assembles to form a nano­brous matrix. The localized delivery of CDN from this matrix in STINGel improved the overall survival in MOC2-E6E7 murine model of HNSCC compared to controls as shown in Fig.3.4 [34]. It is well established that the pro-tumorigenic enzyme inducible nitric oxide synthase (iNOS) is highly upregulated in several can­cers and promotes conditions favorable to tumor growth [35, 36]. iNOS promotes activation of immunosuppressive tumor-inltrating myeloid-derived suppressor cells (MDSCs) [37]. The small molecule drug, N6-(1-iminoethyl)-L-lysine (L-NIL), has been used to selectively inhibit iNOS and regulate downstream effects that favor tumor growth [35]. Therefore, the ability to modulate iNOS activity at the tumor site

analysis. Drug repurposing of demethylating drugs has the potential to reverse cisplatin- resistance. Cancer vaccines targeting “driver” oncogenes show promising therapeutic potential. Injectable biomaterials demonstrate not only the therapeutic power of using localized, controlled-release drug delivery to reduce systemic toxic­ity and improve treatment response, but can also serve as drug mimetics themselves. The studies reviewed here highlight the critical role of intra- and inter-university collaborations and the profound discoveries that can result from these endeavors. Future areas of study include the use of biomarkers to monitor treatment response and the development of biomaterials for the controlled-release of numerous immunotherapies.

Otologic surgery involves very precise dissection of microscopic structures to eradi­cate pathology, reconstruct anatomy, and restore function. To be done safely and efciently, high magnication and appropriate illumination are required. Traditionally, this has been achieved using binocular microscopy, the workhorse of otologic surgery. The middle ear space is complex with many hidden recesses in all directions. These spaces are challenging to visualize with the fundamental limita­tions of the microscope as its optics remain outside the body at a distance to the tissue of interest. This means that the eld of view is limited by the narrowest part of the ear canal and that attaining a wider eld of view requires destructive mea­sures such as removal of soft tissue and bone. The endoscope is ideal when utilizing small surgical corridors to access the hidden recesses of the middle ear by bypassing the narrow ear canal and bringing the optics only centimeters from the tissue of interest, in turn obviating the need for destructive measures for visualization. Additionally, the microscope presents challenges as it relates to surgeon ergonomics and comfort, requiring prolonged periods of neck exion. Trainee education is also hindered because the operator has a three-dimensional view, and the observer is

only offered a two-dimensional image via the teaching head. The discrepancy in views makes for a frustrating teaching and learning experience. The digital extra­corporeal scope, or exoscope, is complementary to the endoscope and was designed to replace the operating microscope. When compared with the microscope, it pro­vides an immersive surgical view with improved ergonomics and an enhanced teaching experience since all parties have the same high-denition three- dimensional view in an ergonomically favorable neutral neck position. In this chapter, we discuss the advances in visualization for otologic surgery, particularly endoscopic and exo­scopic ear surgery.

In the 1990s, Jean-Marc Thomassin, Dennis Poe, and Muaaz Tarabichi described new otologic applications of endoscopy, including management of cholesteatomas and perilymphatic stulas [1, 2]. In 1997, Tarabichi etal. published outcomes of endoscopic management of acquired cholesteatoma in 38 adult patients; 36 of which underwent transcanal endoscopic ear surgery. Twenty-nine out of 30 were disease free at 1year, 10/13 were disease free at 2years, and 4/6 were disease free at 2years on surgical second look exploration. He concluded that transcanal endo­scopic resection of cholesteatoma is safe and effective [3]. He later published long­term outcome data of 101 ears operated on using the endoscope with up to 5years of follow-up. Three cases were converted into postauricular tympanomastoidec­tomy. There were no iatrogenic facial nerve injuries. Bone thresholds were stable, except in one patient with perilymphatic stula. Six ears required revision surgery, and nine required ofce-based minor procedures. He concluded that minimally invasive management and surveillance of cholesteatoma had long-term results that compared well to those of postauricular methods [4].

Although binocular microscopy has been the workhorse of otologic surgery, the endoscope has gained signicant attention and integrated adoption in recent years. Otoendoscopy is the use of rigid endoscopes to examine the ear. Endoscopes were rst used in otology solely to describe ear anatomy [7, 8]. Outside of the operating room, the endoscope can be used during examination of the outer and middle ear and for debridement of complex mastoid cavities. Endoscopic ear surgery is the use of rigid endoscopes to perform otologic surgery. The binocular microscope provides a great three-dimensional view for line-of-sight surgery but has a signicantly

Performing an endoscopic exploratory tympanotomy with a 0° endoscope provides a view of the entire tympanic membrane and structures within the mesotympanum without any bony removal. Mesotympanic structures that can be seen include the chorda tympani, entire ossicular chain, tympanic portion of the facial nerve, cochle­ariform process, cochlear promontory, round window, pyramidal eminence, and stapes tendon. With adequate experience, tympanoplasty, ossicular chain recon­struction, and stapedectomy can be performed entirely endoscopically.