Innovations in Molecular Biomarkers and Biomaterial-Based Immunotherapies for Head & Neck Cancer.

Purpose of Review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy. Recent Findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease but also have the potential to form immunological memory to prevent future recurrence. Localized controlled-release formulas have further served to reduce toxicity and allow the de-escalation of other treatment modalities. Summary: We review the latest advances in head and neck cancer diagnosis and treatment, including novel molecular biomarkers and immunotherapies.

Perforator-based chimeric ulnar forearm microvascular free tissue transfer reconstruction of post-radiated tracheoesophageal puncture fistulae.

Tracheoesophageal puncture (TEP) performed during total laryngectomy in the primary treatment of laryngeal cancer is the standard method for voice restoration. Following adjuvant radiotherapy, the TEP site can experience complications resulting in a tracheoesophageal fistula (TEF) with chronic leakage making oral alimentation unsafe due to aspiration. Here, we describe a technique using chimeric ulnar artery perforator forearm free flaps (UAPFF) in the reconstruction of these complex deformities. Four patients underwent chimeric UAPFF reconstruction of TEP site TEFs following primary TL with TEP and adjuvant radiotherapy. No flap failures or surgical complications occurred. Average time from end of radiotherapy to persistent TEF was 66 months (range 4-190 months). All patients had resolution in their TEF with average time to total oral diet achievement of 22 days (14-42 days). Chimeric UAPFF reconstruction is a safe and effective method to reconstruct recalcitrant TEP site TEFs.

Implant Survival in Tissue-Engineered Mandibular Reconstruction-Early Experiences.

Study Design: This article is to evaluate the early outcomes of dental implants placed in bone generated with tissueengineering techniques, specifically recombinant human bone morphogenic protein-2 (rhBMP-2), allogeneicbone particulate, and bone marrow aspirate concentrate (BMAC) in patients with resection of benignpathology. Objective: To evaluate the long-term prognosis of dental implants placed in tissue engineered mandibular reconstruction. Methods: We retrospectively evaluated 12 patient records, all of whom underwent segmental mandibular resection of benign pathology and reconstruction with a combination of BMAC, rhBMP-2, and allogeneic bone. Collecteddata points included the patient's age, gender, medical and social histories, implant site and placement date, resection/reconstruction date, final prosthesis, pathology resected, and follow-up dates (average 25 monthsof follow-up). Implant success was defined as clinical osseointegration (immobility), absence of peri-implantradiolucency, and absence of infection. Results: Twelve patients met inclusion criteria with a total of 46 implants. The overall implant survival rate was 91.3%. There were 4 implant failures occurring in two patients: 1 failure in Patient 3 and 3 failures in Patient 8. Neitherpatient had any existing medical comorbidities or social history known to increase the risk for implant failure. The average implant placement occurred 11.6 months after mandibular reconstruction. Conclusions: Preliminary findings of implant placement in bone generated with tissue engineering techniques have shown to be another predictable alternative for orofacial rehabilitation. Practical Implications: Dental rehabilitationusing dental implants is a predictable treatment option for patients that have required reconstruction of largebony defects status post resection of benign pathology using novel tissue engineering techniques.

Osteoradionecrosis of the cervical spine: an analysis of the literature.

OBJECTIVES: The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting symptoms and management strategies of this rare condition. STUDY DESIGN: A systematic review of the literature on C-ORN was completed using PubMed. Nineteen articles met criteria; 97 patient cases were identified. Statistical analysis was completed from the patient cases. RESULTS: Of the analyzed patients, 72% are male and 28% are female with an average age of 57.7 years. Nasopharyngeal carcinoma was the most common initial diagnosis (72%). Thyroid and other lower neck cancers were associated with a later onset of C-ORN compared with other cancers. C-ORN more commonly occurred in the clivus to C2 (55.3%, P = .004). Onset of C-ORN significantly differed for men (n = 6.99 years) and women (n = 17.5 years) (P = .022). CONCLUSION: C-ORN can be a devastating complication of head and neck radiation therapy. C-ORN is associated with nasopharyngeal carcinoma, and most commonly affects the area of the clivus to cervical vertebrae C2. Cancers of the lower neck and female sex are associated with later onset. Initial presentation ranges from asymptomatic to severe neurologic deficits; the degree of intervention should be congruent with the severity of presenting symptoms. As long-term survival of patients with head and neck cancer increase, this complication may become more prevalent.

Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS).

Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

A Combined Transoral and Contralateral Submandibular Approach in the Surgical Management of Osteoradionecrosis of the Mandible With Free Flap Reconstruction.

We describe a method for performing mandibular resection and vascularized tissue transfer via an intraoral and contralateral submandibular approach to minimize the risk of wound complications in a radiated field. Surgery on radiated tissue associated with osteoradionecrosis of the mandible can present with oral cutaneous fistulas, dense fibrotic skin, and altered tissue planes to make dissection through this tissue tedious and can place the marginal mandibular nerve at increased risk of injury. The use of custom plates allows surgeons to minimize incisions and depend less on anatomic/visual cues during surgery to obtain an accurate result. Our experience in 8 patients has shown a predictable method for resection and reconstruction of the mandible, while minimizing the potential complications associated with previously radiated and operated patients.

COVID-Associated Avascular Necrosis of the Maxilla-A Rare, New Side Effect of COVID-19.

PURPOSE: The purpose of this article is to present an interesting, rare case of a patient who experienced avascular necrosis of the maxilla associated with COVID-19 infection. METHODS AND RESULTS: Our team retrospectively evaluated this patient's chart after completion of surgical management. The patient is a 72-year-old male who presented to the University of Texas Health Science Center at Houston for surgical management of his infarcted maxilla, which developed as a sequela of infection with COVID-19. A literature review was completed using PubMed. Twenty-five articles are reviewed and discussed. CONCLUSIONS: Infection with COVID-19 confers a hypercoagulable state in patients, leading to various complications in the head and neck region. In our case report, we present a patient who developed avascular necrosis of the maxilla secondary to infection with COVID-19. Thromboembolic prophylaxis is imperative in COVID-19 patients due to the high rate of potential systemic complications.

Massive macroglossia, a rare side effect of COVID-19: clinical, histologic, and genomic findings in COVID-19-positive versus COVID-19-negative patients.

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia. METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples. RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, which was absent in the COVID-negative patient. Immunohistochemistry confirmed the presence of immune cells. Results from the whole-exome sequencing were inconclusive. CONCLUSION: The findings of this study are consistent with others that have observed a lymphocytic infiltrate in the organs of patients infected with SARS-CoV-2. On histology, IHC highlighted a CD45 + predominance, indicating that a robust immune response is present in the tissues. The pathobiology of this phenomenon and its role in the development and/or persistence of massive macroglossia requires further study.

Advances in Tissue Engineering and Implications for Oral and Maxillofacial Reconstruction.

BACKGROUND: Reconstructive surgery in the oral and maxillofacial region poses many challenges due to the complexity of the facial skeleton and the presence of composite defects involving soft tissue, bone and nerve defects. METHODS: Current methods of reconstruction include autologous grafting techniques with local or regional rotational flaps or microvascular free flaps, allografts, xenografts and prosthetic devices. RESULTS: Tissue engineering therapies utilizing stem cells provide promise for enhancing the current reconstructive options. CONCLUSIONS: This article is a review on tissue engineering strategies applicable to specialists who treat oral and maxillofacial defects. PRACTICAL IMPLICATIONS: We review advancements in hard tissue regeneration for dental rehabilitation, soft tissue engineering, nerve regeneration and innovative strategies for reconstruction of major defects.

Resuming Dental and Craniomaxillofacial Surgical Missions During the COVID-19 Pandemic: Guidelines and Recommendations.

STUDY DESIGN: Descriptive review article. OBJECTIVE: The purpose of this article is to provide guidelines and recommendations for how to safely resume dental and craniomaxillofacial STSMs. The following considerations will be discussed: the need for extensive collaboration between organizations and local leadership, the importance of COVID-19 testing, use and management of personal protective equipment, team selection and training, social distancing protocols, and criteria for patient and case selection. METHODS: A literature review was completed, identifying resources and current data regarding the safe resumption clinical activities during the COVID-19 pandemic. RESULTS: At this time, there are no protocols developed regarding the safe resumption of STSMs. Primary resources, including the CDC, WHO, and FDA should be closely monitored so that developed protocols from these recommendations reflect the latest information. CONCLUSION: This paper outlines general considerations and recommendations for dentists, oral health specialists, and craniomaxillofacial surgeons seeking to safely resume STSMs. These recommendations are designed to minimize the risk of exposure to COVID-19 by reinforcing social distancing protocols, reviewing criteria for patient and case selections, encouraging collaboration between organizations and local leadership, and team training. These guidelines should be tailored to fit the needs of each individual mission while keeping the safety as the main objective.

Answering the Call: How to Establish a Dentoalveolar Surgery Mission in Low- and Middle-Income Countries.

Addressing access to oral health care in many low- to middle-income countries is a complicated issue. Oral and maxillofacial surgeons may help engage with vulnerable populations through carefully planned dentoalveolar mission trips. The process of planning a mission includes selecting a population and identifying their unique needs, designing clinic layouts and workflows, team preparation, collection of supplies, fundraising, and advertising. During the mission, methods for protecting privacy, delivering treatment that is standard of care, and sanitation/sterilization options are reviewed. Ethical considerations include avoiding exploitation of vulnerable populations, offending local hosts, need for data collection, and long-term mission sustainability.

Is Reconstruction of Large Mandibular Defects Using Bioengineering Materials Effective?

PURPOSE: Clinical tissue engineering has revolutionized surgery by improving surgical efficiency and decreasing the risks associated with traditional bone graft procurement techniques. Compared with autogenous bone grafts, composite tissue-engineered grafts fulfill the principles of osteoconduction, osteoinduction, and osteogenesis and provide adequate bone volume for maxillofacial reconstruction with less morbidity. The present study aimed to demonstrate the effectiveness, as defined by our success criteria, of a composite tissue-engineered bone graft in the reconstruction of mandibular defects. PATIENTS AND METHODS: We implemented a retrospective case series and enrolled a sample of patients with mandibular defects that had been reconstructed using allogeneic bone combined with recombinant human bone morphogenic protein-2 and bone marrow aspirate concentrate at our institution during a 5-year period. The success criteria were as follows: 1) bone union, defined as a homogenous radiopaque pattern continuous with native bone without mandibular mobility; and 2) volume of grafted bone adequate for implant placement, defined as at least 1.0 cm (height) by 0.8 cm (width). Clinical examinations and computed tomography scans were performed at 6 months postoperatively. Descriptive statistics were computed for each variable. RESULTS: From 2014 to 2019, tissue engineering reconstruction was used in 31 patients with and 3 patients without mandibular continuity defects, for a total of 34 patients. The median follow-up was 6 months. The mean length of the continuity defects was 5.5 cm (range, 1.0 to 12.5). Of the 30 patients with mandibular continuity defects, 27 achieved success according to our criteria, with an average gained height of 2.12 ± 0.64 cm and width of 1.53 ± 0.46 cm. Of the 34 patients, 1 was lost to follow-up, and treatment failed in 3 patients. CONCLUSIONS: Although the use of autogenous graft remains the reference standard, the evolving science behind clinical tissue engineering has resulted in an effective treatment modality for complex head and neck defects with less morbidity and graft material equal to that of autogenous bone.

Current Methods of Maxillofacial Tissue Engineering.

For several decades, the multidisciplinary field of tissue engineering has striven to improve conventional methods of dental, oral, and craniofacial rehabilitation for millions of people annually. Several bone tissue engineering strategies are now readily available in the clinic. Enrichment of autologous products, growth factors, and combination approaches are discussed as ways to enhance the surgeon's traditional armamentarium. Lastly, cutting-edge research such as customized 3-dimensional printed bone scaffolds, tissue engineering strategies for volumetric muscle loss, and temporomandibular joint disc and condyle engineering are briefly discussed as future applications.