Faculty Bibliography

Introduction/UNASSIGNED:Inhalation injury is an independent risk factor in burn mortality, imparting a 20% increased risk of death. Yet there is little information on the natural history, functional outcome, or pathophysiology of thermal injury to the laryngotracheal complex, limiting treatment progress. Methods/UNASSIGNED:Case series (n=3) of significant thermal airway injury. Results/UNASSIGNED:In all cases, the initial injury was far exceeded by the subsequent immune response and aggressive fibro-inflammatory healing. Serial examination demonstrated progressive epithelial injury, mucosal inflammation, airway remodeling, and luminal compromise. Histologic findings in the first case demonstrate an early IL-17A response in the human airway following thermal injury. This is the first report implicating IL-17A in the airway mucosal immune response to thermal injury. Our 2nd and 3rd patients received Azithromycin targeting IL-17A and showed clinical responses. The third patient also presented with exposed tracheal cartilage and underwent mucosal reconstitution via split-thickness skin graft over an endoluminal stent in conjunction with tracheostomy. This was associated with rapid abatement of mucosal inflammation, resolution of granulation tissue and return of laryngeal function. Conclusion/UNASSIGNED:Patients who present with thermal inhalation injury should receive a thorough multidisciplinary airway evaluation, including early otolaryngologic evaluation. New early endoscopic approaches (scar lysis, and mucosal reconstitution with autologous grafting over an endoluminal stent), when combined with targeted medical therapy aimed at components of mucosal airway inflammation (local corticosteroids and systemic Azithromycin targeting IL-17A) may have potential to limit chronic cicatricial complications.

PURPOSE/OBJECTIVE:Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct glioma molecular subtype for which no effective molecularly-directed therapy exists. Low-grade gliomas, which are 80-90% IDH mutant, have high RNA levels of the cell surface Notch ligand DLL3. We sought to determine DLL3 expression by immunohistochemistry in glioma molecular subtypes and the potential efficacy of an anti-DLL3 antibody drug conjugate (ADC), rovalpituzumab tesirine (Rova-T), in IDH mutant glioma. EXPERIMENTAL DESIGN/METHODS:We evaluated DLL3 expression by RNA using TCGA data and by immunohistochemistry in a discovery set of 63 gliomas and 20 non-tumor brain tissues and a validation set of 62 known IDH wildtype and mutant gliomas using a monoclonal anti-DLL3 antibody. Genotype was determined using a DNA methylation array classifier or by sequencing. The effect of Rova-T on patient-derived endogenous IDH mutant glioma tumorspheres was determined by cell viability assay. RESULTS:Compared to IDH wildtype glioblastoma, IDH mutant gliomas have significantly higher DLL3 RNA (P<1x10-15) and protein by immunohistochemistry (P=0.0014 and P<4.3x10-6 in the discovery and validation set, respectively). DLL3 immunostaining was intense and homogeneous in IDH mutant gliomas, retained in all recurrent tumors, and detected in only 1 of 20 non-tumor brains. Patient-derived IDH mutant glioma tumorspheres overexpressed DLL3 and were potently sensitive to Rova-T in an antigen-dependent manner. CONCLUSIONS:DLL3 is selectively and homogeneously expressed in IDH mutant gliomas and can be targeted with Rova-T in patient-derived IDH mutant glioma tumorspheres. Our findings are potentially immediately translatable and have implications for therapeutic strategies that exploit cell surface tumor-associated antigens.

This evaluation of quality metrics uses data from the National Cancer Database to summarize hospital-level overall quality of care for patients with head and neck cancer in the United States.

BACKGROUND:Oral human papillomavirus (HPV) infection is the principal underlying cause of a dramatic increase in oropharyngeal cancer. Dentistry can play an important role in developing clinical algorithms for secondary prevention. METHODS:The authors conducted this cross-sectional pilot study with practices of The National Dental Practice-Based Research Network. The authors evaluated the feasibility and acceptability of screening and testing procedures as judged by practitioners and patients. The authors used tablet devices for patient screening, obtaining consent, and administering a confidential oral HPV risk factor survey. RESULTS:Most patients (85%) were comfortable being asked about their cigarette use and their sexual behavior (69%) and were interested in participating again (79%). More than 90% of practitioners were comfortable with study procedures except the extra time required for patient participation (75% comfortable). There were no problems with oral rinse collection as reported by patients or practitioners. CONCLUSIONS:It is feasible in community dental offices to collect oral rinses for HPV detection and to ask patients explicit questions about sexual history when using a tablet device for confidentiality. PRACTICAL IMPLICATIONS/CONCLUSIONS:Discussing high-risk types of HPV and appropriately assessing that risk are a challenge for oral health care professionals. These results are positive from a research perspective but do not address the advisability of routine HPV screening in dentistry.

Tissue inelasticity and the hair-bearing nature of the scalp and forehead pose unique challenges during reconstruction. A thorough understanding of the surgical anatomy of the scalp and forehead is paramount for optimal reconstructive outcomes. Primary wound closure is usually preferred over secondary intention healing and skin grafting. Use of dermal alternatives and tissue expansion are adjunctive therapies to facilitate scalp wound closure. Local skin and soft tissue flaps are commonly used for most small to medium defects; however, microsurgical free tissue transfer can be considered for large full-thickness skin defects of the forehead and scalp.

The Dysphagia Handicap Index (DHI) is a 25-item questionnaire assessing the physical, functional, and emotional aspects of dysphagia patients' quality of life (QoL). The study goal was to translate and validate the Hebrew-DHI. 148 patients undergoing fiberoptic endoscopic examination of swallowing (FEES) in two specialized dysphagia clinics between February and August 2017 filled the Hebrew-DHI and self-reported their dysphagia severity on a scale of 1-7. 21 patients refilled the DHI during a 2-week period following their first visit. FEES were scored for residue (1 point per consistency), penetration and aspiration (1 point for penetration, 2 points for aspiration, per consistency). 51 healthy volunteers also filled the DHI. Internal consistency and test-retest reproducibility were used for reliability testing. Validity was established by comparing DHI scores of dysphagia patients and healthy controls. Concurrent validity was established by correlating the DHI score with the FEES score. Internal consistency of the Hebrew-DHI was high (Cronbach's alpha = 0.96), as was the test-retest reproducibility (Spearman's correlation coefficient = 0.82, p < 0.001). The Hebrew-DHI's total score, and its three subscales (physical/functional/emotional) were significantly higher in dysphagia patients compared to those in healthy controls (median 38 pts, IQR 18-56 for dysphagia patients compared to 0, IQR 0-2 for healthy controls, p < 0.0001). A strong correlation was observed between the DHI score and the self-reported dysphagia severity measure (Spearman's correlation coefficient = 0.88, p < 0.0001). A moderate correlation was found between the DHI score and the FEES score (Pearson's correlation coefficient = 0.245, p = 0.003). The Hebrew-DHI is a reliable and valid questionnaire assessing dysphagia patients' QoL.

Background: The reconstruction of major skull base, scalp and calvarial defects with microvascular free flaps has revolutionized the predictable and safe conduct of multidisciplinary oncologic surgery of this region. While extended resections can be more confidently completed, this has not necessarily been accompanied by increased local control or cure. This is due to limitations of radiation tolerance of surrounding tissues, necessary acceptance of involved microscopically close or involved margins, tolerable morbidity, and the lack of specific medical oncologic agents for benign and malignant CNS tumors. Use of coupler devices in routine head and neck defects evolved into use in skull base, calvarial, and intracranial settings where flap loss can be catastrophic.
Method(s): Mechanical microvascular anastomosis became increasingly widely used in head and neck reconstruction in the late 1980s and 1990s as a method to speed the process, and perhaps patency over hand-sewn anastomoses. These have been incorporated primarily in venous interposition graft and end-to-end, and end-to side venous configurations facilitated by vessel pliability and the ability to evert vessel walls over coupler pins. The coupler itself is constructed of 2 polyethylene rings and staggered ferromagnetic pins which match holes on the opposing ring through a friction fit, thus joining the vessels. Because of its construction, and the increased use and preference of MRI for perioperative evaluation early concern for heating and/or rotation, torquing or disruption of new anastomoses, it was studied in a relevant model and found in clinical experience, to be irrelevant.[1]
Conclusion(s): The use of the superficial temporal vessels for recipients is often preferred to save pedicle length, minimize the need for interposition vein grafts (doubling the number of anastomoses and thrombotic opportunity/risk), and often influenced by prior treatment (bicoronal flaps) in which ligation and scar may limit suitability. Additionally, the vein is often thin-walled and technically unusable. The incision for access to these vessels is usually placed immediately in the junctional creases of the ear and cheek, and thus several millimeters removed from the actual course of the vessels. In a broad and significant experience spanning 25 years including 40 skull base microvascular reconstructions, 15 of which used temporal recipient vessels, there have been 2 cases (one calvarial, one intracranial) where the coupler rings have eroded through the temporal skin, and self-ejected, without flap loss, and implying the acquisition of adequate venous supply to support flap survival. Given this observation, unique to this region, hand-sewn anastomoses are specifically recommended when using these vessels so as to minimize potentially catastrophic flap loss. Our experience in microvascular skull base reconstruction in this context is reviewed in support of this recommendation

Background: Large anterior skull base meningiomas with significant extension through the floor of the anterior fossa into the ethmoid and sphenoid sinuses pose a surgical dilemma. Radical resection of these tumors as well as the skull base and sinus component can be curative. This can be achieved through either a transcranial approach or a combined transcranial/endonasal approach depending on the involvement of the sinuses. However, in doing so, patients are at significant risk for postoperative cerebrospinal fluid leak as well as infection. Given these risks and the benign nature of these tumors, especially WHO grade I meningiomas, many surgeons will choose not to resect the portion going through the skull base. The residual tumor can then be observed or radiated if there are signs of growth.
Objective(s): We propose the use of a staged combined approach to maximize resection and minimize risk of CSF leak or infection. Case Presentation: We present the case of a 55-year-old male, BMI of 37, who presented with 3 weeks of left eye blurry vision, 2 years of anosmia, and personality changes. The patient was found to have a 7.3x5.9x4.6 cm anterior skull base meningioma with significant surrounding parenchymal edema in the bilateral frontal lobes as well as extension through the floor of the anterior skull base and into the ethmoid and sphenoid sinuses ([Fig. 1a], b). He was taken for a bifrontal craniotomy and resection of the intracranial component with planned amputation of the tumor at the skull base which was covered with a pericranial flap. He recovered well with return of his vision to normal. Pathology demonstrated a WHO grade II atypical meningioma. Follow-up imaging demonstrated persistent residual tumor within the ethmoid and sphenoid sinus ([Fig. 2]). We discussed an endoscopic endonasal resection of the residual tumor and anterior skull base in a delayed fashion once the pericranial graft healed versus radiation. The patient preferred to proceed with resection. He underwent an endoscopic endonasal resection of the residual tumor within the sinus and remaining anterior skull base. At the time of surgery the tumor was easily separated from the pericranial graft which was well healed. No CSF was observed but a nasoseptal flap was placed for protection. He was discharged on POD2. Postoperative imaging demonstrated gross total resection of the residual tumor ([Fig. 3]).
Conclusion(s): The use of a delayed combined transcranial and endoscopic endonasal approach for anterior skull base meningiomas with significant intracranial and sinus tumor component potentially maximizes surgical resection while reducing the risk of CSF leak and infection. (Figure Presented)