The tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is comprised of cancer-associated fibroblasts (CAFs), immune cells, and other supporting cells. Genetic changes in the carcinoma cells, such as alterations to TP53, NOTCH1, and specific gene expression profiles, contribute to derangements in cancer and microenvironment cells such as increased ROS, overproduction of cytokines, and epithelial to mesenchymal transition (EMT). CAFs are among the most critical elements of the TME contributing to proliferation, invasion, and metastasis. The adaptive immune response is suppressed in HNSCC through overexpression of cytokines, triggered apoptosis of T cells, and alterations in antigen processing machinery. Overexpression of critical cytokines, such as transforming growth factor-β (TGF-β), contributes to EMT, immune suppression, and evolution of CAFs. Inflammation and hypoxia are driving forces in angiogenesis and altered metabolism. HNSCC utilizes glycolytic and oxidative metabolism to fuel tumorigenesis via coupled mechanisms between cancer cell regions and cells of the TME. Increased understanding of the TME in HNSCC illustrates that the long-held notion of "condemned mucosa" reflects a process that extends beyond the epithelial cells to the entire tissue comprised of each of these elements.

Objectives/Hypothesis:Repair of the skull base still begins with a direct repair of the dural defect. We present a new button closure for primary repair of the dura for high flow defects.Study Design:Retrospective review.Methods:We reviewed our 20 cases of primary button grafts and compared the results to the previous 20 high‐flow open‐cistern cerebrospinal fluid (CSF) cases. Subjects were excluded if they had no violation of the arachnoid space or potential for low‐flow CSF leak. The button is constructed so that the inlay portion is at least 25% larger than the dural defect, and the onlay portion is just large enough to cover the dural defect. The two grafts are sutured together using two 4‐0 Neurolon sutures and placed with the inlay portion intradurally and the onlay portion extradurally.Results:The button graft repair of open‐cisternal defects had a drop in CSF leak complications to 10% (2/20), and these two leaks were repaired with the button technique as the salvage surgery. This is a significant improvement over the 45% leak rate in the prebutton graft group (P < .03). In our button graft group we used nasoseptal flaps on 16/20 repairs, and 1/2 repairs that leaked in the button group did not have a nasoseptal flap. Lumbar drains were used in ∼38% in both groups (P = .83).Conclusions:The button graft can be used in conjunction with the nasal septal flap or as a stand‐alone repair with good results reducing the postoperative leak rate to 10% for high‐flow CSF repairs. Laryngoscope, 2010

4. Laryngoscope, 128:2072-2075, 2018.

Object The expanded endoscopic approach to craniopharyngiomas has recently been described in several small case series. The authors present their experience with this technique and review the available literature. Methods Between September 2006 and September 2009, 14 patients underwent a purely endoscopic, endonasal approach for resection of newly diagnosed craniopharyngiomas. These procedures represent index surgeries; no patient had undergone previous tumor resection. A retrospective review of endocrinological and ophthalmological outcomes, extent of resection, and complication prevalence was completed. Additionally, a review of the English literature was performed to evaluate outcomes of similar endoscopic techniques for resection of craniopharyngiomas. Results Four patients (28.6%) underwent gross-total resection; near total resection or better was achieved in 9 patients (64.3%). All patients presented with some form of visual field or acuity deficit. Postoperatively, 12 patients (85.7%) experienced visual improvement, with 6 patients (42.9%) having complete visual recovery. One patient experienced worsening of her visual deficit. Visual acuity improved in 8 patients ((57.1%), while visual field defects improved in 11 (78.6%). The pituitary stalk was preserved in all cases. Eight (57.1%) of 14 patients experienced some form of anterior pituitary dysfunction postoperatively. Although 9 patients (64.3%) were documented to have either transient or permanent new diabetes insipidus immediately after surgery, at 1-month follow-up only 1 patient met clinical criteria. Five patients (35.7%) developed CSF leaks that were successfully treated by subsequent endoscopic revision. All CSF leaks occurred early in the series. Two patients (14.2%) were treated for presumed meningitis postoperatively. Conclusions The endoscopic endonasal approach is a minimally invasive alternative to open transcranial approaches for select craniopharyngiomas. Similar to previous transcranial series, rates of endocrinopathy and gross-total resection were dependent upon the adherence of the tumor capsule to the hypothalamus, pituitary stalk, and associated vasculature. A review of the literature suggests that the results of the current series are similar to other published series on this topic.

Background: Head and neck squamous cell carcinoma (HNSCC) exists within a microenvironment rich in immune cells. Macrophages are particularly abundant in and around tumor tissue, and have been implicated in the growth, malignancy, and persistence of HNSCC ( 1 ). However, current literature reports variable degrees of association between the density of tumor-associated macrophages (TAMs) and clinicopathologic markers of disease ( 2 , 3 ). These inconsistent findings may be a result of differences in approach to TAM detection. Authors have measured total TAMs in tumor tissue, while others have stained tumor samples for individual subtypes of TAMs, which include pro-inflammatory (M1-like) and immunosuppressive (M2-like). Our aim is to more clearly define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC. Methods: We conducted a meta-analysis of the existing publications investigating the relationship between TAMs (total and M2-like subtype) and T stage, nodal involvement, vascular invasion, lymphatic invasion, and tumor differentiation ( Figure 1 ). A total of 12 studies were included. Forest plots and risk ratios were generated to report overall effect. Results: Higher density of both total and M2-like subtype of TAMs in the tumor microenvironment is associated with advanced T stage, increased rates of nodal positivity, presence of vascular invasion, and presence of lymphatic invasion ( p < 0.0001; Figures 2–9 ). There is no significant association between TAM density, either total or M2-like subtype, and tumor differentiation ( Figures 10 , 11 ). Conclusions: Increased density of TAMs, including those of the M2-like phenotype, correlate with poor clinicopathologic markers in HNSCC. Our findings warrant additional investigation into the subpopulations of TAMs, the mechanisms behind their recruitment and differentiation, and the associated influence of each phenotype on tumor growth and invasion. A greater understanding of TAM dynamics in HNSCC is critical for directing further research and employing TAM-targeted adjunct therapies.