Sellar Reconstruction With a Bioabsorbable Plate After Endoscopic Transsphenoidal Pituitary Adenoma Resection: Safe and Efficacious.

OBJECTIVE: To report outcomes of a large cohort of patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for resection of a pituitary adenoma with subsequent Resorb-X plate (RXP) sellar reconstruction. METHODS: A retrospective review of 620 EETS operations performed at a single academic center between 2005 and 2020 was conducted. RESULTS: A total of 215 EETS operations of 208 patients were identified between 2012 and 2020 who underwent reconstruction with the RXP after EETS for pituitary tumor resection with a final pathologic diagnosis of pituitary adenoma. Analysis of pooled data revealed a mean preoperative tumor volume of 6.8 cm3 (range: 0.038-51.03 cm3). Postoperative cerebrospinal fluid leak occurred in 2 patients (0.93%). Postoperative meningitis occurred in 1 patient (0.47%). There were no cases of RXP extrusion. CONCLUSIONS: The rate of postoperative CSF leak and meningitis after use of the RXP for sellar reconstruction compares favorably to other methods, including use of autologous grafts and flaps. Use of RXP during EETS is a safe and efficacious method of sellar reconstruction and may obviate the need for autologous tissue reconstruction after pituitary adenoma resection.

Evaluation of face shields used during aerosol generating procedures.

Transnasal flexible laryngoscopy is considered an aerosol generating procedure. A negative pressure face shield (NPFS) was developed to control aerosol from the patient during laryngoscopy. The purpose of this study was to determine the effectiveness of the NPFS at controlling virus aerosol compared to a standard disposable plastic face shield. The face shields were placed on a simulated patient coughing machine. MS2 bacteriophage was used as a surrogate for SARS-CoV-2 and was aerosolized using the coughing machine. The aerosolized virus was sampled on the inside and outside of the face shields. The virus aerosol concentration was not significantly different between the inside and outside of the traditional plastic face shield (p = 0.12). However, the particle concentrations across all particle sizes measured were significantly decreased outside the face shield. The virus and particle concentrations were significantly decreased (p < 0.01) outside the NPFS operating at a flow rate of 38.6 L per minute (LPM). When the NPFS was operated at 10 LPM, virus concentrations were not significantly different (p = 0.09) across the face shield. However, the number particle concentrations across all particle sizes measured were significantly different (p < 0.05).

Endoscopic Reconstruction of the Anterior Skull Base Following Tumor Resection: Application of a Novel Bioabsorbable Plate.

OBJECTIVE: Endoscopic repair of skull base defects is required following resection of intracranial pathology via the endoscopic endonasal approach (EEA). Many closure techniques have been described, but choosing between techniques remains controversial. We report outcomes of 560 EEA procedures of skull base reconstruction performed on 508 patients over a 15-year-period. Halfway through this period, we adopted the use of a rigid, bioabsorbable extrasellar plate for reconstruction, enabling a comparison between this technique and those used previously. METHODS: All patients undergoing EEA from 2005 to 2019 at our institution were retrospectively reviewed. Demographic information, surgical pathology, tumor dimensions and radiographic features, reconstructive technique, and patient-related outcomes were collected and analyzed with univariate and multivariate statistical modeling. RESULTS: Five-hundred sixty procedures were performed on 508 patients. The series complication rate was 8.2%. Overall, cerebrospinal fluid (CSF) leak rate was 5.0% but varied significantly across closure techniques (p < 0.001). Critically, the CSF leak rate in the 272 cases prior to our 2013 adoption of the Resorb-X Plate (RXP) was 8.5%, whereas leak rate in the subsequent 288 cases was 1.7%. RXP was protective against CSF leak (p = 0.001), whereas gross total resection (GTR) correlated with increased leak rate (p = 0.001). Patient BMI was significantly associated with risk of leak (p = 0.047). Other variables did not impact leak risk. CONCLUSION: Reconstructive technique, extent of resection, and patient BMI significantly contributed to CSF leak rate. GTR was associated with increased leak risk while the RXP was protective. The bioabsorbable RXP is an effective option for rigid skull base repair with comparatively few complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1092-1098, 2023.

Presentation and Outcomes of Non-Squamous Cell Carcinoma Sinonasal Malignancies: A National Perspective.

BACKGROUND: Non-squamous cell carcinoma sinonasal malignancies (NSCCSM) are relatively rare. Neoadjuvant radiotherapy and/or chemotherapy (NTx) have been proposed to improve outcomes compared to surgery alone. In this study, we aim to examine the prevalence of NTx utilization and associated outcomes. METHODS: A retrospective study utilizing the National Cancer Database, 2004 to 2015. The study population included adult patients diagnosed with primary NSCCSM. RESULTS: A total of 574 patients were included. The mean age of the study population was 61.7 ± 16.5 years. The median follow-up time was 40.4 months (interquartile range: 15.3-81.3 months). The histopathological diagnoses identified included: (i) 37.0% adenocarcinoma, (ii) 22.8% adenoid cystic carcinoma, (iii) 20.0% mucosal melanoma, (iv) 11.9% esthesioneuroblastoma, and (v) 8.2% sinonasal undifferentiated carcinoma (SNUC). NTx was utilized in 70 (12.20%) of the study population. Patients who received NTx were more likely to have SNUC or esthesioneuroblastoma (P < .01 each) and to have stage III or IV disease (P < .01 each). NTx was most likely to be administrated in a high-volume center [OR: 3.94, 95%CI: (1.47, 10.53), P = .006]. Patients who received NTx had a significantly lower prevalence of positive margin postoperatively [OR: 0.48, 95%CI: (0.26, 0.87), P = .016]. In patients with NSCCSM, negative margin was associated with improved overall survival [HR: 0.55, 95%CI: (0.36, 0.82), P = .004]. CONCLUSIONS: This study provides an epidemiological perspective regarding NSCCSM and related practice patterns and survival outcomes. Neoadjuvant radiotherapy and/or chemotherapy is likely to decrease the risk of positive margin which ultimately could improve survival in this population.

Minimally Invasive Approaches to Anterior Skull Base Meningiomas.

Objective Anterior skull base meningiomas include olfactory groove, planum sphenoidale, and tuberculum sellae lesions. Traditionally, standard craniotomy approaches have been used to access meningiomas in these locations. More recently, minimally invasive techniques including supraorbital and endonasal endoscopic approaches have gained favor; however there are limited published series comparing the use of these two techniques for these meningiomas. Using our patent database, we identified patients who underwent these two approaches, and conducted a retrospective chart review to compare outcomes between these two techniques. Methods A total of 32 patients who underwent minimally invasive approaches were identified: 20 supraorbital and 11 endoscopic endonasal. Radiographic images, presenting complaints and outcomes, were analyzed retrospectively. The safety of each approach was evaluated. Results The mean extent of resection through a supraorbital approach was significantly greater than that of the endoscopic endonasal approach, 88.1 vs. 57.9%, respectively ( p = 0.016). Overall, preoperative visual acuity and anopsia deficits were more frequent in the endonasal group that persisted postoperatively (visual acuity: p = 0.004; anopsia: p = 0.011). No major complications including cerebrospinal fluid (CSF) leaks or wound-related complications were identified in the supraorbital craniotomy group, while the endonasal group had two CSF leaks requiring lumbar drain placement. Length of stay was shorter in the supraorbital group (3.4 vs. 6.1 days, p < 0.001). Conclusion Anterior skull base meningiomas can be successfully managed by both supraorbital and endoscopic endonasal approaches. Both approaches provide excellent direct access to tumor in carefully selected patients and are safe and efficient, but patient factors and symptoms should dictate the approach selected.

Laser plume containment during flexible transnasal laryngoscopy.

Objective: To evaluate a negative pressure microenvironment designed to contain laser plume during flexible transnasal laryngoscopy. Methods: The Negative Pressure Face Shield (NPFS) was previously reported as well tolerated with initial use on 30 patients. Diagnostic transnasal laryngoscopy was performed on an additional 108 consecutive patients who were evaluated by questionnaires and sequential pulse oximetry. Further study addressed operative transnasal potassium-titanyl-phosphate (KTP) laser laryngoscopy with biopsy done on four patients employing the NPFS. Results: The previously described NPFS version 3 (v.3), a transparent acrylic barrier with two anterior instrumentation ports, was modified by repositioning the side suction port closer to the level of the nose and deepening the lateral sides, squaring off the lower projection. A post-procedure questionnaire employing a 5-point Likert scale ranging from no symptoms (rating of 1) to intolerable (rating of 5) identified excellent patient tolerance of the new design (v.4), among 22 patients evaluated and similar in the comparison to the 116 patients using version 3. Among the 138 patients analyzed, only one patient rated the experience as greater than "mild claustrophobia." 100% of patients answered either "none" or "mild" to the pain and shortness of breath questions. The NPFS (v.4) was then successfully used in four patients for laser laryngoscopy with biopsy of laryngeal papilloma (3/4) and hemorrhagic polyp (1/4). Post-procedure questionnaire identified no shortness of breath (4/4), no claustrophobia (4/4), no pain (4/4) and no significant changes in pulse oximetry during use. Conclusion: Extensive experience in performing diagnostic laryngoscopy with the NPFS directed design changes leading to successful use for transnasal flexible laser laryngoscopy with biopsy in a negative pressure microenvironment. Level of Evidence: Level 2b (Cohort Study).

Sinonasal Squamous Cell Carcinoma Presentation and Outcome: A National Perspective.

BACKGROUND: examine presentation and outcomes of sinonasal squamous cell carcinoma (SCC). METHODS: A retrospective study utilizing the National Cancer Database, 2004 to 2015. The study population included adult patients diagnosed with primary sinonasal SCC. RESULTS: A total of 537 patients were included. The mean age of the study population was 62.6 ± 12.7 years. The median follow-up time was 35.6 months (interquartile range: 8.6-55.9). The histological variants identified are: (i) 66.7% keratinizing SCC, (ii) 21.6% non-keratinizing SCC, (iii) 8.0% papillary SCC, and (iv) 3.7% spindle cell carcinoma. Stage at presentation was: (i) 33.3% T1-2, N0, (ii) 31.8% T3-4a, N0, (iii) 13.8% T1-4a, N+, (iv) 17.0% T4b,N0-3, (v) 4.1% M1. Human papilloma virus (HPV) status was available for 96 patients and tested positive in 24 (25.0%) patients. By histological variants, 5-year survival was lowest for spindle cell carcinoma (40.0%), and highest for papillary SCC (70.1%). HPV negative tumors had a 5-year survival of 26.4%, while HPV positive tumors had a 5-year survival of 57.1% (P = <.001). Of the 255 patients with T1-4a, N0-3, M0 who had surgery of the primary site, 31 (12.2%) patients underwent endoscopic approach. The risk of positive postsurgical margins was not significantly different comparing endoscopic to open approach (23.8% vs 24.1%, P >.99). CONCLUSIONS: Sinonasal SCC could present at advanced stages in two-thirds of the population and exhibit a variety of histological subtypes. Like other sites of head and neck, HPV positive tumors are associated with a favorable prognosis. Endoscopic approach is comparable to open approach in terms of post-surgical margins.

Vascular pedicled flaps for skull base defect reconstruction.

OBJECTIVE: Techniques for reconstruction of skull base defects have advanced greatly since the introduction of the vascular pedicled nasoseptal flap in 2006. The objective of this review is to assess the current state of the field by examining both intranasal and extranasal techniques of vascular pedicled skull base defect repair, their indications and success rates, and novel techniques that are currently under investigation. METHODS: A review of the literature describing the use of vascular pedicled flaps in skull base defect reconstruction was conducted using PubMed and Google Scholar. RESULTS: The nasoseptal flap remains the most widely used vascular pedicled flap for endoscopic repair of skull base defects. Its ease of harvest, wide arch of rotation, and high success rates make it a popular choice among surgeons. Several variations including a "rescue" nasopseptal flap have been developed. Other less commonly used pedicled intranasal flaps include the middle turbinate flap and the posterior pedicled inferior turbinate flap. Additionally, several novel vascular pedicled flaps have been developed and tested in small cohorts of patients. Extranasal flaps such as the pericranial flap and the temporoparietal fascia flap are used less frequently than intranasal flaps. However, they remain valuable options for reconstruction in certain situations. CONCLUSION: Advancements continue to be made in the field of skull base defect reconstruction using vascular pedicled flaps. Though the nasoseptal flap remains the most widely utilized option, additional intranasal techniques continue to be developed and tested to optimize surgical outcomes and patient care. LEVEL OF EVIDENCE: NA.

Negative pressure face shield for flexible laryngoscopy in the COVID-19 era.

OBJECTIVE: Introduce novel methods and materials to limit microdroplet spread when performing transnasal aerosol generating procedures in the COVID-19 era. METHODS: Prototypes of a negative pressure face shield (NPFS) were tested then used clinically to create a suction-clearing negative pressure microenvironment with controlled access to the nose and mouth. Air pressure measurements within prototypes were followed by prospective evaluation of 30 consecutive patients treated with the device assessed through questionnaires and monitoring oximetry. RESULTS: The NPFS is a transparent acrylic barrier with two anterior instrumentation ports and a side port to which continuous suction is applied. It is positioned on a stand and employs a disposable antimicrobial wrap to secure an enclosure around the head. This assembly was successfully used to complete transnasal laryngoscopy in all 30 patients studied. Tolerance of the design was excellent, with postprocedure questionnaire identifying no shortness of breath (27/30), no claustrophobia (27/30), no pain (29/30), and no significant changes in pulse oximetry. CONCLUSION: Diagnostic laryngoscopy was successfully performed in a negative pressure microenvironment created to limit dispersion of aerosols. Further application of the NPFS device is targeted for use with transnasal laryngeal laser and biopsy procedures to be followed by additional modification to enable intranasal and intraoral procedures in a similar protected environment. LEVEL OF EVIDENCE: Level 2b (Cohort Study).

Immunoglobulin replacement therapy reduces chronic rhinosinusitis in patients with antibody deficiency.

BACKGROUND: Patients with primary antibody deficiencies have an increased frequency of sinonasal and pulmonary infections. Immunoglobulin (Ig) replacement is a standard therapy for common variable immunodeficiency (CVID) and other antibody deficiency diseases. Although there is convincing evidence that Ig replacement reduces pulmonary infections, there is little evidence that it reduces sinus infections or abates chronic rhinosinusitis (CRS). This study aims to identify the impact of Ig replacement on CRS in antibody deficiencies. METHODS: A single-center, retrospective chart review of adult patients from 1995 to 2015 was performed. Inclusion criteria were diagnosis of CVID or specific antibody deficiency (SAD), history of CRS requiring medical and/or surgical management within the year prior to presentation, treatment with Ig replacement therapy, and follow-up interval of at least 1 year after initiating Ig replacement. Patients with secondary immune deficiencies were excluded. Thirty-one patients met criteria. Data collected included pretreatment and posttreatment Lund-Mackay scores, and frequency of sinusitis and pulmonary infections requiring rescue antibiotics. Statistical analysis was performed using Wilcoxon signed-rank tests. RESULTS: A significant decline in the Lund-Mackay score was evidenced from pretreatment to posttreatment (p < 0.01). Treatment also resulted in significantly lower rates of sinusitis (p < 0.01) and pulmonary infections (p < 0.01). Additionally, 56% of patients who were on prophylactic antibiotics prior to Ig replacement were able to discontinue their use. CONCLUSION: We present objective evidence showing that Ig replacement therapy has a positive impact on the frequency of sinusitis and confirm its positive impact on pulmonary infections in adult patients with CVID and SAD.

TGF-beta regulation of focal adhesion proteins and motility of premalignant oral lesions via protein phosphatase 1.

Premalignant oral lesions have a high incidence of recurrence and progression to malignant disease and, although studies have shown the contribution of transforming growth factor ß (TGF-ß) to cancer progression, none have been conducted with premalignant oral lesion cells to determine the impact of TGF-ß in stimulating properties that are characteristic of more invasive cells. The present study focused on TGF-ß-modulation of paxillin and the serine/threonine protein phosphatase PP-1, and the impact on cellular motility. These studies show that TGF-ß stimulates premalignant lesion cell motility and up regulates expression of paxillin, as well as its co-localization with PP-1, while concurrently diminishing the level of paxillin serine phosphorylation. The TGF-ß-mediated up regulation of paxillin and co-localization with actin, as well as the TGF-ß-stimulated motility of premalignant lesion cells, were all blocked by inhibiting PP-1, indicating their dependence on PP-1 activity. These studies suggest interplay between TGF-ß and PP-1 in promoting a more malignant phenotype in premalignant oral lesion cells.

Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells.

Motility of endothelial cells is a requirement for the vascularization of solid malignancies. While tumors have been shown to produce a host of angiogenic factors, including TGF-ß, the mechanisms by which such factors regulate endothelial cell motility have not yet been defined. Thus, the role of the serine/threonine phosphatase PP-1 in regulating endothelial cell motility and cytoskeletal architecture was studied. The present study demonstrated that TGF-ß stimulation of motility is dependent on PP-1. Likewise, TGF-ß was shown to up-regulate paxillin expression through a process that was PP-1 dependent. The interplay between PP-1 and TGF-ß was further observed by the induction of cell rounding and the loss of paxillin-actin co precipitations upon PP-1 inhibition and the compensation for these effects by TGF-ß. Studies initiated to determine how PP-1 might regulate motility showed its role in maintaining cytoskeletal organization and its capacity to directly dephosphorylate the focal adhesion scaffolding protein paxillin. These studies suggest that the interplay between TGF-ß and PP-1 regulates the motility of endothelial cells that is critical to the process of angiogenesis.

Use of alpha,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma.

Prior studies have shown that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduced intratumoral levels of immune inhibitory CD34(+) progenitor cells while increasing levels of mature progeny dendritic cells. This finding was extended to a pilot study to determine whether 1,25(OH)(2)D(3) treatment concurrently increases levels of intratumoral CD4(+) and CD8(+) T cells, increases intratumoral levels of immune cells expressing the early activation marker CD69, and prolongs time to HNSCC recurrence. The clinical trial comprised 16 patients with newly diagnosed HNSCC being untreated and 16 patients being treated with 1,25(OH)(2)D(3) during the 3-week interval between cancer diagnosis and surgical treatment. Immunologic effects of treatment were monitored by immunohistochemical analyses of surgically removed HNSCC. Clinical effectiveness of 1,25(OH)(2)D(3) treatment in this study was measured by the time to HNSCC recurrence. HNSCC tissues of patients who received treatment with 1,25(OH)(2)D(3) contained increased levels of CD4(+) cells and, more significantly, CD8(+) T cells. Also prominent was an increase in cells expressing the lymphoid activation marker CD69. Results of this pilot study suggest that patients treated with 1,25(OH)(2)D(3) had a lengthier time to tumor recurrence compared with patients who were not treated before surgery.

Mechanisms of tumor growth and metastasis in head and neck squamous cell carcinoma.

The formation and progression of head and neck squamous cell carcinoma (HNSCC) is multisystemic and involves the immune system, vascularization, and dissemination. Immune involvement includes the subversion of anti-tumor defenses. Vascularization involves both angiogenesis and vasculogenesis. Dissemination involves local tumor invasion as well as distant metastasis through processes including angiogenesis and lymphangiogenesis. Current studies in the dysregulation of various processes, including genetic stability, angiogenesis, lymphangiogenesis, immune regulation, and immune function, are opening opportunities for the development of targeted tumor therapies. The interrelationship of these processes in HNSCC development will be explored in this review.