Inflammatory protein expression in human subglottic stenosis tissue mirrors that in a murine model.

OBJECTIVES: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model. METHODS: Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction. RESULTS: The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor ß1, interleukin 1ß, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ. CONCLUSIONS: This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.

First bite syndrome: Our experience with intraparotid injections with botulinum toxin type A.

OBJECTIVES/HYPOTHESIS: First bite syndrome is the sudden onset of acute and severe pain in the parotid region at the initiation of mastication. Although it generally lasts less than a minute, it is disabling for these individuals and leads to a fear of oral intake. It is typically seen after parapharyngeal or deep parotid space surgery. Intraparotid injection of botulinum toxin A (BTA) has been suggested as a treatment for this condition, but there is little supporting literature to this effect. The purpose of this study is to document our experience using this treatment method for first bite syndrome. STUDY DESIGN: Retrospective case review. METHODS: Five patients with first bite syndrome, developed after parapharyngeal space surgery, were treated by multisite injection of BTA into the parotid gland. Between 17.5 and 50 total U of BTA were injected into four or more sites in the parotid region. The patients were then followed up every 4 months. RESULTS: Three of five patients reported a significant improvement in symptoms at the 4-month follow-up visit, although complete resolution was not reported. One patient reported only moderate improvement, and despite two series of injections there was no improvement in one patient, leading us to question our initial diagnosis. CONCLUSIONS: Unilateral BTA injection into the affected parotid gland produces a decrease in the severity of symptoms. It is a safe and viable noninvasive treatment for this difficult to treat condition and may lead to permanent resolution of symptoms in some patients.

Surgical Treatment of Nasal Obstruction in Rhinoplasty.

The key to a successful septorhinoplasty includes an understanding of nasal anatomy and physiology. This allows the surgeon the ability to properly address both form and function during the operation. History and physical examination are paramount in diagnosing and subsequently treating the epicenter of obstruction, which is commonly found among the internal and external nasal valve, the septum, or the turbinates. Treatment of each of these areas is nuanced and multiple approaches are discussed to provide an understanding of the current surgical techniques that allow for excellent functional and cosmetic rhinoplasty results.

IL-1 Receptor Antagonist Inhibits Early Granulation Formation.

PURPOSE: Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers. METHODS: Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction. RESULTS: There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-ß and IL-1ß between the treated and untreated specimens. CONCLUSIONS: Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.

Temporal patterns of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy.

BACKGROUND: Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18 F-fluorodeoxyglucose (18 FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population. METHODS: A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18 FDG PET/CT standardized uptake value data were collected and compared between various time-points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test. RESULTS: A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months (p = 0.048) as well as 2 to 4 and 5 to 24 months (p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months (p = 0.083). CONCLUSION: Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies.

Primary granulocytic sarcoma of larynx.

BACKGROUND: Granulocytic sarcoma is an extramedullary tumor of myeloblasts. The purpose of this report was to present a case of a primary laryngeal granulocytic sarcoma and review of the literature. METHODS: A literature review was performed using Medline and PubMed databases to search for cases of all primary and secondary myelogenous tumors of the larynx. RESULTS: A 36-year-old man presented with a mass involving the preepiglottic space that was histologically confirmed as an extramedullary acute myeloid leukemia, or granulocytic sarcoma. Our review found 18 cases of secondary involvement of the larynx by myelogenous tumors, and only 1 previously reported case of primary laryngeal granulocytic sarcoma. CONCLUSION: The detection of granulocytic sarcoma is difficult given its rarity and nonspecific presentation. To our knowledge, this is the second reported case of primary granulocytic sarcoma of the larynx reported in the literature.

Pediatric nasoseptal flap reconstruction for suprasellar approaches.

OBJECTIVES/HYPOTHESIS: To determine the pediatric age groups viable for nasoseptal flap (NSF) reconstruction of endoscopic endonasal approaches (EEA) to intracranial pathology of suprasella neoplasms. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of 16 pediatric patients who underwent EEA with NSF reconstruction for a suprasellar defect from 2012 to 2014. Radioanatomic analysis was utilized to assess feasibility of NSF reconstruction of suprasellar neoplasms approached via EEA. Computed tomography (CT) measurements for defect size and potential flap coverage were measured by preoperative maxillofacial CT. Radiographic measurements and surgical outcomes were compared to determine if flap size would be sufficient to cover said defects in two pediatric age groups: those>10 years of age (mean age 14 years) and those<10 years (mean age 6 years). RESULTS: Of all patients encountered in this cohort, one postoperative cerebrospinal fluid leak was identified in the >10 years of age population, and this was not due to insufficient flap coverage. Average potential flap length and width are sufficient to cover average suprasellar defect length and width in both age groups (P<.05 in all age groups). CONCLUSIONS: Patient selection is critical for successful pediatric EEA. Preoperative radiographic assessment of NSF feasibility is a critical to ensure adequate flap coverage for suprasellar defects. NSF appears to provide a sufficient and reliable coverage option in reconstruction of suprasellar defects in pediatric patients. LEVEL OF EVIDENCE: 4.

Pulse steroid therapy inhibits murine subglottic granulation.

OBJECTIVE: Using a functional model of airway granulation tissue in subglottic stenosis, we investigated changes in inflammatory markers within granulation tissue in response to intraperitoneal dexamethasone injections. Changes in inflammatory markers will allow us to identify potential targets for immunological therapy. STUDY DESIGN: Institutional Animal Care and Use Committee-approved animal study. SETTING: Philadelphia Veterans Administration Medical Center animal research facility. SUBJECTS AND METHODS: Laryngotracheal complexes of donor mice underwent direct airway injury and were transplanted into subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal complexes were then harvested, and granulation formation was measured. The messenger RNA (mRNA) expression of transforming growth factor (TGF)-ß(1) and interleukin (IL)-1 was quantified. RESULTS: At 3 weeks posttransplantation, there were statistically significant differences in observable granulation formation as well as mRNA expression of TGF-ß(1) and IL-1ß in all groups within the steroid treated arm as compared with the untreated arm. CONCLUSIONS: Systemic steroids have been used to prevent formation of granulation tissue and subglottic stenosis. However, the study of the immunologic markers and the corresponding changes with steroid treatment has not been well studied in animal models. Using a previously described novel murine model, we begin to delineate inflammatory markers that can be applied for potential therapeutic targets.

Cellular adaptive inflammation mediates airway granulation in a murine model of subglottic stenosis.

OBJECTIVE: To determine the contribution of B- and T-cell-mediated inflammation in a murine airway granulation model. STUDY DESIGN: Pilot study in a modified murine model. SETTING: Philadelphia VA Medical Center Research Building. SUBJECTS AND METHODS: Laryngotracheal complexes (LTCs) from 54 donor C57BL/6 mice were harvested and divided into 3 groups: (1) uninjured, (2) mechanically injured using a wire brush, and (3) chemically injured using hydrochloric acid. One donor LTC from each group was placed in deep dorsal subcutaneous pockets of either severe combined immunodeficiency (SCID)- or C57BL-recipient mice, for a total of 3 transplanted tracheas per recipient mouse. After 3 weeks, the transplanted LTCs were harvested from both C57BL- and SCID-recipient mice. Tissues were fixed, sectioned, and stained with hematoxylin and eosin. Representative slides were reviewed by a blinded pathologist to determine the formation of granulation tissue and graded as to the degree of formation of granulation tissue. RESULTS: Despite significant granulation formation in C57BL-recipient mice, direct airway injury did not induce the formation of granulation tissue under the disrupted epithelium of airway mucosa in SCID mice 3 weeks after injury. CONCLUSION: The data indicate that the immune response that results in the formation of granulation tissue is mediated by circulating B- and/or T-cell processes rather than resident airway immune cells. Further studies focusing on cellular adaptive immune processes in response to airway injury may provide a novel treatment modality for subglottic stenosis.