Effects of Fractional CO2 Laser Treatment on Subglottic Scar in a Rabbit Model.

OBJECTIVE: The objective of this study was to investigate the effects of fractional CO2 laser on subglottic scar. STUDY DESIGN: Randomized controlled animal study. SETTING: Academic medical center. METHODS: Subglottic scar was induced in 12 New Zealand white rabbits via an endoscopic brush technique. This was followed by an open airway surgery that included vertical division of the cricoid and proximal trachea. Eight rabbits underwent fractional CO2 laser treatment of the scar via a Lumenis Ultrapulse Deep FX handpiece. Four rabbits underwent the open surgical approach without laser treatment. Bronchoscopy was performed at weeks 1, 2, 4, and 8. The animals were euthanized and laryngotracheal complexes harvested 12 weeks postsurgery. Immunohistochemistry was performed to determine the collagen composition of treated and untreated scars. RESULTS: All 12 subjects survived to the study endpoint with no significant respiratory complications, despite 10 of 12 developing some degree of lateral tracheal narrowing. The median ratio of type I collagen to type III collagen in the laser group (1.57) was significantly more favorable than that of the untreated group (2.84; P = .03). CONCLUSION: Treatment with fractional CO2 laser appears to have similar effects on subglottic scars as with cutaneous scars, improving the ratio of type I to type III collagen. Additionally, we developed an open airway approach in the rabbit model to deliver fractional CO2 laser treatment to the subglottis without introducing respiratory complications or compromising survival.

Rabbit model of consistently survivable subglottic stenosis using a modified brush technique.

INTRODUCTION: Several animal models of subglottic stenosis (SGS) have been described in the literature, however many result in severe stenosis that requires early intervention and carry a high mortality rate. This limits the application of the model and may require the use of additional animals to achieve desired results due to procedural complications. A novel endoscopic method of inducing SGS in a rabbit model was developed as part of a larger investigation on the treatment of this condition. The objective of this study was to develop an animal model for survivable subglottic stenosis. METHODS: 12 New Zealand white rabbits underwent 2 trials of prolonged intubation that were not successful in inducing SGS. A partially sheathed nylon brush injury technique was then designed and implemented. Airway assessment consisted of rigid bronchoscopy 6 weeks and 8 months after injury. RESULTS: 12 rabbits undergoing subglottic brush injury had focal posteriorly based subglottic stenosis on bronchoscopy at 6 weeks and 8 months post-injury. One rabbit was euthanized after the brush induced subglottic injury but prior to 6 week bronchoscopy due to an unrelated orthopedic injury. This animal was therefore excluded from analysis and replaced. No rabbits required early airway intervention or sacrifice. All survived a period of 8 months. CONCLUSION: Inducing subglottic injury with a partially-sheathed nylon brush safely and reliably creates a controlled SGS with zero procedure-related mortality over 8 months. This model could be the basis for a longer-term evaluation of subglottic scar evolution and intervention.

Parathyroid Computed Tomography Angiography: Early Experience with a Novel Imaging Technique in Primary Hyperparathyroidism.

OBJECTIVES: To describe parathyroid computed tomography angiography (PCTA), determine its accuracy, and, as a secondary objective, calculate its mean radiation dosimetry. STUDY DESIGN: Retrospective chart review of patients who underwent parathyroidectomy for primary hyperparathyroidism from 2007 to 2015. SETTING: Single-center tertiary care academic military hospital. SUBJECTS AND METHODS: PCTA is a 2-phase computed tomography imaging technique that uses individualized timing of contrast infusion and novel patient positioning to accurately identify parathyroid adenomas. Consecutive patients who underwent parathyroidectomy for primary hyperparathyroidism from 2007 to 2015 were reviewed; 55% of patients were women. The mean age was 50.9 years (range, 26-68 years). Sensitivity and specificity were calculated as well as mean radiation dosimetry and timing of contrast. RESULTS: A total of 108 procedures were performed during the study period. Twenty-one patients undergoing 22 PCTAs after prior sestamibi scans were nonlocalizing or equivocal. In this group, there were 15 true-positive, 3 false-positive, 4 true-negative, and 0 false-negative PCTAs. This represents a sensitivity of 100% (95% CI, 74.7%-100%) and a specificity of 57% (95% CI, 20%-88%). The mean calculated radiation dose was 5.15 mSv. In the most recent studies, a mean dose of 4.1 mSv was calculated. The ideal time of image acquisition contrast administration varied from 20 to 30 seconds after contrast infusion. CONCLUSIONS: PCTA is a new technique in anatomic imaging for hyperparathyroidism. In a single-center, single-radiologist retrospective study, it demonstrates excellent accuracy for patients with parathyroid adenomas that are otherwise difficult to localize preoperatively. Preliminary experience suggests that its use may be indicated as a primary imaging modality in the future.

Congenital complete absence of tracheal rings with trifurcate carina: Case report of a rare clinical and endoscopic presentation.

We describe the case of a child with isolated absence of cartilaginous tracheal rings and a trifurcate carina. At 6 months of age, the patient presented to our multidisciplinary airway clinic with stridor and recurrent severe respiratory infections requiring hospitalization. Radiographs showed airway narrowing. Exam demonstrated biphasic stridor. Flexible fiberoptic laryngoscopy demonstrated only mild laryngomalacia. Operative bronchoscopy demonstrated severe tracheomalacia with absence of any visible tracheal rings and a trifurcate carina. Subsequent CT imaging corroborated these findings and did not demonstrate any other major abnormality. The patient did not require operative intervention and his subsequent course was uncomplicated.

A Case of an Epithelioid Hemangioendothelioma Arising from the Innominate Vein Mimicking Cervical Metastatic Lymphadenopathy.

Background. Epithelioid hemangioendothelioma (EHE) is a rare tumor usually presenting in soft tissue. EHE is a vascular malignancy of intermediate clinical behavior, with a histologic appearance of endothelial cells growing in nests or cords. Although EHE often originates from a vessel, it is relatively rare for a primary vascular EHE to originate from a large vein or artery. Occurrence in the mediastinum is exceptionally rare. There are no known associations with other malignancies. Case Presentation. We present a case of mediastinal invasive EHE in a 39-year-old female with concurrent papillary thyroid cancer. She initially presented with a thyroid mass found by her primary care provider, with preoperative imaging concerning for extension into the superior mediastinum. Operative exploration revealed a mediastinal mass distinct from her thyroid carcinoma with invasion into the great vessels, requiring off-pump interposition graft bypass for en bloc resection. Final pathology confirmed pT3N1b multifocal papillary thyroid carcinoma with a separate grade 1 pT1b EHE. Review of the literature describes the demographics, updated pathologic outcomes, histologic findings, and reported incidence of EHE. Conclusions. This is the first reported case of thyroid malignancy with separate and concurrent EHE. Surgeons should remain aware of this entity given its variable behavior. Although initially described as an indolent neoplasm, tumors with poor prognostic factors have been shown to be locally aggressive.

Pediatric head and neck malignancies: incidence and trends, 1973-2010.

OBJECTIVE: Determine the current epidemiology of head and neck (H&N) cancer in the US pediatric population. STUDY DESIGN: Analysis of national tumor registries comparing childhood H&N cancer trends to overall childhood cancer trends. SUBJECTS AND METHODS: The SEER (Surveillance, Epidemiology, and End Results) database was accessed to gather epidemiologic data regarding pediatric H&N cancer between 1973 and 2010. Specific trends related to demographic background, histologic diagnosis, tumor location, and incidence, as well as general trends of all pediatric cancers, were extracted. RESULTS: The total burden and incidence rates of pediatric cancer as well as H&N cancer continue to rise. Cancer was diagnosed in children <15 years old at a rate of 12.5 cases (95% confidence interval [CI], 11.9-13.1) per 100,000 from 1973 to 1975 and 17.3 (95% CI, 16.7-17.9) from 2007 to 2009, an increase of 38%. H&N cancers in the same age group increased from 1.1 (95% CI, 0.9-1.2) in 1973-1975 to 1.6 (95% CI, 1.4-1.8) in 2007-2009, an increase of 45%. Despite this apparent increased incidence, the proportion of H&N cancers to all cancers in the pediatric population has remained stable. CONCLUSION: As with all pediatric cancer, the public health burden of pediatric H&N cancer continues to rise. The proportion of H&N malignancy to all pediatric cancer is stable. With the incidence increasing, however, work to identify treatment strategies remains crucial.

Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory responses in non-haematopoietic cells.

Inhibition of the CD40-CD154 pathway controls inflammatory disorders. Unfortunately, administration of anti-CD154 monoclonal antibodies causes thromboembolism. Blockade of signalling downstream of CD40 may represent an approach to treat CD40-driven inflammatory disorders. Blocking tumour necrosis factor receptor-associated factor 6 (TRAF6) signalling downstream of CD40 in MHC II(+) cells diminishes inflammation. However, CD40-TRAF6 blockade may cause immunosuppression. We examined the role of CD40-TRAF2,3 and CD40-TRAF6 signalling in the development of pro-inflammatory responses in human non-haematopoietic and monocytic cells. Human aortic endothelial cells, aortic smooth muscle cells, renal proximal tubule epithelial cells, renal mesangial cells and monocytic cells were transduced with retroviral vectors that encode wild-type CD40, CD40 with a mutation that prevents TRAF2,3 recruitment (ΔT2,3), TRAF6 recruitment (ΔT6) or both TRAF2,3 plus TRAF6 recruitment (ΔT2,3,6). Non-haematopoietic cells that expressed CD40 ΔT2,3 exhibited marked inhibition in CD154-induced up-regulation of vascular cell adhesion molecule 1, intercellular adhesion molecule 1 (ICAM-1), monocyte chemotactic protein 1 (MCP-1), tissue factor and matrix metalloproteinase 9. Similar results were obtained with cells that expressed CD40 ΔT6. Although both mutations impaired ICAM-1 up-regulation in monocytic cells, only expression of CD40 ΔT6 reduced MCP-1 and tissue factor up-regulation in these cells. Treatment of endothelial and smooth muscle cells with cell-permeable peptides that block CD40-TRAF2,3 or CD40-TRAF6 signalling impaired pro-inflammatory responses. In contrast, while the CD40-TRAF2,3 blocking peptide did not reduce CD154-induced dendritic cell maturation, the CD40-TRAF6 blocking peptide impaired this response. Hence, preventing CD40-TRAF2,3 or CD40-TRAF6 interaction inhibits pro-inflammatory responses in human non-haematopoietic cells. In contrast to inhibition of CD40-TRAF6 signalling, inhibition of CD40-TRAF2,3 signalling did not impair dendritic cell maturation. Blocking CD40-TRAF2,3 signalling may control CD40-CD154-dependent inflammatory disorders.

Proinflammatory responses induced by CD40 in retinal endothelial and Müller cells are inhibited by blocking CD40-Traf2,3 or CD40-Traf6 signaling.

PURPOSE: The cell surface receptor CD40 is required for the development of retinopathies induced by diabetes and ischemia/reperfusion. The purpose of this study was to identify signaling pathways by which CD40 triggers proinflammatory responses in retinal cells, since this may lead to pharmacologic targeting of these pathways as novel therapy against retinopathies. METHODS: Retinal endothelial and Müller cells were transduced with vectors that encode wild-type CD40 or CD40 with mutations in sites that recruit TNF receptor associated factors (TRAF): TRAF2,3 (ΔT2,3), TRAF6 (ΔT6), or TRAF2,3 plus TRAF6 (ΔT2,3,6). Cells also were incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. We assessed intercellular adhesion molecule-1 (ICAM-1), CD40, monocyte chemoattractant protein-1 (MCP-1), VEGF, and prostaglandin E2 (PGE2) by fluorescence-activated cell sorting (FACS), ELISA, or mass spectrometry. Mice (B6 and CD40(-/-)) were made diabetic using streptozotocin. The MCP-1 mRNA was assessed by real-time PCR. RESULTS: The CD40-mediated ICAM-1 upregulation in endothelial and Müller cells was markedly inhibited by expression of CD40 ΔT2,3 or CD40 ΔT6. The CD40 was required for MCP-1 mRNA upregulation in the retina of diabetic mice. The CD40 stimulation of endothelial and Müller cells enhanced MCP-1 production that was markedly diminished by CD40 ΔT2,3 or CD40 ΔT6. Similar results were obtained in cells incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. The CD40 ligation upregulated PGE2 and VEGF production by Müller cells, that was inhibited by CD40 ΔT2,3 or CD40 ΔT6. All cellular responses tested were obliterated by expression of CD40 ΔT2,3,6. CONCLUSIONS: Blockade of a single CD40-TRAF pathway was sufficient to impair ICAM-1, MCP-1, PGE2, and VEGF upregulation in retinal endothelial and/or Müller cells. Blockade of CD40-TRAF signaling may control retinopathies.