Optical imaging with a high-resolution microendoscope to identify sinonasal pathology.

OBJECTIVES: High-resolution microendoscopy (HRME) is an optical imaging modality that allows real time imaging of epithelial tissue and structural changes within. We hypothesize that HRME, using proflavine, a contrast agent that preferentially stains cell nuclei and allows detection of cellular morphologic changes, can distinguish sinonasal pathology from uninvolved mucosa, potentially enabling real-time surgical margin differentiation. STUDY DESIGN: Ex vivo imaging of histopathologically confirmed samples of sinonasal pathology and uninvolved, normal sinus epithelium. SETTING: Single tertiary-level institution. SUBJECTS AND METHODS: Five inverted papillomas, one oncocytic papilloma, two uninvolved sinus epithelia specimens, and three inflammatory polyps were imaged ex vivo with HRME after surface staining with proflavine. Following imaging, the specimens were submitted for hematoxylin and eosin staining to allow histopathological correlation. RESULTS: Results show that sinonasal pathology and normal sinus epithelia have distinct HRME imaging characteristics. Schneiderian papilloma specimens show increased nuclear-to-cytoplasmic ratio, nuclear crowding, and small internuclear separation, whereas normal sinus epithelia specimens show small, bright nuclei with dark cytoplasm and relatively large internuclear separation. Inflammatory polyps, however, have varying imaging characteristics, that resemble both Schneiderian papilloma and normal sinus epithelia. CONCLUSIONS: This study demonstrates the feasibility of HRME imaging to discriminate sinonasal pathology from normal sinus epithelia. While the system performed well in the absence of inflammation, discrimination of inflamed tissue was inconsistent, creating a significant limitation for this application. Novel imaging systems such as HRME with alternative contrast agents may assist with real-time surgical margin differentiation, enabling complete surgical resection of inverted papilloma and reducing recurrence rates.

Tonsillectomy on rivaroxaban.

OBJECTIVE: The objective of this case report is to increase awareness regarding a new category of drugs, new direct oral anticoagulants (specifically, rivaroxaban), which are increasingly being used instead of the more traditional vitamin K antagonists, to highlight the current recommendations for perioperative management of rivaroxaban, and to demonstrate a clinical scenario where a tonsillectomy was successfully performed in a patient requiring anticoagulation with rivaroxaban. METHODS: A literature review and a case report are presented. PubMed was reviewed for evidence based recommendations regarding the perioperative management of rivaroxaban and the recommendations for reversal in the event of a hemorrhagic complication. There is no evidence in the literature regarding the use of rivaroxaban in patients undergoing tonsillectomy. We present the case of a 38year old female on rivaroxaban for history of deep vein thrombosis and pulmonary embolism who successfully underwent tonsillectomy using the current recommendations for perioperative management of rivaroxaban. RESULTS: Our patient had no thrombotic or hemorrhagic complications during the postoperative period. This is the first report in the literature regarding the use of a new direct oral anticoagulant, rivaroxaban, in the setting of tonsillectomy. This case report suggests that tonsillectomy can be performed in patients anticoagulated with rivaroxaban. CONCLUSION: With the increasingly common use of new direct oral anticoagulants for short and long-term anticoagulation, further research is necessary to compare the efficacy and safety profile of the new direct oral anticoagulants to the more traditional vitamin K antagonists when performing tonsillectomy. Otolaryngologists should be familiar with the new oral anticoagulants and understand the proposed perioperative management as practitioners are increasingly likely to encounter patients using this new class of medication in clinical practice.

High-resolution microendoscope imaging of inverted papilloma and normal sinonasal mucosa: evaluation of interobserver concordance.

BACKGROUND: High-resolution microendoscopy (HRME) enables real-time imaging of epithelial tissue. The utility of this novel imaging modality for inverted papilloma has not been previously described. This study examines the ability of otolaryngologists to differentiate between images of inverted papilloma and normal sinonasal mucosa obtained with a HRME. METHODS: Inverted papilloma and normal sinonasal mucosa specimens were stained with a contrast agent, proflavine. HRME images were subsequently captured. Histopathological diagnosis was obtained for each sample. Quality-controlled images were used to assemble a training set. After reviewing the training images, 6 otolaryngologists without prior HRME experience reviewed and classified test images. RESULTS: Five samples of inverted papilloma and 2 normal sinonasal mucosa samples were collected. Four representative images from each specimen were used for the 28-image test set. The mean accuracy among all reviewers was 89.9% (95% confidence interval [CI], 84.3% to 94.0%). The sensitivity to correctly identify inverted papilloma was 86.7% (95% CI, 79.2% to 92.2%), and the specificity was 92.9% (95% CI, 89.0% to 100.0%). The Fleiss kappa interrater reliability score was 0.80 (95% CI, 0.70 to 0.89). CONCLUSION: Inverted papilloma and normal sinonasal mucosa have distinct HRME imaging characteristics. Otolaryngologists can be successfully trained to distinguish between inverted papilloma and normal sinonasal mucosa. HRME is a feasible tool for identification of inverted papilloma. By conducting future in vivo trials, HRME potentially may enable real-time surgical margin determination during surgical excision of inverted papilloma.

Increased radiation sensitivity of head and neck squamous cell carcinoma with sphingosine kinase 1 inhibition.

BACKGROUND: Sphingosine kinase 1 (SphK1) is an important regulator of apoptosis, survival, and proliferation in cancer cells. SphK1 expression in head and neck squamous cell cancer (HNSCC) cell lines and tumor tissue was assessed, and the efficacy of SphK1 knockdown in increasing tumor radiosensitivity was evaluated in vitro and in vivo. METHODS: Expression of SphK1 was determined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (RT-PCR) in 34 prospectively collected HNSCC tumor samples. HNSCC cell lines squamous cell carcinoma (SCC)-15 and SCC-25 were treated with SphK1 inhibitor SKI-II and siRNA targeting SphK1 with and without radiation, and the cell viability was assessed. SCC-15 cells with and without transfection of SphK1 siRNA were then injected into athymic nude mice to develop tumor xenografts, and these 2 groups were further divided into 1 group that received radiation and 1 group that did not. Tumor size was measured over 18 days, when the animals were killed and the tumors were evaluated by immunohistochemistry. RESULTS: SphK1 is found in both HNSCC cell lines and human tumor samples, with higher expression correlated with advanced tumor stage, nodal involvement, and recurrence. In vitro, both SCC-15 and SCC-25 were found to be radioresistant; however, they were sensitized by administration of SKI-II and transfection with siRNA targeting SphK1. In vivo, SphK1-siRNA transfected xenografts were decreased in size compared with both nonradiated control and radiated control mice, whereas mice with both SphK1-siRNA and radiation treatment showed a synergistic reduction in tumor volume. Histopathologic analysis demonstrated a decreased proliferative state in SphK1-siRNA transfected tumors. CONCLUSION: SphK1 is upregulated in HNSCC, and inhibition of SphK1 sensitizes HNSCC to radiation-induced cytotoxicity.