Terry Y. Shibuya

In Vivo Optical Coherence Tomography of the Human Larynx: Normative and Benign Pathology in 82 Patients

Objectives: Optical coherence tomography (OCT) is an emerging imaging modality that combines low‐coherence light with interferometry to produce cross‐sectional images of tissue with resolution about 10 μm. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo.

Optical coherence tomography of laryngeal cancer.

Objectives: Optical coherence tomography (OCT) is a high‐resolution optical imaging technique that produces cross‐sectional images of living tissues using light in a manner similar to ultrasound. This prospective study evaluated the ability of OCT to identify the characteristics of laryngeal cancer and measure changes in the basement membrane, tissue microstructure, and the transition zone at the edge of tumors.

Cavernous carotid injury during functional endoscopic sinus surgery : Case presentations and guidelines for optimal management

Background Surgery in the parasellar and paranasal regions is technically challenging because of the complex anatomic relationships between the sphenoid sinus, cavernous sinus, optic nerve, and internal carotid artery. Normal anatomic variations and pathological changes can lead to disastrous outcomes including carotid artery injury. Methods We present two cases of carotid injury managed at our institution. The first case involves an elective endoscopic biopsy of a clival tumor encasing a friable carotid artery. The second case features a patient transferred emergently to our medical center when brisk bleeding was encountered during functional endoscopic sinus surgery (FESS). Both carotid injuries were managed via balloon embolization with close interaction between otolaryngology and interventional radiology. We review pertinent anatomic and surgical considerations as a backdrop to a treatment algorithm for cavernous carotid hemorrhage secondary to FESS complication. Results The treatment algorithm prevented mortality and minimized morbidity in the two cases considered. Conclusion Through rare, injury to the cavernous carotid during FESS can be managed successfully given efficient hemostasis and seamless cooperation among emergency room physicians, otolaryngologists, and interventional radiologists.

In vivo optical coherence tomography of the nasal mucosa.

Background Optical coherence tomography (OCT) is an emerging imaging modality that uses light to produce in vivo high-resolution cross-sectional images (7 μm) of tissues to depths of up to 3 mm. OCT is analogous to ultrasound, but relies on interferometry and low-coherence optical sources to produce images of tissue structure at the histological level. Methods In this study, OCT was used to image the mucosa overlying structures in the nasal cavity to obtain information regarding normative in vivo tissue microstructure. An OCT system using a Michaelson interferometer and a 1.3-μm broadband light source was incorporated into a fiber-optic imaging device that was inserted into the nasal cavity. Cross-sectional tomographic images of the anterior and posterior nasal septum, turbinates, and vestibule were acquired in 44 patients in either the office or the operating room during surgical endoscopy. Results OCT images of the nasal mucosa identified the distinct boundaries between the epithelium, lamina propria, and underlying bone/cartilaginous tissue. Within the lamina propria, features consistent with glands, ducts, and blood vessels were clearly identified. In patients who underwent decongestant therapy, before and after images showed distinct morphological changes in the mucosa. The thickness of the epithelium was tabulated, as well. Conclusion This study establishes the potential of using OCT to produce high-resolution images of the nasal mucosa. As an in vivo tissue microstructural imaging modality, OCT may be valuable in studying the impact of allergic and infectious disease on the nasal mucosa and monitoring its response to pharmacologic therapy.

Enhancement of Ad-p53 therapy with docetaxel in head and neck cancer.

Objective: The objective of this project was to determine the mechanisms in which docetaxel enhances Ad‐p53 tumor suppressive effects in head and neck cancer.

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

Background: The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system. Hypothesis: We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties. Study Design: Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes. Method: Polyester suture was acid hydrolyzed followed by reacting with 1‐ethyl‐3(‐3‐dimethylamino propyl carbodiimide) (EDAC) to create a suture‐EDAC intermediate. Next, selected proteins (horseradish peroxidase [HRP] or bovine serum albumin [BSA]) or cytokines (interleukin [IL]‐2 or interferon [IFN]‐γ) were reacted with the suture‐EDAC intermediate to test the covalent linkage of the selected protein or cytokine to suture. Functional activity of the linked proteins was measured spectrophotometrically. The linking of cytokines to suture was tested by stimulating normal donor peripheral blood lymphocytes (PBL) or HNSCC patients lymphocytes. The functional activity was confirmed by proliferation, enzyme linked immuno‐adsorbent assay (ELISA), and phenotype expression of T cells. Results: The conditions for optimally linking a protein to polyester suture were defined using HRP as a model protein. HRP retained its enzymatic activity. The optimal conditions for linking IL‐2 or IFN‐γ were defined. The covalently linked cytokines retained their immune enhancing properties for stimulating PBL and lymph node lymphocytes (LNL) from HNSCC patients to proliferate, generate a TH1 immunologic profile of cytokines (IL‐2, IL‐12, IFN‐γ), and stimulate T lymphocytes. Conclusion: This is the first report to demonstrate that cytokines can be covalently linked to surgical sutures and retain their immune‐stimulating properties. Proteins linked to suture also retained their enzymatic activity. The clinical implications of functionally active cytokines or proteins linked to surgical suture may be very significant in the future for manipulating the immune system in vivo or enhancing wound healing.

The effects of exogenous p53 overexpression on HPV‐immortalized and carcinogen transformed oral keratinocytes

Overexpression of p53 in head and neck carcinoma cells has demonstrated tumor growth suppression using in vitro and in vivo models. The effects of exogenous overexpression of wild‐type p53 on human papilloma virus (HPV)–immortalized and carcinogen transformed oral keratinocytes were determined.

Craniocervical Necrotizing Fasciitis Resulting from Dentoalveolar Infection

Craniocervical necrotizing fasciitis is a rare infectious process that can be life-threatening. It most commonly occurs as a result of a severe dentoalveolar infection. This article reviews the diagnosis, microbiology, anatomy, and pathophysiology behind this infectious process; the incidence; and the recommended treatments and therapies. It is hoped that this article provides the treating health care provider with an up-to-date review of this serious infectious process.

Bioactive Suture: A Novel Immunotherapy for Head and Neck Cancer

Purpose: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a TH1 immune response and to define the immune-stimulating half-life of the sutures. Experimental Design: Bioactive sutures of interferon γ (IFNγ), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor κB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. Results: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ generated a prolonged TH1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-κB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. Conclusions: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged TH1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.

In Vivo Characteristics of HPV-Immortalized and Carcinogen Transformed Oral Keratinocytes†

Purpose To characterize in vivo features of HPV‐immortalized and carcinogen transformed oral keratinocytes.