Emiro Caicedo-Granados

Reverse rotation flap for reconstruction of donor site after vascular pedicled nasoseptal flap in skull base surgery.

Endonasal skull base surgery is growing exponentially as a subspecialty. In recent years, advances in endoscopic techniques and intraoperative navigation systems have allowed us to expand the indications of endoscopic skull base surgery. Major skull base centers worldwide are addressing larger and more complex lesions using endoscopic techniques. As a consequence, the skull base defects are more challenging to reconstruct. In this report, we present a novel technique to reconstruct the denuded septum remaining after the use of the vascular pedicled nasoseptal flap. Laryngoscope, 2010

Oncologic and Functional Outcomes of Partial Laryngeal Surgery for Intermediate-Stage Laryngeal Cancer

Objective To evaluate the oncologic and functional outcomes of partial laryngeal surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell carcinoma (LSCC). Study Design Historical cohort study. Setting Single tertiary care center. Subjects and Methods Retrospective review of oncologic and functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC patients who underwent TLM or SCL from 1998 to 2010. Results Sixty patients were included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%), respectively, for recurrence-free survival (RFS). There was no difference between the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of patients avoided adjuvant therapy. Communication Scale and Functional Outcome Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97% and 91% of patients, respectively, reflecting functional voice and swallowing postoperatively. Eighty-eight percent of patients retained a functional larynx. Conclusion PLS provides excellent oncologic and functional outcomes for intermediate-stage LSCC and should be considered an alternative to chemoradiation or total laryngectomy in selected patients.

Minimally invasive surgery for parapharyngeal space tumors

Parapharyngeal space (PS) tumors are surrounded by critical anatomical structures. Resection is often challenging due to limited surgical exposure. Herein, we report a novel transcervical, minimally invasive, video‐assisted technique that facilitates the resection of PS lesions.

The Effect of Indomethacin on Paclitaxel Sensitivity and Apoptosis in Oral Squamous Carcinoma Cells: The Role of Nuclear Factor–κB Inhibition

OBJECTIVE To investigate new strategies to intensify chemosensitivity in head and neck squamous cell carcinoma. DESIGN Oral squamous carcinoma cells were examined for nuclear factor-κB (NF-κB) activation and binding activity by paclitaxel, an agent currently used in head and neck cancer chemotherapy. Electromobility shift assays were used to assess the effect of indomethacin on NF-κB binding activity. Cell proliferation assays were used to study cell sensitivity to paclitaxel. To examine whether cytotoxicity could be increased by specifically inhibiting NF-κB, a dominant negative cell line, inhibitor kappa B-alpha (IκBα), was stably expressed in CA-9-22 cells. RESULTS Paclitaxel possessed the capacity to functionally activate NF-κB, as demonstrated by luciferase reporter gene assays and electromobility shift assay. Indomethacin was able to inhibit paclitaxel-mediated NF-κB activation and promote apoptosis of paclitaxel-treated cells at 24 hours. Indomethacin augmented the paclitaxel cell-killing effect. The dominant negative IκBα cell line exhibited increased chemosensitization to paclitaxel by 2- to 10-fold. CONCLUSIONS Paclitaxel has the capacity to activate NF-κB in oral squamous carcinoma cells. Indomethacin can reverse this activation to decrease cell proliferation and increase apoptosis. Treatment strategies that combine paclitaxel with indomethacin may have therapeutic benefits attributable to paclitaxel chemosensitization through NF-κB inhibition.

Wild-type p53 reactivation by small-molecule Minnelide™ in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma

OBJECTIVES The incidence of high-risk human papillomavirus (HR-HPV) head and neck squamous cell carcinoma (HNSCC) continues to increase, particularly oropharyngeal squamous cell carcinoma (OPSCC) cases. The inactivation of the p53 tumor suppressor gene promotes a chain of molecular events, including cell cycle progression and apoptosis resistance. Reactivation of wild-type p53 function is an intriguing therapeutic strategy. The aim of this study was to investigate whether a novel compound derived from diterpene triepoxide (Minnelide™) can reactivate wild-type p53 function in HPV-positive HNSCC. MATERIALS AND METHODS For all of our in vitro experiments, we used 2 HPV-positive HNSCC cell lines, University of Michigan squamous cell carcinoma (UM-SCC) 47 and 93-VU-147, and 2 HPV-positive human cervical cancer cell lines, SiHa and CaSki. Cells were treated with different concentrations of triptolide and analyzed for p53 activation. Mice bearing UM-SCC 47 subcutaneous xenografts and HPV-positive patient-derived tumor xenografts were treated with Minnelide and evaluated for tumor growth and p53 activation. RESULTS In HPV-positive HNSCC, Minnelide reactivated p53 by suppressing E6 oncoprotein. Activation of apoptosis followed, both in vitro and in vivo. In 2 preclinical HNSCC animal models (a subcutaneous xenograft model and a patient-derived tumor xenograft model), Minnelide reactivated p53 function and significantly decreased tumor progression and tumor volume. CONCLUSION Triptolide and Minnelide caused cell death in vitro and in vivo in HPV-positive HNSCC by reactivating wild-type p53 and thus inducing apoptosis. In addition, in 2 HPV-positive HNSCC animal models, Minnelide decreased tumor progression and induced apoptosis.

Enforced expression of nuclear factor kappa B in p53 deficient keratinocytes induces cell cycle, angiogenic potential and tumorigenesis

Multiple genetic mutations with subsequent molecular events are required for progression of normal epithelial cells to cancer, with p53 mutations being a very common event in squamous carcinogenesis. Upregulation of nuclear factor kappa B (NF-κB) is an associated feature of malignancy, however studies have not examined purposeful overexpression of the NF-κB p65 subunit in in vitro models of oral carcinogenesis. Our objective is to demonstrate that NF-κB p65 transfection into p53 deficient Rhek keratinocytes produces carcinogenic progression. We constitutively over-expressed NF-κB p65 in Rhek keratinocytes, previously immortalized by SV 40 thus inactivating p53, and studied NF-κB dependent events. NF-κB p65 overexpression provided functional upregulation of NF-κB and produced cyclin D1-mediated proliferation and interleukin 8 transcription and secretion. Consequently, we demonstrated tumorigenesis in athymic mice with NF-κB p65 overexpressing cells. We conclude NF-κB p65 overexpression in p53 inactivated immortalized keratinocytes produces tumorigenesis, and that this single alteration in NF-κB expression on a p53 inactivated background is sufficient for squamous carcinogenesis features, thus providing evidence that p65 may act as a gain of function oncogene in this setting.

N-methylnitrosourea–induced carcinoma as a model for laryngeal carcinogenesis.

Preclinical animal models to study laryngeal cancer are nonexistent. The purpose of this study was to describe a novel mice laryngeal cancer model.

Imaging features of sinonasal tumors on positron emission tomography and magnetic resonance imaging including diffusion weighted imaging: A pictorial review

INTRODUCTION Sinonasal inflammatory conditions account for a major component of head and neck pathologies, whereas neoplasms involving the sinonasal region make up only 2-3% of all head and neck lesions. The symptoms of sinonasal tumors are nonspecific; imaging plays a critical role in distinguishing benign and malignant disease and may illustrate characteristic radiological features of specific sinonasal tumors. OBJECTIVE Aim was to determine the utilization of multimodality imaging, specifically the metabolic information provided by 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and diffusivity characteristics seen with diffusion weighted images (DWI) of magnetic resonance imaging (MRI), in a wide range of benign and malignant sinonasal tumors drawn from over 200 sinonasal lesions from our institution and supplemented by the literature. CONCLUSION In this pictorial essay, we have reviewed common imaging characteristics of frequently encountered in sinonasal tumors and divided them into benign and malignant categories to facilitate creation of focused differential diagnoses.

Partial Laryngeal Surgery for Intermediate Larynx Cancer

Objective: Chemoradiation trials over the past 2 decades have assumed that the primary surgical option for intermediate stage laryngeal cancer (T2-T3/N0-N1) was total laryngectomy. However, partial laryngeal surgery (PLS), including transoral laser microsurgery (TLM) and supracricoid partial laryngectomy (SCL), can provide sound oncologic and functional outcomes, often without adjuvant therapy. Method: We retrospectively evaluated oncologic and functional outcomes in laryngeal squamous cell carcinoma (LSCC) patients who underwent TLM or SCL from 1998-2010. Overall survival (OS) and recurrence-free survival (RFS) were calculated. The Communication Scale (CS) and Functional Outcome Swallowing Scale (FOSS) were used to evaluate speech and swallowing, respectively. Results: Eighty-one patients were analyzed with median follow-up of 31 months. Eighty-four percent were T2-T3/N0-N1. Two- and 5-year OS probabilities were 84.2% (95% CI: 73.0-91.0%) and 59.3% (95% CI: 41.4-73.3%), respectively. There was no difference between the TLM and SCL cohorts in OS (P = .781) or RFS (P = .456). Ninety-four percent of patients still had a larynx at median 31 months. Seventy-five percent of patients avoided adjuvant therapy, including 67% of TLM and 84% of SCL patients. CS and FOSS were 2-or-better in 95% and 88%, respectively, designating functional postoperative voice and swallowing. TLM patients were more likely to have a CS of 2-or-better postoperatively (P = .041). Conclusion: PLS can provide good oncologic and functional outcomes for intermediate stage LSCC and is an alternative to chemoradiation or total laryngectomy in select patients.