Marilene Wang

Rhinocerebral Mucormycosis: Evolution of the Disease and Treatment Options†

Rhinocerebral mucormycosis is recognized as a potentially aggressive and commonly fatal fungal infection. The classic presentation is involvement of nasal mucosa with invasion of the paranasal sinuses and orbit. Mucormycosis is most commonly seen in association with diabetic ketoacidosis, but disease demographics have changed with the onset of AIDS and the advent of powerful immunosuppressive drugs. Treatment includes aggressive debridement, systemic antifungal therapy, and control of underlying comorbid factors. Although surgical intervention remains essential, advances in medical therapy have permitted a more limited surgical approach to minimize functional loss without compromising survival. We present the UCLA experience with rhinocerebral mucormycosis from 1955 to 1995, with emphasis on the evolution of disease presentation and alternative treatment options.

Prevalidation of Salivary Biomarkers for Oral Cancer Detection

Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL). Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL. Results: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts. Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. Cancer Epidemiol Biomarkers Prev; 21(4); 664–72. ©2012 AACR.

Transsphenoidal Surgery for Prolactinomas

Dopamine agonist therapy is considered first-line treatment for the great majority of prolactinomas. Although highly effective in normalizing serum prolactin levels and reducing tumor size, in clinical practice, a significant proportion of patients may ultimately choose transsphenoidal surgery. Indications include dopamine agonist resistance, intolerance as a result of side effects or adverse reactions, severe apoplexy, cerebrospinal fluid leak, and patient preference. In all cases, the goal is cure: in terms of both tumor resection and restoration of endocrine function. Patient selection is paramount to achieving this goal. Patients with localized tumor without extension outside the sella or into neighboring structures have been shown to have greater rates of normoprolactinemia following surgical extirpation. Moreover, those that are treated at dedicated pituitary centers by surgeons that specialize in pituitary surgery also enjoy greater rates of remission following operative treatment. Closer consideration of the surgical prolactinoma population as a heterogeneous patient set with individual tumor and patient characteristics that may prognosticate who will respond best to transsphenoidal surgery will aid patient counseling and surgical decision making in the future.

Otolaryngic Manifestations of Cushing Disease

Cushing disease is a relatively rare cause of Cushing syndrome secondary to a hyperfunctioning pituitary adenoma. In addition to signs and symptoms of hypercortisolism, Cushing disease may present with diverse otolaryngic manifestations, which may guide diagnosis and management. We performed a retrospective chart review of patients who were found to have Cushing disease and who underwent transnasal transsphenoidal surgery for pituitary adenomas between January 1, 2007, and July 1, 2014, at a tertiary academic medical center. There were 37 consecutive patients in this series with Cushing disease caused by a pituitary adenoma. Fifteen (41%) patients complained of visual changes. Five (14%) patients suffered from obstructive sleep apnea. Four (11%) patients had thyroid disease. Other symptoms included hearing loss, vertigo, tinnitus, epistaxis, dysphagia, and salivary gland swelling. Although Cushing disease traditionally presents with classic Cushingoid systemic features, it also may present with various otolaryngic manifestations. A thorough workup by otolaryngologists is critical in the comprehensive management of these patients.

Sinonasal Mucosal Melanoma: 20-Year Experience at a Tertiary Referral Center:

Objectives: Sinonasal melanoma (SNM) is a rare cancer with extremely poor prognosis. Detecting melanoma on frozen section has historically been considered to be unreliable. A review of cases of SNM treated at a tertiary referral center was conducted with emphasis on investigating the correlation between detecting melanoma on frozen section and permanent analysis. Methods: An institutional review board (IRB)-approved search of the pathology database for cases of primary SNM treated between 1991-2011 was performed. The medical charts were then reviewed. Results: Fourteen cases of SNM were identified. Eleven arose from the nasal cavity, 2 arose from the maxillary sinus, and 1 from bilateral ethmoids. At average follow-up period of 22 mos (2-85 mos), 13 patients were alive. Five cases were free of disease (NED), 6 had recurrent disease (RD), and 3 had unknown disease status. Patients with NED presented at an average age 67 years (47-82 years). On pathological analysis, average melanoma size was 5.2cm (2-9cm), all had clear margins, 2 had perineural invasion (PNI), and 1 had lymphovascular invasion (LVI). Four received adjuvant radiation (XRT). Of the RD patients, average age was 63.7 years. On pathologic analysis, average size of the tumor was 2.3cm (0.5-3.5cm); margin status was positive in 2, clear in 2, and not evaluated in 2 cases. Ten cases had evaluation of intraoperative frozen sections. When compared with final pathology, FS correlated with permanent section 100% cases. One had LVI with PNI, and 5 cases received XRT. Conclusions: Based on this series, intraoperative frozen section analysis of SNM correlates well with final pathology.

Acute Sinusitis Following Endoscopic Skull Base Surgery

OBJECTIVE: Endonasal surgery of the cranial base requires extensive training in anatomy and endoscopic techniques. A training model for simulation of endoscopic surgery of the paranasal sinuses and cranial base was developed that 1) replicates the surgical experience and 2) provides a measurable learning curve. METHOD: The anatomical model is generated from CT data and has bone generated from a 3D printer and silicone applied to recreate nasal soft tissue. Design requirements were surgical simulation with real surgical instruments and the objective detection of injured structures at risk (orbit, dura, internal carotid artery, and optic nerve). RESULTS: Using this teaching model, it is possible to demonstrate a learning curve and track the progress of a surgeon (duration of surgery, number and location of injuries). Anatomical and pathological variations can be introduced to provide a varied surgical experience. CONCLUSION: This model replicates the surgical experience and allows the surgeon to monitor the learning curve. The use of actual surgical instruments provides realistic haptic feedback. Future trials will demonstrate the contribution of surgical simulation on surgical proficiency in the operating room.