Estimation of serotonin transporter parameters with 11C-DASB in healthy humans: reproducibility and comparison of methods.

UNLABELLED: The aim of the present study was to define the optimal analytic method to derive accurate and reliable serotonin transporter (SERT) receptor parameters with (11)C-3-amino-4-(2-[(dimethylamino)methyl]phenylthio)benzonitrile ((11)C-DASB). METHODS: Nine healthy subjects (5 females, 4 males) underwent two (11)C-DASB PET scans on the same day. Five analytic methods were used to estimate binding parameters in 10 brain regions: compartmental modeling with 1- and 2-tissue compartment models (1TC and 2TC), data-driven estimation of parametric images based on compartmental theory (DEPICT) analysis, graphical analysis, and the simplified reference tissue model (SRTM). Two variations in the fitting procedure of the SRTM method were evaluated: nonlinear optimization and basis function approach. The test/retest variability (VAR) and intraclass correlation coefficient (ICC or reliability) were assessed for 3 outcome measures: distribution volume (V(T)), binding potential (BP), and specific to nonspecific equilibrium partition coefficient (V(3)''). RESULTS: All methods gave similar values across all regions. The variability of V(T) was excellent (< or =10%) in all regions, for the 1TC, 2TC, DEPICT, and graphical approaches. The variability of BP and V(3)'' was good in regions of high SERT density and poorer in regions of moderate and lower densities. The ICC of all 3 outcome measures was excellent in all regions. The basis function implementation of SRTM demonstrated improved reliability compared with nonlinear optimization, particularly in moderate and low-binding regions. CONCLUSION: The results of this study indicate that (11)C-DASB can be used to measure SERT parameters with high reliability and low variability in receptor-rich regions of the brain, with somewhat less reliability and increased variability in regions of moderate SERT density and poor reproducibility in low-density regions.

Superior laryngeal nerve quantitative intraoperative monitoring is possible in all thyroid surgeries.

OBJECTIVES/HYPOTHESIS: To report normative electromyography (EMG) data on the external branch of the superior laryngeal nerve (EBSLN) and to compare this to analogous data of the recurrent laryngeal nerve (RLN) and vagus nerve (VN) during intraoperative neural monitoring (IONM) using both the standard monopolar stimulator probe and a novel bipolar stimulator probe. STUDY DESIGN: Prospective multiple tertiary care center study. METHOD: A prospective study of EBSLN, RLN and VN EMG data in 22 thyroid surgeries was performed. Subjects with preoperative vocal fold paralysis were excluded. Postoperative laryngoscopy was normal in all subjects. Normative EMG data were acquired using both a standard monopolar and a novel bipolar stimulator probe, as well as a novel endotracheal tube. Cricothyroid muscle (CTM) twitch response during EBSLN stimulation was analyzed. RESULTS: In 100% of cases, EBSLN was identified and quantifiable EMG response was observed. EMG amplitude did not change despite extensive nerve dissection and multiple nerve stimulations. EBSLN amplitude was similar for left and right sides for patients under age 50 and aged 50 or older, for both genders, and with monopolar and bipolar stimulators. CONCLUSIONS: Intraoperative neural monitoring may be used to safely assist in EBSLN identification during thyroid surgery in 100% of patients. A novel endotracheal tube allows for quantifiable EBSLN EMG activity in 100% of cases. Monopolar and bipolar stimulator probes produce similar EMG data. LEVEL OF EVIDENCE: 4.

Electrophysiologic monitoring characteristics of the recurrent laryngeal nerve preoperatively paralyzed or invaded with malignancy.

OBJECTIVE: To elucidate electrophysiologic responses of the recurrent laryngeal nerves that were preoperatively paralyzed or invaded by malignancy and to use this information as an added functional parameter for intraoperative management of recurrent laryngeal nerves with malignant invasion. STUDY DESIGN: Case series with chart review. SETTINGS: Academic, tertiary care center. SUBJECTS AND METHODS: All consecutive neck surgeries with nerve monitoring performed by senior author (GWR) between December 1995 and January 2007 were reviewed after obtaining Institutional Review Board approval from Massachusetts Eye and Ear Infirmary Human Subjects Committee and the Partners Human Research Committee. Electrophysiologic parameters in all cases with preoperative vocal cord paralysis/paresis, and the recurrent laryngeal nerve invasion by cancer, were studied. RESULTS: Of the 1138 surgeries performed, 25 patients (2.1%) had preoperative vocal cord dysfunction. In patients with preoperative vocal cord dysfunction, recognizable recurrent laryngeal nerve electrophysiologic activity was preserved in over 50% of cases. Malignant invasion of the recurrent laryngeal nerve was found in 22 patients (1.9%). Neural invasion of the recurrent laryngeal nerve was associated with preoperative vocal cord paralysis in only 50% of these patients. In nerves invaded by malignancy, 60% maintained recognizable electrophysiologic activity, which was more commonly present and robust when vocal cord function was preserved. CONCLUSION: Knowledge of electrophysiologic intraoperative neural monitoring provides additional functional information and, along with preoperative vocal cord function information, aids in constructing decision algorithms regarding intraoperative management of the recurrent laryngeal nerve, in prognosticating postoperative outcomes, and in patient counseling regarding postoperative expectations.

Reduced Cx43 gap junction plaque expression differentiates thyroid carcinomas from benign disease.

OBJECTIVE: To investigate the expression of connexin 43 (Cx43) in benign vs malignant thyroid tissue for potential use as a diagnostic marker. DESIGN: Retrospective study. SUBJECTS: Thyroid specimens were obtained from 50 patients who underwent partial or total thyroidectomy at the New York Eye and Ear Infirmary, New York, New York, between 1999 and 2007. They included goiter (n = 5), follicular adenoma (n = 15), follicular carcinoma (n = 17), papillary thyroid carcinoma (PTC) (n = 7) and the follicular variant of PTC (n = 6). INTERVENTIONS: Tissue sections (5 µm) were immunohistochemically stained for Cx43 with the avidin-biotin-peroxidase method using an automated stainer. The Cx43 membrane staining pattern was evaluated. RESULTS: Twenty-three of 30 cancer specimens (77%) revealed a loss of Cx43 plaque staining at the cellular membrane compared with only 3 of 20 benign specimens (15%). Among the malignant specimens, loss of Cx43 plaque staining was observed in 11 of 17 follicular carcinomas (65%), 5 of 6 follicular variants of PTC (83%), and 7 of 7 PTCs (100%). In contrast, only 3 of 15 adenomas (20%) and 0 of 5 goiter samples demonstrated loss of Cx43 plaque staining at the cell membrane. CONCLUSION: Our data provide evidence that the absence of Cx43 plaque staining is associated with thyroid cancer and thus holds potential clinical utility as a marker for malignant disease.

Conservative management of advanced external auditory canal cholesteatoma.

OBJECTIVE: To investigate the spectrum of disease presentation and clinical management of primary external auditory canal cholesteatoma (EACC). STUDY DESIGN: Case series with chart review. SETTING: Specialty teaching hospital. SUBJECTS AND METHODS: Ten cases of primary EACC were identified in nine patients treated over 14 years (1995-2009). Cases were reviewed with regard to demographics, presentation, physical examination, CT findings, and clinical management. RESULTS: The most common symptoms were otalgia and hearing loss, followed by otorrhea and tinnitus. Erosion was present in the mastoid air cells in seven patients, middle ear in six, temporomandibular joint in two, otic capsule in two, and fallopian canal in one patient. Eight of nine patients were managed with serial debridement. CONCLUSIONS: EACC is associated with adjacent bony erosion, most often involving the inferior EAC. Despite the potentially destructive nature of these lesions, most cases can be successfully managed with serial debridement.