Faculty Bibliography

Because primary myelofibrosis (PMF) originates at the level of the pluripotent hematopoietic stem cell (HSC), we examined the effects of various therapeutic agents on the in vitro and in vivo behavior of PMF CD34(+) cells. Treatment of PMF CD34(+) cells with chromatin-modifying agents (CMAs) but not hydroxyurea, Janus kinase 2 (JAK2) inhibitors, or low doses of interferon-α led to the generation of greater numbers of CD34(+) chemokine (C-X-C motif) receptor (CXCR)4(+) cells, which were capable of migrating in response to chemokine (C-X-C motif) ligand (CXCL)12 and resulted in a reduction in the proportion of hematopoietic progenitor cells (HPCs) that were JAK2V617F(+). Furthermore, sequential treatment of PMF CD34(+) cells but not normal CD34(+) cells with decitabine (5-aza-2'-deoxycytidine [5azaD]), followed by suberoylanilide hydroxamic acid (SAHA; 5azaD/SAHA), or trichostatin A (5azaD/TSA) resulted in a higher degree of apoptosis. Two to 6 months after the transplantation of CMAs treated JAK2V617F(+) PMF CD34(+) cells into nonobese diabetic/severe combined immunodeficient (SCID)/IL-2Rγ(null) mice, the percentage of JAK2V617F/JAK2(total) in human CD45(+) marrow cells was dramatically reduced. These findings suggest that both PMF HPCs, short-term and long-term SCID repopulating cells (SRCs), are JAK2V617F(+) and that JAK2V617F(+) HPCs and SRCs can be eliminated by sequential treatment with CMAs. Sequential treatment with CMAs, therefore, represents a possible effective means of treating PMF at the level of the malignant SRC.

Cochlear implant (CI) users' spectral resolution is limited by the number of implanted electrodes, interactions between the electrodes, and the underlying neural population. Current steering has been proposed to increase the number of spectral channels beyond the number of physical electrodes, however, electric field interactions may limit CI users' access to current-steered virtual channels (VCs). Current focusing (e.g tripolar stimulation) has been proposed to reduce current spread and thereby reduce interactions. In this study, current steering and current focusing were combined in a four-electrode stimulation pattern, i.e quadrupolar virtual channels (QPVCs). The spread of excitation was measured and compared between QPVC and Monopolar VC (MPVC) stimuli using a forward masking task. Results showed a sharper peak in the excitation pattern and reduced spread of masking for QPVC stimuli. Results from the forward masking study were compared with a previous study measuring VC discrimination ability and showed a weak relationship between spread of excitation and VC discriminability. The results suggest that CI signal processing strategies that utilize both current steering and current focusing might increase CI users' functional spectral resolution by transmitting more channels and reducing channel interactions.

The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorgammaT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes

BACKGROUND: BRAF mutations activate the mitogen-activated protein kinase pathway and often confer an aggressive thyroid cancer (TC) phenotype. Spry2 is an inducible negative feedback regulator of the mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to investigate the role of Spry2 in TC. METHODS: TC cell lines were analyzed for Spry2 expression and MAPK pathway activation. Cells were treated with MEK inhibitor and Spry2 small hairpin RNA. Cells were analyzed for Spry2 expression and MEK/ERK phosphorylation (pMEK, pERK). Thirty human papillary TCs were analyzed for mitogen-activated protein kinase pathway activating mutations and Spry2 expression. RESULTS: Increased baseline pMEK levels and Spry2 expression was found in BRAF V600E mutant (BRAF+) cells. MEK inhibition in BRAF+ cells showed decreased Spry2 expression and decreased pMEK/pERK levels. From our tissue samples, 10 papillary TCs had BRAF mutation, and increased Spry2 expression was found only in BRAF+ tumors. CONCLUSION: Spry2 expression correlates with BRAF status in vitro and in human tissue. Spry2 may serve as a negative feedback regulator of the mitogen-activated protein kinase pathway in BRAF+ TC. Increased Spry2 expression may serve as a surrogate marker of mitogen-activated protein kinase pathway activation with prognostic and therapeutic implications

BACKGROUND: The 2009 ATA Guidelines state 'lobectomy alone may be sufficient treatment for small (<1 cm), low risk, unifocal, intrathyroidal papillary carcinomas in the absence of . . . nodal metastases.' We determined how often these criteria are satisfied, and whether tumor size alone can dictate operative management. METHODS: Medical records of 346 patients with well-differentiated thyroid cancer (WDTC) who underwent thyroidectomy from January 1, 2007 to November 10, 2009, were reviewed. There were 130 patients with tumors </=1 cm and negative lateral nodes. Pathology reports were reviewed to identify adverse features including multifocality, extrathyroidal extension, vascular invasion, and central node metastases. RESULTS: Eighty-four percent underwent total thyroidectomy and 16% central node dissection. All but 2 patients had papillary cancer. Sixty-one percent with cancers 6-10 mm (group 1) had adverse pathologic features compared with 32% with cancers <6 mm (group 2). Multifocality was most common: 55% in group 1 versus 32% in group 2 (P = .004). Positive central nodes were identified in 23% of group 1 versus 4% of group 2 (P = .004). Of patients in group 1, 88% had positive or suspicious fine-needle aspiration biopsy (FNAB) preoperatively. CONCLUSION: We recommend that total thyroidectomy be considered as the initial operation for thyroid tumors 6-10 mm in size in which the preoperative FNAB is diagnostic or suspicious for WDTC

OBJECTIVE: To systematically review outcomes of reinnervation techniques for the management of unilateral vocal fold paralysis (UVFP). DATA SOURCES: Medline and Cochrane databases for English-language studies published between 1966 and 2009 on the surgical management of UVFP. REVIEW METHODS: Studies were excluded if they reported on bilateral vocal fold paralysis, used nonhuman subjects, or did not assess clinical outcomes. Outcomes of interest were visual analysis, acoustic analysis, perceptual analysis, and electromyography. RESULTS: Of 686 initial studies, 14 studies encompassing 329 patients were eligible for analysis. All studies had a case-series design. Of reported patients, 60.2 percent were men, with mean age of 51 years (range, 12-79 years). The most common reinnervation technique was ansa cervicalis-to-recurrent laryngeal nerve (RLN), which was most commonly performed after thyroidectomy (43.5%). Other techniques with reportable outcomes included primary RLN anastomosis, ansa-to-RLN combined with cricothyroid muscle-nerve-muscle pedicle, ansa-to-thyroarytenoid neural implantation, ansa-to-thyroarytenoid neuromuscular pedicle, and hypoglossal-to-RLN. Median postsurgical follow-up was 12 months, and mean time to first signs of reinnervation was 4.5 months (SD 2.9 months). Visual analysis of glottic gap showed the greatest mean improvement with ansa-to-RLN, from 2.25 (SD 0.886) to 0.75 (SD 0.886) mm (P < 0.01). Acoustic analysis showed greatest improvement with neural implantation, with a change in mean phonation time from seven (SD 1.22) to 16 (SD 5.52) seconds (P < 0.01). Perceptual analysis and electromyography demonstrated improvement in all studies. CONCLUSION: Reinnervation is effective in the management of UVFP, although the specific method may be dictated by anatomical limitations. Prospective studies utilizing uniform and consistent outcome parameters are necessary.

Vocal fold injection is a procedure that has over a 100 year history but was rarely done as short as 20 years ago. A renaissance has occurred with respect to vocal fold injection due to new technologies (visualization and materials) and new injection approaches. Awake, un-sedated vocal fold injection offers many distinct advantages for the treatment of glottal insufficiency (vocal fold paralysis, vocal fold paresis, vocal fold atrophy and vocal fold scar). A review of materials available and different vocal fold injection approaches is performed. A comparison of vocal fold injection to laryngeal framework surgery is also undertaken. With proper patient and material selection, vocal fold injection now plays a major role in the treatment of many patients with dysphonia

INTRODUCTION: The current study seeks to provide preliminary data regarding this central, adaptive response during tongue motor tasks utilizing functional magnetic resonance imaging (fMRI) before and after glossectomy. METHODS: Six patients, with confirmed histological diagnoses of oral tongue cancer, underwent fMRI before and 6 months after partial glossectomy. These data were compared to nine healthy controls. All subjects performed three tongue motor tasks during fMRI: tongue tapping (TT), dry swallow (Dry), and wet swallow (Wet). RESULTS: Following surgery, increased activation was subjectively observed in the superior parietal lobule, supplementary motor area, and anterior cingulate. Region of interest (ROI) analysis of the precentral gyrus confirmed increased cortical activity following surgery. In addition, comparisons between pre-surgical scans and controls suggested the dry swallow task was sensitive to elicit tongue-related activation in the precentral gyrus (p </= 0.05). CONCLUSIONS: The adaptive changes in the cortex following partial glossectomy reflect recruitment of the parietal, frontal, and cingulate cortex during tongue motor tasks. In addition, post-operative activation patterns more closely approximated control levels than the pre-operative scans. Furthermore, the dry swallow task appears most specific to elicit tongue-related cortical activity

OBJECTIVE: To demonstrate similar improvement in pediatric sleep-disordered breathing (SDB) as determined by polysomnography (PSG) with microdebrider-assisted partial intracapsular tonsillectomy and adenoidectomy (PITA) versus Bovie electrocautery complete tonsillectomy and adenoidectomy (T&A). METHODS: In this retrospective cohort study, 30 children found to have SDB by PSG who have undergone either PITA (15 participants) or T&A (15 participants) as treatment were evaluated with standardized history and physical examination and unattended home overnight PSG. RESULTS: Median change in apnea-hypopnea index (AHI) was 1.7 (-4.9 to 29.8) for the PITA group and 2.3 (-10.9 to 64.1) for the T&A group, although there was substantially more variability in the T&A group. A mixed linear model evaluating the relation of surgical group with change in AHI demonstrated no significant differences in group means (F[1,13]=0.31, P=.590) but the variances differed significantly (residual likelihood ratio chi-square=5.24, df=1, P=.022). Five of 15 (33%) PITA patients and 4 of 15 (27%) T&A patients had postoperative AHI scores of </=5; this difference was not statistically significant (Fisher exact test P=1.000). There was no significant interaction or substantial confounding effect of age, sex, race, preoperative tonsil size, preoperative AHI, or body mass index in the model relating surgery type to reduction of postoperative AHI to </=5. CONCLUSIONS: Our study demonstrates no clinically or statistically significant differences in PSG and clinical outcomes between PITA and T&A for treatment of pediatric SDB in otherwise healthy children

The nose is the most prominent of all facial structures and is susceptible to many types of trauma. All soft tissue injuries of the nose have the potential to distort its appearance and adversely affect the patient's self-image and self-esteem. Once life-threatening injuries are stabilized, a careful history and physical exam should be completed and treatment individualized. The ultimate objective of treatment is to achieve both functional and cosmetic restoration with timely diagnosis and repair. Immediate nasal reconstruction is ideal when medically possible because this decreases long-term sequelae