Faculty Bibliography

Oral squamous cell carcinoma (SCC) is characterized by invasive growth and the propensity for distant metastasis. The expression of specific adhesion receptors promotes defined interactions with the specific components found within the extracellular matrix (ECM). We previously showed that the alpha v beta 6 fibronectin receptor is highly expressed in oral SCC. Here we forced expression of the beta 6 subunit into poorly invasive SCC9 cells to establish the SCC9 beta 6 cell line and compared these two cell lines in several independent assays. Whereas adhesion to fibronectin was unaffected by the expression of beta 6, migration on fibronectin and invasion through a reconstituted basement membrane (RBM) were both increased. Function-blocking antibodies to alpha v beta 6 (10D5) reduced both migration on fibronectin and invasion through an RBM, whereas anti-alpha 5 antibodies were effective only in suppressing migration on fibronectin, not invasion. Expression of beta 6 also promoted tumor growth and invasion in vivo and modulated fibronectin matrix deposition. When grown as a co-culture with SCC9 cells, peritumor fibroblasts (PTF) organized a dense fibronectin matrix. However, fibronectin matrix assembly was decreased in co-cultures of SCC9 beta 6 cells and PTF and this decrease was reversed by the addition of function-blocking anti-alpha v beta 6 antibodies. The expression of beta 6 also resulted in increased levels of matrix metalloproteinase 3. Addition of the general MMP inhibitor GM6001 to SCC9 beta 6/PTF co-cultures dramatically increased fibronectin matrix assembly in a similar fashion as incubation with anti-alpha v beta 6 antibodies. These results demonstrate that expression of beta 6 (1) increases oral SCC cell motility and growth in vitro and in vivo; (2) negatively affects fibronectin matrix assembly; and (3) stimulates the expression and activation of MMP3. We suggest that the integrin alpha v beta 6 is a key component of oral SCC invasion and metastasis through modulation of MMP-3 activity

Isolated sphenoid sinus disease (ISSD) is a relatively uncommon disease. The present study is a retrospective review of 122 patients with ISSD who were treated at the Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital at Shanghai Medical University over a 25-year period. The diagnosis of ISSD was made on the basis of history and physical examination, signs and symptoms, nasal endoscopy, and computed tomography (CT) and magnetic resonance imaging (MRI). The final diagnosis of ISSD was confirmed by histopathologic and microbiological examinations of the surgical specimens. The pathological findings in this study included sphenoid cyst (47 cases), sphenoid sinusitis (31 cases), fungal disease (19 cases), inverted papilloma (4 cases), sphenochoanal polyp (1 case), foreign body (8 cases), malignant tumors (8 cases), and others (4 cases). The most common initial symptom was headache, followed in decreasing order by visual changes, cranial nerve palsies, and nasal symptoms. The more frequent use of routine CT and MRI scanning, as well as endoscopy, in the diagnosis of sinus disease has led to an increase in the early diagnosis of ISSD. The recent advances in endoscopic sphenoidotomy has allowed for relatively safe and immediate treatment of ISSD, preventing late extension into adjacent vital structures, which is commonly fatal. Endoscopic surgery also enables the surgeon to make a precise pathological diagnosis

BACKGROUND: Few sinonasal malignancies can manifest, histologically, as clear cell neoplasia. The most likely such tumor to be encountered is metastatic renal cell carcinoma. Primary sinonasal tumors that can appear as clear cell malignancies include squamous cell carcinoma and mucoepidermoid carcinoma. Primary salivary clear cell carcinoma occurs almost exclusively in the oral cavity and has not been described in the nasal cavity. OBJECTIVE: To report a unique sinonasal clear cell malignancy that mimicked metastatic renal carcinoma. STUDY DESIGN: Case report. OUTCOME MEASUREMENTS: Radiography, histology, histochemistry, immunohistochemistry, and electron microscopy. RESULTS: Histologically, the tumor was identical to renal cell carcinoma. No evidence of renal malignancy was found by abdominal computed tomographic scan or gadolinium-enhanced magnetic resonance imaging. Histochemistry confirmed the presence of tumor glycogen but no mucin. Immunohistochemistry confirmed strong expression of low- and high-molecular-weight keratin and S100, and no vimentin expression. Electron microscopy showed tumor myofibroblastic differentiation and cytoplasmic glycogen, neutral lipid vacuoles, and cholesterol. CONCLUSIONS: There was no clinical evidence of renal cell carcinoma. The immunohistochemical and ultrastructural findings were inconsistent with the diagnosis of renal cell carcinoma and showed features also inconsistent with the diagnosis of primary salivary clear cell carcinoma. We therefore conclude that this tumor represents a new and distinct entity, notable in its presentation as a 'counterfeit renal cell carcinoma.'

OBJECTIVES/OBJECTIVE:To report recurrent uveitis as a manifestation of poststreptococcal syndrome and discuss a role of adenotonsillectomy as a treatment option. STUDY DESIGN/METHODS:Case study. METHODS:A case report of a 6-year-old, otherwise healthy girl with group A streptococcal uveitis managed successfully with adenotonsillectomy. RESULTS:In the year after surgery there were only two episodes of uveitis, contrasted with a preoperative 3-year history of 8 to 10 annual episodes despite corticosteroid therapy. Moreover, as a result of the postoperative improvement the child was able to avoid impending methotrexate therapy. CONCLUSIONS:Although the role of tonsillectomy in managing poststreptococcal uveitis is unknown, our results suggest a positive impact independent of the baseline tonsillitis frequency. Otolaryngologists should be aware of these uncommon sequelae of streptococcal infection and the potential role of tonsillectomy in treatment.

BACKGROUND: Complete circumferential pharyngoesophageal reconstruction has undergone remarkable changes and developments during the last three decades. Gastric transposition and microvascular techniques are the standards of care. However, in cases of failure, or where other factors such as severe comorbidities prevent the use of microvascular techniques, reconstruction with local flaps provide a reliable option. We have used the Wookey flap technique in six patients with complete circumferential loss of the pharynx and upper esophagus. To make the procedure more reliable, we added a 'delay' stage. METHODS: Retrospective review of charts of six Wookey-type reconstructions of the pharynx and upper esophagus done in our department at SUNY-HSC, Brooklyn, and The Long Island College Hospital. RESULTS: Five of the six patients had successful reconstruction of complete circumferential pharyngoesophageal resection. All five resumed oral alimentation. The flap failed in one patient. CONCLUSIONS: The Wookey flap may still provide surgeons with a 'last resort' reconstructive option after complete, circumferential pharyngoesophageal resection

The strength of the connection between two neurons can be modified by activity, in a way that depends on the timing of neuronal firing on either side of the synapse. This spike-timing-dependent plasticity (STDP) has been studied by systematically varying the intervals between pre- and postsynaptic spikes. Here we studied how STDP operates in the context of more natural spike trains. We found that in visual cortical slices the contribution of each pre-/postsynaptic spike pair to synaptic modification depends not only on the interval between the pair, but also on the timing of preceding spikes. The efficacy of each spike in synaptic modification was suppressed by the preceding spike in the same neuron, occurring within several tens of milliseconds. The direction and magnitude of synaptic modifications induced by spike patterns recorded in vivo in response to natural visual stimuli were well predicted by incorporating the suppressive inter-spike interaction within each neuron. Thus, activity-induced synaptic modification depends not only on the relative spike timing between the neurons, but also on the spiking pattern within each neuron. For natural spike trains, the timing of the first spike in each burst is dominant in synaptic modification