Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer-associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CAFs promoted HNSCC cell proliferation, in vitro cell migration, cell invasion and chemotherapy resistance, compared to normal fibroblasts. Furthermore, examination of the in vivo impact of CAF pathophysiology in the tumor microenvironment in animal xenograft models revealed that HNSCC cell lines in combination with CAFs promoted tumor growth and increased incidence of lymphovascular metastasis as compared to injection of tumor cells or CAF cells alone. Using pharmacological and genetic alterations, we mechanistically demonstrate the critical importance of BDNF-TrkB signaling in the tumor microenvironment. These investigations further support the rationale for BDNF/TRKB targeted therapy against in the treatment of HNSCC.

Sinonasal adenocarcinoma: a 16-year experience at a single institution.

BACKGROUND: Adenocarcinoma is a rare tumor of the sinonasal tract. The purpose of this study was to characterize a single institution's experience with this malignancy. METHODS: Retrospective review was performed of patients with adenocarcinoma of the sinonasal tract from 1993 to 2009. Demographic data, disease presentation, treatment, and survival rates were collected and evaluated. RESULTS: We identified 66 patients with sinonasal adenocarcinoma; 48 were men and 18 women. Average age at time of diagnosis was 57.1 years (range, 20-88 years), and median follow-up was 55.3 months (range, 1-238 months). The ethmoid sinus (38%) and nasal cavity (36%) were the most common sites of origin. Nasal obstruction (36%), epistaxis (30%), and nasal discharge (21%) were the most common presenting symptoms. Fifty-one percent of patients presented with T1 or T2 tumors. Surgery was the primary form of treatment in 81% of patients. Twenty-six percent of surgical patients underwent an endoscopic tumor resection. Adjuvant radiation was utilized in 50% of patients and chemotherapy in 10%. Recurrence was seen in 24 patients (37%): 29% recurred locally and 7.6% recurred distantly. The overall 5-year survival was 65.9%. Survival was decreased significantly in patients with T4 tumors (p < .05), high-grade histology (p < .05), and sphenoid sinus involvement (p < .05). Survival was not affected by surgical approach between endoscopic and open approaches (p = .76). CONCLUSION: Sinonasal adenocarcinomas are commonly identified in the sinonasal cavity and are associated with a relatively favorable prognosis, despite a substantial local failure rate of 30%. Advanced-stage tumors, sphenoid sinus and skull base invasion, and high-grade histology portend poor prognosis. In our experience, endoscopic resection was not associated with adverse outcomes and suggests that this minimally invasive approach can provide acceptable oncologic outcomes in selected patients.

Multimodality treatment for sinonasal neuroendocrine carcinoma.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the paranasal sinuses is rare, accounting for 5% of sinonasal malignancies. The purpose of this study was to assess prognostic factors and survival rates for sinonasal NEC. METHODS: A retrospective review of patients with NEC treated from 1990 to 2004 was performed. Patient demographics, TNM classification, treatment modality, recurrences, and survival were evaluated. RESULTS: NEC was identified in 28 patients; the most common primary site was the ethmoid sinuses. Most patients presented with advanced tumors; few had regional or distant metastasis. Local recurrence rate was 21%. Five-year overall survival (OS) and disease-specific survival (DSS) rates were 65% and 78%, respectively. Response to chemotherapy predicted for improved survival, although no differences in outcomes were noted between definitive management strategies. CONCLUSION: NEC of the paranasal sinuses is an exceedingly rare malignancy of the paranasal sinuses. Our data suggests definitive management with surgery or radiotherapy offers durable control. The response to chemotherapy may predict for overall outcomes.

Theraputic targeting of Trk supresses tumor proliferation and enhances cisplatin activity in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a biologically aggressive disease that has been modestly impacted by improvements in therapeutic strategies. Several lines of evidence support the role of TrkB for invasion and metastasis in various solid tumor models, and we have shown an important function of this receptor in HNSCC tumor biology. Therapeutic modulation of TrkB function has been supported in the literature by the development of small molecule inhibitors (SMI) with minimal success. To assess the validity of targeting TrkB in HNSCC, we tested a novel agent, AZ64 and show significant dose and time-dependent inhibition of cellular proliferation in cell lines. Genetic studies revealed the specificity of this compound for the TrkB receptor, as exposure of cells that had genetic suppression of TrkB did not demonstrate abrogated oncogenic signaling. We next assessed the impact of AZ64 as a chemotherapy-sensitizer and identified an enhancement of cisplatin-mediated anti-proliferation across all cell lines. We then demonstrated that AZ64 can overcome chemotherapy resistance in a novel model of cisplatin resistance in HNSCC. Modulation of the pro-oncogenic STAT3 and Src pathways was identified, suggesting molecular mechanisms of action for AZ64. In this study, we demonstrate the feasibility of targeting TrkB and suggest a novel approach for the treatment of some chemotherapy-resistant HNSCC.

Comparison of adenoidectomy methods: examining with digital palpation vs. visualizing the placement of the curette.

OBJECTIVE: To evaluate the effectiveness of adenoidectomy by defining the remnant volume and localization in nasopharynx, following being satisfied with completeness of removal of the adenoid tissue with digital palpation. METHODS: A prospective study conducted on 99 patients undergoing adenoidectomy+/-tonsillectomy. The main mass of the patient's adenoid tissue was removed with a sharp adenoid curette without visualization and the surgeon was allowed to palpate the adenoid bed and repeat the curettage until satisfied with completeness of removal. Then nasopharynx was visualized with a laryngeal mirror for defining the anatomical localization of the residual adenoid tissue and curettage completed under indirect mirror visualization. The volumes of the adenoid tissue excised at both stages were measured. RESULTS: By blunt curettage and digital palpation, only 20.2% of the patients (20) had no residual adenoid tissue. In patients who had residual adenoid tissue, the proportion of the median percentage of residual adenoid tissue to total adenoid tissue was 19.98% (range 3.22-50%). The anatomical localization of the residual adenoid tissue were, along the torus tubarius on either side of the nasopharynx in 9 (11.4%), on the pharyngeal roof near choanal openings in 64 (81%), along the torus tubarius on either side of the nasopharynx+on the pharyngeal roof near choanal openings in 5 (6.3%), and on the pharyngeal roof near choanal openings+on the posterior wall of nasopharynx in 1 (1.3%) patients. There was no difference found among surgeons in the percentage and the location of the residue left (p>0.05). CONCLUSION: Digital palpation is not a dependable technique and visualization of the nasopharynx is crucial for a complete adenoidectomy.

Comparing the effectiveness of "plasma knife" tonsillectomy with two well-established tonsillectomy techniques: cold dissection and bipolar electrocautery. A prospective randomized study.

OBJECTIVE: To evaluate the effectiveness of a new device "plasma knife" for tonsillectomy by comparing to two well-established tonsillectomy techniques: cold dissection, and bipolar electrocautery. METHODS: A prospective, randomized study conducted on 110 patients undergoing tonsillectomy. Subjects were randomized to plasma knife (PKT), cold dissection (CDT) and bipolar electrocautery (BET) groups. Operative time, intraoperative blood loss and postoperative complications were recorded. Pain/discomfort level of patients and healing time of the tonsillar fossae were assessed postoperatively. Data were recorded and statistically analyzed. RESULTS: Operative time with plasma knife and bipolar electrocautery were associated with a significant decrease in operative time compared to cold dissection (p<0.05). Intraoperative blood loss was significantly decreased with plasma knife, compared to cold dissection and bipolar electrocautery (p<0.05). Less postoperative pain was observed with plasma knife compared to bipolar electrocautery but more postoperative pain was observed with both compared to CDT (p<0.05). Postoperative healing time was longer with plasma knife and bipolar electrocautery, compared to cold dissection (p<0.05). CONCLUSION: Plasma knife is a useful and safe device in tonsillectomy. Its use reduces intraoperative blood loss and provides a fast tonsillectomy with acceptable morbidity.

Role of Helicobacter pylori in pathogenesis of upper respiratory system diseases.

Helicobacter pylori (H. pylori) is one of the frequently encountered micro-organisms in the aerodigestive tract. Although infections caused by H. pylori are this common, the exact mode of transmission has not been fully understood yet. Oral-oral, fecal-oral and gastrointestinal-oral routes are the possible modes of transmission. This infection is usually acquired in childhood and may persist for the whole life of the patient. However, about 80% of the infected humans are asymptomatic. Human stomach was considered to be the only reservoir of H. pylori until bacteria were discovered in human dental plaque, in oral lesions, in saliva, in tonsil and adenoid tissue. It is suggested that H. pylori enters the nasopharyngeal cavity by gastroesophageal reflux and colonize in the dental plaques, adenoid tissues and tonsils. From these localizations, the bacteria ascend to the middle ear and to the paranasal sinuses directly or by the reflux again and may trigger some diseases, including otitis, sinusitis, phyrangitis, laryngitis and glossitis. But still, the exact mechanism remains unclear.