[A Case of Oropharyngeal Large Cell Neuroendocrine Carcinoma].

The large cell neuroendocrine carcinoma (LCNEC) of the lung was first reported in detail by Travis et al. in 1991. Extrapulmonary LCNEC rarely occurs, and only 22 cases have been reported in the head and neck mucosal regions. Today LCNEC of the larynx is contained in the moderately differentiated/Grade 2 category. However some authors advocate that LCNEC of the larynx should be separated from this category because of the difference in the clinical manifestations and pathological features. Standard treatment for head and neck mucosal LCNEC (M-LCNEC) has not been confirmed. However we suggested the efficacy of postoperative chemotherapy for M-LCNEC. This report describes a case of an LCNEC of the oropharynx. The patient was a 64-year-old man. We treated him with surgery and chemoradiotherapy. He has been disease-free for 36 months after adjuvant-chemotherapy.

[Closed Septorhinoplasty for Caudal Septum Deviation: A Japanese Rhinologic Perspective].

Caudal septum deviation is one of the most difficult tasks in nasal surgeries even for the experienced surgeons. Correction of the deviated nose presents a challenge because frequently a functional as well as an aesthetic problem must be addressed. In patient with caudal septum deviation, a proper correction of the deviated septal cartilage is a critically important factor for surgical success. For successful correction of caudal septum deviation, the skill to precisely execute the surgical steps is required to alter and control the septum thorough a thorough understandings of nasal anatomy and physiology, accurate preoperative analysis and intraoperative diagnosis, together with an understanding of the physiology of cartilage and its healing. The closed (endonasal) septorhinoplasty approach provides a wide surgical filed that enables the surgeon to implement various surgical procedures. For correction of the caudal septal strut, placement of a batten graft on the concave side after scoring incisions can also be used, resulting in successful correction of caudal deviation. A functional septorhinoplasty with the ultimate purpose of improving nasal obstruction is expected to develop from the Japanese rhinologic perspective. In the current study, closed septorhinoplasty proved to be one of the most effective methods for correcting caudal septum deviation.

[Serological Study of Otitis Media with ANCA Associated Vasculitis (OMAAV)].

Otitis media related with ANCA associated vasculitis is an intractable condition conditions that is resistant to conventional conservative treatment or surgical treatments. The name "otitis media with ANCA associated vasculitis (OMAAV)" has been proposed as a new concept for this disease. In the present study, we examined the clinical feature of 14 cases of OMAAV. We also investigated the usefulness of combined tests for ANCA detection. There were 11 females and 3 males, with a median age of 68.5 years. PR3-ANCA was positively detected in 4 (28.6%) patients, MPO-ANCA was detected in 6 (42.9%), and 4 (28.6%) were both ANCAs negative. During the course 6 patients developed pachymeningitis and 5 patients developed facial palsy. Plasma samples from 14 OMAAV patients were tested for the presence of ANCAs with five detection methods (3 PR 3-ANCA kits (direct ELISA, capture ELISA, anchor ELISA), 2 MPO-ANCA kits (direct ELISA, capture ELISA)) and the indirect immunofluorescence (II) technique. Six patients (42.9%) were positive for ANCA in clinical examination (single EIA method), while ANCA was positively detected in 9 patients (64.3%) with combined methods. In ANCA negative cases, ANCA should also be tested with a different technique such as new generation ELISA and IIF.

Th17 cells contribute to nontypeable Haemophilus influenzae-specific protective immunity induced by nasal vaccination with P6 outer membrane protein and α-galactosylceramide.

Nasal vaccination is an effective therapeutic means of preventing upper respiratory infection. Recently, nasal vaccination with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and alpha-galactosylceramide (α-GalCer) was reported to induce NTHi-specific protective immunity. The present study investigated the role of the Th17 cells induced by nasal vaccination. Mice were immunized with P6 and α-GalCer, and their P6-specific immune responses were examined. Cytokine-producing cells were analyzed by flow cytometry, and expression of cytokines in P6-specific CD4+ T cells was determined by reverse transcription-polymerase chain reaction. Bacterial challenges were performed with live NTHi. To examine the role of Th17 cells, bacterial clearance was also evaluated after interleukin (IL)-17 neutralization. P6-specific nasal wash immunoglobulin (Ig) A and serum IgG were increased after immunization with P6 and α-GalCer. Specific IgA-producing cells increased markedly in the nasal passages (NPs) of the immunized mice. In addition to P6-specific Th1 and Th2 cells, IL-17-producing Th17 cells were induced in the NPs and spleen. Bacterial clearance was enhanced by nasal vaccination. Interestingly, impaired NTHi clearance was shown after IL-17 neutralization. These findings suggest that nasal vaccination with P6 and α-GalCer is an effective regimen for the induction of NTHi-specific protective immunity in the upper respiratory tract. In addition to antigen-specific secretory-IgA, specific Th17 cells induced by nasal vaccination contribute to protection against NTHi.

Clinical significance of elevated osteopontin levels in head and neck cancer patients.

OBJECTIVES: Osteopontin (OPN) is associated with several human malignancies, but the role of OPN in head and neck cancer (HNC) remains unclear. We investigated the clinicopathologic relevance of serum OPN levels in HNC patients. METHODS: Serum OPN levels in HNC patients were determined by quantitative sandwich enzyme immunoassay (EIA). OPN levels and their correlation with clinical features were examined. In addition, serum squamous cell carcinoma (SCC) antigen was examined simultaneously. RESULTS: The mean OPN level was significantly higher in HNC patients (99.5 ng/ml) than in control subjects (55.3 ng/ml). OPN levels were significantly higher in patients with advanced stage HNC than in patients with early stage HNC. OPN levels did not correlate with SCC antigen levels. CONCLUSIONS: OPN may play a role in the pathogenesis of head and neck cancer (HNC), and serum OPN may be a potential biomarker of HNC.

Successful treatment of nasal septum hemangioma with the Harmonic Scalpel: a case report.

Hemangioma of the nasal septum, known as "bleeding polyp," is an occasional lesion in adults. We report two cases of bleeding polyps, that were successfully treated by surgery using the Harmonic Scalpel (HS). Two women (aged 58 and 67 years) presented with unilateral nasal hemangioma, which was revealed by unilateral epistaxis. Both the women were treated by surgical excision using the HS under general and local anesthesia, respectively. Treatment involves surgical excision of the tumor including the mucosa and the underlying perichondrium. HS is an effective tool for the excision of bleeding polyps with less bleeding and less tissue injury.

Immunohistochemical detection of cervical lymph node micrometastases from T2N0 tongue cancer.

CONCLUSIONS: These results indicate that extensive, multiple cervical micrometastases occurred from an early stage in patients with T2N0 tongue cancer. The presence of micrometastases suggests the necessity of preventive neck dissection for Level I-IV nodes as a radical treatment. OBJECTIVE: Cervical lymph node metastases occur with a relatively high frequency in patients with T2N0 squamous cell carcinoma of the tongue, and control of the metastases greatly influences the prognosis of patients. In this study, micrometastases in the cervical lymph nodes were investigated to clarify the necessity and required extent of preventive neck dissection. MATERIAL AND METHODS: We investigated micrometastases in 24 subjects who had previously been diagnosed with T2N0 tongue cancer. We performed immunostaining with anti-cytokeratin antibody cocktail AE1/AE3 of sections of 401 paraffin-embedded lymph nodes obtained from these patients. RESULTS: Micrometastases were observed in 14 patients (58%) and were most abundant in Level II nodes (n=11; 46%). Micrometastases were observed in the Level IV nodes of 3 patients (13%), and upstaging to pN2b occurred in 7 patients (29%).

Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in human maxillary cancer cells.

Cisplatin plays an important role in the therapy for human head and neck cancers. However, cancer cells develop cisplatin resistance, leading to difficulty in treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3 cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin-induced apoptosis through induction of G2/M arrest, which allows cancer cells to repair damaged DNA and survive. In the present study, we specifically examined Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A, resulting in G2/M arrest. PCBP4 plays important roles in the induction of cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular target for the therapy of head and neck cancers, especially cisplatin-resistant cancers.

Wegener's granulomatosis with extensive bone abnormalities mimicking fungal sinusitis.

Abnormalities of the underlying bone of the paranasal sinuses have sometimes been shown in Wegener's granulomatosis (WG). We describe an interesting case of WG with extensive bone abnormalities in the sinuses mimicking fungal sinusitis. A 30-year-old woman presented with intermittent unilateral epistaxis. Biopsy was performed for the granulation tissue in the right nasal cavity, and she was diagnosed as having WG. Computed tomography (CT) revealed a ring-like calcification, mimicking a fungus ball, in the right maxillary sinus. Endoscopic sinus surgery was performed to confirm the diagnosis. A spherical bony structure, surrounded by granulation tissue, was identified in the maxillary sinus. The wall of the "bony ball" was fragile, like an egg shell. No fungus was found in the sinus. Thus, the extensive bone abnormalities were due to WG.

Expression of bone morphogenic protein in sinonasal inverted papilloma with new bone formation.

Inverted papilloma (IP) is a common benign tumor in the nose and sinus. Osteogenesis in sinonasal IP is extremely rare; to date, only five cases of IP with new bone formation appear in the literature. In addition, the mechanism of osteogenesis in IP remains unclear. Here, we describe three cases of IP with new bone formation and an investigation into a possible role for bone morphogenic protein (BMP) in osteogenesis. Of three patients with sinonasal IP with new bone formation, two were treated by endoscopic sinus surgery and one was followed up with watchful waiting. Tumor tissues were subjected to immunohistochemistry to detect BMP expression. The patients were successfully treated surgically and showed no evidence of recurrence postoperatively. Follow-up examination is ongoing. Immunohistochemically, the tumors expressed BMP-4 but not BMP-2 or BMP-7. ESS could be successfully used to achieve complete removal of the sinonasal IPs with new bone formation. BMP-4 might be associated with new bone formation in the tumor.

Toll-like receptor 3 signaling induces apoptosis in human head and neck cancer via survivin associated pathway.

The innate immune system builds up host defense against a huge diversity of pathogens, such as viruses, bacteria and fungi. Toll-like receptors (TLRs) are one of the pattern recognition receptors that trigger the initiation of various defense mechanisms. The expression of TLRs represents an important link between innate and adaptive immune responses. The expression of TLRs in several cancer cell types has been reported; however, the exact roles they play in cancers are still unclear. In this study, we investigated the expression and signaling of TLRs in human head and neck squamous cell carcinomas (HNSCCs). The expression of TLRs in 8 HNSCC cell lines was examined by Western blot analysis and flow cytometry. The expression of TLR mRNA was also examined by quantitative RT-PCR. Cells were incubated with poly I:C, a TLR3 ligand, and cell viability was tested by MTT assay. In addition, apoptosis was analyzed by flow cytometry with Annexin V and propidium iodide staining. The expression of survivin, a member of the inhibitors of the apoptosis protein family, was also investigated. TLR2 and TLR3 were widely expressed in human HNSCCs. Interestingly, the stimulation of TLR3 by poly I:C induced apoptosis in cancer cells in a dose-dependent manner. The expression of survivin was down-regulated during apoptosis, suggesting that TLR signaling affects survivin-mediated signal transduction in apoptosis. In the present study, we demonstrated the proapoptotic activity of TLR3 expressed by HNSCCs. These results suggest that TLR3 could be a new target for therapy in HNSCCs.

Correlation between anti-survivin antibody and survivin mRNA expression in head and neck cancer patients.

CONCLUSIONS: Survivin may act as a major cancer antigen in head and neck cancer, and the present study revealed a link between systemic anti-survivin antibody responses and survivin expression in cancer tissues in patients with head and neck cancer. OBJECTIVES: Survivin is highly expressed in cancer cells, but is expressed at low levels or not at all in normal tissues. Little is known about the relationship between survivin expression and antibody responses to survivin in patients with head and neck cancer. METHODS: Anti-survivin antibody responses in sera of head and neck cancer patients were investigated by enzyme-linked immunosorbent assay. The expression of survivin mRNA in the cancer tissues from larynx and hypopharynx was examined by quantitative RT-PCR. RESULTS: Sera from 42 of 55 patients (76.4%) were positive for anti-survivin. High levels of anti-survivin were detected in patients in the advanced stage of disease. Most cancer tissues, but not normal adjacent tissues, expressed survivin mRNA, and a significant correlation between the levels of anti-survivin antibody in the serum and survivin mRNA in cancer tissues was detected.