Jayakar V. Nayak

Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL

Squamous cell carcinoma of the head and neck (SCCHN) cells are poorly recognized in vitro by CTL despite expressing the restricting HLA class I allele and the targeted tumor Ag (TA). Several lines of evidence indicate that the lack of SCCHN cell recognition by CTL reflects defects in targeted TA peptide presentation by HLA class I Ag to CTL because of Ag-processing machinery (APM) dysfunction. First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-γ-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin. Second, SCCHN cell recognition by CTL is restored by pulsing cells with exogenous targeted TA peptide. Third, the restoration of CTL recognition following incubation of SCCHN cells with IFN-γ is associated with a significant (p = 0.001) up-regulation of the APM components TAP1, TAP2, and tapasin. Lastly, and most conclusively, SCCHN cell recognition by CTL is restored by transfection with wild-type TAP1 cDNA. Our findings may explain the association between APM component down-regulation and poor clinical course of the disease in SCCHN. Furthermore, the regulatory nature of the APM defects in SCCHN cells suggests that intralesional administration of IFN-γ may have a beneficial effect on the clinical course of the disease and on T cell-based immunotherapy of SCCHN by restoring SCCHN cell recognition by CTL.

Deferring Planned Neck Dissection Following Chemoradiation for Stage IV Head and Neck Cancer: The Utility of PET-CT†

Objective: To determine whether combined positron emission tomography and computed tomography (PET‐CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC).

Nationwide incidence of major complications in endoscopic sinus surgery

Endoscopic sinus surgery (ESS) is one of the most commonly performed procedures in otolaryngology. Major complications are estimated to occur in 1–3% of cases, based on early studies with relatively small patient cohorts in academic institutions. The aim of this study was to update data regarding major complication rates associated with ESS by analyzing a large patient database.

Experience with the expanded endonasal approach for resection of the odontoid process in rheumatoid disease.

Background One of the common indications for removal of the odontoid process includes decompression of the cervicomedullary junction in patients with arthritic degeneration. Resection of the odontoid process can be accomplished using a completely transnasal endoscopic approach. Methods A retrospective review was performed of patients with rheumatoid pannus undergoing transnasal endoscopic resection of the odontoid to assess preoperative characteristics, postoperative complications, and outcomes. Patients were followed for a minimum of 3 months in the postoperative period and/or until death. In addition to the primary procedure, those patients with preoperative cervical instability underwent posterior fusion of the upper cervical spine to the occiput for stabilization during the same hospitalization. Results Nine patients underwent transnasal endoscopic resection of the odontoid process for rheumatoid or degenerative pannus and brainstem compression. Perioperatively, four patients required a tracheostomy; two of whom had significant preoperative pharyngeal dysfunction. Two patients experienced postoperative velopharyngeal incompetence, which was transient. No patients had cerebrospinal fluid leaks, and there were no perioperative infectious complications noted. There was one delayed death in this patient cohort because of a presumed pulmonary embolus. Otherwise, all patients showed an improvement of their preoperative neurological symptoms. Conclusion This early series of patients with rheumatoid pannus shows the feasibility of a fully endoscopic, completely transnasal approach for the resection of the odontoid process. Potential advantages include improved visualization, limited morbidity, decreased pain, and faster recovery than traditional approaches.

Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo.

The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs. Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 microg/ml and remained above 1 microg/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12. The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively. These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.

Survival outcomes in acute invasive fungal sinusitis: A systematic review and quantitative synthesis of published evidence

Acute invasive fungal sinusitis (AIFS) is an aggressive and often fatal infection. Despite improvements in medical and surgical therapy, survival remains limited and the factors that contribute to patient outcomes remain poorly understood. The current study systematically reviews and quantitatively synthesizes the published literature to characterize prognostic factors associated with survival.

Current use of 18F-fluorodeoxyglucose positron emission tomography and combined positron emission tomography and computed tomography in squamous cell carcinoma of the head and neck.

The history and physical examination, computed tomography (CT) and magnetic resonance imaging are the cornerstones for identifying new and recurrent cancers of the head and neck. The advent of positron emission tomography (PET) and combined PET/CT imaging technology is a promising development. These modalities have the potential to help stage patients presenting with head and neck cancer, identify responses to nonsurgical therapy, and allow earlier detection of recurrence in the hope of improving survival. The following paper provides a brief history of PET and PET/CT imaging. The current PET and PET/CT literature for squamous cell carcinoma of the head and neck is reviewed, and specific recommendations for its use are provided.

Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses.

Vaccination with antigenic peptides encoding tumor antigens has the potential to be an effective treatment for cancer. To induce tumor-specific cellular immune responses, a peptide antigen must be presented by antigen-presenting cells (APCs) to T-cells in the lymphatic tissues. Effective in vivo delivery of peptide antigens to APCs has been problematic. Here we use a model antigen from the HPV16 E7 protein to formulate LPD/E7 particles that upon iv administration are internalized by CD11c(+) and CD11b(+) cells in the marginal zone of the spleen. Either iv or sc vaccination with LPD/E7 particles induces E7-specific CTL responses stronger than those obtained using previously described liposome/peptide strategies and prevents the establishment of E7-expressing tumors. Furthermore, the administration of LPD/E7 particles to tumor-bearing mice caused complete tumor regression in 100% of the treated animals. Based on these studies, the entrapment of peptide antigens inside LPD particles may be an effective and generally applicable strategy for the enhancement of peptide vaccine potency.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Isam Alobid, MD, PhD1, Nithin D. Adappa, MD2, Henry P. Barham, MD3, Thiago Bezerra, MD4, Nadieska Caballero, MD5, Eugene G. Chang, MD6, Gaurav Chawdhary, MD7, Philip Chen, MD8, John P. Dahl, MD, PhD9, Anthony Del Signore, MD10, Carrie Flanagan, MD11, Daniel N. Frank, PhD12, Kai Fruth, MD, PhD13, Anne Getz, MD14, Samuel Greig, MD15, Elisa A. Illing, MD16, David W. Jang, MD17, Yong Gi Jung, MD18, Sammy Khalili, MD, MSc19, Cristobal Langdon, MD20, Kent Lam, MD21, Stella Lee, MD22, Seth Lieberman, MD23, Patricia Loftus, MD24, Luis Macias‐Valle, MD25, R. Peter Manes, MD26, Jill Mazza, MD27, Leandra Mfuna, MD28, David Morrissey, MD29, Sue Jean Mun, MD30, Jonathan B. Overdevest, MD, PhD31, Jayant M. Pinto, MD32, Jain Ravi, MD33, Douglas Reh, MD34, Peta L. Sacks, MD35, Michael H. Saste, MD36, John Schneider, MD, MA37, Ahmad R. Sedaghat, MD, PhD38, Zachary M. Soler, MD39, Neville Teo, MD40, Kota Wada, MD41, Kevin Welch, MD42, Troy D. Woodard, MD43, Alan Workman44, Yi Chen Zhao, MD45, David Zopf, MD46

Endoscopic Reconstruction of Surgically Created Skull Base Defects A Systematic Review

Objectives To systematically review the literature concerning techniques of closure of endoscopically created skull base defects based on site of skull base defect and flow rate of cerebrospinal fluid (CSF). Data Sources PubMed, SCOPUS, and Cochrane databases. Review Methods A comprehensive systematic literature review. Results The literature search produced a total of 1708 studies. Of these, 1585 studies were excluded based on title and/or abstract review. A total of 123 articles remained for full-text review, 101 of which were subsequently excluded primarily because of lack of detailed information as to the reconstructive techniques used or clinical outcomes. Of the 22 studies remaining for final analysis, all were case series. A total of 673 patients were included in the analysis, with an overall postoperative CSF leak rate of 8.5%. Subgroup analysis was performed based on location of the skull base defect and presence and quality of intraoperative CSF leak. Conclusions Based on level 4 evidence, in cases of low-flow intraoperative CSF leaks, skull base reconstruction with multilayered free grafts and synthetic materials offers similar outcomes to vascularized flaps. In cases of high-flow intraoperative CSF leaks, pedicled vascularized flaps appear to be superior. Location of the defect does not seem to be a significant factor in determining successful closure, with the exception of clival defects. In all other sites, good closure may be achieved by multiple reconstructive approaches. More consistency in data reporting and higher levels of evidence will ultimately be necessary to make definitive recommendations.