Effective treatment of head and neck squamous cell carcinoma by an oncolytic herpes simplex virus.

BACKGROUND: The prognosis of patients with advanced or recurrent head and neck squamous cell carcinoma remains poor despite refinements in multimodality therapies. This study evaluates the efficacy of a replication-competent, attenuated, oncolytic herpes simplex virus, NV1020, as a novel agent in the treatment of human head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Five different HNSCC lines were exposed to NV1020 in vitro at varying viral concentrations. The ability of the virus to lyse and replicate within these cancer cells in vitro was determined by cytotoxicity assay and plaque assay, respectively. Three HNSCC lines were grown in the subcutaneous flanks of athymic nude mice and treated with an intratumoral injection of NV1020 or saline as a control. Tumor dimensions were subsequently measured at serial time points and tumor volumes were calculated. Herpes simplex virus (HSV)-1 immunohistochemistry was performed on excised tumors to determine the efficacy of in vivo tumor infection by NV1020. RESULTS: NV1020 was highly cytotoxic in vitro to all five human HNSCC lines at a concentration of one infectious viral particle per cancer cell, and had variable cytotoxicity at a 100-fold lower concentration. Viral replication in vitro by NV1020 was efficient in four of five HNSCC lines with a greater than 200-fold increase in viral titers. Flank tumors treated with intratumoral injections of NV1020 resulted in significant regression of all tested HNSCC lines. HSV-1 immunohistochemistry of excised flank tumors treated with NV1020 demonstrated positive cytoplasmic staining and areas of tumor necrosis at 24 hours after injection. CONCLUSIONS: NV1020 is an oncolytic HSV that displays efficient replication and oncolysis in human HNSCC lines in vitro. Injection of NV1020 into murine flank tumors demonstrated effective tumor regression. Treatment of HNSCC with NV1020 is a promising form of therapy with potential clinical applicability in humans.

Effect of tracheotomy tube occlusion on upper esophageal sphincter and pharyngeal pressures in aspirating and nonaspirating patients.

The biomechanics of the pharyngeal swallow in patients with a tracheotomy tube were investigated with manometry. Upper esophageal sphincter (UES) and pharyngeal pressure recordings were made with and without occlusion of the tracheotomy tube. Criteria for selection were ability to tolerate tracheotomy tube occlusion for both 5 minutes prior to and during the first manometric analysis, absence of surgery to the upper aerodigestive tract other than tracheotomy, and no history of oropharyngeal cancer or stroke. Aspiration was determined objectively by fiberoptic endoscopic evaluation of swallowing (FEES) immediately prior to manometric recording. Eleven adult individuals with tracheotomy participated; 7 swallowed successfully and 4 exhibited aspiration on FEES. The results indicated no significant effect of tracheotomy tube occlusion on UES or pharngeal pressures in either aspirating or nonaspirating patients. It was concluded that the biomechanics of the swallow as determined by UES and pharyngeal manometric pressure measurements were not changed significantly by tracheotomy tube occlusion in aspirating or nonaspirating patients. These results support previous observations that subjects either aspirated or swallowed successfully regardless of tracheotomy tube occlusion status.

Efficacy of adjunctive cricopharyngeus myotomy in supraglottic laryngectomy.

This study investigates prospectively the effect of concurrent cricopharyngeus myotomy (CPM) on swallowing following horizontal supraglottic laryngectomy (SL) using fiberoptic, radiographic, and manometric evaluations and suggests possible mechanisms regarding the role of CPM following SL. Six patients undergoing horizontal SL between 1995 and 1997 were enrolled in a prospective evaluation with a followup of 0.5-2.25 years. Three patients underwent concurrent CPM and three did not. Fiberoptic, radiographic. and manometric assessments were performed postoperatively. Although mean resting pressures at the upper esophageal sphincter were reduced significantly by myotomy (12 mm Hg) compared with nonmyotomized patients (57 mm Hg), p < 0.01, no rehabilitative advantage was observed in the former group. In fact, of the myotomized patients, two required feeding gastrostomy tubes with resumption of an oral diet in one year and in two months, respectively, while the nonmyotomized patients were all capable of resuming a full oral diet within four weeks. It appears that CPM provides no rehabilitative advantage in patients undergoing SL.

Documentation of variations in sinonasal anatomy by intraoperative nasal endoscopy.

OBJECTIVES: Functional endoscopic sinus surgery (FESS) requires a thorough understanding of the variability in sinonasal anatomy. Previous reports have relied primarily on anatomic studies of cadaveric specimens or skulls, or on radiographic analysis. Relatively few comparative anatomic data have been accumulated with endoscopic examination of living patients. STUDY DESIGN: Retrospective review of video recordings of 119 consecutive patients undergoing intraoperative nasal endoscopy at the time of sinonasal surgery. METHODS: At the beginning of each surgical procedure, endoscopic examination of the nasal cavities was performed with 0 degrees and 30 degrees telescopes and recorded with a three-chip video camera on 3/4-inch U-matic videotape. These video records were then reviewed with attention to variations in anatomical configuration of different sinonasal structures. RESULTS: Data demonstrating variations in the anatomical configuration of the following structures of the lateral nasal wall are presented. Middle turbinate: typical (63%), concha bullosa (15%), sagittal cleft (6%), laterally displaced (4%), "L" shaped (3%), medially bent (3%), laterally bent (3%), medially displaced (2%), and transverse cleft (0.5%). Uncinate process: typical (85%) and medially rotated (15%). Ethmoid bulla: typical or balloon (45%), sausage-shaped (34%), and flat (21%). Accessory ostium: round (50%), oval (46%), and kidney-shaped (4%). Sphenoid sinus ostium: oval (42%), slit (32%), and round (26%). The classification system for the anatomical categories is illustrated with digitized images. CONCLUSIONS: This study attempts to provide statistical data regarding variations in sinonasal anatomy in living subjects. Familiarity with such anatomy is important in differentiating normal variants from pathological conditions to optimize surgical treatment of sinus disease, while avoiding complications.