Videostroboscopy of the pharyngoesophageal segment in laryngectomy patients treated with botulinum toxin.

OBJECTIVES: The purpose of this investigation was to use videostroboscopy to study the physiologic and biomechanical effects of botulinum toxin (Botox) injection on the pharyngoesophageal segment (PES) in total laryngectomy patients with poor-quality tracheoesophageal puncture (TEP) voice caused by PES spasm. METHODS: The following was a prospective study. Videostroboscopy of the PES and videotaped recordings of patients performing TEP voice tasks were conducted before and after Botox injection of the PES. Ratings of videostroboscopic and speech samples were performed by 3 blinded judges with extensive experience with this patient population. RESULTS: Perceptually, TEP voice was more fluent and less strained after injection. Videostroboscopically, patients demonstrated improved PES volitional control and mucosal wave characteristics after Botox injection. CONCLUSION: Botox injection in total laryngectomy patients with poor-quality TEP voice caused by PES spasm provides improved physiologic and biomechanical function of the PES, as demonstrated for the first time videostroboscopically. These findings help explain the perceptual ratings of TEP voice improvement noted after Botox injection. Videostroboscopy can be used to provide diagnostic information to help confirm the clinical impression of PES spasm, as well as to document the effects of Botox injection on PES function.

Anti-CD3/anti-CD28 bead stimulation overcomes CD3 unresponsiveness in patients with head and neck squamous cell carcinoma.

OBJECTIVES: To test whether T-cell CD3 responses are altered in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC) and whether anti-CD3/anti-CD28 (alphaCD3/alphaCD28) bead stimulation could reverse CD3 unresponsiveness. DESIGN: Anti-CD3 (alphaCD3) monoclonal antibody immobilized on tissue culture plastic was used to stimulate lymph node mononuclear cells (LNMCs) and peripheral blood mononuclear cells (PBMCs) from patients with advanced-stage HNSCC. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation. Immune-enhancing properties of alphaCD3/ alphaCD28 beads were also tested on LNMCs and PBMCs. Cytotoxicity of bead-activated T cells (ATCs) was measured against autologous and allogeneic HNSCC. RESULTS: Six patients were nonresponders to alphaCD3 stimulation defined by tritium (3H) incorporation of less than 3500 cpm, whereas 11 patients were responders with 3H incorporation of 3500 cpm or more. Responders produced higher levels of interleukin (IL)-12 and interferon gamma (IFN-gamma) after alphaCD3 stimulation than nonresponders. No phenotypic or clinical differences were identified between groups. Stimulation with alphaCD3/alphaCD28 beads enhanced IFN-gamma and IL-2 produced by both groups. Bead ATCs were generated from PBMCs of patient 11 in the responder group and lysed (+/- SD) 100% +/-1% of autologous tumor and 49% +/-1% of allogeneic tumor. Bead ATCs from LNMCs of this patient lysed 58%+/-1% of autologous tumor and 63%+/-1% of allogeneic tumor. CONCLUSIONS: A subpopulation of patients with HNSCC who are nonresponders to alphaCD3 stimulation has been identified, showing reduced proliferation and IL-12 and IFN-gamma secretion. Nonresponders stimulated with alphaCD3/alphaCD28 beads reversed immune unresponsiveness and induced a type 1 cytokine response. Bead-generated ATCs from patient 11 in the responder group lysed autologous and allogeneic HNSCC in vitro, suggesting a possible effective immunotherapeutic modality in the treatment of HNSCC.

Anti-CD3/anti-CD28 monoclonal antibody-coated suture enhances the immune response of patients with head and neck squamous cell carcinoma.

OBJECTIVE: To test whether anti-CD3/anti-CD28 (alphaCD3/alphaCD28) monoclonal antibodies could be coated on surgical suture and used to enhance T-cell immune function in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). DESIGN: AlphaCD3/alphaCD28 monoclonal antibodies at varying concentrations and ratios were coated on surgical sutures and tested on peripheral blood mononuclear cells from normal donors to identify the optimal stimulating condition. Immune-enhancing properties of alphaCD3/alphaCD28 monoclonal antibody suture were tested on peripheral blood mononuclear cells and regional lymph node mononuclear cells isolated from patients with advanced HNSCC and on normal donor peripheral blood mononuclear cells. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation with alphaCD3/alphaCD28 suture and compared with alphaCD3/alphaCD28-coated tissue culture plastic, a previously recognized carrier. RESULTS: Optimal stimulation was observed with monofilament nylon incubated with alphaCD3/alphaCD28, 2 microg/mL, at a 1:1 ratio for 18 hours at 37 degrees C. Strong proliferation of peripheral blood mononuclear cells and lymph node mononuclear cells in patients with HNSCC was induced by alphaCD3/alphaCD28 suture. There was no difference in maximal proliferation between alphaCD3/alphaCD28 plastic and suture. On day 6 after alphaCD3/alphaCD28 suture stimulation, T-cell subpopulations expressing CD3, CD4, CD8, CD28, and CD45RO were enhanced. Suture stimulation significantly enhanced interleukin 2 secretion when compared with plastic stimulation (P = .01). Both alphaCD3/alphaCD28 suture and plastic stimulated interferon gamma secretion. CONCLUSIONS: To our knowledge, this study is the first to report the modification of surgical suture to create an immunomodulant. AlphaCD3/alphaCD28-coated suture expanded T cells from patients with HNSCC and induced a T(H)1 immune response, which may be a useful therapeutic tool in the treatment of HNSCC and other diseases.

Botulinum toxin injection to improve tracheoesophageal speech after total laryngectomy.

Total laryngectomy patients, after undergoing a tracheoesophageal puncture (TEP), may have poor TEP speech because of hypertonicity or spasm of the pharyngoesophageal segment (PES). Conventional treatment options include speech therapy, PES dilation, pharyngeal neurectomy, and myotomy. Botulinum toxin injection into the PES has recently been reported to be effective for this disorder. However, data accumulated were based primarily on subjective analyses. This prospective investigation used both qualitative and quantitative measures to assess the effects of videofluoroscopy-guided botulinum toxin injection on TEP voice quality in laryngectomees with PES dysfunction. Patients underwent voice analyses, tracheal air pressure measures, and barium swallows before and after botulinum toxin injection. Seven of 8 patients had significant voice quality improvement, and tracheal air pressures normalized in 6 of 8 patients after injection. Videofluoroscopic botulinum toxin injection into the PES is efficacious, safe, and cost-effective and should be considered as a first-line therapy for the treatment of laryngectomees with poor quality TEP speech caused by PES dysfunction.

Videostroboscopy of the pharyngoesophageal segment in total laryngectomees.

OBJECTIVES: The reconstructed pharyngoesophageal segment (PES) serves as the neoglottis following total laryngectomy, as it provides the source of vibration for production of tracheoesophageal puncture (TEP) voice. To date, little information exists regarding the vibratory characteristics of the PES. The purpose of this investigation was to study the anatomy and physiology of the PES using videostroboscopy. STUDY DESIGN: Prospective study investigating the anatomy and physiology of the PES in 34 laryngectomees who used TEP speech as their primary form of communication. MATERIALS AND METHODS: Videostroboscopy and voice recordings were graded by three trained, blinded judges using a seven-point scale. RESULTS: The patients demonstrated differences that allowed for separation of patients into two main groups: "poor" and "effective" TEP speakers. The voice quality differences were explained by anatomic and physiologic characteristics of the PES. Redundant, thick, and dyssynchronous PES features were observed in patients with poor TEP speech skills; the effective speakers exhibited less redundant, thinner mucosa and more synchronous vibratory patterns. Moreover, the latter subgroup consistently demonstrated a greater degree of volitional PES control and less spasmodic activity than their poorly speaking counterparts. Length of the PES opening (measured in the horizontal plane) as well as amount and consistency of secretions did not appear to influence TEP speech or voice proficiency. CONCLUSION: Videostroboscopy in laryngectomees is a noninvasive, inexpensive, easily performed procedure that may contribute valuable information regarding the anatomy and physiology of the PES, especially in patients who experience difficulties achieving satisfactory TEP voice and speech production.

Normal adult swallowing of liquid and viscous material: scintigraphic data on bolus transit and oropharyngeal residues.

Scintigraphic data are provided for 20 normal control subjects, 39-65 years of age. Each subject swallowed 10 cc of water and 10 cc of a more viscous material (1,100 centipoise) consisting of apple juice thickened with Thick-It, a commercial food thickener. The test substances were combined with 2.5 mCi Tc-99m sulfur colloid. Scintigraphic data were acquired in dynamic mode for 10 sec at 25 frames/sec as the subject swallowed. Time-activity (TA) data were used to compute transit times, percentage residues in the mouth and pharynx, percent ingested, and a derived swallow efficiency score. The liquid was ingested in a single swallow by all subjects, and 9 cc was actually transferred to the esophagus. In contrast, for the viscous material, 11/20 subjects performed a second clearing swallow within the 10-sec interval. On the first swallow with the viscous substance, an average of 7 cc was transferred to the esophagus. Scintigraphy offers an excellent technique for determining natural and preferred volumes for swallowing a variety of bolus consistencies, since it can quantify the volume of each swallow or partial swallow. In this group of subjects the oral discharge time was shorter with the viscous material than with the water, but the pharyngeal transit times were not significantly different for the two bolus consistencies. Numerical efficiency scores were lower for the viscous material, indicating that such a measure is bolus dependent.