Bridget Hathaway

Decreased Absolute Counts of T Lymphocyte Subsets and Their Relation to Disease in Squamous Cell Carcinoma of the Head and Neck

Purpose: Apoptosis of circulating CD8+ T cells seen in patients with squamous cell carcinoma of the head and neck [SCCHN (Hoffmann T, et al. Clin Cancer Res 2002;8:2553–62)] suggested a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of lymphocyte subsets were examined in the peripheral blood of SCCHN patients and controls. Experimental Design: Venous blood was obtained from 146 patients with SCCHN and 54 normal volunteers. Absolute numbers of CD3+, CD4+, and CD8+ T lymphocytes were determined using fluorobeads in a flow cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped at the time of blood draw [active versus no evidence of disease (NED), type of therapy administered, and the length of follow-up]. Results: Patients with SCCHN had significantly lower absolute numbers of CD3+ CD4+, and CD8+ T cells than normal controls. However, no differences in the percentages of T-cell subsets between patients and normal controls were observed. Patients with active disease had significantly lower CD3+ and CD4+ T-cell counts than those with NED. Patients who had NED after surgery and radiotherapy had the lowest T-cell counts among the NED cohort. Patients who had NED for >2 years did not recover their T-cell counts, and the T-cell imbalance was evident many years after curative surgery. The tumor-node-metastasis (TNM) stage or site of the disease was not related to the absolute T-cell count. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+ T-cell counts. Conclusions: Patients with SCCHN have altered lymphocyte homeostasis, which persists for months or years after curative therapies.

Imbalance in Absolute Counts of T Lymphocyte Subsets in Patients with Head and Neck Cancer and Its Relation to Disease1

Apoptosis of circulating CD8+T cells seen in patients with squamous cell carcinoma of the head and neck (HNSCC) suggests a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of T lymphocyte subsets were examined in the peripheral blood of patients with HNSCC and age-matched controls. Venous blood was obtained from 148 patients with HNSCC and 54 normal volunteers. Absolute numbers of CD3+, CD4+ and CD8+ T lymphocytes were determined using fluorobeads in a flow-cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped, at the time of blood draw (active vs. no evident disease, NED), type of therapy administered and the length of follow-up. Patients with HNSCC were found to have significantly lower absolute numbers of CD3+, CD4+and CD8+T cells than normal controls (NC). However, no differences in the percentages of T cell subsets between patients and NC were observed. Patients with active disease had significantly lower CD3+ and CD4+ T cell counts than those with NED. Patients with NED after surgery and radiotherapy had lower T cell counts than those treated by surgery alone. Patients who remained without evident disease for more than 2 years did not recover their T cell counts, and the T cell imbalance was evident many years after curative surgery. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+T cell counts. The TNM stage or site of the disease were not related to the absolute T cell count. Our data indicate that patients with HNSCC have altered lymphocyte homeostasis, which persists for months or years after curative therapies.

A nomenclature paradigm for benign midmembranous vocal fold lesions

There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature.

Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients.

Objective: Our objective was to characterize cytokine profiles in the systemic circulation of patients with active squamous cell carcinoma of the head and neck (SCCHN) compared with long‐term tobacco smokers as controls. Furthermore, we hypothesized that persistent immune dysregulation in patients cured of their disease may be reflected in altered cytokine profiles in the systemic circulation.

Safety of Uvulopalatopharyngoplasty As Outpatient Surgery

OBJECTIVE: Determine the admission rate and characterize the complications in uvulopalatopharyngoplasty (UPPP) patients scheduled to have outpatient surgery. STUDY DESIGN AND SETTING: Retrospective review of patients undergoing UPPP between 2000 and 2004 in a tertiary care setting. RESULTS: UPPP alone or in conjunction with tonsillectomy, septoplasty, or supraglottoplasty was carried out in 110 patients. Average preoperative respiratory disturbance index (RDI) was 35. Admission was required in 20 (18%) patients whereas 90 (82%) were discharged on the day of surgery. Admission due to desaturation was noted in 3 (3%) patients. The most common reasons for admission included pain and nausea. There were no major complications. CONCLUSIONS: Careful preoperative selection of patients should permit many patients to undergo UPPP as outpatient surgery. Factors requiring admission may be assessed in the early postoperative period. The rate of respiratory events requiring postoperative admission after UPPP is low. SIGNIFICANCE: UPPP can be carried out safely on an outpatient basis.

Chemoradiation for Metastatic SCCA: Role of Comorbidity†

Objectives A previous study of 371 patients with extracapsular spread (ECS) of cervical metastases from squamous cell carcinoma (SCCA) of the head and neck revealed a survival advantage for patients treated with adjuvant chemoradiation, compared with those treated with surgery and radiation or surgery alone. While all patients in the study were offered adjuvant chemotherapy, only 35% selected this option. Comorbidity was identified as a reason for declining chemotherapy. Recently, Piccirillo demonstrated that the Modified Medical Comorbidity Index (MMCI) is a valid instrument to classify and quantify severity of comorbidity. We applied this instrument to previously reported patients with ECS to determine 1) how comorbidity affected treatment selection, 2) whether the survival advantage of adjuvant chemoradiation persisted after controlling for comorbidity, and 3) the impact of comorbidity on outcome.

Transfection of human monocyte-derived dendritic cells with native tumor DNA induces antigen-specific T-cell responses in vitro.

Objective: Nucleofection of genomic tumor (Tu) DNA into human monocyte-derived dendritic cells (hMoDC) was evaluated for use in producing anti-tumor vaccines able to induce effective T-cell specific immune responses. Methods: Cultured hMoDC obtained from HLA-A2+ normal donors were nucleofected with genomic DNA extracted from an HLA-A2+gp100+ Mel 526 cell line and 3’end-labeled with biotinylated TdT nucleotides or from a genetically-modified Mel 526 expressing enhanced green fluorescent protein (EGFP). An Amaxa Nucleofector™ system was used for electroporation. Nucleofected hMoDC were matured in the presence of cytokines and examined in ELISPOT assays for the ability to present the gp100209-217 epitope to epitope-specific T cells or to prime autologous naïve T cells in culture. Results: The nucleofected hMoDC presented gp100 protein to HLA-A2+gp100-specific T cells as observed in IFN-γ ELISPOT assays. Spot formation was inhibited by anti-HLA class I and HLA-A2 but not anti-HLA class II antibodies (Abs). Tu DNA-nucleofected hMoDC also primed naïve autologous peripheral blood T cells in culture to develop into Tu-reactive effector cells (CTL). These CTL recognized Tu cells which had donated genomic DNA, and these responses were MHC class I- and class II-restricted. The CTL recognized shared Tu antigens encoded in Tu-derived DNA. Conclusion: Nucleofection of hMoDC with genomic Tu-derived DNA is a useful strategy for Tu vaccine production: it is feasible, does not require Tu epitope isolation, can be used when few Tu cells are available, and avoids Tu-induced DC suppression.

Frailty Measurements and Dysphagia in the Outpatient Setting

Objective: Deconditioning and frailty may contribute to dysphagia and aspiration. Early identification of patients at risk of aspiration is important. Aspiration prevention would lead to reduced morbidity and health care costs. We therefore wondered whether objective measurements of frailty could help identify patients at risk for dysphagia and aspiration. Methods: Consecutive patients (n = 183) were enrolled. Patient characteristics and objective measures of frailty were recorded prospectively. Variables tested included age, body mass index, grip strength, and 5 meter walk pace. Statistical analysis tested for association between these parameters and dysphagia or aspiration, diagnosed by instrumental swallowing examination. Results: Of variables tested for association with grip strength, only age category (P = .003) and ambulatory status (P < .001) were significantly associated with grip strength in linear regression models. Whereas walk speed was not associated with dysphagia or aspiration, ambulatory status was significantly associated with dysphagia and aspiration in multivariable model building. Conclusion: Nonambulatory status is a predictor of aspiration and should be included in risk assessments for dysphagia. The relationship between frailty and dysphagia deserves further investigation. Frailty assessments may help identify those at risk for complications of dysphagia.

Handgrip strength and dysphagia assessment following cardiac surgery

Prolonged intubation has been recognized as a risk factor for dysphagia following cardiac surgery. We conducted a study to determine whether those patients intubated longer than 12 hours following cardiac surgery exhibit low handgrip strength and if dysphagia is prevalent in those with low handgrip strength.