The aim of this study was to test reliability, content, construct, and external validity of a new modified barium swallowing study (MBSS) tool (MBSImp) that is used to quantify swallowing impairment. Multiple regression, confirmatory factor, and correlation analyses were used to analyze 300 in- and outpatients with heterogeneous medical and surgical diagnoses who were sequentially referred for MBS exams at a university medical center and private tertiary care community hospital. Main outcome measures were the MBSImp and index scores of aspiration, health status, and quality of life. Inter- and intrarater concordance were 80% or greater for blinded scoring of MBSSs. Regression analysis revealed contributions of eight of nine swallow types to impressions of overall swallowing impairment (p ≤ 0.05). Factor analysis revealed 13 significant components (loadings ≥ 0.5) that formed two impairment groupings (oral and pharyngeal). Significant correlations were found between Oral and Pharyngeal Impairment scores and Penetration-Aspiration Scale scores, and indexes of intake status, nutrition, health status, and quality of life. The MBSImp demonstrated clinical practicality, favorable inter- and intrarater reliability following standardized training, content, and external validity. This study reflects potential for establishment of a new standard for quantification and comparison of oropharyngeal swallowing impairment across patient diagnoses as measured on MBSS.

Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Objective To test a novel intervention to train swallowing to occur in the mid-to-low expiratory phase of quiet breathing to improve swallowing safety and efficiency. Design Safety and efficacy non-randomized clinical trial with one-month follow-up. Setting Head and neck cancer (HNC) ambulatory clinics. Participants Thirty patients with HNC and chronic dysphagia completed the intervention. Fifteen of these patients participated in a one-month follow-up visit. Interventions Training protocol based on hierarchy of motor skill acquisition to encourage autonomous and optimal respiratory-swallowing coordination. Visual feedback of respiratory phase and volume for swallowing initiation was provided by nasal airflow and rib cage/abdomen signals. Main Outcome Measures Respiratory-swallow phase pattern, Modified Barium Swallow Impairment Profile™© (MBSImP) scores, Penetration Aspiration Scale (PAS) scores, M.D. Anderson Dysphagia Inventory scores Results Using visual feedback, patients were trained to initiate swallows during the mid-expiratory phase of quiet breathing and to continue to expire after swallowing. This optimal phase patterning increased significantly after treatment (p <0.0001). Changes in respiratory-swallowing coordination were associated with improvements in three MBSImP component scores: laryngeal vestibular closure (p = 0.0004), tongue base retraction (p <0.0001), and pharyngeal residue (p = 0.01). Significant improvements were also seen in PAS scores (p <0.0001). Relative to pre-treatment values, patients participating in one-month follow-up had increased optimal phase patterning (p <0.0001), improved laryngeal vestibular closure (p = 0.01), tongue base retraction (p = 0.003), and pharyngeal residue (p = 0.006) MBSImP scores, and improved PAS scores (p <0.0001). Conclusions Improvements in respiratory-swallowing coordination can be trained using a systematic protocol and respiratory phase-lung volume related biofeedback in patients with HNC and chronic dysphagia, with favorable effects on airway protection and bolus clearance.

Osteoprotegerin (OPG), a critical regulator of osteoclastogenesis, is expressed by prostate cancer cells, and OPG levels are increased in patients with prostate cancer bone metastases. The objective of this study was to investigate the effects of OPG overexpression on prostate cancer cells and prostate cancer/bone cell interactions in vitro and in vivo. OPGtransfected C4-2 cells expressed 8.0 ng OPG per mL per 10 6 cells, whereas no OPG was detected in the media of C4-2 cells transfected with a control plasmid. OPG overexpressed by C4-2 cells protected these cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis and decreased osteoclast formation. Subcutaneous OPG-C4-2 and pcDNA-C4-2 tumors exhibited similar growth and take-rate characteristics. However, when grown in bone, tumor volume was decreased in OPG-C4-2 versus pcDNA-C4-2 (P = 0.0017). OPG expressed by C4-2 cells caused increases in bone mineral density (P = 0.0074) and percentage of trabecular bone volume (P = 0.007), and decreases in numbers of osteoblasts and osteoclasts when compared with intratibial pcDNA-C4-2 tumors (P = 0.003 and P = 0.019, respectively). In summary, our data show that increased expression of OPG in C4-2 cells does not directly affect proliferation of prostate cancer cells but indirectly decreases growth of C4-2 tumors in the bone environment. Our data also show that OPG expressed by C4-2 cells inhibits bone lysis associated with C4-2 bone metastasis, which results in net increases in bone volume. We therefore hypothesize that OPG expressed in prostate cancer patient bone metastases may be at least partially responsible for the osteoblastic character of most prostate cancer bone lesions. (Cancer Res 2005; 65(5): 1710-8)