[Post-operative prevalence of dysphagia in head-and-neck cancer patients in the acute care units]. / Postoperative Dysphagieprävalenz bei Kopf-Hals-Tumorpatienten im akutstationären Setting.

OBJECTIVE: Dysphagia constitutes a frequent post-operative functional impairment in head-and-neck cancer patients. This impairment can result in aspiration/penetration and limitations of oral intake. Therefore, often it requires a therapeutic intervention. In this study, prevalence of post-operative dysphagia and its associations with the tumour stage, localisation, patients' age, and biological sex were analysed for the inpatient treatment setting. MATERIAL AND METHODS: A total of 201 adult head-and-neck cancer patients (mean age 63 years) were analysed prospectively by FEES in two university hospitals in regard to their penetration/aspiration, limitations of oral intake, and need for therapeutic interventions directly after the operative tumour treatment. Additionally, the influence of the same patients' characteristics on these three parameters were analysed by means of univariate and multivariate statistical methods. RESULTS: Out of 201 patients, 66.7 % needed a therapeutic intervention because of their dysphagia, 57.2 % needed a nasogastral or PEG tube due to limitations of oral intake, 45.3 % had an aspiration. In the latter subgroup, 38.5 % had a silent aspiration. Higher tumour stage, patients' higher age and male sex were shown to be significant influence factors for dysphagia, tumour localisation showed only a marginally significant result. CONCLUSIONS: The study demonstrated a clinical importance and relevance of the consequent and systematic treatment of post-operative dysphagia in head-and-neck cancer patients in the acute care units as a constituent of a modern oncological therapy.

Cell death and autophagy: cytokines, drugs, and nutritional factors.

Cells may use multiple pathways to commit suicide. In certain contexts, dying cells generate large amounts of autophagic vacuoles and clear large proportions of their cytoplasm, before they finally die, as exemplified by the treatment of human mammary carcinoma cells with the anti-estrogen tamoxifen (TAM, < or = 1 microM). Protein analysis during autophagic cell death revealed distinct proteins of the nuclear fraction including GST-pi and some proteasomal subunit constituents to be affected during autophagic cell death. Depending on the functional status of caspase-3, MCF-7 cells may switch between autophagic and apoptotic features of cell death [Fazi, B., Bursch, W., Fimia, G.M., Nardacci R., Piacentini, M., Di Sano, F., Piredda, L., 2008. Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy 4(4), 435-441]. Furthermore, the self-destruction of MCF-7 cells was found to be completed by phagocytosis of cell residues [Petrovski, G., Zahuczky, G., Katona, K., Vereb, G., Martinet, W., Nemes, Z., Bursch, W., Fésüs, L., 2007. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Diff. 14 (6), 1117-1128]. Autophagy also constitutes a cell's strategy of defense upon cell damage by eliminating damaged bulk proteins/organelles. This biological condition may be exemplified by the treatment of MCF-7 cells with a necrogenic TAM-dose (10 microM), resulting in the lysis of almost all cells within 24h. However, a transient (1h) challenge of MCF-7 cells with the same dose allowed the recovery of cells involving autophagy. Enrichment of chaperones in the insoluble cytoplasmic protein fraction indicated the formation of aggresomes, a potential trigger for autophagy. In a further experimental model HL60 cells were treated with TAM, causing dose-dependent distinct responses: 1-5 microM TAM, autophagy predominant; 7-9 microM, apoptosis predominant; 15 microM, necrosis. These phenomena might be attributed to the degree of cell damage caused by tamoxifen, either by generating ROS, increasing membrane fluidity or forming DNA-adducts. Finally, autophagy constitutes a cell's major adaptive (survival) strategy in response to metabolic challenges such as glucose or amino acid deprivation, or starvation in general. Notably, the role of autophagy appears not to be restricted to nutrient recycling in order to maintain energy supply of cells and to adapt cell(organ) size to given physiological needs. For instance, using a newly established hepatoma cell line HCC-1.2, amino acid and glucose deprivation revealed a pro-apoptotic activity, additive to TGF-beta1. The pro-apoptotic action of glucose deprivation was antagonized by 2-deoxyglucose, possibly by stabilizing the mitochondrial membrane involving the action of hexokinase II. These observations suggest that signaling cascades steering autophagy appear to provide links to those regulating cell number. Taken together, our data exemplify that a given cell may flexibly respond to type and degree of (micro)environmental changes or cell death stimuli; a cell's response may shift gradually from the elimination of damaged proteins by autophagy and the recovery to autophagic or apoptotic pathways of cell death, the failure of which eventually may result in necrosis.