[Pediatric cost-benefit analysis]. / Kosten-Nutzen-Analyse der Cochlea-Implantation bei Kindern.

BACKGROUND: The aim of this study was to explore the cost-benefit-ratio of pediatric cochlear implantation for congenitally deaf and prelingually deafened children compared to children with hearing aids. The payers' perspective was chosen as this is the most relevant for cost discussions. The study should verify the hypothesis that educational and associated full costs increase with the age at implantation and that these can be below costs for children with hearing aids. METHODS: Children implanted at different ages (group 1: 0 - 1.9 yr., group 2: 2 - 3.9 yr., group 3: 4 - 6.9 yr.) were compared with deaf children using hearing aids (group 4). Payers were sick funds and public authorities, the first paying for medical and indirect costs, the latter paying for education. Educational settings were used as measure for benefit. All costs related to the hearing deficiency were included up to the age of 16 years (end of primary education) based on 1999 costs. RESULTS: Discounted medical and indirect costs for a pediatric cochlear implant user varied between DM 112,000 (53,300 US dollars) and DM 91,000 (43,300 US dollars) depending on the age at implantation. Costs for a hearing aid user added up to DM 36,000 (17,100 US dollars). These costs were paid by the sick funds. Costs for education varied between DM 159,000 (75,700 US dollars) for group 1 and DM 257,000 (122,400 US dollars) for group 3 compared to DM 277,000 (131,900 US dollars) for hearing aid users. These differences are mainly based on the use of mainstream schools. Total costs for sick funds and public authorities ad up to DM 271,000 (129,000 US dollars), DM 334,000 (159,000 US dollars) and DM 348,000 (165,700 US dollars), respectively, for the three age groups of implanted children compared to DM 313,000 (148,600 US dollars) for hearing aid users. CONCLUSION: This study supports the view that pediatric cochlear implantation provides positive cost-benefit ratios compared to hearing aid users depending on the age at implantation. From a societal/payer perspective implantation of prelingually deafened children is especially recommended for children under the age of 2 years. Implantation between ages 2 and 3,9 can be recommended from an educational perspective. Implantation at ages >7 years must be based on individual decisions considering psychosocial environment, speech and language status and type of communication.

Cost-benefit analysis of pediatric cochlear implantation: German experience.

HYPOTHESIS: To explore, from the payers' perspective, the cost-benefit ratio of pediatric cochlear implantation for congenitally deaf and prelingually deafened children compared with children with hearing aids. The study should verify the hypothesis that educational and associated costs increase with age at implantation and that these can be below costs for children with hearing aids. METHODS: Children who received implants at the Medical University of Hanover at different ages (Group 1, 0-1.9 yr; Group 2, 2-3.9 yr; Group 3, 4-6.9 yr) were compared with deaf children using hearing aids (Group 4). Sick funds were the payers for direct and indirect costs, and public authorities were the payers for educational costs. Educational settings were used to measure for benefits. All costs related to the hearing deficiency were included up to the age of 16 years on the basis of 1999 currency values. A scenario analysis was used to explore the impact of variation of costs and discount rates. RESULTS: Total costs for the three age groups of children with implants were from euro 138,000 (approximately US$113,100) to euro 177,000 (approximately US$152,700), compared with euro 160,000 (approximately US$138,000) for hearing aid users. CONCLUSION: This study supports the view that pediatric cochlear implantation provides positive cost-benefit ratios compared with hearing aid users, depending on the age at implantation. Implantation is strongly recommended from the payers' perspective for children implanted before the age of 2 years.

A novel host/tumor cell interaction activates matrix metalloproteinase 1 and mediates invasion through type I collagen.

Along with degradation of type IV collagen in basement membrane, destruction of the stromal collagens, types I and III, is an essential step in the invasive/metastatic behavior of tumor cells, and it is mediated, at least in part, by interstitial collagenase 1 (matrix metalloproteinase 1 (MMP-1)). Because A2058 melanoma cells produce substantial quantities of MMP-1, we used these cells as models for studying invasion of type I collagen. With a sensitive and quantitative in vitro invasion assay, we monitored the ability of these cells to invade a matrix of type I collagen and the ability of a serine proteinase inhibitor and all-trans-retinoic acid to block invasion. Although these cells produce copious amounts of MMP-1, they do not invade collagen unless they are co-cultured with fibroblasts or with conditioned medium derived from fibroblasts. Our studies indicate that a proteolytic cascade that depends on stromal/tumor cell interactions facilitates the ability of A2058 melanoma cells to invade a matrix of type I collagen. This cascade activates latent MMP-1 and involves both serine proteinases and MMPs, particularly stromelysin 1 (MMP-3). All-trans-retinoic acid (10(-6) M) suppresses the invasion of tumor cells by several mechanisms that include suppression of MMP synthesis and an increase in levels of tissue inhibitor of metalloproteinases 1 and 2. We conclude that invasion of stromal collagen by A2058 melanoma cells is mediated by a novel host/tumor cell interaction in which a proteolytic cascade culminates in the activation of pro-MMP-1 and tumor cell invasion.

Human breast cancer cells activate procollagenase-1 and invade type I collagen: invasion is inhibited by all-trans retinoic acid.

Matrix metalloproteinases (MMPs) play an important role in tumor cell invasion and metastasis. These processes require the dissolution of the basement membrane and invasion of the stromal matrix (ECM), and are mediated by MMPs. Consequently, MMP inhibitors may be attractive as new anticancer agents. To examine the potential contribution of collagenase-1 (MMP-1) in invasion of stromal matrix, we used the highly invasive and metastatic breast cancer cell line MDA-MB-231 as a model system. These cells express procollagenase-1 constitutively and this expression can be repressed by all-trans retinoic acid. Invasion of these cells into a collagen type I matrix was assessed by scanning electron microscopy (SEM), and was quantitated with a computer program and confocal laser scanning microscopy (CLSM). We found that MDA-MB-231 cells freely invaded the collagen type I matrix, suggesting that these cells possess a mechanism for activating the latent collagenase-1. In contrast, down-regulation of collagenase-1 expression by all-trans retinoic acid caused these cells to become less invasive. To confirm a role for collagenase-1 in mediating collagen type I invasion, assays were carried out in the presence of FN-439, an inhibitor of collagenase-1 enzyme activity. We found that in the presence of the proteinase inhibitor, invasion of type I collagen by MDA-MB-231 cells was also reduced. These results indicate that collagenase-1 produced by the breast tumor cells may enhance stromal matrix degradation by enabling the tumor cells to modulate their own invasive behavior, and suggest that decreasing collagenase-1 levels may be effective in breast cancer therapy.

Retinoid-mediated suppression of tumor invasion and matrix metalloproteinase synthesis.

Cancer mortality usually results from the tumor invading the local environment and metastasizing to vital organs, e.g. liver, lung, and brain. Degradation of the extracellular matrix is, therefore, the sine qua non of tumor cell invasion. this degradation is mediated mainly by MMPs, and thus, inhibition of MMP synthesis is a target for anticancer agents. Tumor cells must traverse both the basement membrane (type IV collagen) and the interstitial stroma (type I collagen). Therefore, we used scanning electron microscopy to examine the invasive behavior of several aggressive tumor cell lines, A2058 melanoma cells, and SCC and FaDu squamous cell carcinomas through these matrices; and we monitored the ability of all-trans retinoic acid and several RAR-specific ligands to block invasion. We demonstrate that several retinoids, which are specific RAR alpha, beta, or gamma agonists/antagonists, selectively inhibited MMP synthesis in the three tumor cell lines. However, there was not a common pattern of MMP inhibition by a particular retinoid. For instance, a RAR alpha antagonist suppressed MMP-1 and MMP-2 synthesis in the melanoma cell line, but not in the FaDu or SCC-25 cells. On the other hand, synthesis of MMP-1 and MMP-9 by the FaDu cells was affected hardly at all, while a RAR gamma antagonist reduced the levels of MMP-2. Only all-trans retinoic acid reduced MMP-1 synthesis in these cells. We postulate that the differences may be related to a differential pattern of RAR expression in each of these cells, and that the RARs expressed by each cell line may not be targets of these RAR specific compounds. All-trans retinoic acid is a pan ligand, binding to all three RARs and, therefore, may modulate gene expression more generally. We conclude that the power of these new ligands lies in their specificity, which can be directed towards modulating expression of certain RARs and, thus, of certain MMPs. By blocking MMP synthesis, retinoids may be effective in cancer therapy by decreasing tumor invasiveness.

Xanthelasma palpebrarum: treatment with the ultrapulsed CO2 laser.

BACKGROUND AND OBJECTIVE: Due to its delicate location near the eye and the high recurrence rate, the therapy of xanthelasma palpebrarum is a difficult surgical task. Besides chemical, physical, and surgical procedures, various laser systems have been used to treat these lesions (argon laser, pulsed dye laser, and CO2 laser). This study was designed to critically evaluate the use of the ultrapulsed CO2 laser for the treatment of xanthelasma palpebrarum. STUDY DESIGN/MATERIALS AND METHODS: We report about the standardized treatment of 23 patients (52 periorbital xanthelasmas) and the results obtained after one treatment with a new generation, ultrapulsed CO2 laser (COHERENT Ultrapulse 5000C, Palo Alto, CA; 250-500 mJ; 600-900 microsec; 10,600 nm). The followup time was 10 months. RESULTS: All lesions could be removed completely with a single laser treatment. As for side effects, only transient pigmental changes (4% hyperpigmentations, 13% hypopigmentations) and no visible scarring was observed. Three patients (13%) developed a recurrence of xanthelasma. CONCLUSIONS: The ultrapulsed CO2 laser is an effective and safe therapeutic alternative to the hitherto described approaches.

Cell adhesion receptors and gap junctions in normal and neoplastic transformed thyrocytes.

In the thyroid cell adhesion receptors and gap junctions establish a complex modular network defining the structural properties of cells, their interactions with neighboring cells and the extracellular matrix. Neoplastic alterations of this network can lead to an imbalance of cell to cell communication and allows transformed cells to escape from the tissue to generate metastases. The present manuscript summarizes general and thyroid-specific aspects of the molecular basis of cell-cell contacts, an expanding field of tumor biology.