E M Ehlers

Purpose: Diffuse malignant pleural mesothelioma is the most common primary pleural malignancy. At the beginning of the last century, this tumor was of minor incidence. Meanwhile, the use of asbestos has led to and is still leading to a rise in pleural mesothelioma incidence. There is no standard therapy for this highly aggressive disease and the development of new therapeutic strategies is imperative. Methods: We, therefore, investigated the morphological and pharmakokinetic effects of a combined thermochemotherapy consisting of the administration of different dosages of mafosfamide with and without the application of a 1-h hyperthermia at 41.7 °C on the human biphasic malignant pleural mesothelioma cell line MSTO-211H. After therapy, cells were prepared for light and electron microscopy. BrdU-incorporation for the S-phase fraction, TUNEL-labeling for detection of apoptosis, and quantitative assessments using the MTT assay were performed. Results: Our results demonstrate that the combination of mafosfamide with hyperthermia leads to qualitatively and quantitatively enhanced cellular damage compared to monotherapy. During combined thermochemotherapy, cell damage and death is already induced at lower mafosfamide concentrations than without hyperthermia which suggests an additive effect from hyperthermia to the action of the alkylating drug mafosfamide. Cell death thereby mostly occurs as necrotic cell death rather than as apoptosis, although in a combined thermochemotherapy apoptosis is induced temperature-dependently, when comparing temperatures from 37 °C to 43 °C. Conclusions: We suggest that the effect of substances such as ifosfamide and cyclophosfamide which are in clinical use, might be enhanced by the combination of local or regional hyperthermia in order to improve the therapeutical index of these substances in the treatment of pleural mesothelioma.

Owing to the poor regenerative capacity of cartilage, cartilaginous defects are considered to represent pre-arthrotic factors. In addition to autologous and allogenic osteochondral fragments, proliferative tissue, such as periosteum and perichondrium are increasingly being used as graft material. The aim of treatment is to eliminate the defect and to restore the load-bearing capacity and function of the affected joint. A new, recently introduced, approach aims to stimulate the formation of new cartilage via autologous cultured chondrocyte implantation (ACI). The rationale for this treatment is the restoration of loadable hyaline or hyaline-like articular cartilage. Although long-term results are not yet available, clinical follow-up data obtained so far are encouraging. In addition to existing methods of treating cartilaginous defects, this article describes a modified method of transplantation of autologous chondrocytes. With this method the periosteal flap used to cover a defect is replaced by an absorbable collagenl/III membrane (Chondrogide, Geistlich Wolhusen, Switzerland) that is used as a carrier for the patient's own chondrocytes. After placement in the defect, the membrane is fixed in place with fibrin glue (MACI).