Preclinical study for treatment of hypospadias by advanced therapy medicinal products.

PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.

[Extreme stapedectomy]. / La stapedotomia estrema.

Extreme stapedectomy is an operation aimed at restoring a serviceable hearing in patients affected by far-advanced otosclerosis with profound hearing loss. Surgery is performed on the understanding that the hearing aid will still be needed after the operation. Therefore, patient's expectations should be confined to possibly improved performance with a hearing aid as a consequence of the operation. Clinical as well as audiological preoperative assessment must be very rigorous. Counselling is mandatory and a trial period with a hearing aid is strongly advisable. Our experience is based on 15 cases, operated on between 1984 and 1988. A small fenestra technique was performed using wire-teflon piston prostheses. Results were satisfactory and in accordance with the ratio of the procedure in 8 cases (53%). 7 patients (47%) yielded an unsuccessful outcome and 2 of them had a dead ear (13%). This high rate of labyrinthine failure, the improvement in hearing aids and cochlear implants technologies well are likely to reduce the number of potential candidates for an extreme stapedectomy. However, this operation should be still kept in the otologist's armamentarium as a possible option in borderline cases.