Cochlear implant (CI) provision provides children with congenital SSD with significant audiological and subjective benefits which can be seen even in children implanted after the age of 3;6. The problem of limited use and nonuser, however, should not be ignored and has to be considered for further studies.

Glioblastoma multiforme (GBM) is an incurable malignancy with inherent tendency to recur. In this study, we have comparatively analyzed the epigenetic profile of 32 paired tumor samples of relapsed GBM and their corresponding primary neoplasms with special attention to genes involved in the mitochondria-independent apoptotic pathway. The CpG island promoter hypermethylation status was assessed by methylation-specific polymerase chain reaction and selected samples were double checked by bisulfite genomic sequencing. Thirteen genes were analyzed for DNA methylation: the pro-apoptotic CASP8, CASP3, CASP9, DcR1, DR4, DR5 and TMS1; the cell adherence CDH1 and CDH13; the candidate tumor suppressor RASSF1A and BLU; the cell cycle regulator CHFR and the DNA repair MGMT. The CpG island promoter hypermethylation profile of relapsed GBM in comparison with their corresponding primary tumors was identical in 37.5% of the cases, whereas in 62.5% of patients, differences in the DNA methylation patterns of the 13 genes were observed. The most prominent distinction was the presence of previously undetected CASP8 hypermethylation in the GBM relapses (P = 0.031). This finding was also linked to the observation that an unmethylated CASP8 CpG island together with methylated BLU promoter in the primary GBM was associated with prolonged time to tumor progression (P = 0.0035). Our data strongly suggest that hypermethylation of the pro-apoptotic CASP8 is a differential feature of GBM relapses. These remarkable findings may foster the development of therapeutic approaches using DNA demethylating drugs and activators of the extrinsic apoptotic pathway to improve the dismal prognosis of GBM.

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Induction chemotherapy followed by primary radiotherapy in responders is considered an alternative to surgery for advanced cancer of the larynx and hypopharynx (LHC). Comparison of therapeutic approaches is challenging and must respect oncological and functional outcome as well as quality of life during and after treatment. One aspect of primary radiochemotherapy is the option of salvage surgery in case of residual tumor. The outcome after salvage surgery following new organ-preserving strategies has to be examined. All patients undergoing induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy from 01/96 to 07/05 were included. Salvage surgery was performed either for local recurrence or suspected persistent nodal disease. Complete tumor removal, perioperative morbidity, and overall survival were analyzed in a retrospective study. 28 out of 134 patients underwent salvage surgery after primary treatment with induction chemotherapy and radiotherapy for advanced LHC. 15 patients had laryngectomy (LE) with neck dissection (ND), while 1 patient had lasersurgical partial laryngeal resection with ND for local recurrences. Twelve patients had salvage ND for suspicion of persistent lymph node metastases. 73% of LE patients had major postoperative problems such as pharyngocutaneous fistulas. In 56% of the cases, tumor removal turned out to be microscopically incomplete. Eight out of 12 patients who underwent salvage ND because of suspicious lymph nodes (66%) were free of vital tumor. When metastatic disease was present in the neck (4/12), recurrences occurred in 75% during postoperative follow-up. Only 2 out of 20 patients undergoing surgery for histologically proven recurrence after radiochemotherapy (10%) are actually tumor-free and alive after a mean observation time of 43.9 months. Salvage surgery for local recurrence is associated with high morbidity and poor oncological and functional outcome. ND for suspicious persistent nodal disease after radiochemotherapy can be an over-treatment. In our patients, it was burdened with cervical recurrences and distant metastases in presence of histologically confirmed lymph node metastases. In the light of our results, unfavourable outcome after salvage surgery must be pointed out when initially informing patients about different therapeutic options for advanced LHC.