Current treatment paradigms in the management of lymphatic malformations.

Lymphatic malformations (LMs) are benign abnormalities of the lymphatic system that can be significantly infiltrative and intimately involve critical structures of the head and neck, making their management difficult. Historically, LMs have been managed by surgical excision, but this treatment approach results in significant morbidity and a high recurrence rate secondary to subtotal resection. As an alternative to surgery a variety of drugs have been used as intralesional sclerosants and immunotherapeutics. These agents offer improved outcomes with lower morbidity as compared to surgery when targeted to macrocystic LMs. However intralesional therapy is not effective in the treatment of microcystic LMs. The development of treatments that are effective for all types of LMs will require further understanding of lymphangiogenesis and the pathogenesis of LMs.

Interaction of neurotrophin signaling with Bcl-2 localized to the mitochondria and endoplasmic reticulum on spiral ganglion neuron survival and neurite growth.

Enhanced spiral ganglion neuron (SGN) survival and regeneration of peripheral axons following deafness will likely enhance the efficacy of cochlear implants. Overexpression of Bcl-2 prevents SGN death but inhibits neurite growth. Here we assessed the consequences of Bcl-2 targeted to either the mitochondria (GFP-Bcl-2-Maob) or the endoplasmic reticulum (ER, GFP-Bcl-2-Cb5) on cultured SGN survival and neurite growth. Transfection of wild-type GFP-Bcl-2, GFP-Bcl-2-Cb5, or GFP-Bcl-2-Maob increased SGN survival, with GFP-Bcl-2-Cb5 providing the most robust response. Paradoxically, expression of GFP-Bcl-2-Maob results in SGN death in the presence of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF), neurotrophins that independently promote SGN survival via Trk receptors. This loss of SGNs is associated with cleavage of caspase 3 and appears to be specific for neurotrophin signaling, insofar as coexpression of constitutively active mitogen-activated kinase kinase (MEKDeltaEE) or phosphatidyl inositol-3 kinase (P110), but not other prosurvival stimuli (e.g., membrane depolarization), also results in the loss of SGNs expressing GFP-Bcl-2-Maob. MEKDeltaEE and P110 promote SGN survival, whereas P110 promotes neurite growth to a greater extent than NT-3 or MEKDeltaEE. However, wild-type GFP-Bcl-2, GFP-Bcl-2-Cb5, and GFP-Bcl-2-Maob inhibit neurite growth even in the presence of neurotrophins, MEKDeltaEE, or P110. Historically, Bcl-2 has been thought to act primarily at the mitochondria to prevent neuronal apoptosis. Nevertheless, our data show that Bcl-2 targeted to the ER is more effective at rescuing SGNs in the absence of trophic factors. Additionally, Bcl-2 targeted to the mitochondria results in SGN death in the presence of neurotrophins. (c) 2010 Wiley-Liss, Inc.

Split-thickness skin grafting in postmastoidectomy revision and in lateral temporal bone resection.

OBJECTIVES: Use of split-thickness skin grafts (STSG) in revision canal wall-down (CWD) mastoidectomy was compared with STSG in lateral temporal bone resection (LTBR). STUDY DESIGN AND SETTING: A retrospective study of 11 patients undergoing revision CWD mastoidectomy and 6 patients undergoing LTBR with STSG in an academic health center setting. RESULTS: Successful epithelialization of the mastoid cavity occurred in 9 patients (82%) undergoing CWD mastoidectomy. Subjective success, measured as reduction in complaints of otorrhea, occurred in 10 patients (91%). In the 6 patients who underwent LTBR and STSG successful epithelialization of the temporal bone defect occurred in 5 patients (83%). CONCLUSIONS: Successful and rapid epithelialization occurred in the revision mastoidectomy cohort as well as in the primary temporal bone resection cohort. SIGNIFICANCE: Placement of STSG is a useful adjunct in revision CWD mastoidectomy as well as in primary LTBR for cancer.