Richard J. Vivero

Comparison of transnasal endoscopic and open craniofacial resection for malignant tumors of the anterior skull base

Craniofacial resection (CFR) represents the traditional approach for resection of anterior skull base (ASB) malignancies. However, this past decade has witnessed the emergence of transnasal endoscopic ASB resection (TER) as a feasible alternative. The aim of this study was to compare TER and CFR for ASB malignancy resection.

Improvement in neuronal survival after ischemic preconditioning in hippocampal slice cultures

The main goals of the current study were to assess: (a) whether a sublethal ischemic insult could protect the CA1 subregion of the hippocampus in organotypic slices against a lethal ischemic insult; and (b) whether this protection is long lasting as determined with an accurate immunohistochemical neuronal marker, NeuN. Hippocampal slice cultures were grown for 12-14 days in vitro. Slices were exposed either to oxygen/glucose deprivation (OGD) for 45 min (ischemia), or OGD for 15 min (ischemic preconditioning), 48 h prior to 45 min OGD, or were untreated (sham). Cell death was estimated by propidium iodide fluorescence 1 day after OGD and by NeuN immunohistochemistry 7 days after OGD. Image analysis was employed to measure the relative optical density of the NeuN-signal in all groups. After ischemia, damaged neurons were shrunken or lost and NeuN immunoreactivity was reduced. Relative optical density of NeuN (ROD [NeuN]) was 0.193+/-0.015 in control (sham) (n=9). In slices that underwent ischemia, ROD [NeuN] declined to 0.108+/-0.018 (n=5) in CA1 (*P<0.05 ROD [NeuN] in preconditioned slice cultures was 0.190+/-0.037 (76% higher than the ischemia group). Similar results were found after measuring PI fluorescence. In the CA1 sub-region, PI fluorescence was about 13, 47 and 17% in the sham, ischemic and IPC groups, respectively. We suggest that the immunohistochemical approach validates the dye uptake method used in slice cultures and yields quantitative data specific for neurons. We also conclude that the organotypic hippocampal slice model is useful for studying delayed ischemic preconditioning that is maintained for hours or days after the preconditioning event.

Endoscopic reconstruction of large anterior skull base defects using acellular dermal allograft.

Background Endoscopic repair of small- to medium-sized anterior skull base (ASB) defects using bone, cartilage, fascia, fibrin glue, lipolized dura, and, more recently, acellular dermal allograft have all been described with equal efficacy. The purpose of this study was to review our experience with the use of acellular dermis as the sole graft material in endoscopic reconstruction of large ASB defects. Methods A retrospective chart review of all patients who underwent endoscopic repair of ASB defects at the University of Miami between the years of 2001 and 2006 was conducted. Fifty-six patients were identified who met these criteria. All repairs were performed by a transnasal, endoscopic approach. Outcome measures included success of graft take and incidence of major and minor complications. Dural defect size was defined as small (<0.4 cm), intermediate (0.4–2.0 cm), and large (>2.0 cm). Results AlloDerm (AlloDerm. LifeCell Corp. Woodlands, TX) was used as the primary graft material in 30/55 (55%) cases; 16/55 (29%) of the repaired defects were classified as large. Graft success was 97% in the AlloDerm group and 92% in the non-AlloDerm group. The incidence of major and minor complications in the AlloDerm group was 0 and 3.3%, respectively. In the non-AlloDerm group, the incidence of major and minor complications was 4 and 12%, respectively. There were no statistical differences in the complication rates based on the type of repair or defect size. Conclusion Alloderm can be used successfully to repair ASB defects, including large defects that are >2 cm in size with little or no morbidity.

Dexamethasone Base Conserves Hearing from Electrode Trauma‐Induced Hearing Loss

Objective/Hypothesis: Local treatment of the cochlea after electrode insertion trauma with dexamethasone base conserves hearing against trauma‐induced loss.

Mechanisms of hearing loss from trauma and inflammation: otoprotective therapies from the laboratory to the clinic.

This article reviews a series of in vitro and in vivo studies that examined the otoprotective efficacy of locally delivered dexamethasone and explored the mechanisms by which dexamethasone protects auditory hair cells. These studies used auditory threshold testing in response to pure tone stimuli, organ of Corti explant cultures, FITC-phalloidin-stained explants, and surface preparations to determine hair cell density, osmotic pump delivery of dexamethasone into the scala tympani, an animal model of electrode insertion trauma (EIT)-induced hearing loss, and real-time RT-PCR studies of gene expression levels. Local delivery of two different formulations of dexamethasone conserved hearing and protected hair cells in an animal model of cochlear implantation. Dexamethasone treatment protected hair cells in organ of Corti explants exposed to an ototoxic level of an inflammatory cytokine, and gene expression studies showed that this protection was accomplished by increased expression levels of anti-apoptosis genes (e.g. Bcl-2) and decreased levels of pro-apoptosis genes (e.g. Bax). We conclude that dexamethasone is an effective otoprotective drug for both the conservation of hearing and preservation of hair cells against trauma-induced losses. Locally delivered dexamethasone is a promising therapeutic approach for the conservation of hearing during the process of cochlear implantation.

Efficacy of transnasal endoscopic resection for malignant anterior skull-base tumors†

Craniofacial resection (CFR) has been the standard of care for malignant tumors of the anterior skull base (ASB). However, during the past 2 decades, transnasal endoscopic resection (TER) has gained significant popularity. The purpose of this study is to compare CFR and TER with respect to perioperative and oncologic outcomes.

Cochlear implantation in common forms of genetic deafness.

Genetic factors are among the main etiologies of severe to profound hearing loss and may play an important role in cochlear implantation (CI) outcomes. While genes for common forms of deafness have been cloned, efforts to correlate the functional outcome of CIs with a genetic form of deafness carried by the patient have been largely anecdotal to date. It has been suggested that the differences in auditory performance may be explained by differences in the number of surviving spiral ganglion cells, etiology of hearing loss, and other factors. Knowledge of the specific loci and mutations involved in patients who receive cochlear implants may elucidate other factors related to CI performance. In this review article, current knowledge of cochlear implants for hereditary hearing loss will be discussed with an emphasis on relevant clinical genotype-phenotype correlations.

Conservation of hearing and protection of auditory hair cells against trauma-induced losses by local dexamethasone therapy: molecular and genetic mechanisms.

Abstract Hypothesis: Dexamethasone (DXM) protects hearing against trauma-induced loss. Materials: in vivo: A guinea pig model of electrode induced trauma (EIT)-induced hearing loss was used to locally deliver dexamethasone. In vitro: TNF-α-challenged organ of Corti explants treated with DXM or polymer-eluted DXM +/− PI3K/Akt/PkB/NFkB inhibitors were used for hair cells count and gene expression studies. Results: in vivo: local DXM treatment of EIT-animals prevents trauma-induced loss of ABR thresholds that occurs in EIT-animals and EIT-animals treated with the carrier solution (i.e., AP), and prevented loss of auditory hair cells. In vitro: DXM and polymer-eluted DXM were equally effective in protecting hair cells from ototoxic levels of TNF-α Inhibitor treated explants demonstrated that DXM treatment requires both Akt/PKB and NFkB signalling for otoprotection. DXM treatment of explants showed up regulation of anti-apoptosis related genes (i.e., Bcl-2, Bcl-xl) and down regulation of pro-apoptosis related genes (i.e., Bax, TNFR-1). Conclusions: DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.

L-N-Acetylcysteine treatment is associated with improved hearing outcome in sudden idiopathic sensorineural hearing loss.

Abstract Conclusion: Combination therapy corticosteroids plus an oral antioxidant L-N-acetylcysteine (LNAC) was associated with improved hearing over corticosteroids alone, particularly at the 6-month follow-up and at high frequencies (i.e. 4000 Hz). This is the first report of a beneficial effect of LNAC in sudden idiopathic sensorineural hearing loss (SISNHL). Objective: To determine the association between antioxidant treatment and functional outcomes in SISNHL. Methods: This was a case-control study of adult patients with SISNHL, treated with oral prednisone plus intratympanic dexamethasone either alone or in combination with LNAC. The outcome measure was change in pure-tone thresholds at 500–4000 Hz. Hearing recovery was also recorded as the percentage of subjects with final pure-tone threshold average (PTA) within 50% of the difference between the initial value of the affected ear and the value of the unaffected ear. Comparisons were made between combination (corticosteroids plus LNAC) and single (no LNAC use) therapy groups. Results: At 6 months, the mean PTA improvements were 26.1 dB and 15.1 dB for the combination and single therapy groups, respectively (p = 0.046). Higher gains at 4000 Hz were noted with LNAC use. The percentage of patients with at least 50% recovery was 63% and 35% for the combination and single therapy groups, respectively (p = 0.0319).

En bloc resection of lacrimal sac tumors and simultaneous orbital reconstruction: Surgical and functional outcomes

Purpose: To describe a surgical technique of en bloc resection of lacrimal sac tumors by the shared expertise of 2 specialists to achieve optimal tumor margin clearance and the simultaneous reconstruction of the bony defect to preserve ocular functions and cosmesis. Methods: All patients who had resection of malignant nasolacrimal drainage system tumors using the combined technique and posttreatment protocol between 1997 and 2011 were studied in this retrospective, noncomparative, interventional case series. A combined medial maxillectomy and medial orbitotomy for en bloc resection of the lacrimal sac tumor was followed by reconstruction with a tailored contoured titanium mesh to support the globe and eyelid. Disease relapse, disease survival, ocular functions (vision loss, motility, globe dystopia, and diplopia), and cosmesis (medial canthal tendon dystopia and eyelid retraction) were documented. Results: Fourteen patients with malignant lacrimal sac tumors underwent en bloc resection. Postoperative radiation was ultimately administered to 9 patients. All patients but one were alive at last follow up. Tumor recurred locally in 2 patients with a regional recurrence in a third patient. Complications from radiation therapy included skin breakdown over the mesh (9/14 patients) with nasocutaneous fistula, medial canthal tendon dystopia (2/14 patients), and corneal perforation in a patient with recurrent disease. Despite removal of the tear drainage system, only 7 of 14 patients reported epiphora. None of the patients developed diplopia after resection and radiation therapy. Conclusions: The combined sinus–orbit approach is an effective method of managing lacrimal sac tumors to achieve optimal tumor clearance from the orbit and nasal cavity. Simultaneous reconstruction of the bony defect with a contoured titanium mesh provides a fixation anchor for the medial canthal tendon and globe support and serves as a supporting platform for the lower eyelid and cheek to minimize midface collapse. Postoperative radiation is associated with skin flap breakdown and nasocutaneous fistula formation.