Hydroxyapatite Use in Repair of Lateral Skull Base CSF Leaks Via Transmastoid Approach: When Does It Work?

OBJECTIVE: The objective of this study is to evaluate the efficacy and outcomes of using a transmastoid approach with hydroxyapatite cement to repair lateral skull base cerebrospinal fluid (CSF) leaks. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary-level care hospital. PATIENTS: Surgical patients 18 years or older between 2013 and 2022 with spontaneous CSF leak. INTERVENTIONS: Trans-mastoid approach for skull base repair using hydroxyapatite cement. MAIN OUTCOME MEASURES: Failure rate of repair; location and size of defect, patient demographic factors. RESULTS: Of the 60 total defects (55 patients, 5 bilateral repairs) that underwent CSF leak repair using hydroxyapatite cement, the success rate was 91.66% (55 successful repairs). The average defect size in unsuccessful repairs was 1.15 cm compared with 0.71 cm for successful repairs. In addition, 80% (4/5) of the failed repairs were in the tegmen tympani region. Higher failure rate was noted in women (3/5) and in former smokers (4/5). Average time to recurrent symptoms was 1.75 years in the failed repair cohort. Of the patients with failed repairs, 4/5 were prescribed acetazolamide before their second procedure with successful second repair. In addition, five patients experienced postoperative headaches, three (5.4%) of whom required placement of VP shunts to relieve increased intracranial pressure. Two patients (3.6%) had complications of either infection or hearing loss. CONCLUSIONS: Transmastoid approach utilizing hydroxyapatite is a successful approach for CSF leak repair, with a low complication and failure rate. Women, prior smoking history, and larger defects in the tegmen tympani region may need alternative materials or approach for repair. Long follow-up is warranted as recurrence of symptoms might be delayed. In cases of benign intracranial hypertension, adjuvant treatment with either acetazolamide or VP shunt placement may prevent failures.

24R,25-Dihydroxyvitamin D3 regulates breast cancer cells in vitro and in vivo.

BACKGROUND: Epidemiological studies indicate high serum 25(OH)D3 is associated with increased survival in breast cancer patients. Pre-clinical studies attributed this to anti-tumorigenic properties of its metabolite 1α,25(OH)2D3. However, 1α,25(OH)2D3 is highly calcemic and thus has a narrow therapeutic window. Here we propose another metabolite, 24R,25(OH)2D3, as an alternative non-calcemic vitamin D3 supplement. METHODS: NOD-SCID-IL2γR null female mice with MCF7 breast cancer xenografts in the mammary fat pad were treated with 24R,25(OH)2D3 and changes in tumor burden and metastases were assessed. ERα66+ MCF7 and T47D cells, and ERα66- HCC38 cells were treated with 24R,25(OH)2D3in vitro to assess effects on proliferation and apoptosis. Effects on migration and metastatic markers were assessed in MCF7. RESULTS: 24R,25(OH)2D3 reduced MCF7 tumor growth and metastasis in vivo. In vitro results indicate that this was not due to an anti-proliferative effect; 24R,25(OH)2D3 stimulated DNA synthesis in MCF7 and T47D. In contrast, markers of invasion and metastasis were decreased. 24R,25(OH)2D3 caused dose-dependent increases in apoptosis in MCF7 and T47D, but not HCC38 cells. Inhibitors to palmitoylation, caveolae integrity, phospholipase-D, and estrogen receptors (ER) demonstrate that 24R,25(OH)2D3 acts on MCF7 cells through caveolae-associated, phospholipase D-dependent mechanisms via cross-talk with ERs. CONCLUSION: These results indicate that 24R,25(OH)2D3 shows promise in treatment of breast cancer by stimulating tumor apoptosis and reducing metastasis. GENERAL SIGNIFICANCE: 24R,25(OH)2D3 regulates breast cancer cell survival through ER-associated mechanisms similar to 24R,25(OH)2D3 effects on chondrocytes. Thus, 24R,25(OH)2D3 may modulate cell survival in other estrogen-responsive cell types, and its therapeutic potential should be investigated in ER-associated pathologies.