Browsing by Author "Hansen, Marlan R."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Middle Cranial Fossa (MCF) Approach without the use of Lumbar Drain for the Management of Spontaneous Cerebral Spinal Fluid (CSF) Leaks
    (Lippincott, Williams, and Wilkins, 2016-12) Nelson, Rick F.; Roche, Joseph P.; Gantz, Bruce J.; Hansen, Marlan R.; Department of Otololaryngology-Head and Neck Surgery, IU School of Medicine
    Objective: To determine the efficacy and morbidity of repairing spontaneous cerebrospinal fluid (CSF) leaks with the middle cranial fossa (MCF) approach without the use of a lumbar drain (LD), as perioperative use of LD remains controversial. Study Design: Retrospective review from 2003 to 2015. Setting: University of Iowa Hospitals and Clinics and Indiana University Health Center. Patients: Those with a confirmed lateral skull base spontaneous CSF leaks and/or encephaloceles. Intervention: MCF approach for repair of spontaneous CSF leak and/or encephalocele without the use of lumbar drain. Assessment of patient age, sex, body mass index (BMI), and medical comorbidities. Main Outcome Measure: Spontaneous CSF leak patient characteristics (age, sex, BMI, obstructive sleep apnea) were collected. Length of stay (LOS), hospital costs, postoperative complications, CSF leak rate, and need for LD were calculated. Results: Sixty-five operative MCF repairs were performed for spontaneous CSF leaks on 60 patients (five had bilateral CSF leaks). CSF diversion with LD was used in 15 of 60 patients, mostly before 2010. After 2010, only three of 44 patients (6.7%) had postoperative otorrhea requiring LD. The use of LD resulted in significantly longer LOS (3.6 ± 1.6 versus 8.7 ± 2.9 d) and hospital costs ($29,621). There were no postoperative complications in 77% (50 of 65) of cases. Three cases required return to the operating room for complications including frontal subdural hematoma (1), subdural CSF collection (1), and tension pneumocephalus (1). No patients experienced long-term neurologic sequelae or long-term CSF leak recurrence with an average length of follow-up of 19.5 months (range 3–137 mo). The average patient BMI was 37.5 ± 8.6 kg/m2. The average age was 57.5 ± 11.4 years and 68% were female. Obstructive sleep apnea was present in 43.3% (26 of 60) of patients. Conclusion: The morbidity of the MCF craniotomy for repair of spontaneous CSF leaks is low and the long-term efficacy of repair is high. Universal use of perioperative lumbar drain is not indicated and significantly increases length of stay and hospital costs. Obesity and obstructive sleep apnea are highly associated with spontaneous CSF leaks.
  • Thumbnail Image
    Item
    Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801
    (American Association of Neurological Surgeons, 2022-09-09) Dougherty, Mark C.; Shibata, Seiji B.; Clark, J. Jason; Canady, Franklin J.; Yates, Charles W.; Hansen, Marlan R.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objective: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. Methods: Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. Results: Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. Conclusions: The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.