Pilot Validation of a 3-Dimensional Printed Pituitary Adenoma, Vascular Injury, and Cerebrospinal Fluid Leak Surgical Simulator.

BACKGROUND AND OBJECTIVES: Endoscopic skull base surgery is a subspecialty field which would benefit significantly from high-fidelity surgical simulators. Giving trainees the opportunity to flatten their learning curve by practicing a variety of procedures on surgical simulators will inevitably improve patient outcomes. METHODS: Four neurosurgeons, 8 otolarynologists, and 6 expert course faculty agreed to participate. All participants were asked to perform a transsphenoidal exposure and resection of a pituitary adenoma, repair a cerebrospinal fluid (CSF) leak, control a carotid injury, and repair a skull base defect. The content, face, and construct validity of the 3-dimensional printed model was examined. RESULTS: The heart rate of the participants significantly increased from baseline when starting the carotid injury simulation (mean 90 vs 121, P = .029) and significantly decreased once the injury was controlled (mean 121 vs 110, P = .033, respectively). The participants reported a significant improvement in anxiety in facing a major vascular injury, as well as an increase in their confidence in management of major vascular injury, resecting a pituitary adenoma and repair of a CSF leak using a 5-point Likert scale (mean 4.42 vs 3.58 P = .05, 2 vs 3.25 P < .001, 2.36 vs 4.27 P < .001 and 2.45 vs 4.0 P = .001, respectively). The mean Objective Structured Assessment of Technical Skills score for experienced stations was 4.4, significantly higher than the Objective Structured Assessment of Technical Skills score for inexperienced stations (mean 3.65, P = .016). CONCLUSION: We have demonstrated for the first time a validated 3-dimensional printed surgical simulator for endoscopic pituitary surgery that allows surgeons to practice a transsphenoidal approach, surgical resection of a pituitary adenoma, repair of a CSF leak in the diaphragma sellae, control of a carotid injury, and repair of skull base defect.

Recreating the microscopic direct access Draf 2a frontal sinusotomy in the endoscopic era and comparison to an angled instrument approach.

PURPOSE: Microscopic Draf 2a frontal sinusotomy relied on direct access. However, the modern-day endoscopic approach is hindered by the anterior-posterior dimensions of the frontal recess. The nasofrontal beak, angled endoscopes, and variable frontal recess anatomy make the surgery challenging. Carolyn's window frontal sinusotomy removes the limitation of anterior-posterior dimensions and is an endoscopic version of the microscopic Draf 2a. This study aims to compare the perioperative outcomes and morbidity from endoscopic direct access Draf 2a compared to angled access Draf 2a. METHODS: Consecutive adult patients (> 18 years) seen at a tertiary referral clinic who underwent Draf 2a frontal sinus surgery using either endoscopic direct access (Carolyn's window) or endoscopic angled instrumentation were included. Patients who underwent Carolyn's window were compared to those with angled Draf 2a frontal sinusotomy. RESULTS: One hundred patients (age 51.96 ± 15.85 years, 48.0% female, follow-up 60.75 ± 17.34 months) were included. 44% of patients used Carolyn's window approach. 100% [95% CI 98.2-100%] of patients achieved successful frontal sinus patency. Both groups were comparable for early morbidities (bleeding, pain, crusting, and adhesions) and late morbidities (retained frontal recess partitions). There were no other morbidities in the early and late postoperative periods. CONCLUSION: The endoscopic direct access Draf 2a, or Carolyn's window, removes the anteroposterior diameter limitation. The frontal sinus patency and early and late surgical morbidities of direct access Draf 2a were comparable with the angled Draf 2a frontal sinusotomy. Surgical modifications, often with drills and bone removal, can be successfully made to enhance access in endoscopic sinus surgery without concern for additional morbidity.

Endoscopic Endonasal Biopsy for Diagnosis of Undifferentiated Lesions of the Cavernous Sinus.

BACKGROUND: Radiologically undifferentiated lesions of the cavernous sinus can pose a diagnostic challenge. Although radiotherapy is the mainstay for treatment of cavernous sinus lesions, histologic diagnosis allows access to a wide variety of alternative treatment modalities. The region is considered a high-risk area for open transcranial surgical access, and the endoscopic endonasal approach presents an alternative technique for biopsy. METHODS: A retrospective case series was performed of all patients undergoing endoscopic endonasal biopsy of isolated cavernous sinus lesions at 2 tertiary institutions. The primary outcomes were the percentage of patients in whom a histologic diagnosis was achieved and the proportion of patients in whom therapy differed from radiotherapy alone. Secondary outcomes included preoperative and postoperative 22-item Sino-Nasal Outcome Test symptom scores, as well as perioperative adverse outcomes. RESULTS: Eleven patients underwent endoscopic endonasal biopsy, with a diagnosis achieved in 10 patients. The most common diagnosis was perineural spread of squamous cell carcinoma, followed by perineuroma and single cases of metastatic melanoma, metastatic adenoid cystic carcinoma, mycobacterium lepri infection, neurofibroma, and lymphoma. Six patients had treatments other than radiotherapy, including immunotherapy, antibiotics, corticosteroids, chemotherapy, and observation alone. There was no significant difference in prebiopsy and postbiopsy 22-item Sino-Nasal Outcome Test scores. There was 1 case of epistaxis requiring return to theater for cautery of the sphenopalatine artery and there were no mortalities. CONCLUSIONS: In a limited case series, endoscopic endonasal biopsy was safe and effective in obtaining diagnosis for cavernous sinus lesions and had a significant impact on therapeutic decision making.

Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients: A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses.

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous histological type (P = 0.004), COX-2 (P = 0.042), and p73 expression (P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P = 0.033) and with WRAP53 expression (P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P = 0.015), AEG-1 (astrocyte elevated gene-1) (P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.

Acute radiology rarely confirms sinus disease in suspected recurrent acute rhinosinusitis.

BACKGROUND: Episodic or recurrent sinonasal symptoms are often suspected as "sinus" in origin. With normal sinus radiology between events, the diagnosis of recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can produce episodic symptoms. In this study we analyze acutely performed computed tomography (CT) in a population with suspected or self-diagnosed "sinus" disease. METHODS: Patients referred to a tertiary clinic for suspected RecARS were assessed. Sinus changes were defined by CT (initial assessment) and during the acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal thickening, ostiomeatal compromise, and severe septal deformity were recorded. Symptom profile was assessed during both time-points with the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Forty-eight patients (49.5 ± 14.7 years of age, 70.8% female) were assessed. At presentation, 75% were resolute in a diagnosis of "sinus." Baseline Lund-Mackay scores were <6 (median 0 [interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and subdomains were similar to baseline. Septal deviation was similar (13.6% vs 15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%) and the other with triptan-responsive migraine, with incidental sinus changes. Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain otherwise undefined (12.5%). CONCLUSION: Patients with a history of "recurrent acute sinusitis" and normal CT scans between episodes rarely have abnormal CT findings during acute exacerbations of symptoms. Antibiotics and surgical intervention are often inappropriate in this population.

Tuning of the ocular vestibular evoked myogenic potential (oVEMP) to air- and bone-conducted sound stimulation in superior canal dehiscence.

Recent studies have demonstrated the frequency selectivity of air-conducted (AC) and bone-conducted (BC) stimuli in eliciting ocular vestibular evoked myogenic potentials (oVEMPs). In this study, frequency tuning of the oVEMP was assessed in patients with superior canal dehiscence (SCD) and compared with responses previously reported for healthy subjects. Six (five unilateral) SCD patients were stimulated using AC sound (50-1,200 Hz) and BC transmastoid vibration (50-1,000 Hz). Stimuli were delivered at two standardized intensities: one the same as previously used for healthy controls and the other at 10 dB above vestibular threshold (a similar relative intensity to that used in controls). For AC stimulation, SCD patients had larger oVEMP amplitudes across all frequencies tested for both stimulus intensities. Normalized tuning curves demonstrated greater high-frequency responses with the stronger stimulus. For BC stimulation, larger oVEMP amplitudes were produced at frequencies at and above 100 Hz using standard intensity stimuli. For the matched intensity above vestibular threshold, enhancement of the oVEMP response was present in SCD patients for 500-800 Hz only. We conclude that SCD causes greater facilitation for AC than BC stimuli. The high-frequency response is likely to originate from the superior (anterior) canal and is consistent with models of inner ear changes occurring in SCD.

Tuning of the ocular vestibular evoked myogenic potential to bone-conducted sound stimulation.

Ocular vestibular evoked myogenic potentials (oVEMPs) are a recently described clinical measure of the vestibulo-ocular reflex. Studies demonstrating differences in frequency tuning between air-conducted and bone-conducted (BC) oVEMPs suggest a separate vestibular (otolith) origin for each stimulus modality. In this study, 10 healthy subjects were stimulated with BC stimuli using a hand-held minishaker. Frequencies were tested in the range of 50-1,000 Hz using both a constant-force and constant-acceleration method. Subjects were stimulated at the mastoid process and the forehead. For constant-force stimulation at both sites, maximum acceleration occurred around 100 Hz, in differing axes. Both forms of stimulation had low-frequency peaks of oVEMP amplitudes (constant force: mastoid, 80-150 Hz; forehead, 50-125 Hz; constant acceleration: mastoid, 100-200 Hz; forehead, 80-150 Hz), for both sites of application, despite differences in the magnitude and direction of evoked head acceleration. For mastoid stimulation, ocular responses changed from out of phase to in phase for 400 Hz and above. Our results demonstrate that BC stimuli show tuning around 100 Hz, independent of stimulus site, that is not due to skull properties. The findings are consistent with an effect on a receptor with a resonance around 100 Hz, most likely the utricle.

Tuning of the ocular vestibular evoked myogenic potential (oVEMP) to AC sound shows two separate peaks.

The ocular vestibular evoked myogenic potential (oVEMP) is a relatively new method used to assess otolith-ocular pathways in humans. When elicited using air-conducted (AC) sound stimulation, the oVEMP is thought to reflect mostly saccular activation. However, it has been recently suggested that utricular afferents may also contribute to the AC evoked oVEMP. While previous frequency tuning studies of the AC evoked oVEMP report predominately high frequency sensitivity (>400 Hz), few have included the lower frequencies (<200 Hz) at which it has been proposed the utricle is most sensitive. In this study, ten normal subjects were stimulated with AC sound delivered unilaterally using headphones over frequencies from 50 to 1,200 Hz at a near constant A-weighted intensity of 120 dB peak sound pressure level. For AC stimulation, the oVEMP demonstrated maximum amplitudes around 600 Hz, with a second, smaller peak occurring around 100 Hz. The AC evoked oVEMP tuning has two peaks, a dominant one consistent with excitation of the saccule and a smaller one consistent with excitation of the utricle.