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Clough Shelton

Publications and source records attributed to Clough Shelton.

At least 19 recordsLinked to original sources
PubMed2007

Combined petrosal approaches in the management of temporal bone meningiomas.

OBJECTIVES: To evaluate the indications and outcomes of the combined petrosal approaches in the surgical management of temporal bone meningiomas. STUDY DESIGN: Retrospective chart review. SETTING: University teaching hospital. PATIENTS: Adults with temporal bone meningiomas. INTERVENTION(S): Meningioma removal using a combined petrosal approach. MAIN OUTCOME MEASURE(S): Cranial nerve outcomes, complications, completeness of resection, and recurrence rates. RESULTS: Forty-nine patients underwent surgical excision of a temporal bone meningioma between 1996 and 2004 at our institution. Nineteen of these patients required a combined petrosal approach for excision. The most common presenting complaints were balance disturbance, 11 (58%); hearing loss, 10 (53%); headache, 10 (53%); and tinnitus, 9 (47%). The most common tumor origin was of the petrous ridge (14; 74%). Average tumor size was 3.1 cm. Complete resection was possible in 17 (89%) patients. Upper cranial nerve (III-VI) function was improved in two (11%) patients and worsened in three (16%) patients. Lower cranial nerve (IX-XII) function improved in one (5%) patient and was worsened in one (5%) patient. Postoperative facial nerve function was Grades I to II in 16 (84%) patients and Grades III to IV in 1 (5%) patient at last follow-up. Hearing data were available in 14 patients. Of those patients, 11 (85%) had serviceable hearing after surgery. The most common surgical complication was a cerebrospinal fluid leak, with three (16%) incidences. There were no reported incidents of stroke, death, or meningitis in the cohort. CONCLUSION: The use of the combined petrosal approach for temporal bone meningioma resection results in favorable outcomes for the patient. The incidence of complications is acceptably low, and cure rates are high.

Adult↗
PubMed2007

Electrode independence in intraneural cochlear nerve stimulation.

OBJECTIVES/HYPOTHESIS: We have previously reported feline electrophysiological and anatomical studies focused on the development of an intraneural auditory neuroprosthesis. Because only the tips of the electrodes implanted in the cochlear nerve are the stimulating elements that abut the nerve axons, we hypothesize that intraneural stimulation will be highly focal in nature. In this article, we report the electrophysiological characterization of the selective activation of subpopulations of cochlear nerve fibers via electrodes implanted in feline cochlear nerve. STUDY DESIGN: We have used a forward-masking paradigm to estimate the extent of stimulation overlap produced by pairs of electrodes implanted into the cochlear nerve. METHODS: The technique uses sequential stimulation via masking and probe electrodes and monitoring of the electrically evoked auditory brain stem response as an index of cochlear nerve fiber recruitment. We investigated overlap in all possible electrode pair combinations. RESULTS AND CONCLUSION: Many electrode pairs manifest virtually no overlap in the subpopulations of fibers excited by perithreshold stimuli, whereas most had considerable overlap at higher stimulation levels. However, we also noted that our measured overlap was similar across electrodes possibly because of lack of specificity of the whole nerve electrically evoked auditory brain stem response as an assay for this parameter. These findings indicate that direct cochlear nerve stimulation via intraneural electrodes provides selective excitation of small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve stimulation may selectively evoke narrow-band frequency percepts.

Animals↗
PubMed2007

The surgical learning curve in aural atresia surgery.

OBJECTIVE: The objective of this retrospective case review is to examine the effect of surgical learning on hearing outcomes and complications in congenital aural atresia surgery. PATIENTS: Sixty-four consecutive ears (in 60 patients) operated on during the period of 1994 to 2004 at a tertiary referral center were studied. INTERVENTION(S): Intervention consisted of aural atresiaplasty through an anterior approach by the same surgeon (C.S.). MAIN OUTCOME MEASURE(S): Hearing outcomes and complication rates were compared between four temporally sequential groups of 16 ears. Acceptable hearing and complication rate outcomes were defined as results comparable to larger series in the literature. RESULTS: Hearing results, in the short term, comparable to larger series were achieved during the first group of ears (nos. 1-16). A plateau in the learning curve for short-term hearing outcomes was achieved after the first two groups, that is, after 32 ears. Hearing outcomes, in the long term (>1 year) comparable to larger series, were achieved in the second group of ears (nos. 16-32). The learning curve for long-term hearing demonstrated a significant improvement in outcomes in the final group of 16 ears compared with the first 48 ears. Long-term hearing results for the final group show closure of the postoperative air-bone gap to less than 30 dB in 94% of cases. Postoperative complication rates were equivalent to larger series in the first group of 16 ears and showed no statistically significant difference between the four groups. There was one patient with sensorineural hearing loss after surgery; there were no anacoustic ears and no facial palsies in the study group. CONCLUSIONS: A learning curve of at least 32 ears was required to achieve stable short-term hearing results. To achieve stable long-term hearing results required a learning curve of at least 48 patients in our series. Complication rates remained stable throughout the study period.

Adolescent↗
PubMed2006

Reversible peripheral vestibulopathy: the treatment of superior canal dehiscence.

OBJECTIVE: Superior canal dehiscence (SCD) is a recently described disorder that results from absence of bone over the superior semicircular canal. We have reviewed 30 cases of SCD found at our institution and report their presentation, workup, and response to therapy. STUDY DESIGN: Retrospective chart review of all patients diagnosed with SCD from 1999 to 2004 at the University of Utah. RESULTS: Thirty patients were identified with SCD. Patients presented with chronic disequilibrium (63%), Tullio's phenomenon (41%), pressure evoked vertigo (44%), hearing loss (30%), and pulsatile tinnitus (7%). ENG performed early in our series revealed abnormal nystagmus with sound presentation, Valsalva, or tympanogram; however, history and CT examination alone was used to identify this condition in most of our patients. Twenty-seven of the 30 patients had some symptoms related to SCD; the other 3 were found to have incidental SCD on CT examination. Of these patients, 14 had severe enough symptoms to warrant operative intervention. All, but one had resolution of their symptoms after completion of intervention. CONCLUSIONS: Superior canal dehiscence is a highly treatable form of vestibulopathy once recognized. When patients present with typical symptoms, workup with CT is reliable and accurate. Surgical intervention results in reversal of symptoms in most cases with low morbidity. EBM RATING: C-4.

Acoustic Impedance Tests↗
PubMed2006

Stapedectomy in congenital stapes fixation: are hearing outcomes poorer?

OBJECTIVE: To evaluate outcomes of stapedectomy surgery for congenital stapes fixation. STUDY DESIGN: Retrospective chart review. METHODS: The charts of 463 stapedectomies performed by 1 surgeon from 1996 to 2003 were reviewed. Patients with a history of childhood hearing loss and operative findings consistent with congenital fixation of the stapes were included. Patients with a history of trauma or chronic otitis media and those with otosclerosis were excluded. Thirty-six patients underwent stapedectomy for congenital fixation. Revision cases and those with inadequate postoperative bone or air conduction data were excluded. Inclusion criteria were met for 25 patients. Operative findings and hearing outcomes were evaluated. RESULTS: The study group was comprised of 25 stapedectomies. Closure of the air-bone gap to less than 10 dB was achieved in 48% of cases, and 80% had closure within 20 dB. A gap of more than 30 dB remained in 3 cases. There were 2 cases of sensorineural hearing loss with worsening of the bone conduction thresholds by 15 dB and 30 dB. There were no instances of perilymph gusher. In addition to an excluded case that was not reconstructed because of facial nerve position, 3 of the included patients were found to have a dehiscent facial nerve at surgery. There were no facial nerve injuries, and fixation of the malleus or incus was not found in any of the included patients. When hearing outcomes were compared with our results for otosclerosis over the same time period, rates of closure to within 10 dB and 20 dB were significantly worse in the congenital group. CONCLUSION: Closure of the air-bone gap in this population differs from our results in stapedectomy done for otosclerosis. This difference likely reflects subtle anatomic variations in the congenital group that affect the effectiveness of the prosthesis. Despite the difference in results, stapedectomy for congenital fixation remains an effective method to achieve significant hearing improvement in the majority of patients. EBM RATING: B-3b.

Adolescent↗
PubMed2006

The radiologic diagnosis of endolymphatic sac tumors.

OBJECTIVE: To identify and classify radiologic criteria for the diagnosis of endolymphatic sac tumors. STUDY DESIGN: Retrospective case review. Tertiary referral center. METHODS: 31 adult patients (32 tumors) with imaging (computed tomography [CT], magnetic resonance imaging [MRI], and/or angiography) and histopathologic diagnoses of lesions that involved the posterior temporal bone from July 1995 to August 2004 were included in the study. Interventions were diagnostic. Main outcome measures were CT, MRI (T1, T1 with gadolinium enhancement and T2-weighted), and angiographic features of seven patients (eight temporal bones) with endolymphatic sac tumors were examined and compared to the radiologic findings of the 24 historical control patients with various lesions involving the posterior temporal bone. RESULTS: CT findings of endolymphatic sac tumors revealed lesions centered over the endolymphatic sac, retrolabyrinthine, and presigmoid regions of the temporal bone. Central calcific spiculation and posterior rim calcification was present in all lesions (100%) on CT examination. T1-weighted MRI scans showed hyperintense foci in seven of eight lesions (88%). T1-weighted post-gadolinium scans showed heterogeneous enhancement in all cases (100%). T2-weighted images showed heterogeneous signals in all lesions (100%). Angiography (traditional or magnetic resonance angiography [MRA]) identified exclusive external carotid supply for lesions less than 3 cm. Tumors greater than 3 cm were supplied by external carotid, internal carotid, and posterior fossa circulation arteries. CONCLUSIONS: Reliable radiologic criteria to preoperatively identify endolymphatic sac tumors exist. Preoperative diagnosis of posterior temporal bone lesions enables appropriate surgical planning and treatment of the pathology.

Adult↗
PubMed2005

Two families with nonsyndromic low-frequency hearing loss harbor novel mutations in Wolfram syndrome gene 1.

Although hereditary hearing loss is highly heterogeneous, only a few loci have been implicated with low-frequency hearing loss. Mutations in one single gene, Wolfram syndrome 1 (WFS1), have been reported to account for most familial cases with this type of hearing impairment. This study was conducted to determine the cause of nonsyndromic low-frequency hereditary hearing impairment in two large families. Two large families from Switzerland and United States with low-frequency hearing loss were identified. Genomewide linkage analysis was performed followed by mutation screening in the candidate gene WFS1 with direct DNA sequencing and restriction fragment analysis. Both families were linked to DFNA6/14/38 with lod scores>3. Two novel heterozygous missense mutations in WFS1 were identified: c.2311G>C leading to p.D771H in the Swiss family and c.2576G>C leading to p.R859P in the US family. The sequence alteration was absent in 100 control chromosomes. Nonsyndromic low-frequency hereditary hearing impairment seems to be predominantly a monogenic disorder due to WFS1. We confirm that most mutations in WFS1 associated with isolated low-frequency hearing loss are clustered in the C-terminal protein domain coded by exon 8.

Adult↗
PubMed2005

Ventilation tubes and cochlear implants: what do we do?

OBJECTIVE: To determine current practice management with respect to ventilation tubes and cochlear implants. STUDY DESIGN: Questionnaire. SETTING: All members of the American Neurotology Society were sent questionnaires. MAIN OUTCOME MEASURES: Members were asked a series of questions including how they deal with ventilation tubes before cochlear implantation, how they manage serous otitis media in patients undergoing cochlear implantation, and how they manage otitis prone children with cochlear implants. RESULTS: Two hundred and twenty members returned questionnaires. Surgeons who replied perform an average of 25 implants per year: 15 in adults and 10 in children. Analysis of the data revealed a wide practice variation between surgeons. Fifty-six percent of surgeons will place a cochlear implant in a patient with a clean, dry ventilation tube in place. More than half the surgeons will place a ventilation tube in a child with serous otitis media, let the ear settle down, and perform the cochlear implant at a second operation. Wide variation in the management of otitis prone children with cochlear implants exists with respect to placement of ventilation tubes. Only 5% of surgeons reported any complications with cochlear implants that they attributed to ventilation tubes. There were a number who suggested their practice had changed since the recent identification of issues involving meningitis in implantees. CONCLUSION: Wide practice variation exists with the management of ventilation tubes in cochlear implant patients. On the basis of the results of this survey, it is acceptable to place cochlear implants in patients with clean, dry ventilation tubes. It also acceptable to place ventilation tubes in otitis prone children with cochlear implants. Despite theoretic concerns, the reported incidence of complications is low.

Cochlear Implantation↗
PubMed2005

Stapedectomy outcomes: titanium versus teflon wire prosthesis.

OBJECTIVE: To compare the effectiveness of two stapes prostheses in hearing improvement of patients undergoing stapes surgery for otosclerosis. STUDY DESIGN: Retrospective chart review. METHODS: Titanium and Teflon wire stapes prostheses were compared with regard to effectiveness in closing the air-bone gap. The charts of 461 stapedectomies performed by one surgeon from 1996 to 2001 were reviewed. Patients who underwent stapedectomy for reasons other than otosclerosis, revision cases, and those with inadequate preoperative or postoperative bone-conduction threshold data were excluded. Small fenestra technique using either laser or drill was used for all patients. Inclusion criteria were met by 218 patients. Patients were then grouped according to type of prosthesis used, and hearing outcomes were compared. Measured outcomes were four frequency air-bone gap closure, pure-tone threshold, and rate of sensorineural hearing loss (SNHL). RESULTS: The study group was comprised of 35 titanium and 183 Teflon wire prostheses. Closure of the air-bone gap to less than 10 dB was achieved in 86% of the patients with Teflon prosthesis compared with 71% of those with titanium prostheses. The groups were equivalent in regard to site of otosclerotic disease as well as technique, laser or drill, used to create the fenestra. Rate of SNHL was low for both groups and not significantly different. CONCLUSIONS: Both prostheses provided comparable results, although the Teflon platinum wire prosthesis was slightly superior. The smaller numbers in the titanium group may confound these results. The design of the titanium prosthesis provides a crimp that is circumferential around the incus, and that prosthesis was selected in cases with a narrow incus. The selection bias may also influence the results seen in this study.

Adolescent↗
PubMed2005

Jugular foramen schwannomas: diagnosis, management, and outcomes.

OBJECTIVES/HYPOTHESIS: To describe the presentation, radiographic findings, and surgical management of seven patients who have been diagnosed and treated with jugular foramen schwannomas at the University of Utah. STUDY DESIGN: Retrospective chart review. METHODS: The charts of seven patients diagnosed with jugular foramen schwannomas were reviewed for presentation symptoms, radiographic findings, and physical examination findings. For the six who underwent surgical excision, the surgical procedure used, cranial nerve function results, audiometric results, perioperative complications, and other follow-up data are presented. RESULTS: Seven patients were identified from ages 24 to 69 years. Six of the seven underwent surgical excision. Primary presentation symptoms included dizziness, hearing loss, dysphagia, diplopia, tongue paresis, and hoarseness. The choice of surgical approach was based on the size and location of the tumor. All patients had complete excision of their tumors. The nerve of origin included the glossopharyngeal, vagus, and spinal accessory nerves. Preoperative cranial nerve dysfunction continued postoperatively for lower cranial nerves but resolved in patients who were noted to have preoperative dysfunction of cranial nerve V and VI. The rate of new lower cranial nerve injury was 15% and was only seen in the cranial nerves that were determined to be the nerve of origin. In two cases, a temporary feeding tube was required. No recurrences have been noted to date. CONCLUSIONS: Jugular foramen schwannomas can be successfully diagnosed preoperatively with computed tomography and magnetic resonance imaging. These tumors can be successfully managed with surgery and low morbidity.

Adult↗
PubMed2005

Implantation of the ossified cochlea: management with the split electrode array.

OBJECTIVES/HYPOTHESIS: To describe indications for, the surgical technique required, and the expected functional results of split electrode array cochlear implants. STUDY DESIGN: Retrospective chart review. METHODS: Data collected included etiology of deafness, radiographic findings, pre- and postoperative aided pure tone thresholds, and speech perception testing. Adult speech perception outcomes were measured using the Consonant Nucleus Consonant (CNC) monosyllable words and Hearing in Noise Test (HINT) in quiet/noise (+10 dB). The children were assessed using the Infants and Toddlers Meaningful Auditory Integration Scale. RESULTS: Five patients were implanted with a split electrode array. This included two adults and three children. Both adults had preoperative binaural aided pure tone averages worse than 50 dB and scores of 0% on both HINT quiet and CNC words. The children had undetectable preoperative aided thresholds and scored an average 4/40 on the IT-MAIS. Postimplant, the average threshold gain was 38.5 dB in the adults and 81.5 dB in the children. One adult improved to score 51%/22% on HINT quiet/noise at 6 months and 72%/30% at 12 months. The other adult continued to score 0% on HINT at 12 months but claimed substantial subjective auditory improvement after the first year of device use. The children averaged 28/40 on the IT MAIS at 6 months after implantation. Forty-two of 48 implanted electrodes were functional. CONCLUSIONS: The split electrode array is a useful alternative to traditional cochlear implants in treating deafened patients with cochlear ossification. Patients implanted with the split array show marked improvement in sound and speech perception.

Adult↗
PubMed2004

Meningioma of the jugular foramen: glomus jugulare mimic and surgical challenge.

OBJECTIVES: Meningiomas involving the jugular foramen are rare lesions, with approximately 34 cases reported in the English literature. Clinically, these tumors mimic the more common glomus jugulare tumor. After surgical resection, meningiomas have worse cranial nerve outcomes and higher recurrence rates than glomus tumors. There is controversy regarding the selection of surgical approach, particularly with regard to management of the facial nerve. A reliable means of accurate preoperative diagnosis would help surgical planning and patient counseling. STUDY DESIGN: We present a series of six consecutive large jugular foramen meningiomas resected by a single surgeon from 1996 to 2002. METHODS: Retrospective case series (chart review). RESULTS: The preoperative diagnosis was correct in nearly all (6/7) cases on the basis of the characteristic imaging findings seen with a combination of temporal bone dedicated computed tomography and high-resolution enhanced magnetic resonance imaging. Five of six patients had lateral facial nerve rerouting (infratemporal fossa Fisch type A), and three patients also had posterior rerouting (transcochlear approach with division of greater superficial petrosal nerve). Total tumor removal was accomplished in 83%. One patient suffered recurrence over a mean follow-up period of 2.5 years. New postoperative vocal cord palsies occurred in 50% of patients, and all required vocal cord medialization. At 1 year, 50% of patients had normal or near normal (House-Brackmann I or II) facial function. Postoperative cerebrospinal fluid leaks occurred in two patients, and both eventually required ventriculoperitoneal shunts. CONCLUSIONS: Meningiomas involving the jugular foramen are surgically challenging tumors that pose unique diagnostic issues. The majority of these lesions can be completely resected. A relatively high postoperative complication rate, which can be controlled with appropriate intervention, is seen with these surgeries.

Cranial Nerve Diseases↗
PubMed2004

Infratemporal fossa approach to the hypoglossal canal: practical landmarks for elusive anatomy.

OBJECTIVE: At the conclusion of the article the readers should be able to safely and reliably find the hypoglossal canal using the infratemporal fossa approach. HYPOTHESIS: Very little has been written on the regional anatomy of the hypoglossal canal as seen through a transtemporal approach. This project attempts to further define the anatomy of the hypoglossal canal and provide the surgeon with guidelines for reaching it. Our hypothesis is that the hypoglossal canal can be safely and consistently reached by way of the temporal bone with preservation of hearing and cranial nerves (CN) IX to XI. STUDY DESIGN: Prospective anatomic study. METHODS: The study was performed using cadaver temporal bones. Infratemporal fossa Fisch type-A dissections were performed. The hypoglossal canal was then completely exposed. The distance from the canal to the jugular bulb, carotid artery, round window, lateral canal, and roots of CN IX to XI were recorded. RESULTS: Fifteen temporal bones were dissected and measured. The position of the hypoglossal canal is consistently located anterior, inferior, and medial to the jugular bulb. The distance from midcanal to the jugular bulb and the roots of CN IX to XI at the posterior fossa dura was 5.3 mm +/- 0.82 and 7.1 mm +/- 2.49, respectively. The distance from the carotid artery where it meets the jugular vein to the midcanal was 15.3 mm +/- 2.09. The distance from the round window to the canal was 21.7 mm +/- 3.17. CONCLUSIONS: The hypoglossal canal can be consistently reached using the infratemporal fossa approach. Hearing and CN IX to XI can be preserved. The distance from the jugular bulb and roots of CN IX to XI can be used as guideposts. If a tumor is involving the bulb, then the carotid artery and the round window are the next most reliable indicators of position.

Accessory Nerve↗
PubMed2004

Intralabyrinthine schwannomas: diagnosis, management, and a new classification system.

OBJECTIVE: To outline the diagnosis and management of intralabyrinthine schwannomas and to propose a new classification system to further define them. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center at a university hospital. PATIENTS: Twenty-eight patients seen at the institution with intralabyrinthine schwannomas between 1996 and 2002 were included in the study. INTERVENTIONS: Diagnosis was made with magnetic resonance imaging in all but one case. Our ability to detect these tumors has been greatly enhanced by the introduction of high-resolution T2-weighted magnetic resonance imaging. Treatment options were observation with serial magnetic resonance imaging versus complete surgical removal via a translabyrinthine or transotic approach. Surgery was indicated for dizziness caused by the tumor or extralabyrinthine growth. MAIN OUTCOME MEASURES: Clinical features, audiology, radiology, and management outcomes were evaluated. RESULTS: Eight patients have undergone successful surgery with removal of their tumors and resolution of symptoms. One patient chose to have stereotactic radiotherapy. Of the 20 patients who were managed with observation and serial magnetic resonance imaging, only 1 has shown significant growth requiring surgical removal. CONCLUSION: Intralabyrinthine schwannomas are uncommon tumors that mimic the clinical features of many other neurotologic conditions. A high index of suspicion and precise imaging are often required to detect these tumors. Surgical treatment is indicated for specific indications and will be needed in the minority of patients with this disorder. The classification system that we propose is helpful in both the diagnosis and the management of these tumors.

Adult↗
PubMed2004

Primary jugular foramen meningioma: imaging appearance and differentiating features.

OBJECTIVE: Primary jugular foramen meningiomas behave differently from meningiomas arising elsewhere. The differences have important clinical, imaging, and surgical implications. We reviewed the imaging appearances of primary jugular foramen meningiomas and evaluated them for features that might assist in differentiating them from other common jugular foramen lesions. MATERIALS AND METHODS: A retrospective review identified five cases of primary jugular foramen meningioma. We defined it as primary when it was centered in the jugular foramen and secondary when it was centered in the posterior fossa with secondary extension into the jugular foramen. Secondary jugular foramen meningiomas were excluded from this study. Eight cases of jugular foramen paraganglioma and 10 cases of jugular foramen schwannoma were reviewed for comparison. RESULTS: Primary meningioma was characterized by centrifugal infiltration surrounding the skull base (5/5), a permeative-sclerotic appearance to the bone margins of the jugular foramen (5/5), and prominent dural tails (5/5). Flow voids were absent in all cases. Paraganglioma showed localized skull base infiltration, with predominant superolateral spread into the middle ear cavity (8/8). Flow voids and permeative destruction of the bone margins of the jugular foramen were typical. Schwannoma caused expansion of the jugular foramen with scalloped well-corticate bone margins, without skull base infiltration. CONCLUSION: Primary jugular foramen meningioma is characterized by extensive skull base infiltration. A centrifugal pattern of spread, a permeative-sclerotic appearance of the bone margins of the jugular foramen, the presence of dural tails, and an absence of flow voids are particularly important features that assist in differentiating primary jugular foramen meningioma other more common jugular foramen lesions.

Adult↗
PubMed2004

Endolymphatic sac tumors in patients with and without von Hippel-Lindau disease: the role of genetic mutation, von Hippel-Lindau protein, and hypoxia inducible factor-1alpha expression.

OBJECT: Endolymphatic sac (ELS) tumors are low-grade malignancies of the temporal bone that are associated with von Hippel-Lindau (VHL) disease but can also occur sporadically. The VHL gene product VHL protein is important in the regulation of hypoxia inducible factor (HIF)-1alpha, which controls expression of molecules that are important in angiogenesis and cell metabolism. In this study the authors examine the role of VHL and HIF-1 in ELS tumors. METHODS: The ELS tumors from three patients were examined using the following method: DNA from tumor tissue was isolated, amplified by polymerase chain reaction and the VHL gene sequence was compared with the known wild-type sequence. Loss of heterozygosity (LOH) studies were performed to confirm the sequencing data. Immunohistochemical evaluation for VHL, HIF-1alpha, vascular endothelial growth factor (VEGF), and carbonic anhydrase IX (CA IX) was performed. Snap-frozen tumor tissue was examined using Western blot and HIF-1 immunoassays for HIF-1alpha and VHL expression. Two patients had sporadic ELS tumors and the other one suffered from VHL disease. Results of VHL gene sequencing were normal in the tissue derived from the sporadic ELS tumors. The ELS tumor, pheochromocytoma, and spinal hemangioblastoma were heterozygous for the same C-to-A transversion found in the germline carried by the patient with VHL disease. No LOH was detected in the tumor tissue obtained in the patient with VHL disease. Expression of HIF-1alpha, VEGF, and CA IX evaluated using immunohistochemical studies was elevated in the VHL-associated tumors. Nevertheless, Western blots and immunoassays for HIF-1alpha did not show elevated expression in these tumors. CONCLUSIONS: The sporadic and VHL disease-associated ELS tumors in this study had normal VHL-mediated HIF-1 regulation. This is a result of normal VHL gene expression in the case of the sporadic ELS tumor. In the VHL-associated ELS tumor, this is due to one normal copy of the VHL gene and adequate VHL gene expression.

Adult↗