Biomedical subjects

D G Hardy

Publications and source records attributed to D G Hardy.

At least 19 recordsLinked to original sources

PubMed1997

Extended temporal bone resection for squamous cell carcinoma.

OBJECTIVE: The aim of this study was to assess the surgical results of a series of patients from this unit who underwent extended temporal bone resection for recurrent squamous cell carcinoma as a salvage procedure. DESIGN: The surgical records of 15 patients were analyzed in detail. Each patient had salvage surgery in the form of an extended temporal bone resection with supraomohyoid block dissection, dural grafting, and free microvascular forearm or scalp rotation flap repair for recurrent squamous cell carcinoma in a radical mastoid cavity. RESULTS: Radical surgery yielded a 47% 5-year survival. Twenty-nine percent of the survivors had temporal lobe involvement that necessitated a partial excision of the temporal lobe of the brain. Histologic evidence of local lymph node involvement in the supraomohyoid neck dissection was present in 13% of cases. Those who died did so in the first postoperative year. All those with poorly differentiated tumors died. The survivors had well or moderately differentiated tumors. CONCLUSIONS: Radiotherapy alone or partial temporal bone resection, most commonly a radical mastoidectomy with or without preoperative or postoperative radiotherapy is used by the majority of otolaryngologists in treating squamous cell carcinoma of the temporal bone. The 5-year survival rate after this treatment remains depressingly low and the prognosis gloomy, particularly for advanced tumors. The findings in this series of extended temporal bone resections as salvage surgery in recurrent disease is encouraging, and radical surgery combined with radiotherapy from the outset may give much better 5-year survival figures in the future than the conventional partial temporal bone resection and radiotherapy.

Adult↗

PubMed1997

A molecular, clinical, and immunohistochemical study of vestibular schwannoma.

The molecular pathogenesis of vestibular schwannoma has been investigated by determining the extent of chromosome 22 loss of heterozygosity in 77 tumors and relating these findings to clinical and immunohistochemical indexes of tumor behavior. Loss of heterozygosity was looked for at eight chromosome 22q loci. Clinical details were obtained in all 77 cases, and a clinical growth index was calculated for each tumor. The proliferative index was estimated in all tumors by using a monoclonal antibody to the proliferating cell nuclear antigen and by calculating the labeling index. Forty percent (31 of 77) of the tumors showed allele loss, and in each case this loss involved the region of the neurofibromatosis type 2 gene. No evidence was found that the presence of chromosome 22 allele loss was associated with the clinical growth index. On the log scale, however, an association was seen between the clinical growth index and the proliferating cell nuclear antigen labeling index p = 0.001). These results suggest that chromsome 22 allele loss is a frequent event in vestibular schwannoma. Tumor behavior, however, appears to be independent of the chromosome 22 mutation. It is proposed that chromosome 22 allele loss and neurofibromatosis type 2 gene inactivation is an early event, possibly involved in the initiation of tumorigenesis in vestibular schwannoma. Tumor growth appears to be independent of this mutation and is likely to be determined by other as yet undefined factors.

Adult↗

PubMed1996

Factors which influence the facial nerve outcome in vestibular schwannoma surgery.

A series of 276 patients with a unilateral vestibular schwannoma has been analysed with respect to the factors affecting post-operative facial nerve outcome. Age, tumour size, operative approach and the use of intra-operative facial nerve monitoring have been examined. The tumours were removed via either a translabyrinthine or a retrosigmoid approach. In this series increasing age and increasing tumour size were associated with a worse facial nerve outcome. The use of intra-operative facial nerve monitoring and the retrosigmoid approach were both associated with a better facial nerve outcome. Those patients having a retrosigmoid approach had a facial nerve result that was over one House grade better than those having translabyrinthine tumour removal.

Facial Nerve↗

PubMed1996

The surgical management of patients with glomus tumours of the skull base.

Total surgical excision is the only treatment modality that offers a cure for patients with glomus tumours of the skull base. The vascularity, inaccessibility and frequently extensive local spread, all contribute to the difficulties encountered in the management of patients with these complex lesions. Owing to the rarity of skull base glomus tumours, experience in their management can only be attained over long periods of time. We describe the surgical management of 20 patients with large glomus tumours of the skull base treated by an otoneurosurgical team over an 11-year period. Overall, 70% of patients had an excellent outcome, 10% a good outcome and 20% a poor outcome at a mean follow-up of 3.1 years. Poor outcomes were due to severe facial nerve palsies in two cases, and poorly accommodated palsies of the bulbar cranial nerves in a further two patients. The management of postoperative neurological deficits is discussed in detail. We conclude that in the majority of patients with skull base glomus tumours, complete surgical excision can be safely achieved.

Adult↗

PubMed1996

Surgical results in unusual cerebellopontine angle tumours.

Vestibular schwannomas account for 84% of cerebellopontine angle (CPA) lesions. The remaining CPA tumours comprise a fascinating group of lesions which may present in a similar fashion. Fortunately, advances in neuroradiology have increased our diagnostic accuracy of these lesions. This paper describes the surgical results of a series of 69 CPA lesions which were not vestibular schwannomas. The majority of these unusual CPA tumours were meningiomas, cholesteatomas and neuromas of other cranial nerves in the posterior fossa.

Adult↗

PubMed1996

Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma.

The authors investigated the role of somatic mutations of the neurofibromatosis type 2 (NF2) gene in sporadic meningioma. Neurofibromatosis 2 is a dominantly inherited familial tumor syndrome predisposing affected patients to a variety of central nervous system tumors including vestibular schwannoma and meningioma. Neurofibromatosis type 2 is caused by germline mutations in the NF2 tumor suppressor gene. In addition, the authors and others have reported that somatic NF2 gene mutations occur frequently in nonfamilial vestibular schwannoma. In this study, molecular genetic analysis was performed on 23 nonfamilial meningiomas. Paired DNA samples extracted from the blood and tumors of the patients were analyzed for loss of heterozygosity (LOH) in the region of the NF2 gene on chromosome 22 using closely linked DNA markers. The NF2 gene mutations were sought by single-stranded conformation polymorphism analysis and DNA sequencing. Fourteen (61%) of 23 meningiomas showed LOH in the region of the NF2 gene on chromosome 22. Somatic NF2 gene mutations were detected in eight meningiomas (35%) after screening all 17 exons. All tumors with NF2 gene mutations showed simultaneous chromosome 22 LOH. Review of the histopathological findings of the cases studied did not demonstrate any predominance of genetic abnormalities in a particular histological type of meningioma. These results are compatible with the hypothesis that the NF2 gene acts as a tumor suppressor and that its inactivation is important in the pathogenesis of sporadic meningioma.

Chromosomes, Human, Pair 22↗

PubMed1996

Audiovestibular results after surgery for cerebellopontine angle meningiomas.

Meningiomas are the second most common cerebellopontine angle (CPA) tumor. The reported rates of hearing preservation following surgical removal vary between 32% and 100%. There is only one recent report discussing vestibular function after CPA meningioma removal. In this series of 31 patients with CPA meningiomas, 16 patients had their tumors removed via the retrosigmoid approach. All 16 had audiovestibular assessment pre- and postsurgery and were the subjects of this study. Class A hearing is socially useful hearing and is defined as a pure tone average (PTA; average of 500 Hz and 1, 2 and 4 kHz) of < 30 dB and speech discrimination scores (SDS) of > 70%. Class B hearing is serviceable hearing, defined as PTA of < 50 dB and SDS of > 50%. Nine patients had class A hearing, and two had class B hearing presurgery. Socially useful hearing was preserved in six of nine (67%) patients in whom it was present before surgery, and serviceable or better hearing was preserved in eight of 11 (73%). Vestibular symptomatology and examination findings improved despite a decrease in the number of patients with intact caloric function postsurgery. Patients who retained vestibular function on caloric testing were symptomatically better than those who lost caloric function. These results confirm that excellent audiovestibular function is possible after CPA meningioma surgery.

Adult↗

PubMed1996

The operative learning curve and its effect on facial nerve outcome in vestibular schwannoma surgery.

The successful removal of vestibular schwannomas requires a team approach by skillful and appropriately trained surgeons. It is generally perceived that the results of surgery, especially facial nerve outcome, will improve as the surgical team acquires more experience. This study of 300 patients undergoing surgical removal of vestibular schwannomas confirms that there was a significant learning curve for facial nerve outcome. In the first 50 cases, 52% had satisfactory outcomes (House grades I-III), whereas in the last 50 cases 92% had satisfactory outcomes. The major improvement came between the first 50 cases and the second 50 cases (House grades I-III results at 12 months improved from 52% to 78%). After the second 50 patients there was a gradual, but continued improvement, which is also attributable to increased surgical experience. Most of this learning curve was related to the translabyrinthine approach. House grades I-III results were attained for 45% of the first 40 and 70% of the second 40 translabyrinthine tumor removals.

Ear Neoplasms↗

PubMed1995

Thrombosed posterior-inferior cerebellar artery aneurysm: a rare cerebellopontine angle tumour.

A case report of a thrombosed posterior-inferior cerebellar artery aneurysm is described. The tumour masqueraded as a vestibular schwannoma on imaging but the presenting features were unusual, the facial pain and weakness predominating despite well preserved hearing. This is an example of a rare cerebellopontine angle tumour and highlights the need for suspicion when lesions present atypically.

Aneurysm↗

PubMed1995

Referral patterns in vestibular schwannomas.

The investigation and treatment of vestibular schwannomas is an increasingly specialized area in which major advances have been seen over recent years. The effect of these advances on the referral patterns to a centre specializing in such surgery is reviewed. The proportion of referrals with a known diagnosis has increased substantially, allowing the specialist centre to focus on appropriate management rather than diagnosis. The vast majority of vestibular schwannomas are referred by otolaryngologists. The caseload referred by neurologists or neurosurgeons have different presenting symptoms. The incidence of vestibular schwannoma in the Cambridge district is found to be 1 per 50,000 population per year. This is a higher incidence than that recorded in other studies. This may be due to a tight diagnostic strategy and the high level of clinical awareness of the local general practitioners.

Ear Neoplasms↗

PubMed1995

Nervus intermedius function after vestibular schwannoma removal: clinical features and pathophysiological mechanisms.

The results of facial nerve outcome following vestibular schwannoma removal have generally ignored the sensory component of the nerve. This lack of reporting occurs partly because the distress relating to these functions is less obvious to the surgeon, and partly because the facial nerve grading systems currently used do not include the functions of the nervus intermedius. We have estimated the frequency and nature of abnormalities of nervus intermedius function following vestibular schwannoma removal using a retrospective questionnaire. Questionnaires were mailed to 257 patients and correctly completed and returned by 224 (87%) of the patients. Prior to surgery 5 (2%) of the patients complained of crocodile tears, 9 (4%) noted dryness of the eye, and 15 (6%) complained of an abnormality of taste. Postoperative crocodile tears occurred in 98 (44%), an absence or significant reduction in the production of tears was noted in 162 (72%), and a taste abnormality, either a significant reduction or an alteration in character, was noted in 107 (48%). The onset of crocodile tears approximated to a bimodal distribution, and the recovery of nervus intermedius functions was variable. This study has demonstrated that nervus intermedius abnormalities are common following vestibular schwannoma removal. It also documents their natural history and discusses the underlying pathophysiological mechanisms. We suggest that appropriate preoperative counseling be given to all patients undergoing surgery and that the functions of the nervus intermedius be included in the surgical reporting of facial nerve results in cerebellopontine angle surgery.

Facial Nerve↗

PubMed1995

The patient's perspective after vestibular schwannoma removal: quality of life and implications for management.

A postal survey was conducted, using a standardized quality of life questionnaire, of patients who had undergone surgery for removal of vestibular schwannoma between 1981 and 1992. Of 257 questionnaires, 227 (88%) were returned completed. The questionnaire was based on the European Organisation for Research into the Treatment of Cancer (EORTC) core questionnaire. A series of five functional gradings were used to assess the quality of life, and specific questions were also asked. The results were numerically scored and have been correlated with patient and tumor characteristics. There was a significant difference (p = .0001) between the subjective functional outcome for small and intracanalicular tumors when compared with tumors larger than 1.5 cm maximum diameter. However, there was no significant difference when tumors 1.5 to 2.5 cm in diameter were compared to larger tumors. Poor functional outcome did not correlate with the age of the patient, position in the series, or postoperative facial nerve motor function. There also was no significant difference when younger patients (age < 65 yr) were compared with older patients (age 65 - 76 yr). In general, the quality of life following vestibular schwannoma surgery was excellent. Patients with a poor functional outcome were evenly distributed over the medium and large tumor size groups, and patients with small tumors ( < or = 1.5 cm) had a significantly better outcome.

Activities of Daily Living↗

PubMed1994

Sudden deafness in vestibular schwannoma.

Twelve per cent of a series of 284 patients with vestibular schwannoma presented with sudden deafness. If sudden sensorineural hearing loss is present then it is very likely to be the main presenting symptom. The mean length of patients' history is eight months shorter in this group than in the non-sudden deafness group. Sixteen per cent of vestibular schwannoma patients without sudden deafness present with a 'dead' ear whereas 29.5 per cent of those presenting with sudden deafness have total hearing loss. There was no significant difference between the sudden deafness group and the 'all others' group with regard to tumour size, audiogram shape, caloric test, imbalance, and facial numbness. Although the numbers of patients with sudden deafness in this series were too small to reach significance, on the basis of the clinical correlation of vestibular schwannoma morphology it is possible to postulate that compression of the vasculature within the bony internal auditory canal by a laterally arising tumour may be the aetiological factor and may be more likely to occur than in more medially arising tumours.

Adult↗

PubMed1994

Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma.

Vestibular schwannoma occurs both as a sporadic tumour and in the dominantly inherited familial cancer syndrome neurofibromatosis type 2 (NF2). The gene for NF2 has recently been isolated on chromosome 22, and the demonstration of inactivating germline mutations in NF2 patients and NF2 associated tumours suggests that it act as a tumour suppressor. We have investigated 85 sporadic and 2 NF2 associated vestibular schwannomas, and one vagal schwannoma for chromosome 22 allele loss and NF2 gene mutations. A further 7 vestibular schwannomas were investigated for NF2 mutations only. Chromosome 22 allele loss was detected in 34 of 87 vestibular schwannomas and in the vagal nerve schwannoma. Six exons of the NF2 gene were investigated by SSCP analysis in all 95 tumours. Somatic NF2 gene mutations were detected in 13 non-familial vestibular schwannomas and in one of the NF2 vestibular schwannomas. Seven non-familial tumours with an NF2 gene mutation also displayed a chromosome 22 allele loss. Thirteen of the mutations were predicted to produce truncation of the NF2 protein. These results suggest that somatic mutations of the NF2 tumour suppressor gene are a critical step in the pathogenesis of both familial and non-familial vestibular schwannoma and that the mechanism of tumourigenesis complies with a 'two-hit' mutation model.

Adult↗

PubMed1994

Audiological findings in glomus tumours.

Glomus tumours of the skull base are rare, but as they present with symptoms of hearing loss and tinnitus they are a clinical entity of which audiologists should be aware. This paper describes the findings of the major series of skull base glomus tumours found in the literature, and notes that the contribution of conductive and sensorineural components varies with tumour classification. The reported incidence of hearing loss and tinnitus in glomus tympanicum and glomus jugulare is reviewed and compared with the Cambridge series, in which two tumours were Fisch type A, four type B, two type C and five type D. In each case a mixed hearing loss was found, though the extent of sensorineural impairment was variable. The length of history of tumours limited to the middle-ear was far shorter (mean 8 months) than for more extensive lesions (type B, mean 64 months; C, 48 months; and D, 23 months). Eleven patients (85%) reported the symptom of hearing loss, and 12 (92.5%) of tinnitus, and some patients had experienced these symptoms for some time without seeking the advice of an otologist. It may be concluded that the presence of subjective pulsatile tinnitus or a retrotympanic mass should be considered an indication for an otological opinion, wherein the use of high resolution imaging techniques and arteriography will be considered in conjunction with detailed audiological assessment. Audiologists should be aware of the possibility of glomus tumour in such cases.

Adult↗

PubMed1993

Molecular genetic analysis of the mechanism of tumorigenesis in acoustic neuroma.

OBJECTIVE: Acoustic neuroma, both familial and sporadic, is clinically and biologically a heterogeneous condition with a wide variation in age of presentation, length of history, and tumor growth rate. In an attempt to correlate this clinical diversity with the underlying molecular pathology, we have analyzed 43 paired blood-tumor DNA samples from patients with acoustic neuromas. DESIGN: Molecular genetic analysis. SETTING: Molecular genetic research laboratory. PATIENTS: Paired blood-tumor DNA samples were obtained from 43 patients (41 sporadic and two patients with neurofibromatosis type 2). MAIN OUTCOME MEASURES: Loss of constitutional heterozygosity was looked for in the region of tumor suppressor genes on chromosomes 3p, 5q, 11p, 17p, 17q, and 22. RESULTS: We found loss of heterozygosity exclusively for markers on chromosome 22. Thirty-nine percent of tumors showed allele loss, and in each case the loss of heterozygosity included the region of the neurofibromatosis type 2 (NF2) gene. No loss of heterozygosity was detected in the region of known or putative suppressor genes in chromosomes 3p, 5q, 11p, 17p, and 17q. CONCLUSIONS: This study has demonstrated that (1) chromosome 22 allele loss is a frequent event in sporadic acoustic neuroma; (2) the minimal region of loss of heterozygosity in acoustic neuroma includes the NF2 gene; (3) the known tumor suppressor genes investigated (VHL, adenomatous polyposis coli, WT2, p53, and NF1) do not appear to be important in the pathogenesis of acoustic neuroma; and (4) patients with extensive chromosome 22 loss tended to be younger and with a slightly shorter clinical history than those with no detectable allele loss.

Adult↗

PubMed1993

Clinical correlates of acoustic neuroma morphology.

Thirty-eight patients with vestibular schwannomas were reviewed. A correlation was found between tumour morphology and clinical presentation. Based on our knowledge of the variability in the neurilemmal-neurologlial junction and therefore the site of origin of these tumours in relation to the internal auditory canal, a classification into three different appearances on magnetic resonance imaging was possible. Dumbbell shaped tumours (21 per cent) represented laterally arising schwannomas, lollipop shaped tumours (18 per cent) were medially arising and cone shaped tumours (61 per cent) were the more common intermediate form. Patients with laterally arising dumb-bell shaped tumours were more likely to present early with hearing loss and had smaller tumours than patients with medially arising lollipop shaped ones. The relatively well preserved hearing in patients with medially arising tumours made them more likely to present at a later stage with signs of trigeminal compression, cerebellar dysfunction and raised intracranial pressure.

Cranial Nerve Neoplasms↗

PubMed1993

Unusual cerebello-pontine angle tumours.

Fifty-nine unusual cerebello-pontine angle tumours have been studied. These lesions represent 19.3 per cent or 1 in 5 of a series of 305 cerebello-pontine angle tumours of which the rest, 246 (80.7 per cent), were acoustic neuromas. An analysis of the relative incidence, histology and presenting clinical features has been carried out. The various radiographical features and imaging techniques used to diagnose these fascinating tumours have been described and also the otoneurosurgical procedures necessary to excise them.

Adolescent↗