Predictors of speech and swallowing function following primary surgery for oral and oropharyngeal cancer.
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Biomedical subjects
Publications and source records attributed to P H Rhys-Evans.
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We studied the profile of four c-erbB receptors in head and neck squamous cell carcinomas (HNSCC) and to determine whether their expression was associated with clinicopathological features and key molecules involved in angiogenesis and metastasis. We also assessed the impact of expression on survival. This study included 54 cases of primary HNSCC, of which 27 cases showed lymph node metastasis. The expression of c-erbB receptors, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) family members was analysed in the same tissue homogenates by semi-quantitative RT-PCR. HNSCC frequently co-expressed multiple c-erbB receptors and showed significant correlations amongst their levels. High expression of epidermal growth factor receptor (EGFR), c-erbB-2 or c-erbB-3 was associated with an infiltrating mode of invasion, nodal metastases and advanced pathological stages. EGFR and c-erbB-2 levels were strongly correlated (P=0.0004-0.029) with the expression of MMP-2, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, VEGF-A and VEGF-C whereas the levels of c-erbB-3 and B-4 showed a weaker correlation (P=0.049-0.01) with some MMPs and VEGF-C. Only nodal metastasis and EGFR levels were significantly associated with poor outcome in uni- and multi-variate analysis. We conclude that co-operative signalling of all four c-erbB receptors may play a significant role in the pathogenesis of HNSCC. Amongst these, EGFR appears to be the dominant component controlling the invasive and angio-/lymphangiogenic phenotype in HNSCC via upregulation of multiple MMPs and VEGFs.
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, a detailed analysis of MMPs and tissue inhibitors of MMPs (TIMPs) in relation to the biological behavior of HNSCC has yet to be performed in clinical material. OBJECTIVES: To study a comprehensive profile of MMPs and their 2 main inhibitors in HNSCC tissue samples and to correlate the patterns of expression with clinicopathological characteristics, invasion, and metastasis. DESIGN: This study included 54 consecutive patients with primary HNSCC, 27 of which showed lymph node metastasis. Expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, MMP-14, TIMP-1, and TIMP-2 was simultaneously analyzed in tissue homogenates using semiquantitative reverse transcription-polymerase chain reaction assay. Where feasible, levels of protein and enzyme activity were confirmed by Western blot, enzyme-linked immunosorbent assay, and substrate zymography. Conventional clinicopathological features, including mode of tumor invasion, were also examined. RESULTS: Significantly higher MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, and TIMP-1 levels were found in tumors vs specimens of matched normal mucosa. No difference in the distribution of MMPs and TIMPs in relation to age, sex, tumor site, or histological grade was observed. A significant correlation was demonstrated between levels of MMP-1, MMP-9, and TIMP-1 and advanced T stage and between MMP-9 expression and an infiltrative pattern of growth. Enhanced expression of MMP-9 was strongly correlated (P<.001) and levels of MMP-2, MMP-7, and MMP-11 were weakly correlated (P =.03-.05) with lymph node involvement. CONCLUSIONS: Overexpression of multiple MMPs and TIMPs is characteristic of HNSCC, and analysis of specific MMPs, MMP-9 in particular, might be useful for evaluating the malignant potential in individual HNSCC.
From July 1975 to January 1998, 33 patients underwent partial laryngeal resection for residual or recurrent tumour after primary radical radiotherapy. Sixteen patients had T1 tumours on presentation, 14 were T2 and three were T3. Six patients underwent a supraglottic (horizontal) laryngectomy, 24 had a vertical partial laryngectomy, two had an endoscopic laser resection and one had an endoscopic laser resection followed by a vertical partial laryngectomy. The median time interval between radiotherapy and salvage surgery was 10 months (range 2-188 months). The median follow-up period was 41 months (range 12-185 months). There were five major postoperative complications (15%); two patients developed a pharyngeal fistula and three required further surgery for laryngo-tracheal stenosis. Twenty-five patients (76%) retained their larynx with satisfactory speech and swallowing. Eight patients (24%) had to be converted to a total laryngectomy, seven for recurrent disease and one for laryngeal stenosis. Of the eight patents converted, seven had normal swallowing and six developed good tracheo-oesophageal speech. Seven patients (21%) developed recurrent tumour after partial laryngectomy and were subjected to total laryngectomy; six of these seven were salvaged. Only one of the 33 patients died with recurrent tumour, giving an ultimate disease-related survival of 97%. Conservation laryngeal surgery for salvage of selected patients who fail radical radiation therapy is safe, effective, and results in reasonable preservation of laryngeal function.
BACKGROUND: Neural tumors at the thoracic apex, even when benign, present technical problems for the surgeon because of their inaccessibility. The standard approach from below, using a posterolateral thoracotomy, offers suboptimal access to the vascular and neural structures of the thoracic inlet. METHODS: We present a new technique for the resection of benign tumors of the thoracic inlet, combining an anterior cervical approach with a limited median sternotomy. We do not find it necessary to resect any part of the clavicle or to add a thoracotomy. We used this technique in 4 patients with apical tumors. In 3 patients the tumor arose from the sympathetic chain and in 1 patient from the T1 component of the brachial plexus. RESULTS: The tumors ranged from 30 to 70 mm in diameter, and histologic findings were neurilemoma in 3 cases and ganglioneuroma in 1. There were no complications or deaths. All 4 patients were discharged 3 to 6 days postoperatively. CONCLUSIONS: In our experience this new technique provides improved exposure, good control of the neurovascular bundle, and less morbidity than that associated with thoracotomy. For malignant Pancoast's tumors we would still advocate the approach of Dartevelle or Grunenwald, supplemented by lateral thoracotomy to facilitate systematic intrathoracic evaluation.
Elective treatment of the clinically negative neck in the management of early oral tongue cancers remains controversial. A retrospective review of 71 patients with T1, 2 N0M0 squamous cell carcinoma of the oral tongue treated at the Royal Marsden Hospital was carried out. Cervical nodal recurrence at 2 years was 17% in the group of patients who received elective neck treatment as compared to 43% in the group who had observation of the neck and the difference is statistically significant (P = 0.025). The difference in 5-year survival between the group who had elective neck treatment and the group who did not (75% versus 65%) was not statistically significant. Until future research allows us to be more selective on the basis of a reliable panel of histological and/or biological markers for propensity to nodal metastases, elective neck treatment should be considered in the initial management of the patients with early oral tongue cancer.
A case of a solitary fibrous tumour arising in the deep soft tissues of the neck is reported. This rare tumour has not previously been described in this site. We discuss the clinical presentation and pathological features.
We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.
BACKGROUND: Liposarcoma of the head and neck region represents approximately 1% of head and neck sarcomas. Therefore, there are few data on the natural history, presentation, treatment, and prognosis of this neoplasm. METHODS: This study is a report of data from 76 patients with head and neck liposarcoma of whom 4 were treated at The Royal Marsden Hospital during the past 50 years. RESULTS: The median age of patient presentation was the seventh decade (range, 6 months-86 years), and 65% of the patients were male. The commonest site of presentation was the neck (28%), followed by the larynx (20%) and pharynx (18%). Sixty-two percent of tumors were low grade (well differentiated and myxoid), and 38% were high grade (pleomorphic and round cell). The principal determinant of outcome was histologic grade. Five-year survival by life-table analysis was 67% overall and varied with tumor type as follows: well differentiated 100%, myxoid 73%, pleomorphic 42%, and round cell 0%. Site appears to have had some influence on prognosis. Oral liposarcoma had a poor prognosis with a 5-year survival of 50%, despite the low grade of all tumors; however, the 5-year survival for laryngeal (89%) and head (83%) liposarcoma was considerably better. Tumor size did not affect prognosis. The mainstay of treatment was surgical excision, used alone in 70% of the cases. Radiotherapy was used with other treatments in 25% of the cases. Prognosis was best for patients treated with surgery only (5-year survival, 83%), compared with those receiving surgery plus radiotherapy (5-year survival, 63%), chemotherapy (5-year survival, 33%), and radiotherapy alone (5-year survival, 0%). CONCLUSIONS: Liposarcoma rarely involves the head and neck region. The prognosis for patients with this disease appears to be better than for those with liposarcoma arising elsewhere, particularly in the retroperitoneum. Prognosis is principally dependent on histologic grade. Complete surgical excision provides the most effective treatment.
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The saccules and ampullae of the semicircular canals from human and guinea pig temporal bones were fixed in glutaraldehyde without osmium. Crosslinks were seen between stereocilia of the vestibular hair cells, similar to those previously demonstrated in the guinea pig, although an additional set of crosslinks was displayed: first, horizontal crosslinks were seen between adjacent stereocilia, occupying most of the length of the hair bundle; secondly, a single upward-pointing link ran from the apex of each shorter stereocilium into the shaft of the adjacent taller stereocilium; thirdly, an extensive array of horizontal links were demonstrated between stereocilia close to their insertion into the cuticular plate. We suggest that these basal crosslinks support the long vestibular stereocilia rendering them more rigid, and that the upwind pointing crosslinks are responsible for the initiation of sensory transduction.
Guinea pigs were treated with a single dose of Cisplatin (5 mg IP). After 2-4 days the cochleas were prepared for morphological analysis by scanning electron microscopy and chemical analysis by X-ray dispersive microanalysis. Following Cisplatin, the bundles of stereocilia on the hair cells were found to be rough, disarrayed, fused, and finally absorbed. Significant increases were found in the levels of calcium, sulphur, and phosphorus in the abnormal hair cells. It is suggested that the high calcium levels might be due to the inhibition of enzymes which normally keep cytoplasmic calcium low, and that some of the changes in the stereocilia might be secondary to this.
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A patient with pyrexia of unknown origin (PUO) was investigated for a focal infection using autologous indium-labelled leucocytes. Only one site of increased activity was observed; this was asymptomatic and subsequently proved to be an infected nasal sinus. This case highlights the necessity, in PUO investigations, of carrying out whole-body imaging rather than just investigating the areas with presenting symptoms.
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