Epirubicin, cisplatin and protracted venous infusion 5-Fluorouracil chemotherapy for advanced salivary adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (ACC) is a rare tumour that usually arises in the salivary glands. Initial management is surgery often combined with adjuvant radiotherapy. Chemotherapy is reserved for treatment of symptomatic recurrence. We evaluated the combination of epirubicin, cisplatin and protracted venous infusion 5-fluorouracil (ECF) in the management of ACC. MATERIALS AND METHODS: Patients referred for treatment of advanced, symptomatic ACC were considered. The drugs given were epirubicin 50 mg/m(2) 3-weekly, cisplatin 60 mg/m(2) 3-weekly and protracted venous infusion 5-fluorouracil 200 mg/m(2)/day. RESULTS: Eight patients (median age 46 years) received a median of five cycles of chemotherapy. All patients had had previous surgery, seven had had previous radiotherapy and one had had previous chemotherapy. One patient showed a partial response (duration 34 months) and five showed stable disease (median duration 13.6 months [6.8-15.9+ months]). Median survival was 27 months (3.5-62.3 months). CONCLUSIONS: The activity of ECF in ACC of the head and neck seems to be similar to the combination of cisplatin and 5-fluorouracil and single-agent epirubicin.

Aural exostoses (surfer's ear) provide vital fossil evidence of an aquatic phase in Man's early evolution.

For over a century, otolaryngologists have recognised the condition of aural exostoses, but their significance and aetiology remains obscure, although they tend to be associated with frequent swimming and cold water immersion of the auditory canal. The fact that this condition is usually bilateral is predictable since both ears are immersed in water. However, why do exostoses only grow in swimmers and why do they grow in the deep bony meatus at two or three constant sites? Furthermore, from an evolutionary point of view, what is or was the purpose and function of these rather incongruous protrusions? In recent decades, paleoanthropological evidence has challenged ideas about early hominid evolution. In 1992 the senior author suggested that aural exostoses were evolved in early hominid Man for protection of the delicate tympanic membrane during swimming and diving by narrowing the ear canal in a similar fashion to other semiaquatic species. We now provide evidence for this theory and propose an aetiological explanation for the formation of exostoses.

Anterior cervical-transsternal approach for resection of benign tumors at the thoracic inlet.

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.

C-erbB receptors in squamous cell carcinomas of the head and neck: clinical significance and correlation with matrix metalloproteinases and vascular endothelial growth factors.

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.

Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck.

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.

Excision of adenoid cystic carcinoma of the cervical trachea via an anterior castellated approach.

Adenoid cystic carcinoma of the cervical trachea is rare and its diagnosis and surgical management challenging. We report a case with an unusual presentation and discuss the diagnosis and management. The preferred surgical management is tracheal resection, however this is often not feasible and many alternative techniques have been used. Here an anterior castellated approach is described, a modification of that more commonly used for benign tracheal strictures. We found it gave excellent access to the posterior tracheal wall which we feel is superior to a straight vertical tracheal incision. It also facilitates a tracheal widening procedure if indicated, and safeguards the recurrent laryngeal nerves which are particularly vulnerable in the cervical part of the trachea.

Complications in head and neck surgery and how to avoid trouble.

Increasing litigation in recent years has made it more and more necessary for the surgeon to be aware of the problems, pitfalls and complications which may arise as a result of surgery. The risks are compounded in the head and neck not only because of its complex anatomy but also because of additional difficulties relating to surgery of the upper aero-digestive tract. Some problems are unavoidable. The potential risks of surgery and its complications should be carefully weighed against the natural history of the pathological process and a realistic expectation of the surgical outcome compared with alternative treatments. Other problems may result from genuine mistakes, but a number of complications are caused through actions or omissions which are avoidable and which in certain circumstances may be construed as professional negligence. Some of the more common pitfalls and complications in head and neck surgery are discussed with particular reference to their causation and possible avoidance.

The paranasal sinuses and other enigmas: an aquatic evolutionary theory.

The functional role of the paranasal sinuses in man has long been in dispute and as yet no satisfactory explanation has been offered for these 'unwanted' spaces. An answer may be found by study of the comparative evolutionary development of the sinuses in man and other higher primates. Several unique physical characteristics of man not seen elsewhere in the ape family, or indeed in other terrestrial mammals, including some relating to the upper aerodigestive tract, are not satisfactorily explained by the traditionally held theory of evolutionary development of early man directly from the arboreal ape. It is argued that these developmental differences are much more logically explained by a period of aquatic adaptation at a crucial period in the evolution of pre-hominid man. A new theory is proposed which might explain the importance of the sinus air cavities as buoyancy aids for protection of the upper airway tract in such an aquatic environment. Further evidence is offered relating to a pathological condition of the external ear canal which supports this theory that man at some stage in his early development acquired an affinity for an aquatic environment. Explanation of these unique hominid characteristics in terms of an aquatic evolutionary theory may help to resolve some of the enigmatic inconsistencies between man and other higher primates, and may account for man's eventual emergence as the dominant extant species, and perhaps an explanation for the 'missing link'.

Tracheo-oesophageal puncture without tears: the forceps technique.

Certain problems have been encountered using a rigid endoscopic technique for tracheo-oesophageal puncture in voice restoration following laryngectomy. An alternative method is described using a modified curved abdominal forceps which allows quicker and more predictable access to the puncture site.

Knot to be condemned.

It is common practice following mastoid and middle ear surgery to apply a pressure bandage to the ear for a short post-operative period to reduce local swelling. The bandage is usually secured in such a way as to lift it away from the eye, sometimes with a length of ribbon gauze tied in a knot over the temporal region. Pressure from the knot may cause injury to the underlying tissues leading to post-operative complications which hitherto have not been described.

Crosslinks between stereocilia in hair cells of the human and guinea pig vestibular labyrinth.

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.

Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia.

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.

Solitary fibrous tumour of the deep soft tissues of the neck.

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.

Preservation of neck dissection for histological study.

Dissection of lymphatic nodes in the neck--whether radical or partial, functional or prophylactic--forms an integral part of the surgical management of cancer of the head and neck. Accurate orientation and fixation of the surgical specimen is a prerequisite for correct histopathological study of the extent of the disease and for a complete clinicopathological interpretation, which is of significant therapeutic and prognostic importance.

Secretory otitis media--evidence for an inherited aetiology.

In a study to determine whether or not there is a familial or hereditary predisposition to develop secretory otitis media (SOM), the parents of 73 children with persistent SOM and 35 controls were examined clinically, and abnormalities of the tympanic membrane (TM) noted. Analysis of the findings suggests that heredity plays a large part in determining a child's likelihood of developing SOM.

Early morphological and chemical changes induced by cisplatin in the guinea pig organ of Corti.

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.

Tracheo-oesophageal puncture: a review of problems and complications.

Tracheo-oesophageal puncture now has a well established role and in several units is now the principal means of speech rehabilitation following laryngectomy. Although not a difficult procedure, there are a number of problems and complications that may be encountered. With proper management these can usually be overcome and a useful voice achieved. This study looks at those problems in a series of 119 patients and discusses their management.

Cross-links between stereocilia in the human organ of Corti.

Human cochleae were fixed in glutaraldehyde, without the use of osmium. Cross-links were seen between the stereocilia, similar to those we have previously reported for the guinea pig: first, stereocilia of the same row on each hair cell were joined by horizontally-running links; secondly, the shorter stereocilia had pointed tips, each giving rise to a single, vertically-pointing link, which ran upwards to join the adjacent taller stereocilium of the next row. We suggest that distortion of this link is involved in sensory transduction. The links were sparser than had been seen in the guinea pig which may be a reflection of the vulnerability of the links to non-optimal fixation, and the greater difficulty in producing good fixation in human specimens.

Intralaryngotracheal thyroid--ectopic thyroid or invasive carcinoma?

Intralaryngotracheal thyroid is a rare clinical condition with only about 125 cases described so far in the literature. We present an unusual case of intralaryngotracheal thyroid which had many clinical features of malignancy and yet appeared benign on histology. As in this case, well-differentiated thyroid cancer can present with locally aggressive clinical features and can pose a dilemma in management if treatment decisions are guided solely by histological features.

Tongue resection with the CO2 laser: the effects of past radiotherapy on postoperative complications.

A clinical study was undertaken in 21 patients to assess the effects of past radiotherapy on complications after tongue resection with the CO2 laser. Ten of the 11 irradiated patients experienced postoperative problems such as pain, haemorrhage, oedema, infection, delayed healing and poor function, while only one of the 10 non-irradiated patients had a problem due to minor bleeding after laser surgery. It is concluded that the CO2 laser is useful for primary excision of accessible tumours in the anterior tongue, but may be associated with more postoperative complications if the tongue has previously been irradiated. Where the tongue resection is part of a more radical excision, the CO2 laser is less advantageous.