Squamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early-stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n ‫؍‬ 8) and radiosensitive (n ‫؍‬ 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/ WAF1) and apoptosis (Bcl-2 and BAX) were studied. Ki-67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl-2 and radioresistance (p ‫؍‬ 0.003, Fisher's exact test). We hypothesise that overexpression of the anti-apoptotic protein Bcl-2 allows tumour cells with extensive radiationinduced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance.

The effect of the tonicity of saline nasal douching solutions on mucociliary clearance was studied in order to ascertain whether hypertonicity conferred any advantage. Thirty-eight normal subjects were included in a randomised double-blind crossover trial. Saline douching solutions of 0.9%, 3% and 5% tonicity were used and mucociliary clearance was measured by the saccharin clearance time (SCT). The resultant SCT after administration of 5% saline was significantly reduced compared to both 0.9% (P = 0.005) and 3% saline (P = 0.04). There was no difference between 0.9% and 3% saline administration. Thus hypertonic saline solutions improve mucociliary clearance, although this was only observed with solutions of 5% tonicity. The effect is probably brought about by changes in mucus rheology.

A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. KaplanMeier survival analysis revealed significant correlations between gain of 3q25 -27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.

The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane-bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre-malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre-malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low-to-moderate levels in only 2/6 (33%) pre-malignant and 3/12 (25%) malignant specimens (P < 0.01). This 'loss' of epithelial SSTR2 expression may provide a growth advantage in pre-malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre-malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.

Aims:Acoustic neuroma is a benign tumour, which develops through an overproliferation of Schwann cells along the vestibular nerve. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane bound receptor subtypes. The aim of this study was to determine whether somatostatin receptor subtypes (SSTRs) 1, 2, 3, and 5 are present in acoustic neuromas.Methods:The expression of SSTRs 1, 2, 3, and 5 was studied in both the Schwann cells and blood vessels of eight acoustic neuroma specimens, by means of immunohistochemistry using novel rabbit polyclonal antibodies raised against human SSTR 1, 2, and 5 subtype specific peptides, and a commercial anti-SSTR3 antibody.Results:SSTR2 was the most prevalent subtype in Schwann cells (seven of eight), with intermediate expression of SSTR3 (six of eight), and lower expression of SSTRs 1 and 5 (four of eight and five of eight, respectively). There was ubiquitous vascular expression of SSTR2, with no evidence of SSTR 1, 3, or 5 expression in blood vessels.Conclusion:SSTRs 1, 2, 3, and 5 are differentially expressed in acoustic neuromas. Somatostatin analogues may have a therapeutic role in the management of this rare and challenging condition.

Conventional chemotherapy has no role to play in the curative treatment of laryngeal carcinoma, yet the mortality rate from advanced disease has improved little over the last 20 years. Somatostatin is a naturally occurring peptide, which exerts anti-proliferative and anti-angiogenic effects via 5 membrane-bound receptor subtypes (SSTRs 1-5). We have previously studied the expression of SSTRs 1 and 2 and demonstrated loss of SSTR2 in laryngeal carcinoma. This study was therefore undertaken to study the expression of the remaining SSTR subtypes in laryngeal pathology. The expression of SSTRs 3, 4 and 5 was studied in benign (Reinke's oedema), pre-malignant and malignant laryngeal specimens using immunohistochemistry. There was very little expression of SSTR3, with low to moderate levels detected in just 1/6 (17%) benign and pre-malignant specimens and 3/12 (25%) malignant laryngeal tumours. A variable degree of SSTR4 expression was detected across the three groups, with low to moderate levels in 3/6 (50%) benign specimens, compared to only 1/6 (17%) pre-malignant specimens but 8/12 (67%) malignant laryngeal tumours. The majority of all specimens, however, demonstrated moderate to high levels of expression of SSTR5. This receptor was detected in 4/6 (67%) benign, all pre-malignant (100%) and 10/12 (83%) malignant cases. All the laryngeal carcinomas studied expressed either SSTR4 or SSTR5, with 60% expressing both, but very few expressing SSTR3. Somatostatin receptors warrant further investigation to determine whether they have a therapeutic role in carcinoma of the larynx.

Posterior laryngeal cleft (PLC) is a rare developmental abnormality, which requires early diagnostic laryngoscopy and management if considerable morbidity and mortality are to be avoided. We report the case of a 25-year-old man with a life-long history of a weak, breathy voice, in whom the diagnosis of PLC was made by CT scanning. This is the first reported case of a PLC being diagnosed by CT scanning. Whilst direct laryngoscopy should remain the investigation of choice in congenital stridor, CT scanning may occasionally be useful.