Elevated expression of the c-myc oncoprotein correlates with poor prognosis in head and neck squamous cell carcinoma.

We quantitated c-myc oncoprotein in 44 squamous cell carcinomas of the head and neck using an enzyme-linked immunosorbence assay. The clinicopathological parameters of these patients were followed up for between 3 and 60 months and analysed for any correlations with observed levels of c-myc protein using the Kruskal-Wallis one-way analysis of variance method. Although no statistical correlation was found between different clinicopathological parameters (patient age, sex, TNM staging, number of lymph nodes invaded, extracapsular rupture of the tumour, its histopathological differentiation, or its site), the survival periods of patients with tumours possessing elevated levels of c-myc protein were found to be statistically shorter than those with lower levels of c-myc expression, (P less than 0.02). This indicates that c-myc expression may be an effective prognostic indicator in head and neck cancer.

Comparison of the metabolic effects of continuous postoperative enteral feeding and feeding at night only.

The effects of two different feeding patterns on oxygen consumption, nitrogen balance, blood biochemistry, and urinary catecholamine excretion were investigated over 5 d in patients after major head and neck surgery. Both groups of nine patients each were fed a regimen that provided 4.7 MJ on day 1 and 10 MJ on days 2-5 via a nasogastric tube by continuous infusion with an enteral feeding pump. One group was fed continuously for 24 h, the other was fed only at night, ie, from 1700 to 0900 the next morning. Oxygen consumption was significantly higher (P less than 0.01), nitrogen balance better (P less than 0.05), and urinary catecholamine excretion higher (P less than 0.05) in the 24-h-fed patients than in the night-fed patients. Postoperatively, feeding at night only is more energy efficient than is feeding continuously for 24 h, but is associated with poorer nitrogen balance. These differences may be mediated by sympathoadrenal mechanisms.

A comparison of the effects of intermittent and continuous nasogastric feeding on the oxygen consumption and nitrogen balance of patients after major head and neck surgery.

Ten patients were fed by nasogastric tube for 5 days after major surgery of the head and neck. Five were fed by continuous infusion 24 h/day using an enteral nutrition pump and five were fed comparable quantities by 2-h bolus administration between 0600 and 2200 h. Those fed by bolus had lower resting oxygen consumption on the 4th and 5th postoperative days and better cumulative nitrogen balance over the 5 days than the continuously fed group. It appears that metabolically it may be better to use an intermittent feeding regimen than a continuous one when feeding patients postoperatively via a nasogastric tube.

Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial.

A phase III 2 X 2 factorial trial of cisplatinum and bleomycin in 116 patients with recurrent or advanced squamous cell carcinoma of the head and neck is reported. Thirty percent of patients proved to be unfit for chemotherapy, and of those treated progression of tumour was the commonest "response". However, 25% of patients achieved a partial or complete response, with no significant difference in response rates between the treated arms. The median number of courses received was 1 (range 0-6) and the commonest causes for discontinuation of treatment were renal toxicity and death. Bleomycin reduced survival, but not significantly so, whereas cisplatinum prolonged median survival significantly by 10 weeks. Significant predictors of survival, in addition to treatment by cisplatinum, were age, performance status, N status, number of courses and response of the tumor.

Survival times in end-stage head and neck cancer.

A personal series of 4319 patients with a tumour of the head and neck managed between 1962 and 1988 is presented. Down to the end of 1979, 1678 of these patients had a squamous cell carcinoma that was previously untreated and of this group 200 patients were not treated. This represented 12% of the squamous carcinomas seen in that period. Untreatability ranged from 5% for laryngeal tumours to 25% for hypopharyngeal tumours. The median survival of the whole group was 101 days. Performance status (ECOG classification) was the only significant predictor of survival. Other host factors (age and sex) and all tumour factors (site, T, N and M stage, distant metastases, stage grouping, and histological grade of the tumour) were not significant. Only performance status needs to be used as a stratification factor in trials on this group of patients.

The treatment of early (T1) glottic and supra-glottic carcinoma: does partial laryngectomy have a place?

A series of 900 patients with laryngeal carcinoma is described. Patients with glottic T1N0 tumours were treated by radiotherapy with a 5-year survival of 92%. Seven per cent of patients suffered recurrence and most were salvaged by surgery: vertical hemilaryngectomy was occasionally useful as a salvage procedure. Patients with supra-glottic T1N0 tumours were treated for the first 7 years by supra-glottic laryngectomy and prophylactic neck dissection and thereafter by radiotherapy. The results were equally good in both series: a 5-year survival of 75-80%. Salvage surgery for failed radiotherapy or surgery for supra-glottic carcinoma gave poor results.

Vocal cord paralysis and tumour length in staging postcricoid cancer.

The present UICC classification of postcricoid cancer is based on directions of tumour spread which are uncommon and difficult to assess clinically. The classification takes no note of spread into the cervical oesophagus and fails to correlate staging with survival. The aim of this study was to assess the value of other criteria, including vocal cord paralysis and tumour length, in staging 157 patients with postcricoid cancer. Both vocal cord paralysis and tumour length could be assessed in most patients, and correlated with the mode of treatment. Generalized Linear Interactive Modelling (GLIM) identified vocal cord paralysis (P less than 0.001), performance status (P less than 0.025) and the interaction of length and histological grade (P less than 0.05) as significant predictors of survival. None of these variables is included in the current UICC classification.

Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma.

We have previously demonstrated that the Ha-ras and the Ki-ras oncogenes are overexpressed in squamous cell carcinoma of the head and neck. In this study we have used the Y13-259 monoclonal antibody to p21 ras to determine if expression of the ras oncoprotein correlates with any of the clinico-pathological parameters or with survival in 69 patients with squamous cell carcinoma of the head and neck. Forty-four specimens were from patients with previously untreated tumours and 25 from patients with previously treated disease. We have found a correlation between low levels of ras expression and the disease-free survival period in patients with previously untreated tumours. Three per cent of the patients with ras negative staining were alive 60 months after diagnosis, whereas 54 per cent of the patients with positive staining were still alive after the same time period (P less than 0.05).

C-erbB-2 expression in squamous cell carcinoma of the head and neck.

Seventy-five squamous cell carcinomas of the head and neck were analysed for c-erbB-2 expression using immunohistochemical techniques with four different c-erbB-2 antibodies. No membrane staining was seen in any of the squamous cell carcinomas studied with any of the antibodies; however, c-erbB-2 cytoplasmic staining was seen in 60 per cent of the tumours. The significance of cytoplasmic staining is discussed and that it may possibly represent elevated c-erbB-2 expression in squamous cell carcinomas. C-erbB-2 cytoplasmic staining was also observed in 10 of 23 normal specimens obtained from the resection margin of the tumours. No correlations were found between positive c-erbB-2 cytoplasmic staining and any of the clinicopathological parameters or survival.

Measurement of platinum in saliva of patients treated with cisplatin.

A procedure for the measurement of platinum (Pt) in the saliva of patients treated with cisplatin has been developed. The saliva is collected and solubilized in hyamine hydroxide before analysis by graphite furnace atomic absorption spectrometry using assay by standard additions. The method has an analytical detection limit of 0.025 microgram/mL and is precise, with coefficients of variation of 3-10.0% over a range of 0.05-2.0 micrograms/mL. Platinum was measured in saliva collected during an 8-h infusion of cisplatin from five patients, at the end of a 30-min infusion in nine, and 24 and 48 h later from a further 15 patients, all of whom were treated with cisplatin for squamous cell carcinoma of the neck. The platinum concentration in saliva taken at the end of a 30-min infusion was 0.27 +/- 0.23 microgram/mL (mean +/- 1 SD) but was below the detection limit of 0.025 microgram/mL at 24 and 48 h. After an 8-h infusion the salivary Pt was significantly less (0.12 +/- 0.04 microgram/mL; P < 0.05). The plasma Pt concentrations after 30-min and 8-h infusions were 2.98 +/- 1.03 and 2.54 +/- 0.59 micrograms/mL, respectively, and were not significantly different. The results indicate higher concentrations of free platinum in plasma after 30 min compared with an 8-h infusion. The monitoring of salivary concentrations of platinum may therefore provide a non-invasive way to study the unbound fraction of cisplatin in blood and facilitate optimization of cisplatin treatment.

Morphometric analysis, ploidy and response to chemotherapy in squamous carcinomas of the head and neck.

The histopathology of 54 squamous carcinomas of the head and neck was evaluated by qualitative grading and morphometry in order to identify those features which predicted a good response to cisplatinum chemotherapy. The histopathology of 66 cases was correlated with tumour ploidy, determined by flow cytometry of paraffin-embedded material, since a separate study has shown that aneuploid carcinomas respond better to chemotherapy. The degree of differentiation was a poor predictor of ploidy, although diploid carcinomas did show more keratin and less nuclear pleomorphism than aneuploid carcinomas. The prominence of nucleoli in tumour cells and the surface area to volume (s/v) ratio of the tumour islands were the variables most strongly correlated with ploidy, with diploid carcinomas having prominent nucleoli and a low s/v ratio. A good response to chemotherapy was related partly to the architecture of the carcinoma (pushing border and low s/v ratio), and partly to the tumour cells (well differentiated) and the percentage of necrotic tumour. A lack of inflammatory reaction or desmoplasia was associated with a poor response. The results indicate that both subjective and objective histopathological criteria may be used to predict ploidy and the response to cisplatinum chemotherapy of squamous carcinoma of the head and neck. A combination of s/v ratio and the percentage of necrotic tumour can be used to identify a group of patients with a relatively good survival.

Squamous metaplasia of the subglottic space and its relation to smoking.

A macroscopic staining method was used to assess the incidence and extent of squamous metaplasia of the subglottic portion of the larynx. A total of 226 postmortem specimens were studied, 105 from nonsmokers and 121 from smokers. More than half of the specimens stained showed some metaplasia, but the incidence and extent of metaplasia was greater in smokers than in nonsmokers, and women were more affected than men. The incidence of metaplasia was greater in pipe and cigar smokers than in nonsmokers, but previous smokers did not differ from nonsmokers.

Chronic laryngeal stenosis.

The results of treatment of 82 patients with chronic laryngeal stenosis during a 20-year period are presented. Road traffic accidents accounted for 30% of the cases and iatrogenic disease for 40%. Of the stenoses 10% were supraglottic, 20% glottic, 50% subglottic, and 15% combined. Virtually all patients with supraglottic stenosis had a good result as regards voice and airway, and we describe the use of a laryngeal widening operation for this group of patients. Over 80% of patients with glottic stenosis achieved good results. However, patients with a subglottic stenosis did badly, and only 60% were relieved of their tracheostomies. Patients with stenosis due to previous tracheostomy or to systemic disease such as Wegener's granuloma did badly.

Staging of maxillary cancer. Which classification?

Of the many proposed classifications for staging maxillary sinus cancer, none has been adopted universally and none is known to be superior to the others. This study identified the best of six currently used classifications using data from 53 previously untreated patients with squamous cell carcinoma of the maxillary sinus. Analysis of each classification's ability to stage the majority of patients, produce a balanced distribution of T stages, and correlate T stage with treatment and prognosis revealed Harrison's classification to be the best. Harrison's classification should be adopted worldwide as the classification of choice for staging squamous cell carcinoma of the maxillary sinus.

Osteosarcoma of the larynx.

A case of laryngeal osteosarcoma in a 75-year-old man is described. The osteosarcoma probably arose by dedifferentiation of a chondrosarcoma of the cricoid cartilage. Laryngeal osteosarcoma is rare: the literature is reviewed and management discussed.

Retraction of the delto-pectoral flap. Clinical observations and the design of an experimental model.

The human delto-pectoral flap retracts markedly across its breadth, but remains the same length after elevation. This unindirectional retraction declines with age. Flaps in a similar position on the pig running in the same direction behave in a similar fashion, suggesting that such flaps are a suitable animal model for the study of this property.

A randomized phase III trial of cisplatinum, methotrexate, cisplatinum + methotrexate, and cisplatinum + 5-fluoro-uracil in end-stage head and neck cancer.

In a previous phase III trial of chemotherapy for patients with end-stage squamous cell carcinoma of the head and neck we have shown that Bleomycin shortened the survival period, compared with untreated controls. The survival of patients treated with Cisplatinum and Bleomycin did not differ significantly from untreated patients, but Cisplatinum significantly prolonged survival. A further similar trial is reported here, the four treatment arms were Methotrexate alone, Cisplatinum alone, Cisplatinum + Methotrexate, and Cisplatinum + 5-Fluoro-uracil. The response rates were: Methotrexate alone 19%, Cisplatinum alone 40%, Cisplatinum + Methotrexate 31%, and Cisplatinum + 5-Fluoro-uracil 33%. The median survival time for the Cisplatinum alone group, 260 days, was significantly longer than the 80 days for the Methotrexate alone group. The median survival times for Cisplatinum + Methotrexate (160 days) and for Cisplatinum + 5-Fluoro-uracil (200 days) did not differ significantly from that for Cisplatinum alone.

Failure of a 21-aminosteroid antioxidant to ameliorate cisplatin-induced nephrotoxicity.

1 Lazaroid (U74500A), a 21-aminosteroid antioxidant, was administered to rats at a dose of 10 mg kg-1 in an attempt to reduce the toxicity of cisplatin (5 mg kg-1). 2 No protective effect was apparent under the schedule used and, in contrast to other antioxidants and free-radical scavengers, U74500A offers no potential benefit in cisplatin treatment.

The viability of skin flaps.

The historical development of skin flaps is outlined, and in particular their division into two types: random, which are supplied by small musculocutaneous vessels; and axial flaps, which are supplied by named cutaneous vessels running within the flap. Experiments are described into the viability of random skin flaps, using the pig as an experimental model. These experiments confirm that random flaps should not be designed longer than their base and probably should not exceed 12.5 cm (5 in) in length.

Replacement of the pharynx after pharyngolaryngectomy.

Twenty-two patients undergoing pharyngolaryngectomy and pharyngeal reconstruction are presented. Four patients died before leaving hospital swallowing. Fistulae and stricture formation were fairly common in patients who had been previously irradiated. The 2-year survival was 37%.