Head and neck sarcoma: three-year data from a tertiary referral centre.

INTRODUCTION: Sarcomas of the head and neck are neoplasms arising from the embryonic mesenchyme. They are rare and heterogeneous in nature and are associated with significant morbidity and mortality. This study evaluates patients referred to the Oxford Sarcoma Service, a tertiary referral centre. METHODS: Patients discussed over a three-year period were included. Medical records were analysed using the electronic patient record database. Data were acquired on a range of domains, including: demographics, histopathology, treatment modality, recurrence, mortality, survival, etc. RESULTS: Thirty-two eligible patients, 21 male and 11 female, were identified with a mean age of 58 years; 26 out of 32 patients had high-grade sarcomas. The commonest histological subtype was chondrosarcoma (8/32). Twenty-two underwent planned multidisciplinary team surgical resection after biopsy and staging: negative margins were noted in 9, with close and involved margins in 5 and 8, respectively. Local recurrence was noted in 13 and 6 had metastatic disease out of the 32 eligible patients. Mortality was noted in 10 out of 32 patients. Mean survival was 69.5 months. Five-year overall survival was 64%. Surgery demonstrated statistically significant improvement in survival (p=0.0095). There were no significant differences in survival, recurrence or marginal status between methods of adjuvant or neoadjuvant therapy. CONCLUSION: Outcomes of head and neck sarcomas are inferior compared with other types of sarcoma. The nature of the complex surrounding anatomy presents unique challenges in surgical management. This in turn affects rates of local recurrence and prognosis. Therefore, it is critical that they are managed in tertiary, specialist centres with a multidisciplinary approach.

WITHDRAWN: Can depth of invasion of pT1 carcinoma of the oral tongue predict occult metastases in the neck? A retrospective study.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Effects of exogenous growth hormone on lipid metabolism in the isolated epididymal fat pad of the growth hormone-deficient little mouse.

The effects of two preparations of highly purified human GH (hGH) on lipid metabolism were studied in the GH-deficient little mouse (50-60 days old). Marked decreases in incorporation of [14C]glucose into fatty acid and in the activity of acetyl-CoA carboxylase in the epididymal fat pads were observed after i.p. injection of hGH at a dose of 1.0 microgram/g body weight or after continuous infusion of hGH by osmotic minipump. The rate of glucose incorporation into fatty acid decreased from 107.0 +/- 27.6 (S.E.M.) to 38.1 +/- 19.6 mumol/g tissue per h after a single injection of hGH and from 174.1 +/- 28.5 to 56.3 +/- 20.3 mumol/g tissue per h after continuous infusion of hGH for 2 days. Activity of the lipogenic enzyme acetyl-CoA carboxylase was also reduced by more than 50% in the epididymal fat pad from hGH-treated mice in comparison with the corresponding control animals. Incubation of isolated fat pads with hGH (0.1 microgram/ml) revealed similar inhibitory effects of the hormone on fatty acid synthesis and acetyl-CoA carboxylase activity. No lipolytic effect of hGH was found as determined by the rate of glycerol release from epididymal fat pads of little mice following hormone treatment in vivo or in vitro. The results lend strong support to the conclusion that GH inhibits lipogenesis but has no effect on lipolysis in adipose tissues, and indicate that the physiological role of GH in lipid metabolism is concerned mainly with the regulation of anabolic rather than catabolic processes.

Compensatory renal growth in the mouse. III. Growth hormone and insulin deficiency.

The effect of combined insulin and growth hormone (GH) deficiency on compensatory renal growth (CRG) was studied in the dwarf mouse, "Little," after insulin suppression with streptozotocin (SZ). Nucleic acid and protein estimations were used to assess changes in cellular hyperplasia and hypertrophy. Mice aged 30 days received SZ while controls received buffers solution alone. Left nephrectomy was performed at 35 days of age with removal of the renoprival kidney 15 days later. In mice with normal GH, renoprival kidney weight was unaffected by SZ, but the total DNA (estimate of cell number) was higher than normal in both sham-operated and renoprival kidneys suggesting that insulin suppression may cause greater cell replication during both normal growth and CRG. The ratio of protein to DNA (estimate of cell size) in the renoprival kidney was not suppressed by SZ as reported in muscle. In GH-deficient mice (lit/lit) given SZ, CRG was significantly diminished (P less than 0.001). Total DNA in the renoprival kidney was slightly greater than the sham-operated control (P less than 0.005) but the protein:DNA ratio (cell size) was unchanged. These results suggest that when both GH and insulin are suppressed, adaptive cellular growth is inhibited. The proposal that GH and insulin are the two primary hormones controlling cellular growth is consistent with these results.

Hepatic binding of human and bovine growth hormones and ovine prolactin in the dwarf "little" mouse.

Binding of human (hGH) and bovine (bGH) GH and ovine PRL (oPRL) has been compared in liver membranes from GH-deficient dwarf "little" mice (lit/lit) and their normal-sized littermates (lit/+). Binding of [125I]hGH to lit/lit membranes was dependent on time, temperature, and membrane concentration and was reversible. Scatchard plots of the binding of [125I]hGH to male and female lit/lit and lit/+ membranes were linear, with no significant differences between binding affinities (overall mean +/- SE, 1.42 +/- 0.27 X 10(9) M-1; n = 24). The hormonal specificity of binding was complex, with hGH being displaced by both somatotropic (bGH) and lactogenic (oPRL) competitors, indicating the presence of a mixed population of receptors. This conclusion was supported by the specific binding of both [125I]bGH and [125I]oPRL to membranes from male and female lit/lit and lit/+ mice. No differences in the specific binding of [125I]bGH to any membrane type was observed, indicating that GH receptors were at normal levels in lit/lit mice despite their deficiency of pituitary and serum GH. A sex difference in hGH and oPRL binding was seen only in normal (lit/+) mice. Male and female lit/lit mice exhibited the same degree of binding as normal female mice. These studies have demonstrated that dwarf little mice have normal levels of hepatic GH and PRL receptors, with binding characteristics not different from those of normal mice. Thus, it would appear that the mechanism of regulation of GH receptors by GH itself is different in this animal model of GH deficiency than in the Snell dwarf mouse and the hypophysectomized rat, where GH receptor levels are very low or absent. The failure of lit/lit mice to grow normally despite normal levels of GH receptor raises questions regarding the site and mechanism of the growth defect in the little mouse.

Compensatory renal growth in the mouse. II. The effect of growth hormone deficiency.

Allometry was used to study the effect of growth hormones (GH) deficiency on compensatory renal growth (CRG) in a dwarf mouse strain (Little). Nucleic acid and protein estimations were used to assess changes in cellular hyperplasia and hypertrophy. Nephrectomy was performed at 5, 15, or 35 days of age with removal of the renoprival kidney 15 days later. Controls underwent sham nephrectomies at 35 days of age. The allometric growth of the normal kidney in the homozygote dwarf (lit/lit) between 8 and 50 days of age was closely related to that of the normal heterozygote (lit/+). A regression line for the renoprival kidneys in lit/lit animals was parallel to that of the control right kidney (P less than 0.001). The interval between the regression lines was equivalent to a constant difference of approximately 40% between renoprival and control right kidneys and was similar to that found in the normal heterozygote (43%). Increases in DNA, RNA, and protein in control animals during CRG indicate that cell division and hypertrophy were occurring in similar proportions. In the GH-deficient mouse, the total amount of DNA in renoprival kidneys was 0.451 mg compared with 0.439 mg in controls (NS). This suggests that cell replication was suppressed. The protein:DNA ratio increased from 20.91 to 24.27 (P less than 0.001) and the RNA:DNA ratio increased from 0.732 to 0.912 (P less than 0.001), suggesting that cell size was markedly increased. These findings suggest that reduced amounts of GH may produce a dissociation between hyperplasia an hypertrophy, with CRG occurring predominantly by cellular hypertrophy.

Urinary steroid metabolites and the overgrowth of lean and fat tissues in obese girls.

Studies were made of steroid metabolites excreted in the urine of 17 obese girls 11.4 to 16.8 yr and 17 normal girls 11 to 17 yr. Creatinine excretion (muscle mass), total body water (or deuterium space), lean body mass and body fat were determined in the obese girls. Extracellular volume (corrected bromide space) was also measured and by difference with body water, intracellular water or soft tissue cell mass was calculated. In normal girls 24-h creatinine excretion was determined, but body water was predicted from height and weight. It was found, as in previous studies, that the obese girls had excess muscle mass and soft tissue cell mass for height. The excess growth of muscle, lean tissue, and body length in obese girls correlated with increments in oxosteroid (17 ketosteroid) excretion. The overall weight increase correlated with increased excretion of corticosteroid metabolites--a finding of interest since a physiological Cushing's syndrome was postulated for fat girls many years ago. When the normal and obese girls were divided by age at 14 yr and the subgroups compared (normal obese) the younger girls showed differences with respect to height, weight, total body water, fat and percentage fat. Differences in steroid metabolites were not found. In older girls the same findings were made again, but here it was clear that the increments in body size, particularly muscle mass, correlated with augmented oxosteroid excretion. Evidence is cited that these findings are not just related to a larger steroid pool in obese girls.

Assessment of protein reserves (cellular mass) in Aboriginal children.

The body protein reserves, assessed indirectly by the measurement of intracellular water, was determined in free-living Aboriginal children and adolescents located in Central and Northwestern Australia. Fifty one individuals were studied--31 males and 20 females. Significant reductions were observed in intracellular water or cell mass relative to the cube of body length for Aboriginal females when compared to a control female group. Only marginal or borderline differences for the same parameters were observed when Aboriginal males were compared with controls. Comparison of Aboriginal females with Aboriginal males demonstrated significant reductions in cell mass (intracellular water) relative to body length cubed in the female. This finding in the Aboriginal female is of concern because many become pregnant in the early teenage years. Evidence was found during the course of this study that plasma zinc concentrations were frequently low. This led to a concomitant study on serum and plasma trace metals in two Aboriginal settlements (364 individuals) to be published in a subsequent paper.