High incidence of skin cancer in the Channel Islands.

BACKGROUND: Previous studies looking at rates of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) in the UK have documented one of the highest rates in the southwest of England; however, the incidence of these tumours in Guernsey and Jersey, two of the Channel Islands, has not previously been reported. AIMS: To determine the incidence of cutaneous MM and NMSC in the Channel Islands. METHODS: Data for the period 2005-2009 were obtained from clinical and histopathological records for all MMs excised in the Channel Islands, and from the South-west Cancer Registry for MMs excised in the southwest of England and for NMSCs in both areas. The age-standardized incidence rate (ASRs) per 100,000 of the population in the Channel Islands were compared with those with the southwest of England, the UK and the rest of Europe where available. The MM characteristics of the Channel Islands were then compared with the southwest of England using standardized incidence ratios (SIRs). RESULTS: The ASR/100,000 for cutaneous MM for 2005-2009 was 30 for the Channel Islands (31.3 for Jersey, 28.2 for Guernsey), 20.3 for the southwest of England, and 15.6 for the UK. Comparison with the rest of Europe indicated that the incidence of MM in the Channel Islands is one of the highest in Europe. The highest incidence of MM was in the over 65 years age group on both Guernsey and Jersey, and when divided into 5-year age bands, the 70-74 years age group had the highest rate. This suggests that this particular age group may have previously received greater exposure to some environmental factor that promotes MM development. The ASR/100,000 for NMSC was also higher for the Channel Islands (263.3) than for the southwest of England (174.6) for 2005-2009, and for the UK in 2009 (104.9). CONCLUSIONS: This study indicates that the Channel Islands have a high incidence of skin cancer (both MM and NMSC). In addition, the data show that the ASRs in older people in this population group differ from those in mainland UK, showing higher rates in the over 65 years age group.

Bariatric surgery.

Obesity is fast becoming one of the world's leading health problems and together with its many associated medical sequelae significantly increases morbidity and mortality. In this review, we briefly explore the history of bariatric surgery, the benefits of surgery and the various procedures carried out.

Outcomes of cleft care in Western Australia: a pilot study.

The purpose of this study was to compare outcomes and delivery of cleft care in Western Australia with the average standard of care in the United Kingdom (UK). This was achieved through a cross-sectional study involving children born with unilateral cleft lip and palate between April 1983 and March 1985 (12 year olds) or between April 1990 and March 1992 (5 year olds). A total of 38 children born with unilateral cleft lip and palate were under the care of the cleft team based at Perth's Princess Margaret Hospital. Dental arch relations, facial skeletal pattern, speech, hearing, success of alveolar bone grafting and dental health were measured. It was found that fewer Princess Margaret Hospital children in both age cohorts had revision surgery and speech therapy compared with the UK average. The facial skeletal pattern, speech, hearing and alveolar bone grafting outcomes from Princess Margaret Hospital were similar to the UK at age 12. Seventeen per cent of the Princess Margaret Hospital 12 year olds had a poor dental arch relationship compared with 39 per cent in the UK. In the 5 year olds, most outcomes in Princess Margaret Hospital patients appeared better than the UK with lower residual treatment needs. While it is difficult to draw firm conclusions because of the small numbers involved, this study indicates standards need to be set and determined for Australia.

Initial cleft size does not correlate with outcome in unilateral cleft lip and palate.

Clinical outcomes in children born with a cleft lip and palate (CLP) have been an area of interest for orthodontists for a number of years. Whilst tools for measurement of these outcomes are available, there is no widely accepted measure of initial cleft severity and no known quantitative indices. Therefore, the potential influence of initial severity remains unmeasured and largely ignored. The aim of this investigation was to determine the importance of initial cleft severity in determining patient outcome. The longitudinal records of 49 children born with a unilateral cleft lip and palate (UCLP), and treated in a single centre were examined. An index of initial cleft severity was developed that categorizes the cleft area as a percentage of the total palate area. The dental arch relationships of the same patients at 6 years of age were also determined. The nature of the association between these was investigated for agreement and correlation by calculation of weighted Kappa and Spearman's correlation coefficient, respectively. No evidence was found in this sample that the initial cleft area had any bearing on the quality of outcome at 6 years of age.

Dentoalveolar relations in children born with a unilateral cleft lip and palate (UCLP) in Western Australia.

OBJECTIVE: Our objective was to evaluate complete unilateral cleft lip and palate repair outcome in the Cleft Unit in Perth, Western Australia, by assessment of dentoalveolar relationships. DESIGN: This is a retrospective study. SETTING: Our subjects were individuals under the care of the cleft team in Perth, Western Australia. PARTICIPANTS: All patients with unilateral cleft lip and palate and available 6-year casts who had been born since January 1, 1985, were identified from the cleft unit's database. The nature of the cleft was verified by examination of birth study models and photographs. A total of 54 such patients were identified. MAIN OUTCOME MEASURES: Main outcome measures were identified through dental arch relationship grading of study models using the 5 Year Old Study Model Index. RESULTS: Interexaminer and intraexaminer agreement kappa statistics revealed good to very good agreement using this index. The results indicate that the surgical outcome was graded as excellent, good, or fair for 77% of patients and poor or very poor for 23% of patients. CONCLUSIONS: The results of the Western Australia study compare favorably to the overall U.K. outcome (the Clinical Standards Advisory Group study) but unfavorably to the results of some European centers, such as Oslo.

Craniosynostosis in Western Australia, 1980-1994: a population-based study.

A craniomaxillofacial unit was established recently in Western Australia, and a study was carried out to provide some baseline characteristics of primary craniosynostosis in Western Australia and to investigate whether there has been any significant temporal change in birth prevalence. A case control study was conducted, using cases identified from a population-based register of birth defects, and a random sample of all births without a birth defect formed the control group. All subjects were born in Western Australia over the period 1980-1994 inclusive. The prevalence of craniosynostosis over the period 1980-1994 in Western Australia was 5.06 per 10,000 births. There was a significant linear increase in lambdoid synostosis over this period of 15.7% per year. Craniosynostosis was significantly more common among male infants, infants born preterm (<37 weeks gestation), breech presentation or presentations other than vertex, and infants born to fathers 40 years of age or older, even after accounting for known autosomal dominant syndromes. Other major birth defects were found in 11.2% of children with nonsyndromic craniosynostosis. Only 43 children (25.3%) with craniosynostosis were reported to have been seen by a geneticist. Thus, the prevalence of craniosynostosis in Western Australia is among the lowest reported. There is no current explanation for the increase in lambdoid synostosis. The increased risk of so-called nonsyndromic craniosynostosis with paternal age raises the possibility of undiagnosed new dominant mutations. This, along with the excess of other birth defects in children with craniosynostosis emphasises the need to ensure that these families are offered genetic counseling.

Conjunctival impression cytology in the preterm infant and it's relation to outcome.

UNLABELLED: The preterm infant is deficient in vitamin A (retinol) and this has been implicated in the pathogenesis of chronic lung disease of prematurity. Conjunctival impression cytology (CIC) has been used in adults to assess retinol status. We aimed to assess the feasibility of performing CIC in the preterm infant and to determine the significance of abnormal CIC findings. CIC samples were collected during routine retinopathy screening, and classified as inadequate, normal, borderline normal or abnormal. Ninety preterm infants were studied. Seventy-four (82%) CIC specimens produced a positive yield, whereas 16 (18%) were inadequate. Of the 74 adequate samples, 61 (82%) were normal or borderline normal and 13 (18%) abnormal. Seventy-three CIC specimens were assessed by a second histopathologist with complete agreement on 64 (88%) samples and disagreement on 9 (12%) samples. Ten sets of conjunctival impressions, taken from both eyes, gave identical results in all adequate samples. Birth weight was significantly lower in this abnormal group. Four infants (32%) in the abnormal group required treatment for retinopathy compared to two (3%) in the normal/borderline normal group, (P < 0.01). CONCLUSION: Conjunctival impression cytology is simple and reproducible technique which maybe easily applied to the preterm infant. Abnormal CIC is associated with retinopathy of prematurity requiring treatment.

Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy.

Tumour localisation of anti-tumour antibodies varies greatly between patients. Factors which may be responsible for this have been investigated in 56 patients with colorectal carcinoma with a view to improving radioimmunotherapy. Thirty-seven to seventy-four MBq of 125-I labelled mouse monoclonal antibody to CEA, was given intravenously and tumour resected 70-480 h later. Percentage injected activity kg-1 (% inj.act kg-1) in tumour, was inversely correlated with the time interval between injection and operation (P = 0.004). To assess the influence of other parameters on localisation, patients were divided into two time groups according to time interval between injection and operation, 70-120 h (n = 33) and 144-480 h (n = 23). In neither group was there a significant correlation of % inj.act kg-1 with time. The % inj.act kg-1 in tumour showed a significant correlation with that in the blood for both groups (P = 0.005 and P = 0.01). There was no significant correlation for either time group between % inj.act kg-1 in tumour and serum CEA values, the per cent of tumour cells positive for CEA and vascularity. Tumour to blood ratios varied considerably (range 0.3-28.5:1) suggesting that factors other than time and persistence of activity in the blood contribute to efficient targeting. Tumour to blood ratios were inversely correlated with % inj.act kg-1 in blood for the 70-120 h group (P = 0.007), and were positively correlated with % inj.act kg-1 in tumour (P = 0.012). Autoradiography showed that antibody localised predominantly on tumour cells but was distributed heterogeneously, was not solely related to the expression of antigen and in some cases accumulated in necrotic more than viable areas of tumour. Penetration of antibody into malignant acinar structures was poor and CEA-positive cells closer to the blood supply were targeted to a greater extent than distant cells. Preoperative administration of radiolabelled antibody to CEA may be helpful in selecting patients with favourable localisation for radioimmunotherapy.

Selective uptake of toxic nucleoside (125IUdR) by resistant cancer.

We report uptake of a thymidine analogue 125-Iodine-5-iodo-2'-deoxyuridine (125IUdR) by nude mice bearing human xenografts of choriocarcinoma or colonic cancer. When 125IUdR was given alone, uptake by intestinal tissues was 5-10 times greater than by the tumours as measured by tissue gamma counting. This ratio was reversed when hydroxyurea or cytosine arabinoside were used as inhibitors of ribonucleotide reductase and were given in combination with 5-fluorouracil or methotrexate to inhibit thymidine synthesis shortly before injecting 125IUdR. Counting the radioactivity in tissues removed 24 hours after 125IUdR gave tumour to highest normal tissue ratios of up to 15:1, but the corresponding nuclear grain counts, which is probably a more reliable indicator of selective uptake into DNA, were in excess of 100:1. The addition of unlabelled IUdR to the regimen only reduced the uptake of 125IUdR when given in relatively large amounts. For this approach to be exploited it is concluded that the tumour must be resistant at the cell level to the inhibitor of DNA synthesis either de novo or as a result of prior exposure to it. This inhibitor can then be used to block uptake of the potentially toxic nucleoside analogue by normal renewal tissues while it is taken up by the resistant cancer cells. By inhibiting synthesis of the corresponding normal nucleosides with inhibitors to which the cancer cells are not resistant, incorporation of the toxic analogues into tumour DNA was enhanced. Although 125IUdR is a convenient agent for exploring this approach and is highly cytotoxic when incorporated in DNA, the clinical potential of reverse role chemotherapy probably lies with the development of toxic non-radioactive nucleoside analogues.

Comparison of anti-fetal colonic microvillus and anti-CEA antibodies in peroperative radioimmunolocalisation of colorectal cancer.

Local recurrence of colorectal cancer may result from failure to assess accurately the extent of tumour at operation. It has been suggested that peroperative radioimmunolocalisation may improve this assessment. The degree to which this is possible has been studied using a hand-held gamma detecting probe and comparing two 125I-labelled monoclonal antibodies to colorectal tumours. The antibodies were to fetal colonic microvillus membrane (FM1D10) and to carcinoembryonic antigen (A5B7). Sixty-nine per cent (9/13) of the FM1D10 and 98% (43/44) of A5B7 labelled tumours took up significant amounts of antibody with a tumour to normal colon ratio of more than 1.5:1. The uptake was significantly better for A5B7 with a median tumour to normal colon ratio of 3.3 (1.1-13.8) compared to 1.85 (0.75-7.7) for FM1D10 (P less than 0.001). The tumour: colon ratio of both antibodies was independent of the serum CEA, Dukes' stage or the degree of histological differentiation. There was a linear correlation for tumour to normal colon ratios between the gamma detecting probe and the same tissue examined in a conventional well counter (correlation coefficient r = 0.78, P less than 0.001). Colorectal tumours demonstrate a rapid and reliable uptake of anti-CEA monoclonal antibody A5B7. This antibody can be detected with a peroperative gamma detecting probe and has the potential to improve the surgeon's appreciation of the extent of tumour and therefore may influence the surgery performed. Detailed clinical studies are now being carried out.

Preliminary observations on the microdistribution of labelled antibodies in human colonic adenocarcinoma xenografts: relevance to microdosimetry.

Autoradiography with 125I-labelled antibodies 17-1-A and 11-285-14 (anti-carcinoembryonic antigen) injected singly or together into nude mice carrying two distinct human colorectal cancer xenografts delineates marked changes in distribution and retention of isotope over 72 h, which are relevant to microdosimetry. The antibodies localise independently at low concentrations. Slow accumulation and retention predominantly in membranes of glands and necrotic areas suggest that therapy will succeed best with isotopes whose range, half-life and/or mode of delivery can exploit optimally the greater selectivity of the late retention.

Serial measurements of Ca antigen in sera from patients with advanced malignant breast disease.

Ca antigen levels in serum samples from three groups of patients were assayed. From a survey of 173 patients with various malignancies, elevated levels were found most consistently in patients with metastatic breast cancer. Spearman rank correlation values of Ca and CEA values on individual serum samples, 0.3009, (n = 194), or individual and serial samples, 0.2406, (n = 264) from a total 194 patients with metastatic breast cancer showed that correlation between Ca and CEA values was poor. For a group of 20 patients within the 194, from whom fortnightly serial samples were available, serum levels for 10/20, measured retrospectively, corroborated clinical observations on the course of their disease, although only 4/20 showed marked elevations during active disease. No correlations between expression of the tumour marker and histological type of the primary tumour, age of the patient, site of recurrence nor aberrant elevation in response to cytotoxic drug could be found to explain the non-correspondence of marker behaviour and disease status in the remaining 10 patients. The indications from this small study are that serial Ca antigen serum measurement could be misleading in 50% of patients with metastatic breast cancer, and that the assay is unsuitable for follow-up of patients with breast cancer.

Immunohistological distribution of 5T4 antigen in normal and malignant tissues.

A trophoblast cell surface antigen has been characterised by a monoclonal antibody (mAb) 5T4, raised following immunisation with solubilised wheat germ agglutinin binding glycoproteins from human syncytiotrophoblast plasma membrane (StMPM). The expression of the 72 kDa glycoprotein was assessed on cryostat sections of a range of neoplastic and non-neoplastic tissues, using an avidin-biotin immunoperoxidase technique. In products of conception, intense reactions were noted with villous syncytiotrophoblast membrane in normal early and term placenta, with weaker positivity of placental site trophoblast. Most normal or non-neoplastic tissues were negative, including liver, kidney, spleen, small intestine, ovary and testis. Faint or moderate positive reactions were present in some specialised epithelia. Of 115 neoplasms examined, 76 showed reactions with tumour cells including carcinomas of the bladder, breast, cervix, endometrium, lung, oesophagus, ovary, pancreas, stomach and testicular non-seminomatous germ cell tumours. Choriocarcinomas and placental site trophoblastic tumours were also positive. Most adenocarcinomas of colon and seminomas were negative as were all malignant melanomas and malignant lymphomas. A radioimmunoassay did not detect the antigen in either normal or pregnancy serum. The relatively low level of expression in normal tissues and reactivity with a wide range of carcinomas suggested that the antibody may be useful in diagnostic or targeting studies.

Identification of a human ribosomal protein mRNA with increased expression in colorectal tumours.

A human ribosomal protein cDNA was selected from a normal colon cDNA library on the basis of overexpression in familial adenomatous polyposis. Nucleotide sequence analysis was used to identify this cDNA as corresponding to the human equivalent of the rat ribosomal protein L31 (HL31). We have quantified the expression of HL31 mRNA in colorectal tumours and found overexpression in 23 out of 23 cases. Our results indicate that HL31 is associated with a malfunction of normal growth regulatory mechanisms in these tumours, and suggest a role for HL31 in proliferation and neoplasia.

Vertical parallax radiology to localize an object in the anterior part of the maxilla.

An evaluation has been made of four techniques of assessing, from radiographs, the position of unerupted maxillary teeth, using radio-opaque markers placed in various positions on the maxilla of a dried skull. Application of the parallax principle in a vertical plane, for which only two radiographs are needed, was found to produce as many correct conclusions as other methods.

The reliability of mandibular radiographic superimposition.

Using tracings from thirty pairs of serial cephalometric radiographs, the reliability of three outlines, commonly used for mandibular superimposition, was investigated. There were sizeable errors associated with all three groups, but tracings involving Björk's mandibular structures were found to be the least reliable. Despite the greater validity of the Björk structures for assessment of growth changes, in certain cases the use of the mandibular outline may be of greater value for the superimposition of tracings, especially when the time interval between the radiographs is short, or the patient has passed maturity and the growth rate has declined to a negligible level.

Urinary gonadotrophin peptide--isolation and purification, and its immunohistochemical distribution in normal and neoplastic tissues.

A urinary gonadotrophin peptide (UGP) was isolated and purified from semi-purified human chorionic gonadotrophin (hCG), prepared from pregnancy urine. The peptide showed hCG-B subunit activity and no hCG-alpha subunit activity as demonstrated by binding studies with the relevant antibodies. It had a molecular weight significantly less than hCG-B subunit. The peptide was linked to thyroglobulin and this conjugate used to immunise rabbits and mice. A radioimmunoassay (RIA) using 125I-UGP and the rabbit antiserum (AK12) was used to monitor chromatographed urine fractions from patients with ovarian carcinoma, seminoma and hydatidiform mole. UGP was also found in the urine extract of a healthy male, but at a much lower level. In each case the UGP detected had the same molecular weight as the pregnancy preparation and appeared to be the main gonadotrophin constituent in those urine samples. Initial immunohistochemical screening of normal and neoplastic tissues with the rabbit antibody (AK12) showed reactivity with some tumours including carcinomas of the lung, ovary, cervix and breast as well as trophoblastic and germ cell tumours. Reactions with non-neoplastic tissues were confined to some specialised epithelia and macrophage populations. A more comprehensive immunohistochemical study was made using a monoclonal antibody to UGP (2C2), with a monoclonal antibody to conformational hCG (INN 13) and another monoclonal antibody to free B subunit (1E5) as controls. Similar patterns of reactivity were produced by the AK12 and 2C2 antibodies in both neoplastic and non-neoplastic tissues. Additional tissues were investigated with the three monoclonal antibodies. The 2C2 antibody reacted with 93% (77/83) of tumours examined; the INN 13 antibody reacted with only the syncytiotrophoblast cells of choriocarcinoma, hydatidiform mole, placental site trophoblastic tumour, and in one case of seminoma; the 1E5 reactivity was confined to only choriocarcinoma syncytiotrophoblast cells.

Radiographic localization of unerupted teeth in the anterior part of the maxilla: a survey of methods currently employed.

The radiographic prescribing habits of consultants in orthodontics and oral surgery are described with specific reference to assessment of unerupted maxillary canine teeth. Orthodontists use more radiographs than oral surgeons under these circumstances. The relative radiation for commonly used combinations of radiographs has been summarized and recommendations made regarding the use of certain of these.

Apocrine carcinoma of the breast containing foam cells. An electron microscopic and immunohistological study.

The detailed light and electron microscopic and immunohistological features of an invasive apocrine carcinoma of the breast developing in a 78-year-old woman are presented. The stroma of the tumour contained non-neoplastic lipid-filled (foam) cells. To our knowledge, these cells have not been described before in invasive breast carcinoma. Their electron microscopic and immunohistological features confirm their histiocytic nature.