Rate of positive diagnosis of skin cancer and its stage in two-week wait referrals in England according to age.

BACKGROUND: The incidence of skin cancer is increasing. The two-week wait conversion rate (TWWCR) is the percentage of urgent suspected skin cancer referrals that are confirmed as cancer. AIMS: To examine the relationships between different epidemiological factors and TWWCR for malignant melanoma (MM) and cutaneous squamous cell carcinoma (SCC). METHODS: We extracted data from the National Cancer Data Repository (NCDR) and National Cancer Waiting Times Monitoring Dataset between 2009 and 2010 for MM and SCC in England. We conducted partial correlation and stepwise multiple regression analysis on TWWCR, age, incidence, detection rate, tumour thickness (MM only), percentage MM/SCC and social deprivation. We also looked at the two-week wait referral rate (TWWRR) and incidence rate with respect to age. RESULTS: TWWCR was significantly correlated with age when partial correlation was used to control for the factors described above for MM (P < 0.05) and SCC (P < 0.001). Stepwise regression of these factors returned only age as significant in the final model for MM (P < 0.001) and SCC (P < 0.01). Incidence of MM and SCC increased with age. TWWRR also increase with age, but with higher rate in younger people relative to their incidence. CONCLUSIONS: Age is a predictor of TWWCR independent of the other factors measured, including thickness and incidence. This may be explained by the higher number of referrals for younger patients despite the lower incidence of skin cancer in this group. This may reflect a more appropriate rate of referral in order to achieve earlier diagnosis and better outcomes.

Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project.

Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995-2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000-2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers.

Measuring current and future cost of skin cancer in England.

BACKGROUND: Increasing incidence of and mortality from skin cancer are posing a large financial burden on the NHS in England. Information provided by cost-of-illness (CoI) studies are used in policy making and are particularly useful for measuring the potential savings from averting a case of disease. METHODS: We estimate the cost of skin cancer in England, and model future costs up to 2020. We compare two costing approaches (top-down and bottom-up). RESULTS: We estimate that costs due to skin cancer were in the range of £106-£112 million in 2008. These figures are very closely related to those provided by the Department of Health (estimated to be £104.0 million in 2007-8 and £105.2 million 2008-9). The expected cost per case of malignant melanoma was estimated to be £2607 and £2560, using the bottom-up and top-down approaches, respectively. The mean cost per case of non-melanoma skin cancer was £889 and £1226, respectively. We estimate that the cost to the NHS due to skin cancer will amount to over £180 million in 2020. CONCLUSION: Effective prevention of skin cancer might not only reduce a significant burden of disease but it could also save considerable resources to the NHS.

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.

Incidence and survival of rare urogenital cancers in Europe.

BACKGROUND: The RARECARE project aims at increasing knowledge of rare cancers in Europe. This manuscript describes the epidemiology (incidence, prevalence, survival) of rare urogenital cancers, taking into account the morphological characterisation of these tumours. METHODS: We used data gathered by RARECARE on cancer patients diagnosed from 1995 to 2002 and archived in 64 European population-based cancer registries, followed up to December 31st, 2003 or later. RESULTS: The annual number of males that develop penile cancer in the EU is estimated at 3100, which is equivalent to an age standardised rate (ASR) of 12 per million males. The 5-year relative survival rate is 69%, while squamous cell carcinoma is the predominant morphological entity. Each year around 650 persons in the EU develop cancer of the urethra and 7200 develop cancer of the renal pelvis or ureter (RPU). The ASR for cancer of the urethra and RPU is 1.1 (males 1.6; females 0.6) and 12 (males 16; females 7) per million inhabitants, respectively. The 5-year relative survival rate for cancer of the urethra and RPU is 54% and 51%, respectively. Transitional cell carcinoma is the predominant morphological entity of cancer of the urethra and RPU. CONCLUSIONS: In view of the low number of cases and the fact that one third to one half of the patients die of their disease, centralisation of treatment of these rare tumours to a select number of specialist centres should be promoted.

Descriptive epidemiology of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe.

This work provides descriptive epidemiological data of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe as defined as in the RARECARE project. We analysed 8669 incident cases registered in the period 1995-2002 by 76 population-based cancer registries (CRs), and followed up for vital status to 31st December 2003. Age-standardised incidence to the European standard population was obtained restricting the analysis to 8416 cancer cases collected by 64 not specialised CRs or with information available only for some anatomical sites. Period survival rates at 2000-2002 were estimated on 45 CRs data. Twenty-two CRs which covered the period 1988-2002 were analysed to obtain the 15-year prevalence (1st January 2003 as reference date). Complete prevalence was calculated by using the completeness index method which estimates surviving cases diagnosed prior to 1988 ('unobserved' prevalence). The expected number of new cases per year and of prevalent cases in Europe was then obtained multiplying the crude incidence and complete prevalence rates to the European population at 2008. We estimated 5204 new cases per year (10.5 per million) to occur in Europe, of which 48.7% were melanomas of uvea, 24.8% melanomas of mucosa and 26.5% adnexal carcinomas of the skin. Five-year relative survival was 40.6% and 68.9% for mucosal and uveal melanomas, respectively. Adnexal skin carcinomas showed a good prognosis with a survival of 87.7% 5 years after diagnosis. Northern Europe, United Kingdom (UK) and Ireland showed the highest 5-year survival rate for uveal melanomas (72.6% and 73.4%), while Southern Europe showed the lowest rate (63.7%). More than 50,000 persons with a past diagnosis of one of these rare cancers were estimated to be alive at 2008 in Europe, most of them (58.8%, n=29,676) being patients with uveal melanoma. Due to the good prognosis and high incidence of uveal melanomas, these malignancies are highly represented among the long-term survivors of the studied rare cancer types. Therefore, maximising quality of life is particularly important in treatment of uveal melanoma. As regards mucosal melanomas, the centralisation of treatment to a select number of specialist centres as well as the establishment of expert pathology panels should be promoted. The geographical differences in incidence and survival should be further investigated analysing the centre of treatment, the stage at diagnosis and the treatment.

Social care data in England: what they tell us and what they do not tell us.

A large volume of statistics is published nationally on adult social care in England. The data are used locally to manage and improve delivery of care. Social care data have the potential to give invaluable information on the prevalence of dementia and other chronic conditions, and on end-of-life care. However, examination of these statistics reveals that there are problems with their accuracy and detail which limit their usefulness for describing geographical differences and differences over time. Comparison is made with the national statistics available on health service activity. Linkage of health and social care data would provide a great deal of useful information. It is suggested that the key to improving quality and detail of national social service data is to make greater use of them.

Y configuration of the internal thoracic arteries in myocardial revascularization.

This paper describes the short-term results of surgical myocardial revascularization in 35 patients. Y configuration from one or two internal thoracic arteries was applied for bypass grafting of the left coronary artery. In 4 patients with truncal stenosis of the left coronary artery (LCA) or proximal stenoses of the anterior interventricular artery (AIVA) and circumflex artery, the length of the left internal thoracic artery (LITA) appeared adequate for creation of Y bypass and revascularization of the entire LCA pool. In most cases (28), Y bypass was formed from both ITA, which made it possible to revascularise more distant arteries of the posterolateral wall of the left ventricle. Analysis of bypass-graphies performed in 10 patients after 7 months on the average has demonstrated that occlusion (2) and stenosis of one of the branches (2) of Y bypass were most probably caused by underestimation of the degree of stenosis of the target coronary arteries.

Net energy value of two low-digestible carbohydrates, Lycasin HBC and the hydrogenated polysaccharide fraction of Lycasin HBC in healthy human subjects and their impact on nutrient digestive utilization.

The metabolizable energy content of low-digestible carbohydrates does not correspond with their true energy value. The aim of the present study was to determine the tolerance and effects of two polyols on digestion and energy expenditure in healthy men, as well as their digestible, metabolizable and net energy values. Nine healthy men were fed for 32 d periods a maintenance diet supplemented either with dextrose, Lycasin HBC (Roquette Frères, Lestrem, France), or the hydrogenated polysaccharide fraction of Lycasin HBC, at a level of 100 g DM/d in six equal doses per d according to a 3 x 3 Latin square design with three repetitions. After a 20 d progressive adaptation period, food intake was determined for 12d using the duplicate meal method and faeces and urine were collected for 10 d for further analyses. Subjects spent 36 h in one of two open-circuit whole-body calorimeters with measurements during the last 24h. Ingestion of the polyols did not cause severe digestive disorders, except excessive gas emission, and flatulence and gurgling in some subjects. The polyols induced significant increases in wet (+45 and +66% respectively, P<0.01) and dry (+53 and +75 % respectively, P<0.002) stool weight, resulting in a 2% decrease in dietary energy digestibility (P<0.001). They resulted also in significant increases in sleeping (+4.1%, P<0.03) and daily energy expenditure (+2.7 and +2.9% respectively, P<0.02) compared with dextrose ingestion. The apparent energy digestibility of the two polyols was 0.82 and 0.79 respectively, their metabolizable energy value averaged 14.1 kJ/g DM, and their net energy value averaged 10.8 kJ/g DM, that is, 35 % less than those of sucrose and starch.

Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing.

OBJECTIVES: To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing (Haemoccult) and both tests combined. DESIGN: Patients were randomised to screening by flexible sigmoidoscopy, faecal blood testing, or both tests. The flexible sigmoidoscopy examinations were performed by a general practitioner. SETTING: General practice. SUBJECTS: 3744 patients aged 50-75 years. MAIN OUTCOME MEASURES: Uptake, positive results, detection of neoplasia, complications, and recall for diagnostic colonoscopy. RESULTS: Uptake was significantly higher in the flexible sigmoidoscopy group (46.6%) than in the faecal blood test group (31.6%; P<0.001) or than in the group having both tests (30.1%; P<0.001). Telephone reminders increased uptake of sigmoidoscopy to 61.8%. In total, 1116 sigmoidoscopy examinations were performed without major complication. Polyps were found in 19. 3% (95% confidence interval 17.0% to 21.6%) but only 6.8% (5.3% to 8. 3%) had adenomas and 2.4% (1.5% to 3.3%) "high risk" adenomas. Cancer was detected in four subjects. The faecal blood test yielded positive results in 0.8% (0.2% to 1.4%) but missed at least one cancer and 30 cases of adenoma which were found by sigmoidoscopy in the combined group. Use of histological criteria-shown elsewhere to correlate with future risk of colorectal cancer-to select "positive" patients could reduce recall for diagnostic colonoscopy from about 20% to less than 5%. CONCLUSIONS: Some of the predicted obstacles to screening with flexible sigmoidoscopy are surmountable. Clear evidence relating to efficacy will be obtained only from a randomised controlled trial.

E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival.

To determine the potential prognostic value of epithelial cadherin (E-cadherin), a Ca(2+)-dependent cell-cell adhesion molecule, we have analysed its immunoreactivity and cellular localisation in 67 transitional cell carcinomas (TCC) using an avidin-biotin immunoperoxidase technique on formalin-fixed, paraffin-embedded tissues. These results were correlated with histopathological grade, tumour stage, presence of metastases and survival. In addition, 10 cystitis and 11 normal bladder biopsies were evaluated as controls. E-cadherin was expressed in a normal membranous pattern in all normal and 7 of 10 cystitis biopsies. Loss of normal surface E-cadherin expression was found in 3 of 15 superficial tumours and in 48 of 52 invasive cancers. Abnormal immunoreactivity was strictly related to tumour differentiation and stage. Fifteen of 20 well-differentiated (grade I) tumours showed preserved membranous E-cadherin immunoreactivity, while 46 of 47 moderate and poorly differentiated tumours (grades II and III) demonstrated abnormal staining patterns. Loss of membranous E-cadherin immunoreactivity was also associated with advanced tumour stage. There was a significantly higher 5-year survival rate for patients with preserved membranous staining compared with patients with abnormal staining.

2,3-Dihydro-1-benzofuran-5-ols as analogues of alpha-tocopherol that inhibit in vitro and ex vivo lipid autoxidation and protect mice against central nervous system trauma.

A series of alpha-tocopherol analogues was synthesized with potential therapeutic value for such pathological conditions as stroke and trauma. A set of criteria such as the inhibition of in vitro lipid peroxidation, superoxyl radical scavenging, and brain penetration, as measured by ex vivo inhibition of lipid peroxidation, was applied to select the most effective compound. 2,3-Dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)methyl]-1 - benzofuran-5-ol dihydrochloride (22) was selected because of its superior antioxidant properties and better brain penetration. This compound also protected mice against the effects of head injury. The criteria thus turned out to be useful for the characterization of a neuroprotective analogue of alpha-tocopherol.

Self-administered faecal occult blood tests do not increase compliance with screening for colorectal cancer: results of a randomized controlled trial.

In the UK, compliance with conventional faecal occult blood (FOB) tests such as Haemoccult is about 50% in the general population. It has been postulated that characteristics of the performance of conventional tests, in particular the need for dextrous gathering and manipulation of faeces, delay in receiving results, and the recommended dietary restrictions, may all diminish compliance. New FOB tests have been developed, popularly termed 'magic toilet paper' tests, which not only minimize faecal manipulation but are also self-reported. Compliance rates with two self-administered faecal occult blood tests (Early Detector and Coloscreen Self-Test) were compared with Haemoccult in a randomized trial involving 1,842 subjects aged 40-74 years. Use of self-administered FOB tests did not increase compliance significantly, with rates of 52.1% for Early Detector, 50.6% for Coloscreen and 49.1% for Haemoccult. Moreover, dietary restriction did not reduce compliance significantly (restricted 49.3%, unrestricted 51.8%). A wide variation (from 1.3% to 21.4%) in positivity rates was observed which was dependent on which of the three tests was used and whether dietary restrictions were applied. Since the physical aspects of test performance do not appear to determine an individual's decision to be screened, self-administered tests will not overcome the problem of poor compliance with FOB screening.

Differential and integral W-values for ionization in gaseous water under electron and proton irradiation: consistency of inelastic collision cross sections.

Differential and integral W-values for ionization in gaseous water for electron and proton irradiation have been analyzed from the theoretical point of view for consistency between ionization and total inelastic collision cross sections. For low-energy electrons, which are ubiquitous for all primary radiations, the experimental or compiled cross sections from different sources are sometimes not consistent with one another. A practical, self-consistent procedure is outlined in such cases. The high-energy asymptotic W-values for differential and integral ionization are calculated to be 33.7 and 34.7 eV, respectively, for electron irradiation and 34.6 and 32.5 eV, respectively, for proton irradiation. The computed variations of the W-values with energy are generally in good agreement with experiment. Integral primary W-values due only to the interactions between the incident particle and the water vapor are calculated to be 43.5 and 45.0 eV for electrons and protons, respectively, in the high-energy asymptotic limit.

The effect of self-administered faecal occult blood tests on compliance with screening for colorectal cancer: results of a survey of those invited.

To determine the relative importance of health beliefs and the characteristics of different methods of faecal occult blood screening in predicting acceptance of the test a self completed questionnaire was offered to 590 patients registered with a practice in an Oxfordshire market town. The patients were an age-sex stratified random sample of those who had been offered screening as part of a trial in which one of three different faecal occult blood screening tests, two of which were self-reported, had been offered. The overall adjusted response rate was 70.1%. Those who complied with the test had more positive attitudes to the implications of a positive test, to treatment and to the value of screening in general. The experience of a close relative or friend with bowel cancer was associated with an increased likelihood of compliance [odds ratio = 15.2 (9.4-24.3)]. Three were marked differences between the tests in the proportions of patients finding them 'messy' or 'disgusting' (Haemoccult 72.0%, Coloscreen 48.0%, Early Detector 55.4% chi 2 Haemoccult vs. self-reported = 5.05 P less than 0.05), and the odds of finding the procedure disgusting were significantly higher among patients who did not complete the test [odds ratio 6.9 (3.1-15.5)].

Experiences of patients with false positive results from colorectal cancer screening.

A survey was conducted to study the experiences of patients with false positive results for colorectal cancer. The study patients were participants in a randomized trial of compliance with different methods of colorectal cancer screening by faecal occult blood testing. Fifty four out of fifty six patients (96.4%) with false positive results agreed to be interviewed. An age and sex matched control group of 112 patients with negative test results was identified --92 (82.1%) returned questionnaires. Thirteen of the patients with false positive results (24.1%) and 19 controls (20.7%) were to some extent distressed by the initial letter inviting them to participate in the screening programme. Thirty seven of the patients with false positive results (68.5%) felt some degree of distress at the initial positive test result and 19 (35.2%) some distress because of delays experienced in the process of being screened. Ten false positive patients had colonoscopy and the median waiting time for this procedure was 10 days--half of the patients found this wait distressing. Nevertheless, 53 of the patients with false positive results (98.1%) felt that it had been worthwhile to have had the test. Generally, colorectal screening was as acceptable to the patients who experienced false positive results as to those with negative results.

Is there a preference for different ways of performing faecal occult blood tests?

Low compliance with faecal occult blood screening reduces the power of clinical trials, potential benefit, and efficiency. It has been proposed that the faecal manipulation required to perform conventional guaiac based tests may be an important factor in low compliance. The aim of this study was to evaluate whether use of a new method (vehicle) of stool collection for the faecal occult blood guaiac test would be preferred to the established standard. A novel self-interpreted test, Early Detector (ED), requires the subject to apply a guaiac/peroxide spray to a stool sample collected simply by wiping the anus with a specimen pad. To determine whether this method would be preferred to the stool manipulation required by Haemoccult (HO) and to compare test validity, employees at a London company were invited to use both tests. Eight-hundred and fifty-seven subjects were shown both tests. Before use, 48% indicated a preference for the method of Early Detector; 24% chose Haemoccult (p less than 0.001), while 28% indicated no immediate preference. Seven-hundred and one performed both tests. After use, 74% preferred ED; 5% preferred HO (p less than 0.001); 21% had no preference (NP). The preference for the ED test method was consistent by sex categories, age groups and occupational class. Logistics, aesthetics, and immediacy of results were the main reasons indicated for choosing ED. Whether the preference for ED could result in higher compliance remains to be proven. Its high positivity (14%), however, would preclude its use as a sole test to determine the need for endoscopic and/or radiologic investigation in the screened patient.