Updated investigations of cancer excesses in individuals born or resident in the vicinity of Sellafield and Dounreay.

BACKGROUND: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up. METHODS: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies. RESULTS: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date. CONCLUSIONS: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.

Decline in hand bone mineral density indicates increased risk of erosive change in early rheumatoid arthritis.

OBJECTIVE: Despite better disease suppression with combination disease-modifying antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have progressive erosive disease. The objective of this study was to determine whether hand bone mineral density (BMD) loss in the first 6 months of treatment indicates increased risk of erosions at 12 months. METHODS: Patients with DMARD-naive early RA receiving treat-to-target therapy were studied (n = 106). Hand BMD was measured at baseline and 6 months by dual x-ray absorptiometry. Hand and feet radiographs were performed at baseline and 12 months and scored using the van der Heijde modification of the Sharp method. A K-means clustering algorithm was used to divide patients into 2 groups: the BMD loss group or the no loss group, according to their absolute change in BMD from baseline to 6 months. Multiple regression analysis (hurdle model) was performed to determine the risk factors for both erosive disease and erosion scores. RESULTS: Hand BMD loss at 6 months was associated with erosion scores at 12 months (P = 0.021). In a multiple regression analysis, hand BMD loss (P = 0.046) and older age at onset (≥50 years; P = 0.014) were associated with erosive disease, whereas baseline erosion scores (P = 0.001) and anti-cyclic citrullinated peptide (P = 0.024) were correlated with erosion severity/progression. CONCLUSION: In RA patients receiving treat-to-target therapy, early hand BMD loss could identify patients who are at risk of developing erosive disease at 12 months, potentially allowing intensification of treatment to prevent erosive damage.

Risk of cancer following primary total hip replacement or primary resurfacing arthroplasty of the hip: a retrospective cohort study in Scotland.

BACKGROUND: Release and dispersion of particles arising from corrosion and wear of total hip arthroplasty (THA) components has raised concerns about a possible increased risk of cancer. Concerns have been heightened by a recent revival in the use of metal-on-metal (MoM) hip prostheses. METHODS: From a linked database of hospital discharge, cancer registration, and mortality records, we selected a cohort of patients who underwent primary THA (1990-2009) or primary resurfacing arthroplasty (mainly 2000-2009) in Scotland, with follow-up to the end of 2010. Available operation codes did not enable us to distinguish MoM THAs. Indirectly standardised incidence ratios (SIRs) were calculated for selected cancers with standardisation for age, sex, deprivation, and calendar period. RESULTS: The study cohort included 71 990 patients yielding 547 001 person-years at risk (PYAR) and 13 946 cancers diagnosed during follow-up. For the total period of observation combined, the risks of all cancers (SIR: 1.05; 95% CI: confidence interval 1.04-1.07), prostate cancer (SIR: 1.07; 95% CI: 1.01-1.14), and multiple myeloma (SIR: 1.22; 95% CI: 1.06-1.41) were increased. These modest increases in risk emerged in the context of effectively multiple tests of statistical significance, and may reflect inadequate adjustment for confounding factors. For 1317 patients undergoing primary resurfacing arthroplasty between 2000 and 2009 (PYAR=5698), the SIR for all cancers (n=39) was 1.23 (95% CI: 0.87-1.68). CONCLUSION: In the context of previous research, these results do not suggest a major cause for concern. However, the duration of follow-up of patients receiving recently introduced, new-generation MoM prostheses is too short to rule out a genuinely increased risk of cancer entirely.

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study.

BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000-2007) before the roll out of a national programme. All residents (50-69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83-0.99) overall and 0.73 (95% CI 0.65-0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06-1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

Randomized comparison of two anti-emetic strategies in high-risk patients undergoing day-case gynaecological surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a significant cause of morbidity among patients undergoing general anaesthesia. The optimal strategy for prevention of PONV, however, remains unclear. This study compared two commonly used prophylactic strategies in high-risk, day-case, gynaecological surgery patients. METHODS: We conducted a randomized trial comparing sevoflurane combined with dolasetron (SD), with propofol-based total intravenous anaesthesia (TIVA) in 126 high-risk patients undergoing day-case gynaecological surgery. The primary endpoints included the incidence and severity of nausea or vomiting before discharge and the incidence of nausea or vomiting between discharge and 24 h. To identify the factors most predictive of a complete response (no PONV at any time within the 24 h period), multiple logistic regression models were fitted. RESULTS: Before discharge, there was no significant difference between the two treatment groups with respect to nausea and vomiting outcomes (P = 0.3). Post-discharge nausea and vomiting (PDNV), however, were significantly more common for patients in the TIVA group (nausea, P = 0.004 and vomiting, P = 0.03). Type of anaesthetic, adjusted for weight and anaesthesia duration was significantly associated with complete response (odds ratio = 2.7, 95% confidence interval = 1.15 to 6.4). CONCLUSIONS: Although both TIVA and dolasetron prophylaxis reduce the predicted rate of PONV in the early postoperative period, the anti-emetic effects of propofol are short-lived. A longer-acting drug such as dolasetron may therefore be necessary to prevent PDNV.

Risk of leukaemia among children living near the Solway coast of Dumfries and Galloway Health Board area, Scotland, 1975-2002.

OBJECTIVE: To investigate allegations of an excess risk of leukaemia among children living near the Solway Firth coast of Dumfries and Galloway Health Board area in Scotland, UK. METHODS: Incident cases of childhood leukaemia (International Classification of Diseases, 10th revision, C91-C95, patients aged 0-14 years) for two almost equal calendar periods of diagnosis (1975-89 and 1990-2002) were selected from the Scottish Cancer Registry database and allocated to predetermined study areas, on the basis of proximity of residence to the Solway coast. Expected numbers of childhood leukaemia cases for the study areas were calculated by applying Scotland's age-specific, sex-specific and calendar period-specific rates to estimates of the person-years at risk in each study area. The ratios of observed to expected cases or standardised incidence ratios (SIRs) were calculated overall and for each sex and calendar period category. Exact 95% confidence intervals (CIs) for the SIRs were calculated assuming a Poisson distribution for the observed number of cases of childhood leukaemia. RESULTS: No statistically significantly increased SIRs were found in boys, girls or both combined for any of the areas or periods of diagnosis studied. For the total period of observation (1975-2002), and the more immediate coastal area studied, the SIR for both sexes combined was 1.22 (95% CI 0.53 to 2.40). CONCLUSION: No statistically significant evidence was found of an excess risk of childhood leukaemia in the vicinity of the Solway Firth coast of Dumfries and Galloway Health Board area in Scotland.

Isolated acetabular osteoporosis in TOH in pregnancy: a case report.

Transient osteoporosis of the hip (TOH) is a rare, self-limiting syndrome characterized by hip pain in the 2nd or 3rd trimester of pregnancy. Conventional radiography shows demineralization of the femoral head. Diagnosis is confirmed by MRI scan. Over the course of a few months, the radiological abnormalities and the pain disappear spontaneously with complete resolution. We report the case of a patient with isolated acetabular involvement during pregnancy, confirmed by MRI scan, who obtained spontaneous remission of her symptoms.

Prognostic factors in women with breast cancer: distribution by socioeconomic status and effect on differences in survival.

STUDY OBJECTIVE: To quantify and investigate differences in survival from breast cancer between women resident in affluent and deprived areas and define the contribution of underlying factors to this variation. DESIGN: Analysis of two datasets relating to breast cancer patients in Scotland: (1) population-based cancer registry data; (2) a subset of cancer registration records supplemented by abstraction of prognostic variables (stage, node status, tumour size, oestrogen receptor (ER) status, type of surgery, use of radiotherapy and use of adjuvant systemic therapy) from medical records. SETTING: Scotland. PATIENTS: (1) Cancer registration data on 21,751 women aged under 85 years diagnosed with primary breast cancer between 1978 and 1987; (2) national clinical audit data on 2035 women aged under 85 years diagnosed with primary breast cancer during 1987 for whom adequate medical records were available. MAIN RESULTS: Survival differences of 10% between affluent and deprived women were observed in both datasets, across all age groups. In the audit dataset, the distribution of ER status varied by deprivation group (65% ER positive in affluent group v 48% ER positive in deprived group; under 65 age group). Women aged under 65 with non-metastatic disease were more likely to have breast conservation than a mastectomy if they were affluent (45%) than deprived (32%); the affluent were more likely to receive endocrine therapy (65%) than the deprived (50%). However, these factors accounted for about 20% of the observed difference in survival between women resident in affluent and deprived areas. CONCLUSIONS: Deprived women with breast cancer have poorer outcomes than affluent women. This can only partly be explained by deprived women having more ER negative tumours than affluent women. Further research is required to identify other reasons for poorer outcomes in deprived women, with a view to reducing these survival differences.

Risk of malignancy among patients with rheumatic conditions.

Previous studies have described an increased risk of malignancy in subjects diagnosed with rheumatic conditions, most notably rheumatoid arthritis (RA). Our aim was to quantify and compare risks for site-specific malignancy among hospitalized patients with RA, osteoarthritis (OA) and other rheumatic conditions in a nationwide, population-based cohort. Subjects were identified from Scottish hospital in-patient records from 1981 to 1996 and followed up by computer linkage of the Scottish Cancer Registry and the national registry of deaths. Expected cancer incidence was calculated from national cancer rates and related to the observed incidence by the standardized incidence ratio (SIR). Among RA patients, there was an increased risk for hematopoietic [males SIR= 2.13, 95% confidence interval (CI) 1.7-2.7; females SIR = 1.76, 95% CI 1.5-2.1], lung (males SIR = 1.32, 95% CI 1.2-1.5; females SIR = 1.44, 95% CI 1.3-1.6) and prostate (SIR = 1.26, 95% CI 1.0-1.6) cancers. Reduced risk were seen for colorectal cancer (males SIR = 0.87, 95% CI 0.7-1.1; females SIR = 0.71, 95% CI 0.6-0.9) and, among females, stomach cancer (SIR = 0.70, 95% CI 0.5-1.0). The excess risk for hematopoietic cancer and the reduced risk for colorectal and stomach cancers were sustained over 10 years of follow-up. An overall decreased risk of cancer was observed for patients with OA; the greatest reductions were observed for colorectal (males SIR = 0.88, 95% CI 0.8-1.0; females SIR = 0.84, 95% CI 0.8-0.9), stomach (males SIR = 0.79, 95% CI 0.7-0.9; females SIR = 0.66, 95% CI 0.6-0.8) and lung (males SIR = 0.72, 95% CI 0.7-0.8; females SIR = 0.84, 95% CI 0.8-0.9) malignancies, with decreased risks generally still evident at 10 years of follow-up. Our results support several previous findings regarding the incidence of hematopoietic and colorectal malignancies in RA patients. In addition, we have shown a large decrease in stomach cancer among patients with OA and females with RA that warrants further investigation since it may provide clues to possible prevention strategies. To further our knowledge about the underlying mechanisms of altered risk in cancer patients with rheumatic conditions, population studies requiring primary data collection are required.

Socioeconomic status and risk of adenocarcinoma of the oesophagus and cancer of the gastric cardia in Scotland.

The incidence of oesophageal adenocarcinoma and gastric cardia cancer increased strikingly in Scotland between 1977 and 1996. In contrast to other cancers of the oesophagus and stomach, which showed a clear relationship with socioeconomic status, no trend was evident for oesophageal adenocarcinoma or gastric cardia cancer during 1987-1996.

Rising incidence of prostate cancer in Scotland: increased risk or increased detection?

OBJECTIVE: To assess the extent to which the increasing incidence of prostate cancer in Scotland can be explained by increased detection, particularly through transurethral resection of the prostate (TURP) and use of the prostate-specific antigen (PSA) test. Subjects and methods This population-based study was confined to men resident in Scotland and aged > or =50 years. Temporal trends were examined in age-specific and age-standardized incidence, mortality and TURP rates, and PSA testing rates during 1981-1996. Also analysed were the geographical variations in age-standardized incidence and mortality rates during two distinct periods, 1984-1986 (before PSA testing) and 1994-1996 (after PSA testing). Finally, incidence rates and relative survival at 5 years were calculated by age group and 5-year periods of diagnosis during 1968-1992. RESULTS: The incidence of prostate cancer in men aged > or = 50 years increased from an age-standardized rate of 142.0 per 100 000 in 1981 to 240.9 in 1996, with the steepest increase occurring between 1992 and 1993. The mortality rate increased similarly until 1993, but was relatively stable thereafter, falling slightly in 1996. In 1981-1988, incidence rates were closely correlated with TURP rates (r = 0.98, P<0.001). In 1989-1996, incidence was closely correlated with PSA testing rates (r = 0.98, P<0.001). By 1994-1996, incidence rates varied substantially between Scottish mainland health boards (range 167.7-303.0 per 100 000), with much less variation in mortality rates (90.7-110.0). Relative survival has increased recently in all age groups although, in the era before PSA testing, survival was reasonably stable despite increasing incidence. CONCLUSION: Although there may have been a true increase in risk, much of the observed increase in the incidence of prostate cancer in Scotland between 1981 and 1996 has been caused by increased detection, leading recently to considerable variation among different areas of the country. The extent to which this represents the early diagnosis of tumours which would eventually cause symptoms or be life-threatening, or detection of latent disease which would never have become symptomatic, is not clear. There is no evidence so far that the increased incidence is associated with any substantial reduction in mortality.

Cancer registry data based estimation of regional cancer incidence: application to breast and colorectal cancer in French administrative regions.

STUDY OBJECTIVE: In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. DESIGN: This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. MAIN RESULTS: The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. CONCLUSION: The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available.

Incidence of childhood brain and other non-haematopoietic neoplasms near nuclear sites in Scotland, 1975-94.

OBJECTIVES: To examine the risk of cancers other than leukaemia and non-Hodgkin's lymphoma in children resident in the vicinity of nuclear sites in Scotland. METHODS: The study dataset comprised registrations of cancer other than leukaemia and non-Hodgkin's lymphoma diagnosed in children aged under 15 in the period 1975-94. These were validated for completeness and accuracy and analysed in two groups: (a) tumours of the central nervous system and (b) other malignant tumours (excluding leukaemia and non-Hodgkin's lymphoma). Around each nuclear site observed cases (O) were enumerated and expected numbers (E) calculated with adjustment for age, sex, deprivation, and an urban-rural category. Stone's maximum likelihood ratio test (MLR) was used to determine whether there was any evidence of increased risk of these neoplasms among children living within 25 km of one of the nuclear sites investigated. The significance level of each MLR statistic was estimated by simulation. RESULTS: More tumours of the central nervous system were observed than expected within 25 km of Dounreay (O/E = 1.14), Hunterston (1.14), and Rosyth (1.22). These results were based on 2, 26, and 136 observed cases, respectively. The unconditional MLR was significant only for Rosyth (p = 0.006). The conditional application of the MLR test for Rosyth was not significant (p = 0.771). For the group of other malignant neoplasms, the unconditional MLR test was not significant for any of the seven sites. CONCLUSIONS: There was no evidence for generally increased risk of either tumours of the central nervous system or other malignant tumours in children living near nuclear sites. The significant excess of tumours of the central nervous system around Rosyth is likely to be due to the high incidence of these tumours in east central Scotland. Further investigations in this area are warranted.

Epidemiology of Kaposi's sarcoma in Scotland, 1976-1996.

Based on data from the Scottish Cancer Registry, the epidemiology of Kaposi's sarcoma (KS) in Scotland during the period 1976-96 is described. In males, the annual age-standardized incidence rate (World standard population) increased from less than 0.09 per 100,000 before 1986 to 0.44 in 1991 and then decreased to around 0.17. Peak incidence is now at ages 30-39 compared with ages 80+ during the period 1976-82; and by 1986-96 the standardized incidence ratio for the Health Board which includes Edinburgh had risen to almost four times the national level. These changes are largely consistent with the pattern of HIV infection in Scotland. However, in both sexes, relative to other neoplasms, and in international terms, KS remains rare in Scotland. For patients diagnosed during 1976-92, cumulative observed survival at 5 years was 8.7% at ages 0-49 compared with 49.8% at ages 50-84, reflecting the more aggressive course of AIDS-related KS, as well as the co-morbidity and competing causes of death associated with AIDS.

Incidence of non-Hodgkin's lymphoma in children between 1970 and 1990 in nine European countries.

Data from population-based cancer registries in Europe (nine countries) were used to monitor the incidence of non-Hodgkin's lymphoma in children aged 0-14 years over the 20 year period 1970-1990. The overall annual change in incidence was small--an increase of 0.76% annually, and there was no change at all in infants under one year of age. This differs markedly from the pattern in adults, where quite large increases have occurred.