Cell kinetic analysis of murine squamous cell carcinomas: a comparison of single versus double labelling using flow cytometry and immunohistochemistry.

The study was originally set up to measure accurate cell kinetic parameters in two murine squamous cell carcinomas (scc) for comparison with radiobiological data on proliferation during radiotherapy. The tumours, AT84 and AT478, were both moderately well differentiated aneuploid scc. In the course of the study, several comparisons of techniques were made in two different centres. This paper reports on the results of those comparisons involving two different detection methods (flow cytometry and immunohistochemistry), single vs double labelling, and in vivo and in vitro labelling, the latter using tissue slices incubated under high pressure oxygen. Pulse labelling studies with bromodeoxyuridine (BrdUrd) showed that the labelling indices (LI) were not significantly different after in vitro or in vivo labelling. In addition, the flow cytometry (FCM) and immunohistochemistry (IHC) methods also gave labelling indices which were not significantly different. Only tumour cells were analysed in these studies by selecting cells on the basis of aneuploidy (FCM) or morphology (IHC). The DNA synthesis time of the tumour cells were analysed by both techniques. For FCM, the Relative Movement method was used (Begg et al., 1985). For IHC, a double labelling method was used, employing BrdUrd and triated thymidine (3H-TdR) administered several hours apart, detected simultaneously using immunoperoxidase and autoradiography, respectively. When both labels were administered in vivo, there was good agreement for Ts between the FCM and IHC methods. Attempts were also made to measure Ts in vitro using both techniques. With double labelling, it was found that cells did not take up the second label, implying a failure of cycle progression. This was confirmed by FCM results, showing no movement of labelled cells through the S-phase, despite an initially high uptake. This could not be influenced by lowering the DNA precursor concentration or by adding foetal calf serum. This indicates that DNA synthesis times are difficult or impossible to measure in vitro in fresh tumour explants. Finally, the double labelling IHC method allowed intratumoural variations of both LI and Ts to be studied. Both parameters were found to vary markedly throughout the tumour volume, particularly for larger tumours (600 mg), giving calculated local potential doubling time values (Tpot) ranging from 1-7 days

Risk of coronary stenosis after adjuvant radiotherapy for breast cancer

Purpose Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. Methods A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. Results A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. Conclusion Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.Peer reviewe

Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ

The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS. The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed. Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT). The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.Peer reviewe

Using historical fisheries data to predict tuna distribution within the British Indian Ocean Territory marine protected area, and implications for its management

1. Recently, several large marine protected areas (MPAs) have been established globally and it is hoped that they will aid the recovery of populations of highly-mobile, large pelagic species. Understanding the distribution of these species within MPAs is key to delivering effective management but monitoring can be challenging over such vast areas of open ocean. 2. Historical fisheries data, collected prior to reserve establishment, can provide an insight into the past distributions of target species. We investigated the 10spatial and temporal distribution of yellowfin (Thunnus albacares) and skipjack (Katsuwonus pelamis) tuna catch using logbook data from the purse seine fishery in British Indian Ocean Territory (BIOT) from 1996 to 2010, before it was established as an MPA in April 2010. 3. Generalized additive models (GAMs) were used to predict tuna presence and relative abundance from fishing records in relation to temporal and environmental variables. Significant variables included sea salinity, temperature and water velocity. 4. Predictions from the models identified a distinct hotspot for large yellowfin tuna within the MPA, and areas of high predicted relative abundance of skipjack tuna. We recommend that these areas are used as focal points from which populations can be monitored and investigations into tuna residency time can occur, so that the effectiveness of the MPA in conserving highly-mobile pelagic fish can be determined

Shoulder Capsular Surgery in Finland Between 1999 and 2008 : A Nationwide Register Analysis

Background and Aims: Shoulder capsular surgery is nowadays usually performed arthroscopically, and the proportion of arthroscopic method has rapidly increased during the last two decades. We assessed the incidence of shoulder capsular surgery procedures in Finland between 1999 and 2008. Material and Methods: We gathered the shoulder capsular surgery procedures for all kinds of shoulder instability in Finland between 1999 and 2008 from National Hospital Discharge Register and limited the patient material to include only certain diagnosis (International Classification of Diseases, 10th Edition) and Nordic Medico-Statistical Committee procedure code combinations. We analyzed the data in the whole country, between different age groups, and in university hospital districts. Results: The total incidence of shoulder capsular surgery procedures in Finland increased from 17 to 33 per 100,000 person-years. The incidence of arthroscopic procedures increased from 11 to 30 per 100,000 person-years and the proportion of arthroscopic procedures increased from 63% to 92% between years 1999 and 2007. The incidence of shoulder capsular surgery procedures increased on average around 90% in almost all age groups and particularly in the older age groups. We observed no significant geographical variation between university hospital districts. Conclusion: The incidence of shoulder capsular surgery procedures increased on average round 90% in almost all age groups. It seems to be difficult to support the rapidly increased rates of shoulder capsular surgery procedures or the arthroscopic method based on scientific evidence. While also older patients are treated with shoulder capsular surgery, well-defined indications for surgical intervention are needed so that the operations are conducted for the symptomatic patients benefitting most regardless of patients' age.Peer reviewe

Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85). CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer