The relationship between cardiac dosimetry and tumour quadrant location in left sided whole breast and chest wall adjuvant radiotherapy.

BACKGROUND: Radiotherapy after breast surgery decreases locoregional recurrence and improves survival. This is not without risks from radiation exposure and could have implications in clinical practice. Our study investigates the correlation between tumour location and radiation dose to the heart. METHODS: Left-sided breast cancer patients who had radiotherapy at Aberdeen Royal Infirmary in 2010 were identified. Tumour location was established from notes and imaging. Radiotherapy planning scans were reviewed, and cardiac doses calculated. The mean cardiac dose, maximum dose and volume of the heart in the field, along with V5-V40, were determined. RESULTS: 40 patients had mastectomies and 118 breast conserving surgery. The median percentage of the heart in the field and the Interquartile Range was 0.59% (0.03-1.74) for all patients, with the highest for lower inner quadrant (LIQ) tumours 1.20% (0.29-2.40), followed by mastectomy 0.94% (0.02-1.82). The mean heart dose showed a higher median for mastectomies 1.59 Gy (1.00-1.94), followed by LIQ tumours 1.58 Gy (1.31-2.28), with an overall median of 1.42 Gy (1.13-1.95). The median percentage of the heart in the field, the mean cardiac dose and V5-V30 did not reach statistical significance, however, V40 and the maximum dose did. CONCLUSIONS: The benefits of radiotherapy after breast cancer surgery are established, but with potential harm from cardiac exposure. Our cohort showed higher radiation exposure to the heart in patients with LIQ tumours and mastectomies but reached significance only for V40 and maximum dose. This highlights tumour location as a potentially important risk factor for cardiac exposure with breast radiotherapy.

Current practice of anticoagulant in the treatment of splanchnic vein thrombosis secondary to acute pancreatitis.

BACKGROUND: Severe acute pancreatitis is a common diagnosis in emergency general surgery and can be a cause of significant morbidity and mortality. A consequence of severe acute pancreatitis is thrombus in the splanchnic veins. These thrombi can potentially lead to bowel ischemia or hepatic failure. However, another complication of severe acute pancreatitis is retroperitoneal bleeding. At this time, it is unclear if treating patients for splanchnic vein thrombosis in the context of severe acute pancreatitis is associated with any outcome benefit. A systematic review might clarify this question. DATA SOURCES: A two-fold search strategy (one broad and one precise) looked at all published literature. The review was registered on PROSPERO (ID: CRD42018102705). MEDLINE, EMBASE, PubMed, Cochrane and Web of Science databases were searched and potentially relevant papers were reviewed independently by two researchers. Any disagreement was reviewed by a third independent researcher. Primary outcome was reestablishment of flow in the thrombosed vein versus bleeding complications. RESULTS: Of 1462 papers assessed, a total of 16 papers were eligible for inclusion. There were no randomized controlled trials, 2 were case series, 5 retrospective single-center studies and 9 case reports. There were a total of 198 patients in these studies of whom 92 (46.5%) received anticoagulation therapy. The rates of recanalization of veins in the treated and non-treated groups was 14% and 11% and bleeding complications were 16% and 5%, respectively. However, the included studies were too heterogeneous to undertake a meta-analysis. CONCLUSIONS: The systematic review highlights the lack evidence addressing this clinical question. Therefore a randomized controlled trial would be appropriate to undertake.

Should Total Hip Arthroplasty be Performed Acutely in the Treatment of Acetabular Fractures in Elderly or Used as a Salvage Procedure Only?

BACKGROUND: Total hip arthroplasty (THA) is now an increasingly common procedure for people sustaining acetabular fractures. The incidence of acetabular fractures among the elderly population is increasing, and contemporary treatment aims to avoid the risks of prolonged incumbency associated with poor bone stock for fixation or inability to comply with limited weightbearing in this patient group. The concept of acute hip arthroplasty as a treatment for acetabular fracture is, therefore, becoming more topical and relevant. Our systematic review investigates whether THAs for acetabular fractures should be performed acutely, with a short delay, or as a late procedure for posttraumatic osteoarthritis (PTOA) if it develops. MATERIALS AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed when undertaking this systematic review. Detailed searches were performed on three different databases, using keywords, such as "acetabular fracture," "acetabular trauma," "total hip arthroplasty," "hip arthroplasty," and "hip prosthesis." Studies from 1975 to September 2016 were included in the study. All studies included in the review were independently critically appraised by two of the authors. RESULTS: Forty three studies were included in this review. Only two of them actually compared acute and delayed THAs for acetabular fractures with the rest focusing on one or the other. Results were comparable between acute and late THAs in terms of aseptic loosening, operative time, blood loss, Harris Hip Score, and ability to mobilize postoperatively without aid. Complication rates, however, were much higher in the acute group. CONCLUSION: Evidence based on this topic is scarce and therefore we have to be cautious about drawing a definitive conclusion. The findings of this systematic review do suggest, however, that acute THAs should be considered in elderly patients, where fixation is not possible, or when their health and ability to rehabilitate are poor. It should also be considered in patients where PTOA is very likely, or where there is already some preexisting degenerative osteoarthritis.

A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously.

BACKGROUND: Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously. METHODS: A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case-control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders. RESULTS: A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case-control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: -0.46(-1.41, 0.49), PEG1-MEST: 0.47 (-2.07, 3.01), GRB10: -0.05 (-0.43, 0.33), IGF2: -0.15 (-1.09, 0.79), SNRPN: -0.55 (-1.55, 0.46), KvDMR/KCNQ10T1: -0.16 (-0.34, 0.02) and PEG3: -0.24 (-1.72, 1.24). CONCLUSIONS: There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed.