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Shea-Budgell M.,CancerControl Alberta | Quan M.L.,University of Calgary | Mehling B.,University of Alberta | Temple-Oberle C.,University of Calgary
Canadian Journal of Plastic Surgery | Year: 2014

The side effects of mastectomy can be significant. Breast reconstruction may alleviate some distress; however, there are currently no provincial recommendations regarding the integration of reconstruction with breast cancer therapy. The purpose of the present article is to provide evidencebased strategies for the management of patients who are candidates for reconstruction. A systematic review of meta-analyses, guidelines, clinical trials and comparative studies published between 1980 and 2013 was conducted using the PubMed and EMBASE databases. Reference lists of publications were manually searched for additional literature. The National Guidelines Clearinghouse and SAGE directory, as well as guideline developers' websites, were also searched. Recommendations were developed based on the available evidence. Reconstruction consultation should be made available for patients undergoing mastectomy. Tumour characteristics, cancer therapy, patient comorbidities, body habitus and smoking history may affect reconstruction outcomes. Although immediate reconstruction should be considered whenever possible, delayed reconstruction is acceptable when immediate is not available or appropriate. The integration of reconstruction and postmastectomy radiotherapy should be addressed in a multidisciplinary setting. The decision as to which type of procedure to perform (autologous or alloplastic with or without acellular dermal matrices) should be left to the discretion of the surgeons and the patient after providing counselling. Skin-sparing mastectomy is safe and appropriate. Nipple-sparing is generally not recommended for patients with malignancy, but could be considered for carefully selected patients. Immediate reconstruction requires resources to coordinate operating room time between the general and plastic surgeons, to provide supplies including acellular dermal matrices, and to develop the infrastructure needed to facilitate multidisciplinary discussions.© 2014 Canadian Society of Plastic Surgeons. Source


Chadder J.,Canadian Partnership Against Cancer | Dewar R.,Cancer Care Nova Scotia | Shack L.,CancerControl Alberta | Shack L.,University of Calgary | And 3 more authors.
Current Oncology | Year: 2016

Monitoring and reporting on cancer survival provides a mechanism for understanding the effectiveness of Canada’s cancer care system. Although 5-year relative survival for colorectal cancer and lung cancer has been previously reported, only recently has pan-Canadian relative survival by stage been analyzed using comprehensive registry data. This article presents a first look at 2-year relative survival by stage for colorectal and lung cancer across 9 provinces. As expected, 2-year age-standardized relative survival ratios (arsrs) for colorectal cancer and lung cancer were higher when the cancer was diagnosed at an earlier stage. The arsrs for stage i colorectal cancer ranged from 92.2% in Nova Scotia [95% confidence interval (ci): 88.6% to 95.1%] to 98.4% in British Columbia (95% ci: 96.2% to 99.3%); for stage iv, they ranged from 24.3% in Prince Edward Island (95% ci: 15.2% to 34.4%) to 38.8% in New Brunswick (95% ci: 33.3% to 44.2%). The arsrs for stage i lung cancer ranged from 66.5% in Prince Edward Island (95% ci: 54.5% to 76.5%) to 84.8% in Ontario (95% ci: 83.5% to 86.0%). By contrast, arsrs for stage iv lung cancer ranged from 7.6% in Manitoba (95% ci: 5.8% to 9.7%) to 13.2% in British Columbia (95% ci: 11.8% to 14.6%). The available stage data are too recent to allow for meaningful comparisons between provinces, but over time, analyzing relative survival by stage can provide further insight into the known differences in 5-year relative survival. As the data mature, they will enable an assessment of the extent to which interprovincial differences in relative survival are influenced by differences in stage distribution or treatment effectiveness (or both), permitting targeted measures to improve population health outcomes to be implemented. © 2016 Multimed Inc. Source


Bose P.,University of Calgary | Bose P.,British Columbia Cancer Agency | Brockton N.T.,CancerControl Alberta | Guggisberg K.,Calgary Laboratory Services | And 5 more authors.
BMC Cancer | Year: 2015

Background: The lack of prognostic biomarkers in oral squamous cell carcinoma (OSCC) has hampered treatment decision making and survival in OSCC remains poor. Histopathological features are used for prognostication in OSCC and, although useful for predicting risk, manual assessment of histopathology is subjective and labour intensive. In this study, we propose a method that integrates multiple histopathological features of the tumor microenvironment into a single, digital pathology-based biomarker using nuclear fractal dimension (nFD) analysis. Methods: One hundred and seven consecutive OSCC patients diagnosed between 1998 and 2006 in Calgary, Canada were included in the study. nFD scores were generated from DAPI-stained images of tissue microarray (TMA) cores. Ki67 protein expression was measured in the tumor using fluorescence immunohistochemistry (IHC) and automated quantitative analysis (AQUA®). Lymphocytic infiltration (LI) was measured in the stroma from haematoxylin-eosin (H&E)-stained TMA slides by a pathologist. Results: Twenty-five (23.4%) and 82 (76.6%) patients were classified as high and low nFD, respectively. nFD was significantly associated with pathological tumor-stage (pT-stage; P = 0.01) and radiation treatment (RT; P = 0.01). High nFD of the total tumor microenvironment (stroma plus tumor) was significantly associated with improved disease-specific survival (DSS; P = 0.002). No association with DSS was observed when nFD of either the tumor or the stroma was measured separately. pT-stage (P = 0.01), pathological node status (pN-status; P = 0.02) and RT (P = 0.03) were also significantly associated with DSS. In multivariate analysis, nFD remained significantly associated with DSS [HR 0.12 (95% CI 0.02-0.89, P = 0.04)] in a model adjusted for pT-stage, pN-status and RT. We also found that high nFD was significantly associated with high tumor proliferation (P < 0.0001) and high LI (P < 0.0001), factors that we and others have shown to be associated with improved survival in OSCC. Conclusions: We provide evidence that nFD analysis integrates known prognostic factors from the tumor microenvironment, such as proliferation and immune infiltration, into a single digital pathology-based biomarker. Prospective validation of our results could establish nFD as a valuable tool for clinical decision making in OSCC. © 2015 Bose et al.; licensee BioMed Central. Source


Xu J.-Y.,CancerControl Alberta | Chen C.,Louisiana State University Health Sciences Center
Neuroscientist | Year: 2015

Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic N-methyl-d-aspartate receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca2+. Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or -independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously. © The Author(s) 2014. Source


Friedenreich C.M.,CancerControl Alberta | Friedenreich C.M.,University of Calgary | Neilson H.K.,CancerControl Alberta | Wang Q.,CancerControl Alberta | And 7 more authors.
Endocrine-Related Cancer | Year: 2015

Exercise dose comparison trials with biomarker outcomes can identify the amount of exercise required to reduce breast cancer risk and also strengthen the causal inference between physical activity and breast cancer. The Breast Cancer and Exercise Trial in Alberta (BETA) tested whether or not greater changes in estradiol (E2), estrone, and sex hormone-binding globulin (SHBG) concentrations can be achieved in postmenopausal women randomized to 12 months of HIGH (300 min/week) vs MODERATE (150 min/week) volumes of aerobic exercise. BETA included 400 inactive postmenopausal women aged 50-74 years with BMI of 22-40 kg/m2. Blood was drawn at baseline and 6 and 12 months. Adiposity, physical fitness, diet, and total physical activity were assessed at baseline and 12 months. Intention-to-treat analyses were performed using linear mixed models. At full prescription, women exercised more in the HIGH vs MODERATE group (median min/week (quartiles 1,3): 253 (157 289) vs 137 (111 150); P<0.0001). Twelve-month changes in estrogens and SHBG were<10% on average for both groups. No group differences were found for E2, estrone, SHBG or free E2 changes (treatment effect ratios (95% CI) from linear mixed models: 1.00 (0.96-1.06), 1.02 (0.98-1.05), 0.99 (0.96-1.02), 1.01 (0.95, 1.06), respectively, representing the HIGH:MODERATE ratio of geometric mean biomarker levels over 12 months; n=382). In per-protocol analyses, borderline significantly greater decreases in total and free E2 occurred in the HIGH group. Overall, no dose effect was observed for women randomized to 300 vs 150 min/week of moderate to vigorous intensity exercise who actually performed a median of 253 vs 137 min/week. For total and free E2, the lack of differential effect may be due to modest adherence in the higher dose group. Source

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