Prevalence of upper-body symptoms following breast cancer and its relationship with upper-body function and lymphoedema

This investigation describes the prevalence of upper-body symptoms in a population-based sample of women with breast cancer (BC) and examines their relationships with upper-body function (UBF) and lymphoedema, as two clinically important sequelae. Australian women (n=287) with unilateral BC were assessed at three-monthly intervals, from six to 18 months post-surgery (PS). Participants reported the presence and intensity of upper-body symptoms on the treated side. Objective and self-reported UBF and lymphoedema (bioimpedance spectroscopy) were also assessed. Approximately 50% of women reported at least one moderate-to-extreme symptom at 6- and at 18-months PS. There was a significant relationship between symptoms and function (p<0.01), whereby perceived and objective function declined with increasing number of symptoms present. Those with lymphoedema were more likely to report multiple symptoms and presence of symptoms at baseline increased risk of lymphoedema (ORs>1.3, p=0.02). Although, presence of symptoms explained only 5.5% of the variation in the odds of lymphoedema. Upper-body symptoms are common and persistent following breast cancer and are associated with clinical ramifications, including reduced UBF and increased risk of developing lymphoedema. However, using the presence of symptoms as a diagnostic indicator of lymphoedema is limited.

Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells

The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel synthetic polymer-hydrogel matrices

The aim of this project was to investigate the in vitro osteogenic potential of human mesenchymal progenitor cells in novel matrix architectures built by means of a three-dimensional bioresorbable synthetic framework in combination with a hydrogel. Human mesenchymal progenitor cells (hMPCs) were isolated from a human bone marrow aspirate by gradient centrifugation. Before in vitro engineering of scaffold-hMPC constructs, the adipogenic and osteogenic differentiation potential was demonstrated by staining of neutral lipids and induction of bone-specific proteins, respectively. After expansion in monolayer cultures, the cells were enzymatically detached and then seeded in combination with a hydrogel into polycaprolactone (PCL) and polycaprolactone-hydroxyapatite (PCL-HA) frameworks. This scaffold design concept is characterized by novel matrix architecture, good mechanical properties, and slow degradation kinetics of the framework and a biomimetic milieu for cell delivery and proliferation. To induce osteogenic differentiation, the specimens were cultured in an osteogenic cell culture medium and were maintained in vitro for 6 weeks. Cellular distribution and viability within three-dimensional hMPC bone grafts were documented by scanning electron microscopy, cell metabolism assays, and confocal laser microscopy. Secretion of the osteogenic marker molecules type I procollagen and osteocalcin was analyzed by semiquantitative immunocytochemistry assays. Alkaline phosphatase activity was visualized by p-nitrophenyl phosphate substrate reaction. During osteogenic stimulation, hMPCs proliferated toward and onto the PCL and PCL-HA scaffold surfaces and metabolic activity increased, reaching a plateau by day 15. The temporal pattern of bone-related marker molecules produced by in vitro tissue-engineered scaffold-cell constructs revealed that hMPCs differentiated better within the biomimetic matrix architecture along the osteogenic lineage.

Bone response to unloaded titanium implants in the fibula, iliac crest, and scapula: an animal study in the Yorkshire pig

The reconstruction of extended maxillary and mandibular defects with prefabricated free flaps is a two stage procedure, that allows immediate function with implant supported dentures. The appropriate delay between prefabrication and reconstruction depends on the interfacial strength of the bone–implant surface. The purpose of this animal study was to evaluate the removal torque of unloaded titanium implants in the fibula, the scapula and the iliac crest. Ninety implants with a sandblasted and acid-etched (SLA) surface were tested after healing periods of 3, 6, and 12 weeks, respectively. Removal torque values (RTV) were collected using a computerized counterclockwise torque driver. The bicortical anchored 8 mm implants in the fibula revealed values of 63.73 Ncm, 91.50 Ncm, and 101.83 Ncm at 3, 6, and 12 weeks, respectively. The monocortical anchorage in the iliac crest showed values of 71.40 Ncm, 63.14 Ncm, and 61.59 Ncm with 12 mm implants at the corresponding times. The monocortical anchorage in the scapula demonstrated mean RTV of 62.28 Ncm, 97.63 Ncm, and 99.7 Ncm with 12 mm implants at 3, 6, and 12 weeks, respectively. The study showed an increase of removal torque with increasing healing time. The interfacial strength for bicortical anchored 8 mm implants in the fibula was comparable to monocortical anchored 12 mm implants in the iliac crest and the scapula at the corresponding times. The resistance to shear seemed to be determined by the type of anchorage (monocortical vs. bicortical) and the length of the implant with greater amount of bone–implant interface.

Cell interactions of osteoarthritic subchondral bone osteoblasts and articular chondrocytes aggravate MMP-2 and MMP-9 production through the mediation of ERK1/2 and JNK phosphorylation

Matrix Metalloproteinases (MMP) play a key role in osteoarthritis (OA) development. The aim of the present study was to investigate whether, the cross-talk between subchondral bone osteoblasts (SBOs) and articular cartilage chondrocytes (ACCs) in OA alters the expression and regulation of MMPs, and also to test the potential involvement of mitogen activated protein kinase (MAPK) signalling pathway during this process.

A systematic review of the association between physical activity and colorectal cancer risk

This review evaluated the strength of the evidence for a causal relationship between physical activity (PA) and colorectal cancer (CRC). A systematic review of databases through February 2008 was conducted to identify studies that assessed the association between total or recreational PA and incidence or mortality of CRC (including CRC, rectal cancer, colon cancer, and proximal or distal colon cancer). Studies were evaluated for significant associations between PA and risk of CRC endpoints and for evidence of dose–response relationships in the highest quality studies. Twenty cohort studies were evaluated; 11 were high-quality. Fifty percent of all studies and 64%of highest quality studies reported at least one significant association between PA and risk of a CRC endpoint (Po0.05).However, only 28%of all analyses (31% of analyses of highest quality studies) were significant (Po0.05). Only 40% of analyses of highest quality studies resulted in a significant P for trend (Po0.05); however, a non-significant inverse linear association between PA and colon cancer riskwas apparent.Heterogeneity in the evidence from all studies and from the highest quality studies was evident. Evidence from cohort studies is not sufficient to claim a convincing relationship exists between PA and CRC risk.

Exercise and cancer rehabilitation : a systematic review

Introduction: Cancer is increasingly being viewed as a chronic illness requiring long-term management, and there is a growing need for evidence-based rehabilitation interventions for cancer survivors. Previous reviews have evaluated the benefits of exercise interventions for patients undergoing cancer treatment and long-term survivors, but none have investigated the role of exercise during cancer rehabilitation, the period immediately following cancer treatment completion. This systematic review summarises the literature on the health effects of exercise during cancer rehabilitation and evaluates the methodological rigour of studies in this area to date.----------- Methods: Relevant studies were identified through a systematic search of PubMed and Embase to April 2009. Data on study design, recruitment strategy, participants, exercise intervention, adherence rates, and outcomes were extracted. Methodological rigour was assessed using a structured rating system.---------- Results: Ten studies were included. Breast cancer patients were the predominate patient group represented. Most interventions were aerobic or resistance-training exercise programmes, and exercise type, frequency, duration and intensity varied across studies. Improvements in physical functioning, strength, physical activity levels, quality of life, fatigue, immune function, haemoglobin concentrations, potential markers of recurrence, and body composition were reported. However, all studies were limited by incomplete reporting and methodological limitations.---------- Conclusions: Although the methodological limitations of studies in this new field must be acknowledged, initial evidence indicates that exercise is feasible and may provide physiological and psychological benefits for cancer survivors during the rehabilitation period. Future studies with rigorous study designs are now required to advance the field.

Colorectal cancer survivors’ exercise experiences and preferences : qualitative findings from an exercise rehabilitation programme immediately after chemotherapy

Little is known about cancer survivors’ experiences with and preferences for exercise programmes offered during rehabilitation (immediately after cancer treatment). This study documented colorectal cancer survivors’ experiences in an exercise rehabilitation programme and their preferences for programme content and delivery. At the completion of 12-weeks of supervised exercise, 10 participants took part in one-on-one semi-structured interviews. Data from these interviews were coded, and themes were identified using qualitative software. Key findings were that most participants experienced improvements in treatment symptoms, including reduced fatigue and increased energy and confidence to do activities of daily living. They also reported that interactions with the exercise trainer and a flexible programme delivery were important aspects of the intervention. Most participants reported that they preferred having a choice of exercise, starting to exercise within a month after completing treatment, having supervision and maintaining a one-on-one format. Frustrations included scheduling conflicts and a lack of a transition out of the programme. The findings indicate that colorectal cancers experience benefits from exercise offered immediately after treatment and prefer individual attention from exercise staff. They further indicate directions for the implementation of future exercise programmes with this population.

Zoledronic acid once-yearly : what role in the prevention of non-vertebral osteoporotic fractures?

Osteoporosis is the most common bone disease. Low levels of oestrogens or testosterone are risk factors for primary osteoporosis. The most common cause of secondary osteoporosis is glucocorticoid treatment, but there are many other secondary causes of osteoporosis. Osteoporosis can be secondary to anti-oestrogen treatment for hormone-sensitive breast cancer and to androgen-deprivation therapy for prostate cancer. Zoledronic is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least a year after a single intravenous administration. The efficacy and safety of extended release (once-yearly) zoledronic acid in the treatment of osteoporosis is reviewed.

Resolvin inflammation with pain

Background: Inflammation and pain coexist in conditions such as arthritis, inflammatory bowel disease, and lower back pain. The drugs currently used to treat the combination of inflammation and pain all have disadvantages. Thus, new drugs and new approaches are needed to treat inflammation with pain. The resolvins are considered to be part of the natural resolving mechanism for inflammation, and have been shown to prevent inflammation in animal models. Objectives/methods: To evaluate a paper suggesting that the resolvins RvE1 and RvD1 attenuate inflammatory pain in animal models. Results: RvE1 has been shown to attenuate inflammation and, to a lesser extent, pain in animal models. Limited results are presented of the effectiveness of RvD1 against inflammatory pain. Conclusion: Drugs that mimic or potentiate the effects of the resolvins may be useful for the treatment of some inflammation with pain.

Knowledge and attitudes about Vitamin D and impact on sun protection practices among urban office workers in Brisbane, Australia

Background: Sun exposure is the main source of vitamin D. Increasing scientific and media attention to the potential health benefits of sun exposure may lead to changes in sun exposure behaviors. Methods: To provide data that might help frame public health messages, we conducted an online survey among office workers in Brisbane, Australia, to determine knowledge and attitudes about vitamin D and associations of these with sun protection practices. Of the 4,709 people invited to participate, 2,867 (61%) completed the questionnaire. This analysis included 1,971 (69%) participants who indicated that they had heard about vitamin D. Results: Lack of knowledge about vitamin D was apparent. Eighteen percent of people were unaware of the bone benefits of vitamin D but 40% listed currently unconfirmed benefits. Over half of the participants indicated that more than 10 minutes in the sun was needed to attain enough vitamin D in summer, and 28% indicated more than 20 minutes in winter. This was significantly associated with increased time outdoors and decreased sunscreen use. People believing sun protection might cause vitamin D deficiency (11%) were less likely to be frequent sunscreen users (summer odds ratio, 0.63; 95% confidence interval, 0.52-0.75). Conclusions: Our findings suggest that there is some confusion about sun exposure and vitamin D, and that this may result in reduced sun-protective behavior. Impact: More information is needed about vitamin D production in the skin. In the interim, education campaigns need to specifically address the vitamin D issue to ensure that skin cancer incidence does not increase.

Bone densitometry for the assessment of osteoporosis

The primary clinical role of the non-invasive physical measurement of a bone, generally referred to as ‘bone densitometry,’ is to identify those subjects at risk of an osteoporotic fracture and their subsequent response to pharmaceutical intervention. The true ‘gold standard’ measurement of the mechanical integrity of a bone, and hence its fracture load, is a destructive test, generally performed by compressing either a regular shaped sample or whole bone.

Diagnostic and treatment pathways for men with prostate cancer in Queensland : investigating spatial and demographic inequalities

Background: Patterns of diagnosis and management for men diagnosed with prostate cancer in Queensland, Australia, have not yet been systematically documented and so assumptions of equity are untested. This longitudinal study investigates the association between prostate cancer diagnostic and treatment outcomes and key area-level characteristics and individual-level demographic, clinical and psychosocial factors.---------- Methods/Design: A total of 1064 men diagnosed with prostate cancer between February 2005 and July 2007 were recruited through hospital-based urology outpatient clinics and private practices in the centres of Brisbane, Townsville and Mackay (82% of those referred). Additional clinical and diagnostic information for all 6609 men diagnosed with prostate cancer in Queensland during the study period was obtained via the population-based Queensland Cancer Registry. Respondent data are collected using telephone and self-administered questionnaires at pre-treatment and at 2 months, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months post-treatment. Assessments include demographics, medical history, patterns of care, disease and treatment characteristics together with outcomes associated with prostate cancer, as well as information about quality of life and psychological adjustment. Complementary detailed treatment information is abstracted from participants’ medical records held in hospitals and private treatment facilities and collated with health service utilisation data obtained from Medicare Australia. Information about the characteristics of geographical areas is being obtained from data custodians such as the Australian Bureau of Statistics. Geo-coding and spatial technology will be used to calculate road travel distances from patients’ residences to treatment centres. Analyses will be conducted using standard statistical methods along with multilevel regression models including individual and area-level components.---------- Conclusions: Information about the diagnostic and treatment patterns of men diagnosed with prostate cancer is crucial for rational planning and development of health delivery and supportive care services to ensure equitable access to health services, regardless of geographical location and individual characteristics. This study is a secondary outcome of the randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000233426)

Effect of surgical approach on bone vascularisation, fracture and soft tissue healing : comparison of less invasive to open approach

Over the past ten years, minimally invasive plate osteosynthesis (MIPO) for the fixation of long bone fractures has become a clinically accepted method with good outcomes, when compared to the conventional open surgical approach (open reduction internal fixation, ORIF). However, while MIPO offers some advantages over ORIF, it also has some significant drawbacks, such as a more demanding surgical technique and increased radiation exposure. No clinical or experimental study to date has shown a difference between the healing outcomes in fractures treated with the two surgical approaches. Therefore, a novel, standardised severe trauma model in sheep has been developed and validated in this project to examine the effect of the two surgical approaches on soft tissue and fracture healing. Twenty four sheep were subjected to severe soft tissue damage and a complex distal femur fracture. The fractures were initially stabilised with an external fixator. After five days of soft tissue recovery, internal fixation with a plate was applied, randomised to either MIPO or ORIF. Within the first fourteen days, the soft tissue damage was monitored locally with a compartment pressure sensor and systemically by blood tests. The fracture progress was assessed fortnightly by x-rays. The sheep were sacrificed in two groups after four and eight weeks, and CT scans and mechanical testing performed. Soft tissue monitoring showed significantly higher postoperative Creatine Kinase and Lactate Dehydrogenase values in the ORIF group compared to MIPO. After four weeks, the torsional stiffness was significantly higher in the MIPO group (p=0.018) compared to the ORIF group. The torsional strength also showed increased values for the MIPO technique (p=0.11). The measured total mineralised callus volumes were slightly higher in the ORIF group. However, a newly developed morphological callus bridging score showed significantly higher values for the MIPO technique (p=0.007), with a high correlation to the mechanical properties (R2=0.79). After eight weeks, the same trends continued, but without statistical significance. In summary, this clinically relevant study, using the newly developed severe trauma model in sheep, clearly demonstrates that the minimally invasive technique minimises additional soft tissue damage and improves fracture healing in the early stage compared to the open surgical approach method.

Oxycodone or oxycodone plus paracetamol for acute postoperative pain in adults

In this short communication we wanted to find out what is the analgesic effect of single dose oral oxycodone, with or without the addition of paracetamol, for adults with postoperative pain? Oxycodone at doses of 5mg and above is an effective analgesia for patients with moderate to severe postoperative pain. The efficacy of oxycodone is increased with the addition of paracetamol. The use of oxycodone 10mg plus paracetamol 625mg can be considered for use in the pain relief protocol in post-operative settings. Clinicians should consider a range of factors before prescribing or administering oxycodone for acute post-operative pain, including but not limited to, individual patient clinical profile, adverse effects, cost and patient preference.