Intra-Operative Assessment of Sentinel Lymph Nodes in Breast Cancer

Lymph node status remains an important prognostic indicator for survival in breast cancer. Sentinel lymph node biopsy has become the standard method of assessment of clinically node negative breast cancers. Economic implications as well as patient related factors have lead to the development a number of intra-operative techniques. Review of the emerging trends in the last 4 years show that although routine histological examination remains the gold standard in most centres intra-operative assessment remains the most favourable, timely and cost-effective option to analyse sentinel nodes. Molecular techniques appear to be far more superior to other histological tests such as Frozen Section or Touch Imprint Cytology. Emerging research suggests that molecular techniques can be used to predict the presence of non sentinel node metastasis

Intraoperative Radiotherapy in the Treatment of Breast Cancer: A Review of the Evidence

The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed

Tribological behaviour of AZ31 magnesium alloy reinforced by bimodal size B4C after precipitation hardening

This study investigated dry sliding wear properties of AZ31 magnesium alloy and B4C-reinforced AZ31 composites containing 5, 10, and 20 wt.% B4C with bimodal sizes under different loadings (10–80 N) at various sliding speeds (0.1–1 m/s) via the pin-on-disc configuration. Microhardness evaluations showed that when the distribution of B4C particles was uniform the hardness of the composites increased by enhancing the reinforcement content. The unreinforced alloy and the composite samples were examined to determine the wear mechanism maps and identify the dominant wear mechanisms in each wear condition and reinforcement content. For this purpose, wear rates and friction coefficients were recorded during the wear tests and worn surfaces were characterized by scanning electron microscopy and energy dispersive X-ray spectrometry analyses. The determined wear mechanisms were abrasion, oxidation, delamination, adhesion, and plastic deformation as a result of thermal softening and melting. The wear evaluations revealed that the composites containing 5 and 10 wt.% B4C had a significantly higher wear resistance in all the conditions. However, 20 wt.% B4C/AZ31 composite had a lower resistance at high sliding speeds (0.5–1 m/s) and high loadings (40–80 N) in comparison with the unreinforced alloy. The highest wear resistance was obtained at high sliding speeds and low loadings with the domination of oxidative wear

Photodynamic Therapy in Primary Breast Cancer

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer

Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm

Near-infrared quantum dots for HER2 localization and imaging of cancer cells

BACKGROUND: Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%-30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application. METHODS: Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots. RESULTS: In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 μg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells. CONCLUSION: Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery

Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A trial

Background: The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT). Methods: Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations. Results: Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p \u3c 0.001), 95% CI (0.24, 0.68). Conclusion: Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient’s point of view is the most important. Trial Registration: TARGIT-A ISRCTN34086741, Registered 21 July 2004, retrospectively registered