A surgeon, a rabbi and a lawyer walk in to an OR… Absorbable haemostatic agents and the dangers of product evolution – clinical, religious and legal implications

Adjunctive haemostatic agents have been used in surgery for over 70 years. What surgeons may not know is that products intended for similar applications may have very different biological properties and that occasionally product upgrades may introduce a change in the material’s behaviour. Many of the agents employed to assist in haemostasis may have a biological (animal) origin. A recent case brought to light the need to recognise the possibility of biological interactions. As consideration into this surgical problem unfolded, religious and legal questions began to arise

Microscopic diffusion properties of fixed breast tissue: Preliminary findings

Purpose: To investigate the microscopic diffusion properties of formalin-fixed breast tissue

Intraoperative magnetic resonance: the future of surgery

Intraoperative magnetic resonance imaging (iMRI) is a new development in medicine that bridges the specialties of surgery and radiology. Deficiencies in the visualization of anatomical architecture and the perception of tumour boundaries in conventional open surgery have led to the integration of imaging within surgery. The superior soft tissue and multiplanar imaging features of magnetic resonance (MR) make this imaging modality superior to that of alternatives. The unique properties of MR to detect heat change and perfusion, and diffusion characteristics of tissue enhance the usefulness of this medium. Concurrent developments in computer aided image guidance and thermoablative technology, herald the era of minimally invasive tumour ablation. Applications have been developed for areas such as neurosurgery, general surgery, gynaecology and urology

Microscopic diffusion properties of fixed breast tissue: preliminary findings

Purpose: To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Methods: Diffusion microimaging was performed at 16.4T with 40-mm isotropic voxels on two normal and two cancer tissue samples from four patients. Results were correlated with histology of the samples. Results: Diffusion-weighted images and mean diffusivity maps demonstrated distinct diffusivity differences between breast tissue components. Mean diffusivity (MD) in normal tissue was 0.5960.24 mm2/ms for gland lobule (voxels containing epithelium and intralobular stroma) and 1.2360.34 mm2/ms for interlobular fibrous stroma. In the cancer samples, MD¼0.4560.23 mm2/ms for invasive ductal carcinoma (voxels contain epithelium and intralobular stroma) and 0.6160.35 mm2/ms for ductal carcinoma in situ. There were significant MD differences between all tissue components (P<0.005), except between gland lobule and ductal carcinoma in situ (P¼0.71). The low diffusivity of epithelium-rich cancer tissue and of normal epithelium relative to its supporting fibrous stroma was similar to that reported for prostate tissue and the esophageal wall. Conclusion: Diffusion microimaging demonstrates distinct diffusivity differences between breast tissue glandular structures. Low diffusivity may be a distinctive feature of mammalian epithelia

Understanding the role of the kynurenine pathway in human breast cancer immunobiology

Breast cancer (BrCa) is the leading cause of cancer related death in women. While current diagnostic modalities provide opportunities for early medical intervention, significant proportions of breast tumours escape treatment and metastasize. Gaining increasing recognition as a factor in tumour metastasis is the local immuno-surveillance environment. Following identification of the role played by the enzyme indoleamine dioxygenase 1 (IDO1) in mediating maternal foetal tolerance, the kynurenine pathway (KP) of tryptophan metabolism has emerged as a key metabolic pathway contributing to immune escape. In inflammatory conditions activation of the KP leads to the production of several immune-modulating metabolites including kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, picolinic acid and quinolinic acid. KP over-activation was first described in BrCa patients in the early 1960s. More evidence has since emerged to suggest that the IDO1 is elevated in advanced BrCa patients and is associated with poor prognosis. Further, IDO1 positive breast tumours have a positive correlation with the density of immune suppressive Foxp3+ T regulatory cells and lymph node metastasis. The analysis of clinical microarray data in invasive BrCa compared to normal tissue showed, using two microarray databank (cBioportal and TCGA), that 86.3% and 91.4% BrCa patients have altered KP enzyme expression respectively. Collectively, these data highlight the key roles played by KP activation in BrCa, particularly in basal BrCa subtypes where expression of most KP enzymes was altered. Accordingly, the use of KP enzyme inhibitors in addition to standard chemotherapy regimens may present a viable therapeutic approach.15 page(s

Specificity of choline metabolites for in vivo diagnosis of breast cancer using \ub9H MRS at 1.5T

NRC publication: Ye

Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome

Aims: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC. Methods and results: PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death. Conclusion: While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort