Challenging diagnostic issues in adenomatous polyps with epithelial misplacement in bowel cancer screening: 5 years' experience of the Bowel Cancer Screening Programme Expert Board.

The diagnostic difficulties of differentiating epithelial misplacement from invasive cancer in colorectal adenomatous polyps have been recognised for many years. Nevertheless, the introduction of population screening in the UK has resulted in extraordinary diagnostic problems. Larger sigmoid colonic adenomatous polyps, which are those most likely to show epithelial misplacement, are specifically selected into such screening programmes, because these polyps are likely to bleed and screening is based on the detection of occult blood. The diagnostic challenges associated with this particular phenomenon have necessitated the institution of an 'Expert Board': this is a review of the first five years of its practice, during which time 256 polyps from 249 patients have been assessed. Indeed, the Expert Board contains three pathologists, because those pathologists do not necessarily agree, and a consensus diagnosis is required to drive appropriate patient management. However, this study has shown substantial levels of agreement between the three Expert Board pathologists, whereby the ultimate diagnosis has been changed, from that of the original referral diagnosis, by the Expert Board for half of all the polyps, in the substantial majority from malignant to benign. In 3% of polyp cases, the Expert Board consensus has been the dual diagnosis of both epithelial misplacement and adenocarcinoma, further illustrating the diagnostic difficulties. The Expert Board of the Bowel Cancer Screening Programme in the UK represents a unique and successful development in response to an extraordinary diagnostic conundrum created by the particular characteristics of bowel cancer screening.

Bowel cancer screening-generated diagnostic conundrum of the century: pseudoinvasion in sigmoid colonic polyps.

The introduction of bowel cancer screening, in the United Kingdom, United States of America, and many other Western countries, has provided considerable interest and no little diagnostic consternation for pathologists. In the United Kingdom, the universal introduction of bowel cancer screening, initially by fecal occult blood testing and more recently by the introduction of flexible sigmoidoscopy, has provided four main areas of pathological diagnostic difficulty. This is the biopsy diagnosis of adenocarcinoma, serrated pathology, the diagnosis and management of polyp cancer, and, finally, the phenomenon of pseudoinvasion/epithelial misplacement (PEM), particularly in sigmoid colonic adenomatous polyps. The diagnostic difficulties associated with the latter phenomenon have provided particular problems that have led to the institution of a UK national 'Expert Board', comprising three pathologists, who adjudicate on difficult cases. The pathological features favoring PEM are well recognized but there is no doubt that there can be profound mimicry of adenocarcinoma, and, as yet, no adjunctive diagnostic tools have been developed to allow the differentiation in difficult cases. Research in this area is proceeding and some methodologies do show promise in this difficult diagnostic area.

An Overview of the Current Management of Bilobar Colorectal Liver Metastases.

Bilobar colorectal liver metastases (BCRLM) present a challenging scenario for liver surgeons globally. The following article aims to provide an overview of the different strategies which may be utilised in order to successfully manage advanced BCRLM.

GPIb potentiates GPVI-induced responses in human platelets.

Platelet adhesion to vascular subendothelial proteins at the site of blood vessel injury is critical for initiating haemostasis. Collagen is a major matrix protein that binds plasma von Willebrand factor (vWF) when the endothelium becomes damaged and therefore in vivo platelets are likely to encounter both of these agonists simultaneously, through glycoprotein VI (GPVI) and alpha2beta1 receptors for collagen and GPIb-V-IX and alphaIIbbeta3 receptors for vWF. We hypothesised a potentiatory role for vWF that would synergise with collagen leading to functional activation and show this to be the case for platelet aggregation, 5-HT secretion and calcium responses. Synergy between these two agonists is likely to involve receptors GPVI and GPIb-V-IX, for collagen and vWF, respectively, since 5-HT secretion in response to collagen is potentiated by vWF in the presence of either EGTA or EDTA, which prevent binding to integrins alphaIIbbeta3 (EGTA) or both alphaIIbbeta3 and alpha2beta1 (EDTA). In addition, vWF is also able to potentiate 5-HT secretion responses to collagen-related peptide, confirming that GPVI is able to support synergy with vWF. These findings are important in that they reveal a novel role for vWF in platelet activation as a potentiator of platelet activation by collagen.