Prolonged Ileus after Colorectal Surgery, a Systematic Review.

Background: The development of prolonged post-operative ileus (POI) remains a significant problem in the general surgical patient population. The aetiology of ileus is poorly understood and management options/preventative measures are currently extremely limited. The pathophysiology leading to a post-operative ileus is relatively poorly understood, and there is no validated method to estimate ileus occurrence or duration.

Effectively utilizing publicly available databases for cancer target evaluation.

The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due to lack of efficacy and/or unmanageable toxicity. Robust target evaluation is therefore required before progressing through the drug discovery process to reduce the high attrition rate. There are a wealth of publicly available databases that can be mined to generate data as part of a target evaluation.

Rethinking our approach to cancer metabolism to deliver patient benefit.

Altered cellular metabolism is a major mechanism by which tumours support nutrient consumption associated with increased cellular proliferation. Selective dependency on specific metabolic pathways provides a therapeutic vulnerability that can be targeted in cancer therapy. Anti-metabolites have been used clinically since the 1940s and several agents targeting nucleotide metabolism are now well established as standard of care treatment in a range of indications.

Disease recurrence after right hemicolectomy in Scotland: Is there rationale to adopt complete mesocolic excision (CME)?

Aims: Complete mesocolic excision (CME) has been proposed as a way to improve the oncological outcomes in patients with colon cancer. To investigate whether there is rationale for adopting the technique in Scotland, our aim was to define the incidence of disease recurrence following standard right hemicolectomy and to compare this with published CME outcomes.

Methods: Data was collected on consecutive patients undergoing right or extended right hemicolectomy for colonic adenocarcinoma (2012-2017) at three hospitals in Scotland (Raigmore Hospital, Aberdeen Royal Infirmary and Glasgow Royal Infirmary).

Pathological response post neoadjuvant therapy for locally advanced rectal cancer is an independent predictor of survival.

Aim: Neoadjuvant treatment (NaT) for locally advanced rectal cancer prior to surgery has led to improved outcomes. However, the relationship between pathological response to NaT and survival is not entirely clear. The aim of this study was to assess the degree of pathological response to NaT on survival outcomes.

Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer.

Cyclin-dependent kinases (CDKs) contribute to the cancer hallmarks of uncontrolled proliferation and increased survival. As a result, over the last two decades substantial efforts have been directed towards identification and development of pharmaceutical CDK inhibitors. Insights into the biological consequences of CDK inhibition in specific tumor types have led to the successful development of CDK4/6 inhibitors as treatments for certain types of breast cancer.

Is Liver Ultrasound Useful as Part of the Surveillance Strategy following Potentially Curative Colorectal Cancer Resection?

Background: Optimal surveillance monitoring following curative resection of colorectal cancer remains unclear. Guidelines recommend computed tomography (CT)-based imaging for the initial 3 years following surgical intervention due to the high rates of local and distant recurrence. However, there is currently limited supporting evidence for this strategy.

Can Haematology Blood Tests at Time of Diagnosis Predict Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer?

Background: Outcomes in locally advanced rectal cancer are improved by neoadjuvant therapy followed by surgical resection. Some patients respond completely to preoperative treatment. Therefore, predicting the pathological response to preoperative therapy is of clinical importance.

Prognostic Value of Computed Tomography: Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers.

Background: Previous reports suggest that body composition parameters can be used to predict outcomes for patients with gastrointestinal (GI) cancers. However, evidence for an association with long-term survival is conflicting, with much of the data derived from patients with advanced disease. This study examined the effect of body composition on survival in primary operable GI cancer.

Impact of the Scottish Bowel Cancer Screening Programme on patient and tumour characteristics at a single centre.

Aims: The Scottish National Bowel Cancer Screening Programme aims to detect asymptomatic colorectal carcinomas and improve outcomes by identifying tumours at an earlier stage. We describe the characteristics of bowel cancers diagnosed through the screening programme since it was established in June 2007 by comparison with colorectal carcinomas from all other referral sources.

Methods: All patients with colorectal cancer discussed by our regional colorectal multidisciplinary team (MDT) from June 2007 to August 2011 were included.

The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.

The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage.

Putting guidelines into practice: a tailored multi-modal approach to improve post-operative assessments.

Background: The Scottish Intercollegiate Guideline Network (SIGN) published Postoperative Management in Adults in 2004, advocating post-operative assessments to optimize post-operative care. Our aim was to improve post-operative assessments in a surgical high-dependency unit (HDU).

Methods: A prospective audit of post-operative admissions to surgical HDU over two 4-week periods was performed.

Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.

DNA interstrand crosslinks (ICLs) are highly toxic because they block the progression of replisomes. The Fanconi Anemia (FA) proteins, encoded by genes that are mutated in FA, are important for repair of ICLs. The FA core complex catalyzes the monoubiquitination of FANCD2, and this event is essential for several steps of ICL repair.

Biochemical characterisation of the SWI/SNF family member HLTF.

HLTF is highly similar in domain organisation to yeast Rad5. We identify PTIP and RPA70, both involved in DNA replication and DNA repair, as HLTF-interacting proteins although cells depleted of HLTF did not show defects in cellular responses to DNA damage. In vitro, HLTF has ATPase activity and E3 ubiquitin ligase activity with a range of E2 ubiquitin conjugating enzymes.