NF-κB1, NF-κB2 and c-Rel differentially regulate susceptibility to colitis-associated adenoma development in C57BL/6 mice.

NF-κB signalling is an important factor in the development of inflammation-associated cancers. Mouse models of Helicobacter-induced gastric cancer and colitis-associated colorectal cancer have demonstrated that classical NF-κB signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific NF-κB proteins, including NF-κB1/p50, NF-κB2/p52, and c-Rel, differentially regulate the development of gastric pre-neoplasia. To investigate the effect of NF-κB subunit loss on colitis-associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to C57BL/6, Nfkb1(-/-), Nfkb2(-/-), and c-Rel(-/-) mice. Animals lacking the c-Rel subunit were more susceptible to colitis-associated cancer than wild-type mice, developing 3.5 times more colonic polyps per animal than wild-type mice. Nfkb2(-/-) mice were resistant to colitis-associated cancer, developing fewer polyps per colon than wild-type mice (median 1 compared to 4). To investigate the mechanisms underlying these trends, azoxymethane and dextran sodium sulphate were administered separately to mice of each genotype. Nfkb2(-/-) mice developed fewer clinical signs of colitis and exhibited less severe colitis and an attenuated cytokine response compared with all other groups following DSS administration. Azoxymethane administration did not fully suppress colonic epithelial mitosis in c-Rel(-/-) mice and less colonic epithelial apoptosis was also observed in this genotype compared to wild-type counterparts. These observations demonstrate different functions of specific NF-κB subunits in this model of colitis-associated carcinogenesis. NF-κB2/p52 is necessary for the development of colitis, whilst c-Rel-mediated signalling regulates colonic epithelial cell turnover following DNA damage.

Murine Models of Helicobacter (pylori or felis)-associated Gastric Cancer.

Gastric adenocarcinoma is the fifth most common cancer and third most common cause of cancer-related death in the world. The majority of these cancers develop in genetically susceptible individuals who are chronically infected with the Gram-negative bacterium Helicobacter pylori. Often these individuals have also been exposed to certain environmental factors that increase susceptibility, such as dietary components. Murine models of Helicobacter-induced gastric cancer are valuable tools for investigating the mechanisms responsible for the stepwise pathological changes of chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma. Helicobacter felis colonization greatly accelerates the development of gastric neoplasia in mice, and causes pathologies similar to those observed with Helicobacter pylori-associated gastric carcinogenesis in humans. These mouse models are therefore useful for investigating genetic and environmental factors that may be involved in the pathogenesis and treatment of gastric cancer. Detailed in these protocols are procedures for inducing Helicobacter-associated carcinogenesis in mice as well as the histological analysis and interpretation of gastric pathology in these animals.

Optimal imaging sequence for staging in colorectal liver metastases: analysis of three hypothetical imaging strategies.

BACKGROUND: Computed tomography (CT), positron emission tomography CT (PET-CT) and magnetic resonance imaging (MRI) all play a role in the management of colorectal liver metastases (CRLM), but inappropriate over investigation can lead to delays in treatment and additional cost. This study aimed to determine the optimal sequence for pre-operative imaging pathway to minimise delays to treatment and healthcare costs. METHODS: All patients with colorectal liver metastases referred to a single tertiary liver specialist multidisciplinary team (MDT) between 2008 and 2011 were examined. Primary data of clinical and radiological outcomes of all patients were analysed. These data were used to construct and test 3 hypothetical imaging strategies - 'Upfront', 'Sequential' and 'Hybrid' models. RESULTS: Six hundred and forty four consecutive patients were included. One hundred and sixty five patients were excluded for curative resection following the initial CT review. Subsequently 167/433 patients did not proceed to hepatectomies. Eighty (47.9%) of these patients had extra-hepatic disease identified on PET-CT, and 29 were due to the exclusion by MRI liver. A resectable pattern of liver disease on initial CT did not exclude patients with occult disease on PET-CT. Based on cost analysis, assessment of initial CT, followed by MDT with subsequent PET-CT and MRI imaging thereafter (Hybrid model), was associated with the shortest time-to-decision and lowest cost. CONCLUSIONS: Resectable pattern of liver metastases should not solely be used to determine the application of PET-CT for staging. Hybrid model is associated with the lowest cost and shortest time-to-treatment.

Oxygen therapy in patients with chest pain of acute onset: single centre audit experience.

INTRODUCTION: Although oxygen therapy has been commonly used in the treatment of acute coronary syndromes, evidence shows that oxygen administration is not always beneficial to patients with acute chest pain and in certain circumstances may, in fact, be harmful. Hence, several national and international organizations have issued guidelines restricting its use to hypoxic patients only. AIM: To audit and change the inappropriate practice of administering oxygen therapy indiscriminately to patients with acute chest pain. SETTING: Emergency department, coronary care unit and heart assessment centre in a large teaching hospital. METHODS: The authors identified 100 patients who presented with acute chest pain and collected data on oxygen prescription, administration and documentation from clinical notes and observation charts. RESULTS: Only 71% of patients in a hospital setting were correctly assessed for requiring oxygen therapy. After introducing local guidelines and a series of lectures, this rose to 94%. A third audit showed sustained change, with 96% of patients being appropriately assessed for needing oxygen therapy. DISCUSSION: The introduction of local guidelines and a series of lectures improved handling of oxygen in patients presenting with acute chest pain.