Prognosis following surgical resection versus local excision of stage pT1 colorectal cancer: A population-based cohort study.

AIMS: To evaluate patient management following stage pT1 colorectal cancer (CRC) diagnosis, and to determine if surgical resection improved outcome compared with local excision, within a population-based study. METHODS: Data were collected from the Northern Ireland Cancer Registry. Cases of stage pT1 CRC diagnosed from 2007 to 2012 were identified. Analyses were conducted using Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cancer-specific and all-cause mortality for individuals undergoing formal surgery versus local excision. RESULTS: 394 patients with pT1 CRC were included. Of these, 37.1% were treated by local resection, 36.8% had biopsy followed by surgery and 26.1% had local excision followed by surgery. There were 60 deaths over a mean 4.8 years of follow-up, including 10 CRC-specific deaths. An additional 12 patients had a CRC recurrence or metastases during follow-up. Of the CRC-specific deaths or recurrences, 27.3% had local excision only. Individuals treated by formal surgery did not have a reduced risk of CRC-specific death (adjusted HR = 1.51, 95% CI 0.29, 7.89), but did have a reduced risk of all-cause mortality (adjusted HR = 0.51 95% CI 0.30, 0.87) compared with those undergoing local excision only. CONCLUSIONS: Patients with stage pT1 CRC undergoing formal surgery had a reduced risk of all-cause mortality compared with those treated by local excision only. However, this was not explained by a reduced risk of recurrence/disease-free survival or CRC death, and suggests that the observed benefits may simply reflect selection of a healthier patient population in the formal surgery group.

Splenic injury after colonoscopy requiring splenectomy.

We present a case of a middle-aged woman, who presented with abdominal pain less than 24 h following an uneventful colonoscopy for rectal bleeding. Initial diagnosis was thought to be colonic perforation. An urgent CT scan performed owing to dropping haemoglobin and blood pressure revealed a large perisplenic haematoma. An urgent laparotomy was performed in which the patient had a total blood loss of 2500 ml and required splenectomy. The patient recovered well postoperatively.Colonoscopy is a commonly performed procedure in which complications of perforation and bleeding are well recognised. This case represents one of the rare but serious complications that endoscopists and patients should be aware of to aid prevention and early diagnosis.

Divergent effects of a CLA-enriched beef diet on metabolic health in ApoE-/- and ob/ob mice.

Conjugated linoleic acid (CLA) is found naturally in meat and dairy products, and represents a potential therapeutic functional nutrient. However, given the discrepancies in isomer composition and concentration, controversy surrounds its proposed antidiabetic, antiobesity effects. This study focused on the effects of CLA-enriched beef (composed predominantly of c9, t11-CLA) in two separate models of metabolic disease: proatherosclerotic ApoE(-/-) mice and diabetic, leptin-deficient ob/ob mice. Animals were fed CLA-enriched beef for 28 days, and markers of the metabolic syndrome and atherosclerosis were assessed. Comprehensive hepatic transcriptomic analysis was completed to understand divergent metabolic effects of CLA. CLA-enriched beef significantly reduced plasma glucose, insulin, nonesterified fatty acid and triacylglycerol and increased adiponectin levels in ob/ob mice. In contrast, plasma lipid profiles and glucose homeostasis deteriorated and promoted atherosclerosis following the CLA-enriched beef diet in ApoE(-/-) mice. Hepatic transcriptomic profiling revealed divergent effects of CLA-enriched beef on insulin signaling and lipogenic pathways, which were adversely affected in ApoE(-/-) mice. This study demonstrated clear divergence in the effects of CLA. CLA-enriched beef improved metabolic flexibility in ob/ob mice, resulting in enhanced insulin sensitivity. However, CLA-enriched diet increased expression of lipogenic genes, resulting in inefficient fatty acid storage which increases lipotoxicity in peripheral organs, and led to profound metabolic dysfunction in ApoE(-/-) mice. While CLA may have potential health effects, in some circumstances, caution must be exercised in presenting this bioactive lipid as a potential functional food for the treatment of metabolic disease.

Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion.

There is an acknowledged need to promote and further develop in vitro techniques in order to achieve the goal of improved risk assessment of chemicals and pharmaceuticals to humans. The EU 6th framework project "PREDICTOMICS" was established in order to contribute to the further development of in vitro toxicology, with a particular focus on emerging techniques including toxicogenomics. DNA microarray technology is being used more frequently in the in vitro field, however, only very few studies have assessed the reproducibility of this technique with respect to in vitro toxicology. To this end we conducted an interlaboratory comparison to test the reproducibility of transcriptomic changes induced by the immunosuppressive agent, Cyclosporine A (CsA) on the human renal proximal tubular cell line, HK-2 cell. Four European laboratories took part in this study. Under standardised conditions, each laboratory treated HK-2 cells with 5microM CsA for 12 and 48h. RNA was isolated and hybridised to Affymetrix HGU-133 plus two arrays at three different sites. Analysis of the transcription profiles demonstrated that one laboratory clustered away from the other laboratories, potentially due to an inclusion of a trypsinisation step by this laboratory. Once the genes responsible for this separate clustering were removed all laboratories showed similar expression profiles. There was a major impact of time since feed, due to medium exhaustion in the 48h arrays compared to the 12h arrays, regardless of CsA treatment. Biological processes including general vesicle transport, amino acid metabolism, amino acid transport and amino acid biosynthesis were over-represented due to time since feed, while cell cycle, DNA replication, mitosis and DNA metabolism were under-represented. CsA responsive genes were involved in cell cycle, the p53 pathway and Wnt signaling. Additionally there was an overlap of differentially expressed genes due to CsA and medium exhaustion which is most likely due to CsA induced glycolysis. The glucose deprivation dependent genes HspA5 and GP96 and the Hsp70 chaperones DNAJ/Hsp40, DNAJ/HspB9, DNAJ/HspC3 DNAJ/HspC10 were induced by both CsA and medium exhaustion. We conclude that under standardised conditions the application of Affymetrix DNA microarrays to in vitro toxiciological studies are satisfactorily reproducible. However, confounding factors such as medium exhaustion must also be considered in such analyses.