Background: The use of a loop ileostomy is an effective method in protecting pelvic anastomoses. Its use has increased recently, although there is some debate as to the routine use of a stoma. Reversal of the ileostomy is associated with a significant morbidity, which may be related to impaired function of the bypassed distal limb of the ileum. Aim: To investigate the changes that might occur in the distal limb after an interval of faecal diversion. Methods: Full-thickness intestinal circular muscle (CM) strips were prepared from excised loop ileostomies taken at the time of closure. The study sample was from the distal limb and the control from the proximal limb. Contractile activity was measured using an organ bath set up to record isometric contraction after stimulation by acetylcholine (ACh). Histological sections were assessed for an index of villous atrophy, smooth muscle area, and nerve and vessel density. Analysis was with the Wilcoxon signed ranks test for paired data and the Mann–Whitney U test for unpaired data. Results: Samples were acquired prospectively from 35 consecutive patients. The median time between formation and closure of ileostomy was 34 weeks. Significant reduction was observed in the strength of CM contraction, smooth muscle area and median villous index of the distal limb compared with the proximal limb. Conclusion: Impaired intestinal function has been proposed as a contributory factor in the morbidity that may follow closure of loop ileostomy. Significant loss of contractility and smooth muscle strength and villous atrophy occur in the distal ileal limb after faecal diversion. Methods of preventing these changes should be considered.

Approximately 20% of patients diagnosed with colorectal cancer will present with left-sided large bowel obstruction. The optimal management of this cohort of patients remains unclear. We aimed to review international guidelines to see if there was a consensus on the treatment of this surgical emergency. The PubMed and Medline databases were searched for guidelines on the management of left-sided, malignant large bowel obstruction (MBO) between 2010 and 2018. Nineteen guidelines were identified spanning a range of continents. There was no clear consensus on the management of potentially resectable disease. Eight guidelines (42%) suggested primary surgery, two guidelines (11%) suggested stenting as a bridge to surgery and nine guidelines (47%) suggested surgery or stenting could be performed. Primary resection with or without anastomosis was the most frequently recommended procedure (n = 6 35%), but over a third of guidelines gave no operative recommendations. There was very limited detail on the stenting procedure and how long elective surgery should be deferred. In the palliative situation, there was general agreement that stents should be offered in preference to surgery. International guidelines offer limited and contrasting recommendations on the management of left-sided MBO. There is a lack of high-quality evidence to support whether emergency surgery or stenting as a bridge to surgery is the optimal procedure in terms of morbidity, mortality and long-term oncological outcome.

Objectives: Recent literature has concluded antibiotic therapy results in fewer complications than appendicectomy for patients with uncomplicated appendicitis. This studies aim was to undertake a meta-analysis of major post-intervention outcomes in patients with suspected uncomplicated appendicitis treated with antibiotics or appendicectomy, and determine which treatment is associated with the lowest rate of major complications. Methods: We analysed randomised trials of antibiotics vs. appendicectomy in adults with suspected uncomplicated appendicitis. The primary outcome measure was a composite of major complications, peritonitis and intra-abdominal abscess, occurring after appendicectomy or initiation of therapeutic antibiotics. Results: The rate of major post-intervention complications was 0.8% (2/263) in the appendicectomy group and 10.1% (27/268) in the antibiotic group. This difference was statistically significant by the random effects model: Risk Ratio 7.71, 95% C.I. 2.33 to 25.53, Risk Difference 0.09: 95% C.I. 0.05 to 0.13. The Number Needed to Harm (NNH) from antibiotic therapy is 10.7. Conclusions: Suspected uncomplicated appendicitis has a lower rate of major post-intervention complications when managed with primary appendicectomy compared to antibiotic therapy. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC₅₀ from 9.3 μM to 3.5 μM. Flow cytometry showed a significant increase in the mitotic marker pHH3 (3.4% vs. 56.2%) and DS-DNA break marker γH2AX (5.1% vs. 50.7%) for combination therapy compared with 5-FU alone. Combination therapy also increased the amount of caspase-3 dependent apoptosis compared with 5-FU alone (4% vs. 13%). The addition of exogenous nucleosides to combination therapy significantly rescued the increased DS-DNA breaks and caspase-3 dependent apoptosis almost to the levels of 5-FU monotherapy. In conclusion, AZD1775 enhances 5-FU cytotoxicity through increased DS-DNA breaks, not premature mitosis, in p53-mutated colorectal cancer cells. This finding is important for designers of future clinical trials when considering the optimal timing and duration of AZD1775 treatment.