Development of orthotopic tumour models using ultrasound-guided intrahepatic injection.

Mouse models of human diseases are an essential part of the translational pipeline. Orthotopic tumour mouse models are increasingly being used in cancer research due to their increased clinical relevance over subcutaneous xenograft models, particularly in relation to metastatic disease. In this study, we have developed orthotopic colorectal cancer liver metastases (CRCLM) and primary cholangiocarcinoma (CCA) models in BALB/c nude mice using minimally invasive ultrasound-guided intrahepatic injection. Due to its minimally invasive nature, the method reduced risk from surgical complications whilst being fast and easy to perform and resulted in measurable tumour volumes 1 to 3 weeks post-injection. Tumour volumes were monitored in vivo by weekly high-frequency ultrasound (HF-US) and/or twice weekly bioluminescence imaging (BLI) and confirmed with end-point histology. Take rates were high for human CRC cells (>73%) and for CCA cells (90%). We have demonstrated that this method reliably induces CRCLM and CCAs, in which tumour volume can be monitored throughout using HF-US and/or BLI. This provides a promising experimental tool for future testing of cancer therapeutics in an orthotopic model.

Reversal of loop ileostomy under an Enhanced Recovery Programme - Is the stapled anastomosis technique still better than the handsewn technique?

INTRODUCTION: Recent literature suggests that stapled anastomotic (SA) technique for the reversal of loop ileostomy (LI) may be beneficial in terms of early recovery and reduced incidence of small bowel obstruction when compared to the handsewn anastomosis (HA). Enhanced Recovery Programme (ERP) after colorectal procedures has demonstrated a reduction in some aspects of surgical morbidity. The aim of this study was to investigate the outcomes of patients undergoing reversal of LI within an ERP programme and compare the HA to the SA in relation to clinical outcomes. MATERIAL AND METHODS: All adult patients undergoing elective reversal of loop ileostomy between January 2008 and December 2012 without any additional procedures, were included in our study. Adherence to ERP modules and 30 day postoperative complications were assessed via retrospective review of patient case notes. RESULTS: One hundred and eight patients had an ileostomy reversal; 61 in the SA and 47 in the HA group. There were no demographic differences between the two groups. ERP module compliance was satisfactory (>80%) in 11 of the 14 modules with no difference in individual module compliance between the two groups. The operating times were found to be comparable (p = 0.35). Overall mortality (p = 0.44), anastomotic leak rates (p = 1.00), intra-abdominal collections (p = 0.65), small bowel obstruction (p = 1.00), reoperation rates (p = 0.65), ileus (p = 0.14) and other significant complications (Clavien-Dindo > 2) (p = 0.08) were similar between the two groups. A significantly longer total length of hospital stay (TLOS) was found in the SA group (median 3 Vs 4 days, p = 0.009). CONCLUSION: Reversal of LI under an ERP appears to potentially neutralise the suggested SA benefits in terms of postoperative complications without any additional negative implications. Other non-operative factors may have a potential effect on outcomes such as the TLOS.