Physiotherapy and Anterior Resection Syndrome (PARiS) trial: feasibility study protocol.

INTRODUCTION: Rectal cancer affects more than 600 patients per year in Wales, with a 5-year survival rate of around 60%. A recent report demonstrated that 19% of patients with bowel cancer had difficulty controlling their bowels after surgery, and these patients were twice as likely to report lower quality of life than those who had control. Nearly all patients will experience bowel dysfunction initially following surgery and up to 25% will experience severe bowel dysfunction on a long-term basis. The aim of this study is to test the feasibility of introducing a simple intervention in an attempt to improve bowel function following surgery for rectal cancer. We propose the introduction of an educational session from specialist nurses and physiotherapists prior to surgery and a subsequent physiotherapy programme for 3 months to teach patients how to strengthen their pelvic floor. METHODS AND ANALYSIS: All patients with rectal cancer planned to receive an anterior resection will be approached for the study. The study will take place in three centres over 12 months, and we expect to recruit 40 patients. The primary outcome measure is the proportion of eligible patients approached who consent to and attend the educational session. The secondary outcomes include patient compliance to the pelvic floor rehabilitation programme (assessed by patient paper or electronic diary), the acceptability of the intervention to the patient (assessed using qualitative interviews) and preoperative and postoperative pelvic floor tone (assessed using the Oxford Grading System and the International Continence Society Grading System), patient bowel function and patient quality of life (assessed using validated questionnaires). ETHICS AND DISSEMINATION: Ethics approval was granted. This feasibility study is in progress. If patients find the intervention acceptable, the next stage would be a trial comparing outcomes after anterior resection in those who have and do not have physiotherapy. TRIAL REGISTRATION NUMBER: ISRCTN77383505; Pre-results.

Hughes Abdominal Repair Trial (HART)-abdominal wall closure techniques to reduce the incidence of incisional hernias: feasibility trial for a multicentre, pragmatic, randomised controlled trial.

OBJECTIVES: Incisional hernias are common complications of midline abdominal closure. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. There is evidence to suggest this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared Hughes repair with standard mass closure for the prevention of incisional hernia formation. This paper aims to test the feasibility of running a randomised controlled trial of a comparison of abdominal wall closure methods following midline incisional surgery for colorectal cancer, in preparation to a definitive randomised controlled trial. DESIGN AND SETTING: A feasibility trial (with 1:1 randomisation) conducted perioperatively during colorectal cancer surgery. PARTICIPANTS: Patients undergoing midline incisional surgery for resection of colorectal cancer. INTERVENTIONS: Comparison of two suture techniques (Hughes repair or standard mass closure) for the closure of the midline abdominal wound following surgery for colorectal cancer. PRIMARY AND SECONDARY OUTCOMES: A 30-patient feasibility trial assessed recruitment, randomisation, deliverability and early safety of the surgical techniques used. RESULTS: A total of 30 patients were randomised from 43 patients recruited and consented, over a 5-month period. 14 and 16 patients were randomised to arms A and B, respectively. There was one superficial surgical site infection (SSI) and two organ space SSIs reported in arm A, and two superficial SSIs and one complete wound dehiscence in arm B. There were no suspected unexpected serious adverse reactions reported in either arm. Independent data monitoring committee found no early safety concerns. CONCLUSIONS: The feasibility trial found no early safety concerns and demonstrated that the trial was acceptable to patients. Progression to the pilot and main phases of the trial has now commenced following approval by the independent data monitoring committee. TRIAL REGISTRATION NUMBER: ISRCTN 25616490.

Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.

Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development.