Vertical rectus abdominis myocutaneous flap and quality of life following abdominoperineal excision for rectal cancer: a multi-institutional study.

BACKGROUND: To obtain a clear surgical margin, abdominoperineal excision (APE) for rectal cancer frequently leaves a large perineal defect surrounded by irradiated tissue. A vertical rectus abdominis myocutaneous (VRAM) flap may facilitate healing of this wound. The current study aims to determine the effect of VRAM flap perineal reconstruction following APE on patient quality of life (QOL). METHODS: This is a retrospective cohort study from a prospectively collected database. Data on QOL were assessed via telephone questionnaire using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30, EORTC QLQ-C29 and the Cleveland Clinic QOL questionnaires. RESULTS: Twenty-seven patients underwent primary perineal closure, and 12 patients underwent a VRAM flap perineal reconstruction. The mean duration of follow-up was 16.8 months. Overall, there was no significant difference in the Cleveland Clinic QOL score between groups (VRAM vs. no VRAM: 0.7 ± 0.2 vs. 0.7 ± 0.2, p 0.735). Patients in the VRAM group had lower levels of fatigue (5.5 ± 9.9 vs. 23.6 ± 19.2, p 0.004). Patients in the VRAM group had reduced sore skin scores around the stoma site (11.0 ± 16.2 vs. 31.8 ± 31.1, p 0.036). VRAM flap was associated with an increased incidence of abdominal wall hernia (VRAM vs. no VRAM: 25 % vs. 0 %, p 0.024). CONCLUSIONS: This study is limited by its non-randomized retrospective design and relatively small sample size. A significant difference in patient QOL was not demonstrated between VRAM flap and primary perineal closure after APE for rectal cancer. Further studies in this area are warranted.

In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes.

Interleukin-13 (IL-13) sequentially binds to IL-13Ralpha1 and IL-4Ralpha forming a high affinity signalling complex. This receptor complex is expressed on multiple cell types in the airway and signals through signal transducer and activator of transcription factor-6 (STAT-6) to stimulate the production of chemokines, cytokines and mucus. Antibodies have been generated, using the UCB Selected Lymphocyte Antibody Method (UCB SLAM), that block either binding of murine IL-13 (mIL-13) to mIL-13Ralpha1 and mIL-13Ralpha2, or block recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. Monoclonal antibody (mAb) A was shown to bind to mIL-13 with high affinity (K(D) 11 pM) and prevent binding of mIL-13 to mIL-13Ralpha1. MAb B, that also bound mIL-13 with high affinity (K(D) 8 pM), was shown to prevent recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. In vitro, mAbs A and B similarly neutralised mIL-13-stimulated STAT-6 activation and TF-1 cell proliferation. In vivo, mAbs A and B demonstrated equipotent, dose-dependent inhibition of eotaxin generation in mice stimulated by intraperitoneal administration of recombinant mIL-13. In an allergic lung inflammation model in mice, mAbs A and B equipotently inhibited muc5ac mucin mRNA upregulation in lung tissue measured two days after intranasal allergen challenge. These data support the design of therapeutics for the treatment of allergic airway disease that inhibits assembly of the high affinity IL-13 receptor signalling complex, by blocking the binding of IL-13 to IL-13Ralpha1 and IL-13Ralpha2, or the subsequent recruitment of IL-4Ralpha.