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PTH-264 Preoperative chemoradiotherapy does not appear to have short-term effects on human rectal neuromuscular functions
  1. V Kung1,
  2. J Broad1,
  3. M Machesney2,
  4. M Thaha1,
  5. C Knowles1,
  6. G Sanger1
  1. 1National Centre for Bowel Research and Surgical Innovation, Queen Mary University of London
  2. 2Department of Colorectal Surgery, Whipps Cross University Hospital, Barts Health NHS Trust, London, UK

Abstract

Introduction Preoperative chemoradiotherapy may impair anorectal functions. Its effect on neuromuscular functions was investigated in human rectum ex-vivo.

Method Following informed consent, 3 groups of patients undergoing surgery for anorectal cancer were studied: 13 patients treated by surgery alone (Group I); 13 with long course neoadjuvant chemoradiotherapy (capecitabine) (Group II); and 4 with prior platinum-based chemoradiotherapy (oxaliplatin/capecitabine n = 2, FOLFOX/capecitabine n = 1, carboplatin/paclitaxel n = 1) (Group III). Age and gender were similar between Group I and II. Group III [55 (range=51–60)] were younger than Group I [72 (range=50–87)].

Postoperatively, macroscopically-normal rectum (without taenia) was obtained 5–10cm away from tumour. Mucosa-free circular muscle strips were suspended in tissue baths for isometric recording and electrical field stimulation (EFS, 1–20Hz, 50V, 0.5ms, for 10s) applied.1Data are expressed as median (inter-quartile range) and analysed using ANOVA with multiple comparison post-tests.

Results EFS usually caused contraction (or relaxation at low frequencies), often followed by an ‘after-contraction’ on termination. Amplitudes of contractions during and after EFS, and area under curve (AUC) of the full muscle movement increased with frequency (see table). Contractions were abolished by atropine 1 µM and tachykinin (NK1–3) receptor antagonists (n = 4) and greatly reduced by the neurotoxin tetrodotoxin 1 µM (n = 2).

All parameters of the movements evoked by EFS at all frequencies [AUC, amplitude of responses during EFS and after EFS] were similar amongst the 3 groups. There were no significant differences in tension generated by carbachol 10 µM (maximally-effective concentration) between groups (see Table 1, P > 0.05 for all measurements).

Abstract PTH-264 Table 1

Conclusion In this pilot study, preoperative chemoradiotherapy with capecitabine or platinum-based agents does not appear to have short-term effects on human rectal neuromuscular function. Reported impairment of anorectal function may be due to its long term effects or via other mechanisms.

Disclosure of interest V. Kung Grant/ Research Support from: AgeUK PhD studentship, Barts and the London Charity, J. Broad: None Declared, M. Machesney: None Declared, M. Thaha: None Declared, C. Knowles: None Declared, G. Sanger Grant/ Research Support from: Takeda.

Reference

  1. Broad et al. Br J Pharmacol. 2013;179:1253–61

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