title: Short-term effects of neoadjuvant chemoradiotherapy on internal anal sphincter function:  a human in vitro study.
abstract: BACKGROUND
  Neoadjuvant chemoradiotherapy is recommended in the treatment of locally advanced rectal cancer. Studies have suggested that chemoradiotherapy adversely affects anorectal function. However, the functional implication and the underlying neuromyogenic changes involved in radiation-induced damage are poorly understood.
  
  
  OBJECTIVE
  This study evaluated the functional changes following chemoradiotherapy on the internal anal sphincter.
  
  
  METHODS
  This article describes an in vitro study on the internal anal sphincter collected from patients undergoing abdominoperineal resection or proctectomy. Five patients were treated by surgery alone (control group), and 6 received preoperative chemoradiotherapy (treatment group). Sphincter strips were mounted in organ bath, and the responses to electrical field stimulation and drugs were monitored.
  
  
  METHODS
  The study was performed at the University of Oxford.
  
  
  METHODS
  The end points of this study were to investigate whether chemoradiotherapy has any significant effects on internal anal sphincter function and, subsequently, to establish the type of injury induced.
  
  
  RESULTS
  Chemoradiotherapy strips developed similar tone, but significantly lower spontaneous activity (p = 0.001) than controls. Electrical field stimulation induced relaxation, followed by contraction. At 50 Hz, electrical field stimulation produced 25.6 ± 4.9% (mean ± SE) of maximum relaxation followed by a contraction of 5.5 ± 0.9% of basal tone in chemoradiotherapy strips i9n comparison with 47.0 ± 6.2% (p = 0.009) and 17.7 ± 4.0% (p = 0.007) in controls. Relaxation was significantly attenuated by N-nitro-L-arginine. Significant differences were found in responses to carbachol (p = 0.018) and phenylephrine (p = 0.022), but not to sodium nitroprusside.
  
  
  CONCLUSIONS
  This work was limited by the relatively small number of patients enrolled, because of the difficulty of finding human tissue for laboratory studies, and the lack of long-term results.
  
  
  CONCLUSIONS
  Chemoradiotherapy significantly impairs internal anal sphincter function and intrinsic nerves seem more susceptible than smooth muscle. The exclusion of anal canal from the radiation field is recommended, when oncologically safe.
authors.affiliation: Department of Surgery, University of Siena, Siena, Italy. bruno.lorenzi@yahoo.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Lorenzi
authors.forename: Alison F
authors.initials: AF
authors.lastname: Brading
authors.forename: Jacopo
authors.initials: J
authors.lastname: Martellucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Cetta
authors.forename: Neil J Mc C
authors.initials: NJ
authors.lastname: Mortensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal / Q000503:physiopathology* / Q000601:surgery; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D016022:Case-Control Studies; D059248:Chemoradiotherapy / Q000379:methods*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010656:Phenylephrine / Q000494:pharmacology; D012004:Rectal Neoplasms / Q000503:physiopathology* / Q000601:surgery / Q000628:therapy*
chemical_list: D010656:Phenylephrine; D002217:Carbachol; D001120:Arginine