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.
DESIGN AND PATIENTS
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.
SETTINGS
The study was performed at the University of Oxford.
MAIN OUTCOME MEASURES
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.
LIMITATIONS
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.
Links
Authors
Lorenzi B, Brading AF, Martellucci J, Cetta F, Mortensen NJ
Institution
Department of Surgery, University of Siena, Siena, Italy. bruno.lorenzi@yahoo.it
Source
Diseases of the colon and rectum 55:4 2012 Apr pg 465-72MeSH
AdultAged
Aged, 80 and over
Anal Canal
Arginine
Carbachol
Case-Control Studies
Chemoradiotherapy
Electric Stimulation
Female
Humans
Male
Middle Aged
Neoadjuvant Therapy
Phenylephrine
Rectal Neoplasms
Pub Type(s)
In VitroJournal Article
Research Support, Non-U.S. Gov't
Language
eng
PubMed ID
22426272
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