ArticleUnited European gastroenterology journal2024
The impact of long-course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum.
Article in United European gastroenterology journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Ileostoma as a promising tool in pathophysiological study and clinical intervention: a review from bench to beside.Frontiers in immunology · 2026Review
- Chemotherapy-Induced Neuropathy Affecting the Gastrointestinal Tract.Neurogastroenterology and motility · 2025Review
- The impact of long-course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum.United European gastroenterology journal · 2024Article
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11 authors.
Funding
Abstract
BACKGROUND &
aimsThe long-term effects of chemoradiotherapy on human rectum are poorly understood. The aims were to investigate changes in inflammatory status, myenteric neuron numbers/phenotype, neuromuscular functions and prokinetic drug efficacy.
methodsMacroscopically normal proximal-to-mid rectum was obtained from 21 patients undergoing surgery for bowel cancer, 98 days (range: 63-350) after concurrent capecitabine and pelvic radiotherapy, and 19 patients without chemoradiotherapy. Inflammatory status was measured by H&E, CD45 staining and qPCR. Myenteric neurons were examined by immunohistochemistry. Neuromuscular functions and drug efficacy were studied using exogenous agents and electrical field stimulation (EFS) to activate intrinsic nerves.
resultsInflammation was not detected. Numbers of myenteric ganglia/neurons were unchanged (11.7 ± 2.4 vs. 10.3 ± 2.2 neurons/mm myenteric plexus with/without chemoradiotherapy) as were the numbers of cholinergic/nitrergic neurons. EFS stimulated cholinergic and nitrergic neurons so the contractile response of the muscle was the sum of both but dominated by cholinergic (causing contraction) or less often, nitrergic activity (relaxation), followed, after termination of EFS, by neuronally mediated contraction. Inhibition of nitric oxide synthase (by L-NAME 300 μM) more clearly defined EFS-evoked contractions. The 5-HT
conclusionsSeveral months after chemoradiotherapy, the rectum was not inflamed and myenteric neuron numbers/phenotype unchanged. However, nitrergic activity was increased relative to cholinergic activity, and prokinetic-like drug activity was lost or greatly reduced. Thus, chemoradiotherapy causes long-term changes in neuromuscular functions and markedly reduces the efficacy of drugs for treating constipation.
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