title: Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function.
abstract: Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0-3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function.
authors: University Hospital Coventry, Coventry, CV2 2DX, UK.
authors: E Z H
authors: EZ
authors: Sung
authors: R P
authors: RP
authors: Arasaradnam
authors: E M
authors: EM
authors: Jarvie
authors: S
authors: S
authors: James
authors: S J
authors: SJ
authors: Goodyear
authors: R A
authors: RA
authors: Borman
authors: D
authors: D
authors: Snead
authors: G J
authors: GJ
authors: Sanger
authors: C U
authors: CU
authors: Nwokolo
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D000069287:Capecitabine; D002217:Carbachol / Q000494:pharmacology; D017024:Chemotherapy, Adjuvant; D018679:Cholinergic Agonists / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005725:Ganglia, Autonomic / Q000473:pathology; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D020360:Neoadjuvant Therapy; D013270:Stomach / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018679:Cholinergic Agonists; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D002217:Carbachol; D000110:Acetylcholinesterase; D002945:Cisplatin; D005472:Fluorouracil