Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function

• Published in: Molecular biology reports Vol. 39; no. 12; pp. 9989 - 9994
• Main Authors: Sung, E. Z. H., Arasaradnam, R. P., Jarvie, E. M., James, S., Goodyear, S. J., Borman, R. A., Snead, D., Sanger, G. J., Nwokolo, C. U.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2012; Springer Nature B.V
• Subjects: Acetylcholinesterase - metabolism; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - physiopathology; Aged; Animal Anatomy; Animal Biochemistry; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Cancer surgery; Capecitabine; Carbachol - pharmacology; Chemotherapy; Chemotherapy, Adjuvant; Cholinergic Agonists - pharmacology; Cisplatin - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Epirubicin - administration & dosage; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - physiopathology; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Ganglia, Autonomic - pathology; Gastric cancer; Gastric Emptying - drug effects; Histology; Hormones; Humans; In Vitro Techniques; Life Sciences; Male; Middle Aged; Molecular biology; Morphology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - pathology; Neoadjuvant Therapy; Side effects; Stomach - drug effects; Stomach - metabolism; Stomach - pathology; Stomach - physiopathology; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - physiopathology; Stomach; Chemotherapy; Motility; Acetylcholinesterase; Ghrelin; Cisplatin
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-012-1866-7

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.