Vagotomy and Gastric Tumorigenesis

Abstract

Vagotomy reduces gastric acid secretion and was therefore introduced as a surgical treatment for peptic ulcers in the 1970s. Later, it was replaced by acid reducing medication, such as histamine type 2 (H2) receptor antagonists and proton pump inhibitors (PPIs). A large body of evidence has indicated that drug-induced hypochlorhydria per se does not increase the risk of gastric cancer. Early studies on the effects of vagotomy in chemically-induced rodent models of gastric cancer reported an increased risk of developing gastric cancer. This was most likely due to a delayed gastric emptying, which later has been accounted for by including an additional drainage procedure, e.g. pyloroplasty. In a recent study using three different mouse models of gastric cancer (including genetically engineered, chemically-induced and Helicobacter pylori-infected mice), either unilateral vagotomy or bilateral truncal vagotomy with pyloroplasty was found to significantly attenuate tumorigenesis in the denervated side of the stomach at early preneoplastic stages as well as at later stages of tumorigenesis. Consistently, pharmacological denervation using botulinum toxin A or muscarinic acetylcholine receptor 3 (M3R) blockade inhibited tumorigenesis. Moreover, it was found that recurrence of gastric cancer was reduced in patients following vagotomy. Thus, these new findings suggest the potential treatment strategies to target the nerve, neurotransmitters, corresponding receptors and their downstream signaling pathways for the malignancy.

Innervation of cervical carcinoma is mediated by cancer-derived exosomes

“…In this study, we show the presence of sensory nerves within human cervical cancer specimens and, importantly, suggest a tumor-dependent exosome-mediated mechanism that may allow cervical carcinomas to induce their own innervation. Clinically, the extent of tumor innervation is inversely associated with patient prognosis in several different cancers [4][5][6]. If a similar phenomenon occurs in cervical cancer, tumorassociated nerves and/or the process of exosome-mediated innervation may represent worthy therapeutic targets to improve outcomes in this patient population.…”

“…A thorough mapping of the cell types present and, critically, an understanding of their unique roles in tumor biology will provide new opportunities for therapeutic intervention. Interestingly, tumor innervation is associated with worse clinical outcomes in several solid cancers [4][5][6], emphasizing nerves as microenvironmental factors that may contribute to tumor progression. It is important to note the distinction between innervation and the more commonly recognized perineural invasion.…”

Cancer exosomes induce tumor neo-neurogenesis potentiating tumor growth

“…Introduction: Innervated tumors are more aggressive than less innervated ones (1)(2)(3)(4)(5)(6)(7). For instance, in prostate cancer, recruitment of nerve fibers to cancer tissue is associated with higher tumor proliferative indices and a higher risk of recurrence and metastasis (5).…”

EDITORIAL (Thematic Issue: Brain Gut Axis-New View)

“…Hanne-Line Rabben, Chun-Mei Zhao, Yoku Hayakawa, Timothy C. Wang and Duan Chen [8] review the issue of vagotomy and gastric tumorigenesis and the potential treatment strategies to target the nerve, neurotransmitters, corresponding receptors and their down-stream signaling pathways for the malignancy. This has been done since early studies on the effects of vagotomy in chemically-induced rodent models of gastric cancer and reported an increased risk of developing gastric cancer.…”

“…Further emphasis is on a recent study using three different mouse models of gastric cancer (including genetically engineered, chemically-induced and Helicobacter pylori -infected mice), and evidence that unilateral vagotomy or bilateral truncal vagotomy with pyloroplasty significantly attenuate tumorigenesis in the denervated side of the stomach at early preneoplastic stages as well as at later stages of tumorigenesis. The final emphasis goes to the pharmacological denervation using botulinum toxin A or muscarinic acetylcholine receptor 3 (M3R) blockade and inhibited tumorigenesis [8]. …”