Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) play a central role in regulating the stress response. In response to stress, CRF and AVP neurons in the hypothalamic paraventricular nucleus secrete the peptides to stimulate the release of adrenocorticotropic hormone from the anterior pituitary. Ghrelin, an endogenous ligand of the growth hormone-releasing peptide receptors (GHSR), has been shown to stimulate the release of CRF and AVP by rat hypothalamic explants. However, little is known about the ability of the ghrelin signaling pathways to activate the CRF and AVP genes in the hypothalamus. In the present study, we examined the direct effect of ghrelin on CRF and AVP gene expression in hypothalamic 4B cells, which show the characteristics of the hypothalamic parvocellular paraventricular nucleus neurons. Cells were transfected with CRF or AVP promoter to examine the activity of each promoter. Ghrelin stimulated the promoter activities and mRNA levels for both CRF and AVP. The involvement of a protein kinase pathway was examined using inhibitors. Protein kinase A and phospholipase C pathways were shown to be involved in ghrelin-induced increases in both CRF and AVP promoter activities. GHSR type 1a (GHSR1a) mRNA levels were also increased by ghrelin, and these ghrelin-induced levels were suppressed by a GHSR1a antagonist. Thus, ghrelin-dependent pathways are involved in the regulation of CRF and AVP gene expression in the hypothalamus: ghrelin, an orexigenic hormone, stimulates CRF, an anorexigenic/anxiogenic factor in the hypothalamus, resulting in hypothalamic-pituitary-adrenal axis activation to stimulate the release of glucocorticoids.

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Description Background: As the thoracic esophageal carcinoma has a high metastatic rate of upper mediastinal lymph nodes, especially along the recurrent laryngeal nerve (RLN), it is crucial to perform complete lymph nodes dissection along the RLN without complications. Although Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as the useful tool of visual nerve identification, the utilization of IONM during esophageal surgery has not become common. Here, we describe our procedures focusing on a lymphadenectomy along the RLN utilizing the IONM. Methods and Procedures: We first dissect ventral and dorsal side of the esophagus preserving the membranous structure (mesoesophagus), which contains tracheoesophageal artery, RLN and lymph nodes. We next identify the location of the RLN which runs in the mesoesophagus using IONM before visual contact. After that, we perform lymphadenectomy around the RLN preserving the nerve. To evaluate the efficacy of this method, we compared short term surgical outcome of our 36 consecutive cases (neural monitoring group; Nm) of esophagectomy in prone positioning with 56 of our historical cases (conventional method group; Cm). Results: In all 36 cases of Nm group, we could obtain the location information of the RLN before the visual contact. Although the operation time of thoracic part was significantly longer in Nm group compared to Cm group (281 min vs. 254 min each, P = 0.005), postoperative RLN paralysis according to postoperative laryngoscopy was seen in 3 cases (8.3%) after surgical operation in Nm group, which was significantly lower than that in the Cm group (18/56, 32.1%, P = 0.005). As a result, median postoperative hospital stay was significantly shorter in Nm group than Cm group (22 days vs. 39 days each, P = 0.0003). Conclusion: Mesentery-oriented lymph nodes dissection using IONM has substantial advantages to perform accurate and safe thoracoscopic esophagectomy. It could decrease the RLN paralysis and postoperative hospital stay after esophagectomy. Disclosure All authors have declared no conflicts of interest.

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