Utility of Vaginal Natural Orifice Transluminal Endoscopic Surgery for Permanent Sterilization after Failed Attempt at Bilateral Tubal Ligation at the Time of Previous Cesarean Section.

STUDY OBJECTIVE: To demonstrate the utility of vaginal natural orifice transluminal endoscopic surgery (vNOTES) for opportunistic bilateral salpingectomy for permanent sterilization after a failed attempt at bilateral tubal ligation at the time of previous cesarean section. DESIGN: Stepwise demonstration with narrated video footage. SETTING: There is evidence to support the statistically significant superiority of vNOTES compared with conventional laparoscopy (CL) in terms of patient satisfaction, postoperative pain, time to recovery, and cosmetic results in bilateral salpingectomies for permanent sterilization [1]. Limited studies demonstrate the ease and safety of access to the abdominal cavity in vNOTES while avoiding passage through the abdominal wall, port site complications (infection, hernia, etc.), and those associated with peritoneal adhesions during abdominal laparoscopy or laparotomy [2]. To the best of our knowledge, this would be the first published video of a vNOTES bilateral salpingectomy performed specifically in a patient whose previously attempted bilateral tubal ligation was unsuccessful owing to adhesive disease from 4 previous cesarean sections. INTERVENTIONS: Institutional review board approval was not required. We describe a case of a 31-year-old female, with a history of 4 previous cesarean deliveries and a cholecystectomy, who desired permanent sterilization 3 months after the previous cesarean section. During previous cesarean section, bilateral adnexa were unable to be accessed owing to dense adhesions from previous surgeries. The patient was counseled on various forms of reversible contraceptive methods; however, she desired permanent sterilization with a surgical procedure. She was counseled on the various routes for opportunistic salpingectomy. Risks, benefits, and alternatives of each surgical approach were discussed. The patient consented for vNOTES opportunistic salpingectomy and possible CL. She was aware that she had significant adhesive disease at the time of previous cesarean section, so may potentially require a laparotomy for the procedure. However, she refused a laparotomy if the surgery was unable to be performed minimally invasively. (1) Demonstrate setup of transvaginal access platform for vNOTES bilateral salpingectomy. (2) Abdominal survey and appreciation of severe adhesive disease through posterior cul-de-sac. (3) Bilateral salpingectomy through single-site vaginal natural orifice surgery. CONCLUSION: vNOTES bilateral salpingectomy can be considered as a reasonable alternative to CL in patients with severe abdominal adhesive disease from previous surgeries.

Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons.

OBJECTIVE: Leptin modulates food reward via central leptin receptor (LepRb) expressing neurons. Food reward requires stimulation of midbrain dopamine neurons and is modulated by central leptin action, but the exact central mechanisms remain unclear. Stimulatory and inhibitory leptin actions on dopamine neurons have been reported, e.g. by indirect actions on orexin neurons or via direct innervation of dopamine neurons in the ventral tegmental area. METHODS: We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons). We studied the involvement of GAL-LepRb neurons to regulate nutrient reward in mice with selective LepRb deletion from galanin neurons (GAL-LepRb(KO) mice). RESULTS: We found that the rewarding value and preference for sucrose over fat was increased in GAL-LepRb(KO) mice compared to controls. LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA. Further, expression of galanin and its receptor GalR1 are decreased in the LHA of GAL-LepRb(KO) mice, resulting in increased activation of orexin neurons. CONCLUSION: We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.

Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake.

OBJECTIVE: Leptin responsive neurons play an important role in energy homeostasis, controlling specific autonomic, behavioral, and neuroendocrine functions. We have previously identified a population of leptin receptor (LepRb) expressing neurons within the dorsomedial hypothalamus/dorsal hypothalamic area (DMH/DHA) which are related to neuronal circuits that control brown adipose tissue (BAT) thermogenesis. Intra-DMH leptin injections also activate sympathetic outflow to BAT, but whether such effects are mediated directly via DMH/DHA LepRb neurons and whether this is physiologically relevant for whole body energy expenditure and body weight regulation has yet to be determined. METHODS: We used pharmacosynthetic receptors (DREADDs) to selectively activate DMH/DHA LepRb neurons. We further deleted LepRb with virally driven cre-recombinase from DMH/DHA neurons and determined the physiological importance of DMH/DHA LepRb neurons in whole body energy homeostasis. RESULTS: Neuronal activation of DMH/DHA LepRb neurons with DREADDs promoted BAT thermogenesis and locomotor activity, which robustly induced energy expenditure (p < 0.001) and decreases body weight (p < 0.001). Similarly, intra-DMH/DHA leptin injections normalized hypothermia and attenuated body weight gain in leptin-deficient ob/ob mice. Conversely, ablation of LepRb from DMH/DHA neurons remarkably drives weight gain (p < 0.001) by reducing energy expenditure (p < 0.001) and locomotor activity (p < 0.001). The observed changes in body weight were largely independent of food intake. CONCLUSION: Taken together, our data highlight that DMH/DHA LepRb neurons are sufficient and necessary to regulate energy expenditure and body weight.