Michelle K. Savu

Natural orifice surgery: initial clinical experience

BackgroundNatural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience.MethodsUnder an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance.ResultsNine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred.ConclusionThe limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access.

Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue

The subcutaneous (S) and visceral (V) adipose tissue (AT) depots are increasingly recognized as distinct. To test the hypothesis that depot differences exist for adiponectin, fresh and cultured human VAT and SAT from obese type 2 diabetic (T2D) and obese nondiabetic (ND) subjects was examined to determine whether differences in adiponectin content and secretion occurred as a function of depot studied, diabetic status, and response to thiazolidinedione treatment. VAT and SAT were obtained by biopsy and AT explants cultured in defined media for 7 days. Protein expression was assessed by Western blot. Adiponectin content of conditioned medium was determined by radioimmunoassay. Diabetic status had no effect on adiponectin secretion over days 0-2 of culture. In ND SAT, secretion fell over days 2-4 but was sustained at greater levels vs. T2D SAT. In both ND and T2D VAT, adiponectin secretion was low, similar to T2D SAT. Over the 7-day culture period, cellular adiponectin increased in ND SAT and VAT; it remained unchanged in T2D SAT and VAT. Pioglitazone increased adiponectin secretion and content in all SAT. Pioglitazone failed to increase adiponectin secretion from either ND or T2D VAT and increased cellular content only in ND VAT. AT depot differences exist in the secretion of adiponectin and responsiveness to thiazolidinedione treatment. These data suggest that SAT, not VAT, appears to be the major contributor to increased circulating adiponectin levels in response to pioglitazone treatment.

Hybrid natural orifice translumenal surgery (NOTES) sleeve gastrectomy: a feasibility study using an animal model

BackgroundThe indications for natural orifice translumenal surgery (NOTES) are yet to be determined. Morbidly obese patients may be one population that would benefit from this approach due to the elimination of wound complications and possibly a faster recovery. As a bariatric restrictive procedure, sleeve gastrectomy could be one indication for NOTES. To test the feasibility of this procedure with a NOTES approach, a pig model was used.MethodsAcute studies investigated five 40-kg farm pigs. The rectum was used as the port of entry to the peritoneal cavity, and the stomach was manipulated endoluminally using a gastroscope. Vision was acquired through a 5-mm laparoscope introduced transabdominally (i.e. via the hybrid technique). A 10-mm incision was made on the anterior wall of the rectum and dilated to accommodate a 12-mm trocar introduced through the rectal wall into the peritoneal cavity. The greater curvature of the stomach then was divided and detached, starting from the antrum and proceeding to the esophagogastric junction using a laparoscopic stapler. The sleeve gastrectomy was completed by dividing the short gastric vessels with an ultrasonic scalpel. The gastric pouch then was removed through the rectal incision.ResultsA NOTES gastric sleeve resection was successfully performed in all five pigs. The technique was developed, and feasibility was determined. After resection, the gastric remnant was inflated, with no evidence of leakage. At autopsy, intact suture lines were noted. Closure of the rectal incision was not attempted.ConclusionA NOTES sleeve gastrectomy is feasible in porcine animal models. The rectal port of entry allows rigid laparoscopic instruments to be introduced into the peritoneal cavity and enables performance of gastrointestinal procedures the same as in standard laparoscopic surgery. Extra-long instruments are necessary for dissection and division of the stomach at the esophagogastric junction and for accessing the short gastric vessels.

Response of adiponectin and its receptors to changes in metabolic state after gastric bypass surgery: dissociation between adipose tissue expression and circulating levels

BACKGROUND Adiponectin is an adipokine with anti-atherogenic and insulin-sensitizing properties. Specific adiponectin receptors, adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2), are present in adipose tissue, indicating adiponectin might have autocrine/paracrine effects on its production or action. In addition, endoplasmic reticulum oxidoreductase 1-Lalpha might mediate regulation of its secretion. The study aim was to determine the subcutaneous adipose tissue (SAT) adiponectin gene and protein expression and their correlation to metabolic parameters during metabolically distinct times after gastric bypass surgery. METHODS A total of 12 morbidly obese male patients underwent SAT biopsy during gastric bypass surgery, active weight loss (negative energy state), and at weight stabilization (steady state energy). The SAT mRNA and protein content of adiponectin, AdipoR1 and AdipoR2, and endoplasmic reticulum oxidoreductase 1-Lalpha protein levels and the serum levels of adiponectin were assessed. RESULTS SAT adiponectin, AdipoR1, and AdipoR2 gene expression increased significantly at the negative energy state, with no further change at steady state energy (P<.05, P<.05, and P=.04, respectively), without significant increases in protein at any stage. Changes in SAT adiponectin protein correlated with changes in AdipoR1 and AdipoR2 during steady state energy (P=.003 and P=.002, respectively). Changes in SAT adiponectin expression did not correlate with those in circulating levels. Changes in endoplasmic reticulum oxidoreductase 1-Lalpha did not correlate with either SAT or circulating levels of adiponectin. CONCLUSION Our data indicate distinct functions of adiponectin receptors, AdipoR1 and AdipoR2, mediate the autocrine/paracrine actions of adiponectin. The lack of correlation between changes in SAT adiponectin gene and protein expression and its circulating levels suggests that adipose tissue synthesis and release of adiponectin are highly regulated pathways.