The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease

Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity. We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFα, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions. Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFα levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals. The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES

Natural orifice surgery: initial clinical experience

Natural 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. Under 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. Nine 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. The 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 adipopnectin levels in response to pioglitazone treatment

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery. Thirty 250-g male Sprague–Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained. There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08). Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy

Magnetic retraction for NOTES transvaginal cholecystectomy

Natural orifice translumenal endoscopic surgery (NOTES) has the potential to decrease the burden of an operation on a patient. Limitations of the endoscopic platform require innovative solutions to provide retraction and create an operation comparable with the gold standard, laparoscopic cholecystectomy. Four patients underwent transvaginal cholecystectomy. All procedures were performed under laparoscopic vision to ensure safety. The endoscope and a long articulating RealHand instrument were placed via a 15-mm vaginal trocar. A magnetic retraction system was used to retract the gallbladder safely. Laparoscopic clips were used to ligate the cystic duct and artery. All four gallbladders were successfully removed. No complications occurred. The mean operating time was 102 min. All four procedures were completed without complications. The four patients all were discharged shortly after surgery and reported normal sexual activity without pain. Transvaginal cholecystectomy can be completed safely using current technology. Further studies are needed to determine the safety of the procedure and to determine whether it confers any benefits other than cosmesis

NOTES: transvaginal cholecystectomy with assisting articulating instruments

Transvaginal cholecystectomy has been performed at several institutions using hybrid natural orifice translumenal endoscopic surgery (NOTES) techniques. A 42-year-old woman with symptomatic cholelithiasis was taken to the operating room for transvaginal cholecystectomy after giving informed consent. A single 5-mm laparoscope was placed at the umbilicus, followed by a 15-mm trocar through the vaginal conduit. The endoscope and a long flexible RealHand surgical instrument (Novare, Cupertino, CA) were placed via the vaginal trocar. The cystic duct and artery were identified and clipped using laparoscopic clips from the umbilical port. The long articulating laparoscopic instrument provided stable retraction. Hook cautery was used to dissect the gallbladder, which was removed via the vaginal trocar. The vaginal incision was closed using a single figure-of-eight absorbable suture under direct vision. The procedure lasted 96 min. The cholecystectomy was successfully performed without spillage of bile. The patient was kept overnight for observation only as a precaution. She reported no pain and did not require a discharge prescription for narcotics. The described technique for NOTES cholecystectomy results in a virtually scarless operation. The single 5-mm umbilical trocar allows for safe clipping of the cystic duct. Further work is needed to determine the efficacy of this approach