The presence of Helicobacter pylori is not associated with long-term anastomotic complications in gastric bypass patients.

BACKGROUND: Eradication of Helicobacter pylori prior to Roux-en-Y gastric bypass (RYGB) has been advocated as a measure to reduce the complications of anastomotic ulceration. However, evidence to support a causal relationship between preoperative H. pylori status and postoperative anastomotic ulceration is weak. METHODS: Intraoperative gastric biopsies were obtained on consecutive patients who underwent laparoscopic RYGB at our institution from December 2007 to June 2010. These samples were analyzed by Warthin-Starry stain for H. Pylori organisms. Retrospective chart review was conducted to determine the preoperative presence of acid dyspepsia and acid suppression therapy and to determine postoperative ulcer symptoms, smoking, NSAID or steroid use, and compliance with ulcer prophylaxis. The incidence of ulcer visualization, perforation, and stricture were obtained from a prospectively collected database. Fisher's exact test was used for analyzing associations between discrete groups. Multiple logistic regression was used to assess associations between anastomotic ulcer complications and potential predictors. RESULTS: Histologic evaluation for H. pylori was available in 708 of the 728 patients who underwent RYGB. Fourteen patients were lost to follow up leaving 694 patients available for review. H. pylori was positive in 66 (9.5 %) patients who did not go on to receive definitive treatment for eradication. Marginal ulcers or related late complications were seen in a total of 113 (16.3 %) patients. In the H. pylori positive group, five patients (7.6 %) developed ulcer complications compared to 108 (17.1 %) in the H. pylori negative group (p = 0.05). Groups were not different in terms of preoperative demographics, postoperative ulcer prophylaxis compliance, steroid, NSAIDs, and cigarette use. CONCLUSION: The presence of H. pylori infection at the time of RYGB was found to be associated with a significantly lower incidence of anastomotic ulcer complications postoperatively. This study brings into question efforts and expense allocated to identify and eradicate H. pylori prior to RYGB.

A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity.

Adhesions remain a significant complication of abdominal surgery. There is a growing body of evidence suggesting that remodeling of peritoneal extracellular matrix by matrix metalloproteinases (MMPs) is involved in adhesion formation. We have shown that administration of a specific neurokinin-1 receptor (NK-1R) antagonist (CJ-12,255, Pfizer) to rats within 5 hours of surgery reduces intraabdominal adhesion formation. Because substance P (SP), the primary NK-1R ligand, is known to augment tissue fibrosis, the aim of this study was to determine the effects of NK-1R antagonist administration on peritoneal MMP expression and activity 24 hours after surgery in a rat adhesion model. Following laparotomy, four ischemic buttons were created on the peritoneum of rats that received either an intraperitoneal NK-1R antagonist or a vehicle at surgery. Adhesion formation was assessed 7 days later. Peritoneal fluid and tissue were collected at 24 hours to assess total MMP activity, as well as MMP-2, MMP-8, and MMP-9 activity. Specific MMP and tissue inhibitors of MMP mRNAs were measured, and the effects of SP on MMP-3 expression were determined in Met-5A cells, a human peritoneal mesothelial cell line. NK-1R antagonist administration reduced adhesion formation by 47% (p<0.05) at 7 days and significantly increased the total MMP activity in peritoneal fluid at 24 hours. There was an accompanying increase (p<0.05) in MMP-8 and MMP-9 mRNA expression and activity in peritoneal tissue and fluid, respectively. MMP-3 mRNA was also increased in the 24-hour peritoneal tissue, and exposure of Met-5A cells to SP reduced MMP-3 expression and activity. These data support a role for MMPs, specifically MMP-3, MMP-8, and MMP-9, in intraabdominal adhesion formation and suggest that the NK-1R antagonist may reduce adhesions, in part, by increasing MMP activity in the peritoneum by 24 hours after surgery.

Intraperitoneal administration of methylene blue attenuates oxidative stress, increases peritoneal fibrinolysis, and inhibits intraabdominal adhesion formation.

BACKGROUND: Mounting evidence indicates that postoperative oxidative stress may be linked to decreased fibrinolytic activity and, subsequently, the development of intraabdominal adhesions. The goal of this study was to determine if methylene blue, a highly redox active dye that has been shown to inhibit adhesion formation (1) acts as an antioxidant in the postoperative peritoneum, and (2) subsequently affects fibrinolytic activity. MATERIALS AND METHODS: Intraabdominal adhesions were surgically induced in rats receiving methylene blue (30 mg/kg) or vehicle (sterile water) intraperitoneally at surgery. At 24 h and 7 d following surgery, adhesion formation, oxidative stress, and peritoneal fibrinolytic activity were assessed. RESULTS: Methylene blue did not affect adhesion formation at 24 h, but did induce a >50% regression in adhesions after 7 d (P < 0.05). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO) activities, and 8-isoprostane and thiobarbituric acid-reactive substances were all significantly increased in peritoneal tissue samples (P < 0.05) by 24 h following surgery. Methylene blue inhibited NADPH oxidase by 98% and MPO activity by 78% in the 24 h tissue samples, and blunted the corresponding surgery-induced increases in tissue lipid and protein oxidation. Furthermore, methylene blue significantly increased (P < 0.05) fibrinolytic activity in peritoneal fluid at 24 h. CONCLUSIONS: Methylene blue acts as an antioxidant in this experimental system and may reduce intraabdominal adhesion formation by enhancing peritoneal fibrinolytic activity following surgery.

The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent.

BACKGROUND: Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing. METHODS: Adhesions were surgically induced in rats receiving a single intraperitoneal infusion of the NK-1R antagonist, CJ-12,255, during or 1, 5, 12, or 24 hours after surgery. Adhesion formation was assessed 7 days later. In a subset of animals, tissue plasminogen activator (tPA) activity, which is a measure of peritoneal fibrinolytic activity, was determined in peritoneal fluid 24 hours after surgery (48 hours for animals infused at 24 hours). The tPA activity was also determined in nonoperated animals 24 hours after peritoneal injection of the NK-1R antagonist. Colonic burst pressures were measured 7 days after creation of anastomoses in rats that were administered the antagonist at surgery. RESULTS: The NK-1R antagonist significantly reduced (P=.003) intraabdominal adhesions when administered during or 1 hour after surgery, only moderately reduced (P=.08) adhesions when administered at 5 hours, and had no effect at 12 or 24 hours. Peritoneal tPA activity was significantly increased (P<.05) in peritoneal fluid 24 hours after administration of the NK-1R antagonist regardless of the surgical procedure. The NK-1R antagonist did not alter colonic anastomotic healing. CONCLUSIONS: These data show that some of the events critical to adhesion formation occur within the first 5 hours following an abdominal operation in this model. The fact that the NK-1R antagonist does not impair colonic anastomotic healing enhances its usefulness as a therapeutic agent to inhibit adhesion formation.

Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity.

OBJECTIVES: The aims of this study were to determine if statins reduce adhesion formation in vivo and to identify the mechanism of action in vitro. BACKGROUND: : Intraperitoneal adhesions develop in up to 95% of patients following laparotomy. Adhesions are reduced by mechanisms that up-regulate fibrinolysis within the peritoneum. Statins promote fibrinolysis in the cardiovascular system and may play a role in the prevention of adhesions. METHODS: Adhesions were induced in rats (n = 102) using our previously described ischemic button model. Rats received vehicle (controls), lovastatin (30 mg/kg), or atorvastatin (30 mg/kg) as a single intraperitoneal dose at the time of laparotomy. Animals were killed and adhesions were quantified at day 7. Peritoneal fluid and tissue were collected at day 1 to measure tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) by real-time PCR and ELISA. To assess the effects of statins on wound healing, burst pressures were measured in anastomoses of the colon. The effects of lovastatin on tPA and PAI-1 production were measured in vitro in human mesothelial cells (HMC) in the presence or absence of mevalonate (MVA), geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), all intermediates in the cholesterol pathway downstream of HMG-CoA. The effect of a Rho protein inhibitor, exoenzyme C3 transferase, on tPA production was also determined. RESULTS: Lovastatin and atorvastatin reduced adhesion formation by 26% and 58%, respectively (P < 0.05), without affecting anastomotic burst pressure. At 24 hours, tPA mRNA levels in peritoneal tissue and tPA activity in peritoneal fluid from lovastatin-treated animals were increased by 57% and 379%, respectively (P < 0.05), while PAI-1 levels were unchanged. HMC incubated with either lovastatin or atorvastatin showed concentration-dependent increases in tPA production and decreases in PAI-1 production (P < 0.05). These lovastatin-induced changes in tPA and PAI-1 production were significantly reversed by the addition of MVA, GGPP, and FPP. The Rho protein inhibitor increased tPA production and rescued tPA production from the inhibitory effect of GGPP. CONCLUSION: These data suggest that statins administered within the peritoneum can up-regulate local fibrinolysis, while the in vitro studies show that this effect may be mediated, in part, by intermediates of the cholesterol biosynthetic pathway that regulate Rho protein signaling.