Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease

AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.

Safe procedure in endoscopic submucosal dissection for colorectal tumors focused on preventing complications

Endoscopic submucosal dissection (ESD) is efficient for en bloc resection of large colorectal tumors. However, it has several technical difficulties, because the wall of the colon is thin and due to the winding nature of the colon. The main complications of ESD comprise postoperative perforation and hemorrhage, similar to endoscopic mucosal resection (EMR). In particular, the rate of perforation in ESD is higher than that in EMR. Perforation of the colon can cause fatal peritonitis. Endoscopic clipping is reported to be an efficient therapy for perforation. Most cases with perforation are treated conservatively without urgent surgical intervention. However, the rate of postoperative hemorrhage in ESD is similar to that in EMR. Endoscopic therapy including endoscopic clipping is performed and most of the cases are treated conservatively without blood transfusion. In blood examination, some degree of inflammation is detected after ESD. For the standardization of ESD, it is most important to decrease the rate of perforation. Adopting a safe strategy for ESD and a suitable choice of knife are both important waysof preventing perforation. Moreover, appropriate training and increasing experience can improve the endoscopic technique and can decrease the rate of perforation. In this review, we describe safe procedures in ESD to prevent complications, the complications of ESD and their management.

Lansoprazole ameliorates intestinal mucosal damage induced by ischemia-reperfusion in rats

AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.

Direct cholangioscopy combined with doubleballoon enteroscope-assisted endoscopic retrograde cholangiopancreatography

Double-balloon enteroscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is an effective endoscopic approach for pancreatobiliary disorders in patients with altered gastrointestinal anatomy. Endoscopic interventions via DBE in these postoperative settings remain difficult because of the lack of an elevator and the use of extra-long ERCP accessories. Here, we report the usefulness of direct cholangioscopy with an ultra-slim gastroscope during DBE-assisted ERCP. Three patients with choledocholithiasis in postoperative settings (two patients after Billroth Ⅱ gastrojejunostomy and one patient after Roux-en-Y gastrojejunostomy) were treated. DBE was used to gain access to the papilla under carbon dioxide insufflation, and endoscopic sphincterotomy was performed with a conventional sphincterotome. For direct cholangioscopy, the enteroscope was exchanged for an ultra-slim gastroscope through an incision in the overtube, which was inserted directly into the bile duct. Direct cholangioscopy was used to extract retained bile duct stones in two cases and to confirm the complete clearance of stones in one case. Bile duct stones were eliminated with a 5-Fr basket catheter under direct visual control. No adverse events were noted in any of the three cases. Direct cholangioscopy with an ultra-slim gastroscope facilitates subsequent treatment within the bile duct. This procedure represents another potential option during DBE-assisted ERCP.

Efficient hemostatic method for endoscopic submucosal dissection of colorectal tumors

AIM:To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection(ESD).METHODS:We studied 250 cases,in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2010.We developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick vessels.ESD was performed on 126 cases after adoption of the new method(the adopted group)and the new method was performed on 102 of these cases.ESD was performed on 124 cases before the adoption of the new method (the unadopted group).The details of the new method are as follows:firstly,a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure,and the coagulated vessel was removed using the forceps in the"endocut" mode without perioperative hemorrhage.Secondly,the partial surrounding submucosa was dissected using the forceps in the endocut mode.In the current study,we evaluated the efficacy of this method.RESULTS:Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative hemorrhage.Moderate perioperative hemorrhage occurred in five cases(4.9%);however,it was stopped by immediately reuse of the hemostatic forceps.The partial surrounding submucosa was dissected using the forceps in all 102 cases.In the adopted group,the median operation time was 105 min.The proportion of endoscopic en bloc resection was 92.8%(P<0.01)compared to 80.6%in the unadopted group.The postoperative hemorrhage and perforation rates were 2.3%and 2.3%.The rate of perforation was significantly lower than that in the unadopted group (9.6%,P<0.01).We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases,which were accomplished without any severe hemorrhage.CONCLUSION:The new method effectively treated submucosal thick vessels and shows promise for the prevention of perforation and perioperative hemorrhage in colonic ESD.

Bowel preparation for colonoscopy using standard vs reduced doses of sodium phosphate: A single-blind randomized controlled study

AIM: To evaluate the efficacy of a colonoscopy prepa-ration that utilizes a reduced dose of sodium phosphate(NaP) and an adjunct.METHODS: Sixty-two patients requiring screening colonoscopies were studied. Each patient was randomly allocated to receive either 50 NaP tablets(50 g) or 30 NaP tablets(30 g) with 10 mL of 0.75% sodium pico-sulfate for bowel preparation. NaP was administered at a rate of five tablets(5 g) or three tablets(3 g) every 15 min with 200 mL of water, beginning five to six hours before colonoscopy. The sodium picosulfate was administered with 200 mL of water on the night before the procedure. Both groups were compared in term of the efficacies of colonic cleansing, the time required for completion of the bowel preparation, and acceptability of the preparation.RESULTS: Sixty patients(n = 30 for each group) were analyzed. The cleansing efficacy tended to be higher in the 30 g NaP plus sodium picosulfate group as as-sessed by the mean total Ottawa scale score(50 g NaP6.70 ± 1. 42 vs 30 g NaP plus sodium picosulfate 6.17 ± 1.18 P = 0.072). The mean time for bowel prepara-tion tended to be shorter in the 30 g NaP plus sodium picosulfate group(50 g NaP 189.9 ± 64.0 min vs 30 g NaP plus sodium picosulfate 161.8 ± 57.6 min, P = 0.065). There were no significant differences between the two groups in the acceptability of the preparations(50 g NaP 83.3% vs 30 g NaP plus sodium picosulfate 86.7%, P = 0.500). There were no adverse events re-lated to bowel preparation in either of the groups.CONCLUSION: The colonoscopy preparation that uti-lized 30 g NaP with sodium picosulfate was comparable to that utilizing 50 g NaP. This novel bowel preparation might be useful before colonoscopy.

Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with the preservation of endothelial nitric oxide synthase protein

AIM： To investigate the protective effect of rosuvastatin on ischemia-reperfusion （I-R）-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase （eNOS） protein. METHODS： Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot. RESULTS： The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissueassociated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattracrant-1 （CINC-1） and tumor necrosis factor-α（TNF-α）. These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvo astatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-α was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION： Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.

Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution

AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.