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.

Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis

BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.

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.

Importance of histological evaluation in endoscopic resection of early colorectal cancer

The diagnostic criteria for colonic intraepithelial tumors vary from country to country.While intramucosal adenocarcinoma is recognized in Japan,in Western countries adenocarcinoma is diagnosed only if the tumor invades to the submucosa and accesses the muscularis mucosae.However,endoscopic therapy,including endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD),is used worldwide to treat adenoma and early colorectal cancer.Precise histopathological evaluation is important for the curativeness of these therapies as inappropriate endoscopic therapy causes local recurrence of the tumor that may develop into fatal metastasis.Therefore,colorectal ESD and EMR are not indicated for cancers with massive submucosal invasion.However,diagnosis of cancer with massive submucosal invasion by endoscopy is limited,even when magnifying endoscopy for pit pattern and narrow band imaging and flexible spectral imaging color of enhancement are performed.Therefore,occasional cancers with massive submucosal invasion will be treated by ESD and EMR.Precise histopathological evaluation of these lesions should be performed in order to determine the necessity of additional therapy,including surgical resection.

Image-enhanced endoscopy for diagnosis of colorectal tumors in view of endoscopic treatment

Recently,image-enhanced endoscopy(IEE) has been used to diagnose gastrointestinal tumors.This method is a change from conventional white-light(WL) endoscopy without dyeing solution,requiring only the push of a button.In IEE,there are many advantages in diagnosis of neoplastic tumors,evaluation of invasion depth for cancerous lesions,and detection of neoplastic lesions.In narrow band imaging(NBI) systems(Olympus Medical Co.,Tokyo,Japan),optical filters that allow narrow-band light to pass at wavelengths of 415 and 540 nm are used.Mucosal surface blood vessels are seen most clearly at 415 nm,which is the wavelength that corresponds to the hemoglobin absorption band,while vessels in the deep layer of the mucosa can be detected at 540 nm.Thus,NBI also can detect pit-like structures named surface pattern.The flexible spectral imaging color enhancement(FICE) system(Fujifilm Medical Co.,Tokyo,Japan) is also an IEE but different to NBI.FICE depends on the use of spectral-estimation technology to reconstruct images at different wavelengths based on WL images.FICE can enhance vascular and surface patterns.The autofluorescence imaging(AFI) video endoscope system(Olympus Medical Co.,Tokyo,Japan) is a new illumination method that uses the difference in intensity of autofluorescence between the normal area and neoplastic lesions.AFI light comprises a blue light for emitting and a green light for hemoglobin absorption.The aim of this review is to highlight the efficacy of IEE for diagnosis of colorectal tumors for endoscopic treatment.

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.

Laparoscopic and endoscopic co-operative surgery for nonampullary duodenal tumors

AIM To assess the safety and feasibility of laparoscopic and endoscopic co-operative surgery(LECS) for early nonampullary duodenal tumors.METHODS Twelve patients with a non-ampullary duodenal tumor underwent LECS at our hospital. One patient had two mucosal lesions in the duodenum. The indication for this procedure was the presence of duodenal tumors with a low risk for lymph node metastasis. In particular, the tumors included small(less than 10 mm) submucosal tumors(SMT) and epithelial mucosal tumors, such as mucosal cancers or large mucosal adenomas with malignant suspicion. The LECS procedures, such as full-thickness dissection for SMT and laparoscopic reinforcement after endoscopic submucosal dissection(ESD) for epithelial tumors, were performed for the 13 early duodenal lesions in 12 patients. Here we present the short-term outcomes and evaluate the safety and feasibility of this new technique.RESULTS Two SMT-like lesions and eleven superficial epithelial tumor-like lesions were observed. Seven and Six lesions were located in the second and third parts of the duodenum, respectively. All lesions were successfully resected en bloc. The defect in the duodenal wall was manually sutured after resection of the duodenal SMT. For epithelial duodenal tumors, the ulcer bed was laparoscopically reinforced via manual suturing after ESD. Intraoperative perforation occurred in two out of eleven epithelial tumor-like lesions during ESD; however, they were successfully laparoscopically repaired. The median operative time and intraoperative estimated blood loss were 322 min and 0 mL, respectively. Histological examination of the tumors revealed one adenoma with moderate atypia, ten adenocarcinomas, and two neuroendocrine tumors. No severe postoperative complications(Clavien-Dindo classification grade Ⅲ or higher) were reported in this series, but minor leakage secondary to pancreatic fistula occurred in one patient.CONCLUSION LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors.

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.