Yasuhisa Sakata

Risk factors for complications of endoscopic submucosal dissection in gastric tumors : analysis of 478 lesions

PurposeEndoscopic submucosal dissection (ESD) technique has facilitated en bloc removal of widely spread lesions from the stomach. This retrospective study aimed to determine factors associated with serious complications of ESD.MethodsBetween December 2001 and March 2007, we have performed ESD for 478 lesions in 436 patients. We experienced 39 patients with post-operative bleeding and 17 patients with perforation. Risk factors of patients who received ESD in gastric mucosal tumors for complications were evaluated, focusing on resected size, location, scar lesions, operation time, and experience of endoscopists. We evaluated the patients’ background characteristics including sex, age, body mass index (kg/m2), drug history of anticoagulant, and underlying diseases including cerebrovascular disorder, ischemic heart disease, liver dysfunction, renal dysfunction, hyperuricemia, hypertension and diabetes mellitus.ResultsMultivariate analysis indicated a risk factor for perforation was long operation time. Multivariate analysis indicated a significant risk factor for post-operative bleeding was size of the resected tumor.ConclusionsThis study indicated risk factors for serious complications of ESD. Large resected tumor size was a risk factor for post-operative bleeding, while long operation time was a risk factor for perforation. Information regarding operation risk factors should be useful for planning strategies for ESD.

NSAIDs are a significant risk factor for colonic diverticular hemorrhage in elder patients: Evaluation by a case-control study

Background and Aim:  Diverticular bleeding is a common cause of lower gastrointestinal hemorrhage. Several factors, including use of non‐steroidal anti‐inflammatory drugs (NSAIDs), antithrombotic agents and arteriosclerosis, could be risk factors. The aim of this study is to identify these risk factors.

T cell deficiency leads to liver carcinogenesis in azoxymethane-treated rats

There is an increasing amount of evidence suggesting that T cell deficiency contributes to tumor development. However, it is unclear whether T cell deficiency leads to liver and colon carcinogenesis. The aim of this study was to investigate the role of T cells on liver and colon carcinogenesis. Athymic F344/N Jcl-rnu/- (nu/nu) rats and euthymic F344/N Jcl-rnu/+ (nu/+) rats were administered the carcinogen azoxymethane (AOM) at a dose of 15 mg/kg body wt once a week for 2 weeks. At 48 weeks after the second carcinogen treatment, the rats were sacrificed, and livers and colons were examined. Apoptosis and cell proliferation were evaluated by DNA fragmentation and proliferating cell nuclear antigen assays, respectively. Wild-type p53 and members of the Jun and Fos oncogene families were detected by Western blotting. AOM treatment induced 100% liver tumor and 63.6% colon tumor incidence in T cell–deficient nu/nu rats, compared with 0% and 38.5% incidence in nu/+ rats. T cell deficiency promoted the inhibitory action of AOM on apoptosis in both liver and colon at 48 weeks. In contrast, T cell deficiency increased cell proliferation after AOM treatment in both tissues. Wild-type p53 was reduced in both tissues of T cell–deficient rats. AOM treatment induced c-Jun and c-Fos expressions in the liver but increased only Fos B in the colon, whereas T cell deficiency enhanced c-Jun overexpression in the liver. These results suggest that T cell deficiency leads to liver carcinogenesis partly by a reduction in wild-type p53 and increasing c-Jun expression in AOM-treated rats.

The squamous cell carcinoma antigens as relevant biomarkers of atopic dermatitis.

Background Although it is thought that both Th1‐ and Th2‐type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL‐4 and IL‐13.

Case series of endoscopic balloon dilation to treat a stricture caused by circumferential resection of the gastric antrum by endoscopic submucosal dissection

BACKGROUND Endoscopic submucosal dissection (ESD) plays an important role in the management of gastric neoplasms. There are few reports regarding stricture development caused by ESD of gastric neoplasms. OBJECTIVE The present study aimed to determine the incidence of gastric stricture formation after ESD of gastric neoplasms and to report on the outcome and management of this complication: endoscopic intervention (ie, balloon dilation) versus surgery; the outcome of balloon dilation (success or failure/perforation). DESIGN A case series from a retrospective review of gastric ESDs performed at Saga Medical School over a defined period of time. SETTING Double-center territory, referral hospital. PATIENTS An evaluation was performed in 532 patients with gastric mucosal tumors treated by ESD. A stricture was reported in 5 patients. All the 5 cases were located in the antrum. ESD that was performed in the cardia or the proximal stomach did not induce a stricture. RESULTS Of the 5 cases of symptomatic gastric outlet obstruction, 1 patient required surgical intervention because of a near total gastric outlet obstruction not amenable to endoscopic intervention. The 4 patients underwent step-serial through-the-scope balloon dilations; in 2 patients, the procedure was successful, but in the other 2 patients, the procedure was complicated by a gastric perforation (50% incidence of perforation). LIMITATION A retrospective study. CONCLUSIONS Circumferential or subcircumferential resection by ESD in the antrum caused a stricture. Balloon dilation of the ESD gastric outlet obstruction might be a choice, but it is a risky treatment.

Nutrient-induced inflammation in the intestine

Purpose of reviewTo review our current understanding of the relationship between absorption of nutrients and intestinal inflammatory response. Recent findingsThere is increasing evidence linking gut local inflammatory events with the intake of nutrients. Our recent studies, using the conscious lymph fistula rat model, demonstrate that fat absorption activates the intestinal mucosal mast cells. This is accompanied by a dramatic increase in the lymphatic release of mast cell mediators including histamine, rat mucosal mast cell protease II (RMCPII), as well as the lipid mediator prostaglandin D2 (PGD2). Clinical studies suggest that increased consumption of animal fat may play a role in the pathogenesis of inflammatory bowel disease. This impact of dietary fat may not be restricted to the gut but may extend to the whole body. There is evidence linking a high-fat diet-induced metabolic syndrome, with a low-grade chronic inflammatory state. In this review, we hope to convince the readers that fat absorption can have far reaching physiological and pathophysiological consequences. SummaryUnderstanding the relationship between nutrient absorption and intestinal inflammation is important. We need a better understanding of the interaction between enterocytes and the intestinal immune cells in nutrient absorption and the gut inflammatory responses.

Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.

How dietary corn oil is involved in colon carcinogenesis and cancer development is poorly understood. The aim of this study was to investigate whether long-term dietary corn oil promotes colon cancer by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were injected with AOM or with saline and fed on a basal diet or basal diet supplemented with 10% corn oil for 48 weeks. Colonic aberrant crypt foci (ACF) and tumors, including adenomas and carcinomas, were examined. Colonic apoptosis and cell proliferation were evaluated. Wild type (wt) p53 was analyzed using reverse transcription–polymerase chain reaction (RT-PCR) and Western blotting. In addition, Bcl-2, Bcl-xL, Bax, and Bak localized in the mitochondria were detected. Long-term dietary corn oil increased ACF in AOM-treated rats at 12 weeks and promoted colon cancer invasion at 48 weeks. Cancer invasion was not observed in the AOM-treated rats without dietary corn oil, although colon adenomas and cancers were detected. Apoptosis was decreased and cell proliferation was increased in the AOM-treated rats with dietary corn oil, compared with the AOM-treated rats with dietary basal diet. In these rats, mitochondrial wt p53 was significantly inhibited through decreased mitochondrial localization of wt p53 and increased cytosolic p53, resulting in the upregulation of Bcl-2 and Bcl-xL and the downregulation of Bak in the mitochondria. Results suggest that long-term dietary corn oil promotes AOM-induced colon cancer development partly by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis.

Perforation and Postoperative Bleeding of Endoscopic Submucosal Dissection in Gastric Tumors: Analysis of 1,190 Lesions in Low- and High-Volume Centers in Saga, Japan

Background: This retrospective study aimed to determine risk factors associated with serious complications of endoscopic submucosal dissection of gastric tumors in multicenters compared between high- and low-volume centers. Methods: Between 2001 and 2010, gastric endoscopic submucosal dissection was performed in 1,190 lesions of 1,082 patients in five hospitals in Saga, three high-volume and two low-volume centers. Risk factors for serious complications were evaluated. Patients’ background characteristics were evaluated, including anticoagulants use and underlying diseases. Results: Postoperative bleeding was detected in 75 patients (6.9%), and perforation was detected in 40 patients (3.7%). Most postoperative bleeding and perforation cases were recovered with endoscopic procedures, although one case of each complication was treated by emergency surgery. Multivariate analysis indicated that risk factors for perforation were tumor location, massive submucusal invasion, endoscopists’ experience of 100–149 cases and hypertension, and that risk factors for postoperative bleeding were tumor location, resected tumor size, and scar lesion. The serious complications were not different between high- and low-volume centers. Conclusions: The present study indicated that risk factors for perforation during endoscopic submucosal dissection were tumor, endoscopist and patient related, although risk factors for postoperative bleeding were tumor related. There was no difference in complications between high- and low-volume centers.

Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced colitis in rat ☆

Chronic inflammation of long-term ulcerative colitis contributes to an increased risk of colon cancer. Few studies address whether extra-virgin olive oil (EVOO) intake suppresses inflammation, cell proliferation and signal transducers and activators of transcription (STAT) in the experimental colitis model. The aim of this study was to assess whether a 5% EVOO suppressed inflammation, increased cell proliferation and the expressions of STAT3 and STAT3 phosphorylation (pSTAT3) in dextran sulfate sodium (DSS)-induced colitis. Rats were administered DSS via drinking water (weight percentage: 4%) for 1 week with a 1-week recovery period for three cycles. Rats were divided into three groups: control group, standard diet without DSS; DSS group, standard diet+DSS; and DSS+EVOO group, EVOO diet (weight percentage: 5%)+DSS. Rats were sacrificed 5 weeks after DSS was first administered, and colonic damage was histologically and biochemically evaluated. As a result, chronic feeding of 5% EVOO attenuated inflammation. This was evaluated using a disease activity index, body weight loss and a histological score. Enhanced expressions of STAT3, pSTAT3, COX-2 and iNOS by DSS was attenuated by EVOO. In addition, EVOO attenuated increases in cell proliferation (PCNA) caused by DSS and recovered decreases in apoptosis (cleaved caspase-3). In conclusion, the study indicated that chronic feeding of 5% EVOO inhibited chronic inflammation in DSS-induced colitis in rats and also attenuated cell proliferation and recovered apoptosis in DSS colitis.

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage.

Background Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. Aim We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. Methods We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. Results The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. Conclusions High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. Trial Registration UMIN Clinical Trials Registry UMIN000003463