Tomofumi Akasaka

SHORT-TERM OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC NEOPLASM: MULTICENTER SURVEY BY OSAKA UNIVERSITY ESD STUDY GROUP

Background:  Endoscopic submucosal dissection (ESD) was developed for en bloc removal of large and flat gastrointestinal tract neoplasms. In Japan, ESD is performed under conscious sedation. The risks for sedation‐related complications of ESD, such as postoperative pneumonia, have not been evaluated. The aim of this study was to evaluate the incidence of postoperative pneumonia after ESD in a multicenter survey.

CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis

Objective MicroRNAs (miRNAs) act as tumour suppressor genes or oncogenes in the regulation of multiple carcinogenic processes. Aberrant miRNA expression is reported in Helicobacter pylori (H pylori)-related gastritis and gastric cancer. The cytotoxin-associated gene A (CagA) of H pylori has a pathophysiologically important role in gastric carcinogenesis. A study was undertaken to evaluate the effect of CagA on miRNA expression and its regulatory mechanism. Methods The effect of CagA on miRNA expression was assessed by comprehensive miRNA microarray. The mechanisms of the in vitro and in vivo effects of CagA on histone modification and DNA methylation and the involvement of CagA-dysregulated signal transduction on let-7, an important representative miRNA in gastric carcinogenesis, were investigated. Results In in vitro experiments, CagA significantly attenuated let-7 expression leading to Ras pathway activation. CagA enhanced c-myc, DNA methyltransferase 3B (DNMT3B) and Enhancer of Zeste homologue 2 (EZH2) expression and attenuated miR-26a and miR-101 expression, which resulted in the attenuation of let-7 expression by histone and DNA methylation. Experiments performed in CagA transgenic mice revealed that c-myc, EZH2 and DNMT3B expression were enhanced and let-7 expression was attenuated to induce Ras oncoprotein expression in the stomach, with no associated inflammation. Conclusions H pylori CagA induces aberrant epigenetic silencing of let-7 expression, leading to Ras upregulation.

Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis

Aim:  Disorders of protein metabolism in liver cirrhosis can affect prognosis or cause complications. Treatment with branched‐chain amino acid (BCAA) and zinc supplements has been shown to be effective against abnormal nitrogen metabolism in liver cirrhosis. There are, however, few studies on the effects of combining these supplements. In this study, the effect of combining BCAA and zinc treatment in cirrhosis was investigated.

Clinical features of post-polypectomy bleeding associated with heparin bridge therapy

 Heparin is given to patients undergoing colonoscopic polypectomy at high risk for thromboembolism. Little is known, however, about how heparin bridge therapy (HB) affects post‐polypectomy bleeding (PPB). The present study aimed to identify the clinical features of PPB associated with HB.

Features of electrocoagulation syndrome after endoscopic submucosal dissection for colorectal neoplasm.

Endoscopic submucosal dissection (ESD) is a promising treatment for large gastrointestinal superficial neoplasms, although it is technically difficult, and perforation and delayed bleeding are well‐known adverse events. However, there have been no large studies about electrocoagulation syndrome after colorectal ESD. The aim of this study was to evaluate the incidence and clinical significant risk factors of post‐ESD coagulation syndrome (PECS).

Feasibility of cold snare polypectomy in Japan: A pilot study

AIM To investigate the feasibility of cold snare polypectomy (CSP) in Japan. METHODS The outcomes of 234 non-pedunculated polyps smaller than 10 mm in 61 patients who underwent CSP in a Japanese referral center were retrospectively analyzed. The cold snare polypectomies were performed by nine endoscopists with no prior experience in CSP using an electrosurgical snare without electrocautery. RESULTS CSPs were completed for 232 of the 234 polyps. Two (0.9%) polyps could not be removed without electrocautery. Immediate postpolypectomy bleeding requiring endoscopic hemostasis occurred in eight lesions (3.4%; 95%CI: 1.1%-5.8%), but all were easily managed. The incidence of immediate bleeding after CSP for small polyps (6-9 mm) was significantly higher than that of diminutive polyps (≤ 5 mm; 15% vs 1%, respectively). Three (5%) patients complained of minor bleeding after the procedure but required no intervention. The incidence of delayed bleeding requiring endoscopic intervention was 0.0% (95%CI: 0.0%-1.7%). In total, 12% of the resected lesions could not be retrieved for pathological examination. Tumor involvement in the lateral margin could not be histologically assessed in 70 (40%) lesions. CONCLUSION CSP is feasible in Japan. However, immediate bleeding, retrieval failure and uncertain assessment of the lateral tumor margin should not be underestimated. Careful endoscopic diagnosis before and evaluation of the tumor residue after CSP are recommended when implementing CSP in Japan.

Integrated diagnostic strategy for the invasion depth of early gastric cancer by conventional endoscopy and EUS

BACKGROUND Although conventional endoscopy (CE) and EUS are considered useful for predicting the invasion depth (T-staging) in early gastric cancer (EGC), no effective diagnostic strategy has been established. OBJECTIVE To produce simple CE criteria and to elucidate an efficient diagnostic method by combining CE and EUS for accurate T-staging. DESIGN Single-center retrospective analysis. SETTING Academic university hospital. PATIENTS Consecutive patients with EGC from April 2007 to March 2012 who underwent CE and EUS before treatment. INTERVENTIONS Recorded endoscopic images were independently reviewed by 3 observers. The CE criteria for massive invasion were defined, and their utility and the additional value of EUS were assessed. MAIN OUTCOME MEASUREMENTS The accuracy of CE based on the criteria and the accuracy of EUS. RESULTS Two hundred thirty patients were enrolled: 195 with mucosal cancer or cancer in the submucosa less than 500 μm from the muscularis mucosae and 35 with invasive cancers. Multivariate analysis of the CE findings by 1 observer revealed that an irregular surface and a submucosal tumor-like marginal elevation were significantly associated with massive invasion. The simple CE criteria, consisting of those 2 features, had an overall accuracy of 73% to 82% and no significant differences in the diagnostic yield compared with EUS in all observers. CE accurately revealed mucosal cancer, and EUS efficiently salvaged the lesions that were over-diagnosed by CE. With our strategy, which involved the CE criteria and the optimal use of EUS, the comprehensive accuracy exceeded 85% in each observer. LIMITATIONS Retrospective, single-center study. CONCLUSIONS We demonstrated a practical strategy for T-staging in EGC using simple CE criteria and EUS.

Traction-assisted colonic endoscopic submucosal dissection using clip and line: a feasibility study

Background and study aims: Colonic endoscopic submucosal dissection (ESD) is a challenging procedure because it is often difficult to maintain good visualization of the submucosal layer. To facilitate colonic ESD, we designed a novel traction method, namely traction-assisted colonic ESD using clip and line (TAC), and investigated its feasibility. Patients and methods: We retrospectively analyzed 23 patients with large colonic superficial lesions who had undergone TAC. The main outcome was the procedural success rate of TAC, which we defined as successful, sustained application of clip and line to the lesion until the end of the procedure. Results: The procedural success rate of TAC was 87 % (20/23). In all three unsuccessful cases, the lesions were in the proximal colon and the procedure times over 100 minutes. The overall mean procedure time was 61 min (95 % confidence interval, 18 – 172 min). We achieved en bloc resections of all lesions. There were no perforations or fatal adverse events. Conclusions: TAC is feasible and safe for colonic ESD and may improve the ease of performing this procedure.

Functional analysis of agalactosyl IgG in inflammatory bowel disease patients

Background: Agalactosyl immunoglobulin (Ig) G is increased in inflammatory bowel disease (IBD) similarly to rheumatoid arthritis (RA). The lectin complement pathway is shown to be activated through association of agalactosyl IgG with mannan‐binding lectin (MBL) in RA. Functional changes of IgG agalactosylation in IBD, however, have not yet been clarified. Methods: The ratio of the agalactosyl/non‐agalactosyl fraction in fucosylated IgG oligosaccharides (G0F/G2F) and serum MBL levels were analyzed in 59 patients with Crohns disease (CD), 64 ulcerative colitis (UC), and 39 healthy volunteers (HV). The MBL levels associated with serum IgG were analyzed by enzyme‐linked immunosorbent assay. MBL expression in the intestinal mucosa was analyzed by immunohistochemistry. Phagocytosis of sheep red blood cells (SRBC) reacted with either an agalactosyl or non‐agalactosyl SRBC‐specific IgG antibody was determined by flow cytometry. Results: The serum MBL levels were not significantly different among CD, UC, or HV. In patients with CD, the serum MBL levels were negatively correlated with the Crohns Disease Activity Index (CDAI). The levels of MBL associated with agalactosyl IgG were not different from those associated with non‐agalactosyl IgG. Immunoreactivity to MBL was less in the inflamed mucosa compared with the noninflamed mucosa. Phagocytic activity of SRBC was significantly higher in the presence of agalactosyl IgG compared to non‐agalactosyl IgG. Conclusions: Agalactosyl IgG oligosaccharides enhanced antibody‐dependent phagocytosis in vitro but did not activate the lectin complement pathway. Oligosaccharide alterations of IgG are not only a marker of IBD but also functionally modulate the immune function of IBD. (Inflamm Bowel Dis 2010;)

Incomplete resection rate of cold snare polypectomy: a prospective single-arm observational study

Background and study aims Cold snare polypectomy (CSP) is considered to be safe for the removal of subcentimeter colorectal polyps. This study aimed to determine the rate of incomplete CSP resection for subcentimeter neoplastic polyps at our center. Patients and methods Patients with small or diminutive adenomas (diameter 1 - 9 mm) were recruited to undergo CSP until no polyp was visible. After CSP, a 1 - 3 mm margin around the resection site was removed using endoscopic mucosal resection. The polyps and resection site marginal specimens were microscopically evaluated. Incomplete resection was defined as the presence of neoplastic tissue in the marginal specimen. We also calculated the frequency at which the polyp lateral margins could be assessed for completeness of resection. Results A total of 307 subcentimeter neoplastic polyps were removed from 120 patients. The incomplete resection rate was 3.9 % (95 % confidence interval [CI] 1.7 % - 6.1 %); incomplete resection was not associated with polyp size, location, morphology, or operator experience. The polyp lateral margins could not be assessed adequately for 206 polyps (67.1 %). Interobserver agreement between incomplete resection and lateral polyp margins that were inadequate for assessment was poor (κ = 0.029, 95 %CI 0 - 0.04). Female sex was an independent risk factor for incomplete resection (odds ratio 4.41, 95 %CI 1.26 - 15.48; P  = 0.02). Conclusions At our center, CSP resection was associated with a moderate rate of incomplete resection, which was not associated with polyp characteristics. However, adequate evaluation of resection may not be routinely possible using the lateral margin from subcentimeter polyps that were removed using CSP.Trial registered at University Hospital Medical Information Network (UMIN 000010879).