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Introduction Colonoscopy is an imperfect tool. The term ‘interval’ cancer refers to cancers diagnosed after a colorectal screening examination or test in which no cancer was detected, and before the date of the next recommended exam. From a colonoscopy Quality Assurance perspective, that term is too restrictive, hence the term Post Colonoscopy Colorectal Cancer (PCCRC) was developed, to incorporate non-screening settings. Methods Our goal was to provide a framework on terminology, identification, analysis and reporting of cancers appearing after a negative colonoscopy (PCCRCs) or computed tomographic colonography (Post-Imaging Colorectal Cancers/PICRCs). We based our methodology on the AGREE II tool. A team of gastroenterologists, pathologists, epidemiologists, a radiologist and a patient representative, formed a panel of 20 members. Following literature review, 402 articles provided background for statements, which were then subjected to anonymous voting (modified Delphi approach). The GRADE system was utilised to rate evidence. Results The final output consists of 21 statements, providing guidance on key aspects of PCCRC/PICRC, namely: Definitions/terminology (2 statements) (table 1) Qualitative review of cases/aetiology attribution (8 statements) (figure 1) Quantitative assessment/calculation of PCCRC rate (7 statements) Non–colonoscopic imaging of the colon (4 statements) The PCCRC rate is calculated as the number of PCCRCs divided by the total of the PCCRCs plus the number of detected cancers, expressed as a percentage. A Root-Cause-Analysis checklist, as well as a checklist to assist Peer Review of PCCRC manuscripts have also been developed. Conclusions This is the first consensus aiming to standardise terminology around PCCRC/PICRC, presenting a methodology for analysis of causation of PCCRC/PICRC and defining its potential role as a key quality indicator.

Background In 2013, eculizumab was approved for treatment of the atypical hemolytic–uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of “aHUS” to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. Methods Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event–free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. Results In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes’ variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event–free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. Conclusions This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting. Electronic supplementary material The online version of this article (10.1007/s10157-018-1610-2) contains supplementary material, which is available to authorized users.

Background Eculizumab has been available for the treatment of atypical hemolytic–uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. Methods This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. Results Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. Conclusions This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings. Electronic supplementary material The online version of this article (10.1007/s10157-018-1609-8) contains supplementary material, which is available to authorized users.

BACKGROUND AND AIM The Japan narrow-band imaging (NBI) Expert Team (JNET) was organized to unify four previous magnifying NBI classifications (the Sano, Hiroshima, Showa, and Jikei classifications). The JNET working group created criteria (referred to as the NBI scale) for evaluation of vessel pattern (VP) and surface pattern (SP). We conducted a multicenter validation study of the NBI scale to develop the JNET classification of colorectal lesions. METHODS Twenty-five expert JNET colonoscopists read 100 still NBI images with and without magnification on the web to evaluate the NBI findings and necessity of the each criterion for the final diagnosis. RESULTS Surface pattern in magnifying NBI images was necessary for diagnosis of polyps in more than 60% of cases, whereas VP was required in around 90%. Univariate/multivariate analysis of candidate findings in the NBI scale identified three for type 2B (variable caliber of vessels, irregular distribution of vessels, and irregular or obscure surface pattern), and three for type 3 (loose vessel area, interruption of thick vessel, and amorphous areas of surface pattern). Evaluation of the diagnostic performance for these three findings in combination showed that the sensitivity for types 2B and 3 was highest (44.9% and 54.7%, respectively), and that the specificity for type 3 was acceptable (97.4%) when any one of the three findings was evident. We found that the macroscopic type (polypoid or non-polypoid) had a minor influence on the key diagnostic performance for types 2B and 3. CONCLUSION Based on the present data, we reached a consensus for developing the JNET classification.

Although colonoscopy is the criterion standard for detection of colorectal adenomas, some adenomas are missed. Full-spectrum endoscopy (FUSE) allows for observation with a 330-degree angle of view, which is expected to decrease the miss rate. However, no consensus has been reached regarding the superiority of FUSE over standard forward-viewing colonoscopy (SFVC) for detection of adenomas; we therefore compared new-generation FUSE and SFVC regarding colorectal adenoma miss rate (AMR) in this, the first reported randomized control trial using new-generation FUSE.We enrolled individuals aged 40 to 75 years who had been referred for screening, surveillance, fecal occult blood test positivity, or symptoms in a prospective randomized trial of tandem colonoscopy in 8 institutions. Patients were randomly assigned (1:1) via computer-generated stratified randomization. Neither the endoscopists nor patients were blinded to the allocation. The primary endpoint was AMR per patient (AMR-PP).We enrolled 345 patients and included 319 in the per-protocol analyses. AMR-PP was significantly lower with FUSE (11.7%; 95% confidence interval [CI], 8.0%-15.4%) than with SFVC (22.9%; 95% CI, 17.5%-28.3%; P .001). AMR-PP for lesions ≤5 mm in size was significantly lower with FUSE (10.4%; 95% CI, 6.5%-14.3%) than with SFVC (20.0%; 95% CI, 14.4%-25.6%; P = .0057). Furthermore, AMR-PP in the ascending colon was significantly lower with FUSE (4.3%; 95% CI, 1.4%-7.2%) than with SFVC (10.6%; 95% CI, 6.1%-15.1%; P = .0212).FUSE is superior to SFVC regarding both AMR-PP and AMR; additionally, AMR-PP is both significantly lower with FUSE than SFVC for lesions ≤5 mm in size and in the ascending colon. (Clinical trial registration number: UMIN000020448.).

Background & Aims: Colonoscopy examination does not always detect colorectal cancer (CRC)— some patients develop CRC after negative findings from an examination. When this occurs before the next recommended examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC) was created in 2010. However, PCCRC definitions and methods for calculating rates vary among studies, making it impossible to compare results. We aimed to standardize the terminology, identification, analysis, and reporting of PCCRCs and CRCs detected after other whole-colon imaging evaluations (post-imaging colorectal cancers [PICRCs]).\ud \ud \ud \ud Methods: A 20-member international team of gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non-medical professional met to formulate a series of recommendations, standardize definitions and categories (to align with interval cancer terminology), develop an algorithm to determine most-plausible etiologies, and develop standardized methodology to calculate rates of PCCRC and PICRC. The team followed the Appraisal of Guidelines for Research and Evaluation II tool. A literature review provided 401 articles to support proposed statements; evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The statements were voted on anonymously by team members, using a modified Delphi approach.\ud \ud \ud \ud Results: The team produced 21 statements that provide comprehensive guidance on PCCRCs and PICRCs. The statements present standardized definitions and terms, as well as methods for qualitative review, determination of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the colon.\ud \ud \ud \ud Conclusions: A 20-member international team has provided standardized methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a quality indicator. The team provides recommendations for clinicians, organizations, researchers, policy makers, and patients.

The utility of capsule endoscopy (CE) for the surveillance of small intestinal lesions in familial adenomatous polyposis (FAP) patients has been reported. However, few studies have investigated the safety of CE in FAP patients who have undergone colon surgery. We aimed to assess the safety of surveillance CE in post-colectomy FAP patients and the endoscopic findings associated with small intestinal lesions. We assessed the safety of CE surveillance of small intestinal lesions in 41 FAP patients who had undergone colectomies. Forty-two CEs were performed in 41 patients at our facility from April 2012 to July 2014. CE was conducted safely and none of the capsules were retained, despite the inclusion of patients who had undergone several abdominal surgeries previously. Thirty-nine out of 42 capsules (93 %) were retrieved within the examination timeframe; hence, the retrieval rate was favorable. The findings from this study indicate that surveillance CE can be safely conducted in post-colectomy FAP patients.

Background and study aims: Although endoscopic resection is widely used for the treatment of superficial colorectal neoplasms, the rate of local recurrence of lesions with a positive or indeterminate lateral margin on histologic evaluation is unclear. We aimed to demonstrate the relationship between lateral margin status and local recurrence after the endoscopic resection of intramucosal colorectal neoplasms. Patients and methods: We retrospectively collected the clinical and pathologic data for 844 endoscopically resected colorectal intramucosal neoplasms with a size of 10 mm or larger. We investigated the relationship between the local recurrence rate and the lateral margin status (categorized as LM0 [negative], LM1 [positive], or LMX [indeterminate]). Results: In total, 389 lesions were evaluated as LM0 and showed no local recurrence. Of the 455 lesions evaluated as LMX or LM1, 30 showed local recurrence within a median period of 6.3 months (range, 1.7 – 48.1) from the initial endoscopic resection. The local recurrence rate of the en bloc-LMX group (2.2 %) was significantly lower than that of the piecemeal-LMX group (15.2 %). Of the 30 cases of recurrence, 28 were successfully treated with a second endoscopic resection. Of the two lesions that showed further recurrence, one was treated with a third endoscopic resection, whereas the other – which was a piecemeal-LMX lesion – was eventually diagnosed as invasive cancer and treated with surgery. Conclusions: The local recurrence rate was lower in the en bloc-LMX group than in the piecemeal-LMX group. Thus, we believe that en bloc-LMX lesions that are completely and confidently resected endoscopically can be treated as en bloc-LM0 lesions.

Colonoscopy is considered the best modality for the detection and treatment of colorectal polyps. However, some polyps still may not be detected. Although conventional white-light endoscopy is the gold standard for the detection of colorectal polyps, up to a fifth of lesions may be missed on screening colonoscopy, especially non-polypoid colorectal neoplasms. Recently, many studies have reported on various endoscopic modalities that improve the detection and characterization of colorectal lesions. Newly developed modalities might be helpful to recognize colorectal lesions; however, careful observation is required to identify flat/depressed lesions as well as hidden polyps during screening and surveillance colonoscopy.

Colonoscopy is considered the gold standard for detecting colorectal tumors; however, conventional colonoscopy can miss flat tumors. We aimed to determine whether visualization of colorectal flat lesions was improved by autofluorescence imaging and narrow-band imaging image analysis in conjunction with a new endoscopy system. Eight physicians compared autofluorescent, narrow-band, and chromoendoscopy images to 30 corresponding white-light images of flat tumors. Physicians rated tumor visibility from each image set as follows: +2 (improved), +1 (somewhat improved), 0 (equivalent to white light), -1 (somewhat decreased), and -2 (decreased). The eight scores for each image were totalled and evaluated. Interobserver agreement was also examined. Autofluorescent, narrow-band, and chromoendoscopy images showed improvements of 63.3% (19/30), 6.7% (2/30), and 73.3% (22/30), respectively, with no instances of decreased visibility. Autofluorescence scores were generally greater than narrow-band scores. Interobserver agreement was 0.65 for autofluorescence, 0.80 for narrow-band imaging, and 0.70 for chromoendoscopy. In conclusion, using a new endoscopy system in conjunction with autofluorescent imaging improved visibility of colorectal flat tumors, equivalent to the visibility achieved using chromoendoscopy.

Recently in Japan, the morbidity of colorectal polyp has been increasing. As a result, a large number of cases of colorectal polyps that are diagnosed and treated using colonoscopy has now increased, and clinical guidelines are needed for endoscopic management and surveillance after treatment. Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Ten specialists for colorectal polyp management extracted the specific clinical statements from articles published between 1983 and September 2011 obtained from PubMed and a secondary database, and developed the CQs and statements. Basically, statements were made according to the GRADE system. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid. The professional committee created 91CQs and statements for the current concept and diagnosis/treatment of various colorectal polyps including epidemiology, screening, pathophysiology, definition and classification, diagnosis, treatment/management, practical treatment, complications and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumor/carcinoma). After evaluation by the moderators, evidence-based clinical guidelines for management of colorectal polyps have been proposed for 2014.

Backgrounds/Aim: Colorectal laterally spreading tumors (LSTs) are sometimes difficult to visualize even with image-enhanced endoscopy. γ-Glutamyl-transpeptidase (GGT) is a cell surface-associated enzyme that is overexpressed in various types of human cancers. Furthermore, GGT expression is higher in colorectal cancer cells than in normal colorectal mucosa. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), an activatable fluorescent probe, is nonfluorescent under a neutral pH and normal cellular environment; however, it turns highly fluorescent upon reaction with GGT. We evaluated ex vivo fluorescent imaging of colorectal LSTs using this GGT-activatable fluorescent probe. Methods: Between March 2013 and March 2014, 30 endoscopically resected colorectal LSTs were prospectively included in this study. Each was analyzed by first taking a baseline image before spraying, then spraying with gGlu-HMRG onto the freshly resected specimen, and finally taking fluorescent images 15 min after spraying with a dedicated imaging machine. Results: Of the LSTs, 67% rapidly showed positive fluorescent activity. These activities were shown in adenoma (54%) and carcinoma in adenoma (76%), and in LST-granular type (80%) and LST-nongranular type (40%). Conclusion: Topically spraying gGlu-HMRG enabled rapid and selective fluorescent imaging of colorectal tumors owing to the upregulated GGT activity in cancer cells.

Background and study aims Many studies have reported on laterally spreading tumors (LSTs), but systematic reviews of the data to determine their risk of containing submucosal invasion (SMI) are lacking. We systematically screened and analyzed the available literature to provide a more solid basis for evidence-based treatment. Methods We conducted a systematic search in PubMed, Embase, the Cochrane Library, and Scopus for published articles until July 2017. We estimated pooled prevalence or odds ratios (ORs) with 95 % confidence intervals (CIs), using random-effects models. We classified endoscopic subtypes into granular LST, which comprises the homogeneous and nodular mixed subtypes, and non-granular LST, which comprises the flat elevated and pseudodepressed subtypes. Results We identified 2949 studies, of which 48 were included. Overall, 8.5 % (95 %CI 6.5 % – 10.5 %) of LSTs contained SMI. The risk of SMI differed among the LST subtypes: 31.6 % in non-granular pseudodepressed LSTs (95 %CI 19.8 % – 43.4 %), 10.5 % in granular nodular mixed LSTs (95 %CI 5.9 % – 15.1 %), 4.9 % in non-granular flat elevated LSTs (95 %CI 2.1 % – 7.8 %), and 0.5 % in granular homogenous LSTs (95 %CI 0.1 % – 1.0 %). SMI was more common in distally rather than in proximally located LSTs (OR 2.50, 95 %CI 1.24 – 5.02). The proportion of SMI increased with lesion size (10 – 19 mm, 4.6 %; 20 – 29 mm, 9.2 %; ≥ 30 mm, 16.5 %). The pooled prevalence of patients with one or more LSTs in the general colonoscopy population was 0.8 % (95 %CI 0.6 % – 1.1 %). Conclusion The majority of LSTs are non-invasive at the time of colonoscopic detection and can be treated with (piecemeal) endoscopic mucosal resection. Pretreatment diagnosis of endoscopic subtype, specifying areas of concern (nodule or depression), determines those LSTs at highest risk of containing SMI, where en bloc resection is the preferred therapy.

In paroxysmal nocturnal hemoglobinuria (PNH), various symptoms due to intravascular hemolysis exert a negative impact on patients’ quality of life (QOL). To determine clinical factors related with improvements in QOL in PNH patients treated, we analyzed changes in QOL scales in PNH patients treated with eculizumab based on data collected from post-marketing surveillance in Japan. Summary statistics were obtained using figures from QOL scoring systems and laboratory values, and evaluated by t test. One-year administration of eculizumab improved the most QOL items in comparison with the baseline. In particular, significant improvement of EORTC QLQ-C30 was observed in fatigue, dyspnea, physical function, and global health status. Canonical correlation analysis revealed a high correlation between QOL and laboratory values. Changes in serum lactate dehydrogenase (LDH) and hemoglobin showed strong correlations with QOL improvement. Quality of life improvement was independent of patients’ baseline characteristics of co-occurrence of bone marrow failure (BMF), or the degree of LDH. In this analysis, we found that the degree of QOL improvement was independent of the baseline LDH before eculizumab treatment and of co-occurrence of BMF. Paroxysmal nocturnal hemoglobinuria patients who have not received eculizumab treatment due to mild hemolysis may benefit from eculizumab treatment.

Background and study aims Magnifying narrow-band imaging (M-NBI) enables detailed observation of microvascular architecture and can be used in endoscopic diagnosis of colorectal lesion. However, in clinical practice, differential diagnosis and estimation of invasion depth of colorectal lesions based on M-NBI findings require experience. Therefore, developing computer-aided diagnosis (CAD) for M-NBI would be beneficial for clinical practice. The aim of this study was to evaluate the effectiveness of software for CAD of colorectal lesions. Materials and methods In collaboration with Yamaguchi University, we developed novel software that enables CAD of colorectal lesions using M-NBI images. This software for CAD further specifically divides original Sano’s colorectal M-NBI classification into 3 groups (group A, capillary pattern [CP] type I; group B, CP type II + CP type IIIA; group C, CP type IIIB), which describe hyperplastic polyps (HPs), adenoma/adenocarcinoma (intramucosal [IM] to submucosal [SM]-superficial) lesions, and SM-deep lesions, respectively. We retrospectively reviewed 121 lesions evaluated using M-NBI. Results The 121 reviewed lesions included 21 HP, 80 adenoma/adenocarcinoma (IM to SM-superficial), and 20 SM-deep lesions. The concordance rate between the CAD and the diagnosis of the experienced endoscopists was 90.9 %. The sensitivity, specificity, positive and negative predictive values, and accuracy of the CAD for neoplastic lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively. The values for SM-deep lesions were 83.9 %, 82.6 %, 53.1 %, 95.6 %, and 82.8 %, respectively. Conclusion Relatively high diagnostic values were obtained using CAD. This software for CAD could possibly lead to a wider use of M-NBI in the endoscopic diagnosis of colorectal lesions.

High-quality colonoscopy is mandatory to prevent adenoma recurrence and colorectal cancer. In the past few years, technical advances have been developed with the purpose of improving adenoma detection rate (ADR), one of the most important validated colonoscopy quality benchmarks. Several techniques or devices are used to optimize visualization: observation techniques; add-on devices; auxiliary imaging devices; colonoscopes with increased field of view; and colonoscopes with an integrated inflatable reusable balloon. Image-enhanced endoscopy (IEE) facilitates the detection and characterization of polyps and especially nonpolypoid colorectal neoplasms. Indigo carmine is the most frequently used dye in colonoscopy as it deposits in depressed areas, improving detection of flat and depressed lesions. Virtual chromoendoscopy has emerged as an effective contrast enhancement technology without the limitation of preparing dyes and applying them through the colonoscope working channel. Narrow-band imaging (NBI) enhances the capillary pattern and surface of the mucosa using optical filters, and second-generation NBI provides a twofold brighter image than the previous system, yielding promising ADR results. Moreover, a second-generation blue laser imaging system, LASEREO, has been reported to improve not only polyp detection rate but also ADR, becoming a promising IEE modality. Herein, we describe technical advances in colonoscopy imaging and their effect on ADR.

Colorectal cancer (CRC), one of the most commonly diagnosed cancers, is a major cause of cancer-related death in the world (1). To reduce CRC mortality, the implementation of “appropriate” CRC screening is essential. Thus, it is important to define what constitutes “appropriate” CRC screening. First, it must be effective and safe. There is strong evidence that the fecal occult blood test (FOBT) and sigmoidoscopy are effective CRC screening tools and their value in reducing CRC mortality has been proven in several randomized controlled trials (RCTs) (2-10).

Background— In general, Ras proteins are thought to promote cardiac hypertrophy, an important risk factor for cardiovascular disease and heart failure. However, the contribution of different Ras isoforms has not been investigated. The objective of this study was to define the role of H- and K-Ras in modulating stress-induced myocardial hypertrophy and failure. Methods and Results— We used H- and K-Ras gene knockout mice and subjected them to pressure overload to induce cardiac hypertrophy and dysfunction. We observed a worsened cardiac phenotype in Hras −/− mice, while outcomes were improved in Kras +/− mice. We also used a neonatal rat cardiomyocyte culture system to elucidate the mechanisms underlying these observations. Our findings demonstrate that H-Ras, but not K-Ras, promotes cardiomyocyte hypertrophy both in vivo and in vitro. This response was mediated in part through the phosphoinositide 3-kinase-AKT signaling pathway. Adeno-associated virus–mediated increase in AKT activation improved the cardiac function in pressure overloaded Hras null hearts in vivo. These findings further support engagement of the phosphoinositide 3-kinase-AKT signaling axis by H-Ras. Conclusions— Taken together, these findings indicate that H- and K-Ras have divergent effects on cardiac hypertrophy and heart failure in response to pressure overload stress.

Endoscopic submucosal dissection (ESD) is now becoming a standard treatment for early-stage, large, gastrointestinal (GI) tumors. Although ESD is one of the more difficult procedures in GI therapeutic endoscopy, new devices and strategies have been invented to make it easier and safer. Understanding new methods for ESD may help endoscopists perform safer and more time-saving ESD procedures.

Background and study aims: Compared with any other location in the gastrointestinal tract, the duodenum presents the most challenging site for endoscopic resection. The aim of this study was to analyze the clinical outcomes of duodenal endoscopic resection and to assess the feasibility of the technique as a therapeutic procedure. Patients and methods: A total of 113 consecutive patients with 121 nonampullary duodenal tumors underwent endoscopic resection by endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), or polypectomy between January 2000 and September 2013. Long-term outcomes were investigated in patients with more than 1 year follow-up. Results: The median tumor size was 12 mm (range 3 – 50 mm). Lesions consisted of 63 adenocarcinomas/high-grade intraepithelial neoplasias (53 %) and 57 adenomas/low-grade intraepithelial neoplasias (48 %). Endoscopic resection included 106 EMRs (87 %), 8 ESDs (7 %), and 7 polypectomies (6 %). En bloc resection was achieved in 77 lesions (64 %), and 43 lesions (35 %) underwent piecemeal resection; one procedure was discontinued due to perforation. There were 14 cases of delayed bleeding after EMR (12 %), 1 perforation (1 %) during ESD, and 1 delayed perforation (1 %) after ESD, which required emergency surgery. Of the 76 patients who were followed for more than 1 year, none of the patients died from a primary duodenal neoplasm, and there were no local recurrences during the 51-month median follow-up period (range 12 – 163 months). Conclusions: Duodenal endoscopic resection was feasible as a therapeutic procedure, but it should only be performed by highly skilled endoscopists because of its technical difficulty. Piecemeal resection by EMR is acceptable for small lesions, based on these excellent long-term outcomes.

We assessed the clinicopathological characteristics of patients with serrated polyposis syndrome (SPS) and the incidence of advanced adenoma/colorectal cancer (CRC). We prospectively enrolled 249 consecutive patients who underwent colonoscopy at the National Cancer Center Hospital over a 6-month period. All the polyps were diagnosed using magnification colonoscopy and resection/biopsy. The enrolled patients were divided into two groups, i) those with ≥5 histologically diagnosed hyperplastic polyps (HPs) proximal to the sigmoid colon, with at least 2 polyps >10 mm in diameter and ii) those with ≥20 HPs distributed throughout the colon. The clinical characteristics of the two groups were compared, including lifestyle, family history of CRC and colonoscopic findings. HPs were identified in 228 patients, of whom 21 (8.4%) had SPS. All 21 patients had ≥20 HPs distributed throughout the colon, with none having >2 HPs ≥1 cm in diameter in the right colon. Synchronous advanced adenoma/CRC was diagnosed in 76/249 (30.5%) patients. The prevalence of advanced adenoma/CRC was higher among patients with compared to those without SPS (P=0.075). SPS was also associated with older age and higher body mass index (BMI). Our results suggested that older age and higher BMI are independent risk factors for SPS. Advanced adenoma/CRC tended to occur more frequently among patients with compared to those without SPS, although the difference was not statistically significant.

Background Endoscopic submucosal dissection (ESD) has recently provided a new treatment strategy for large colorectal neoplasms, as an alternative to laparoscopy-assisted colectomy (LAC). Prospective comparative data on the perioperative course of ESD vis-à-vis LAC are scarce. Methods We prospectively evaluated the perioperative course of colorectal ESD in 300 patients. We evaluated en bloc and curative resection, procedure duration, postoperative parameters [white blood cell count (WBC), C-reactive protein (CRP), and hemoglobin], pain, recovery duration (time to achieve full mobilization, normal diet, and length of hospitalization), and complications. We also prospectively evaluated 190 patients undergoing LAC as a control group. Results The median size of the lesions was 30 mm for ESDs (LACs: 20 mm). The median procedure time was 90 min for ESDs (LACs: 185 min). Postoperative pyrexia was reported in 4 % of ESDs (LACs: 54 %). Only 4 % of ESDs required analgesia (LACs: 61 %). Between the preoperative period and postoperative day 1, the mean difference in WBC and CRP was +1,300/μl for ESDs (LACs: +3,100/μl), and +0.91 mg/dl for ESDs (LACs: +3.96 mg/dl), respectively. A ≥2 g/dl decrease in hemoglobin was observed in 5 % of ESDs (LACs: 30.0 %). Complications were seen in 7 % of ESDs (LACs: 15 %). The rate of delayed bleeding and perforation was 5 and 1.7 % of ESDs, respectively. Although only one of them required laparotomy for peritonitis caused by delayed perforation, others could be managed endoscopically. Additional LAC was required in 16 ESDs due to redefined risk for lymph node metastases. The median hospital stay was 5 days for ESDs (LACs: 10 days). These were consecutive patients with prospective data collection. Conclusions Colorectal ESD is effective, minimally invasive and safe in terms of periperative clinical course. Colorectal ESD provides advantages for treatment of large adenomas and early cancers with no risk of lymph node metastasis.

The Hippo pathway, evolutionarily conserved from flies to mammals, promotes cell death and inhibits cell proliferation to regulate organ size. The core component of this cascade, Mst1 in mammalian cells, is sufficient to promote apoptosis. However, the mechanisms underlying both its activation and its ability to elicit cell death remain largely undefined. We here identify a novel signaling cassette in cardiac myocytes consisting of K-Ras, the scaffold RASSF1A and Mst1 that is localized to mitochondria and promotes Mst1 activation in response to oxidative stress. Activated Mst1 phosphorylates Bcl-xL at Ser14, which resides in the BH4 domain, thereby antagonizing Bcl-xL-Bax binding. This, in turn, causes activation of Bax and subsequent mitochondria-mediated apoptotic death. Our findings demonstrate mitochondrial localization of Hippo signaling and identify a novel target of this cascade, Bcl-xL, which is directly modified to promote apoptosis.

Adequate colonoscopic polypectomy is a very important intervention for the prevention of colorectal cancer progression during screening and surveillance colonoscopy. Whereas various techniques are used for the removal of diminutive polyps, including cold biopsy forceps, hot biopsy forceps, hot snare, and cold snare, hot polypectomy techniques with electrocautery have been associated with an increased risk of electrocautery-related complications, including immediate and/or delayed bleeding or perforation. In contrast, recent studies have found a polypectomy technique without electrocautery, so-called cold polypectomy, to be a safer and more efficacious technique. The present article discusses the use of cold polypectomy techniques and describes how cold biopsy forceps polypectomy using jumbo biopsy forceps designed with a greater capacity for removing larger tissue samples, and cold snare polypectomy, are adequate for removing diminutive polyps completely and safely and shorten withdrawal time of the colonoscopy procedure.

During colonoscopy, small and diminutive colorectal polyps are commonly encountered. It is estimated that at least one adenomatous polyp is detected in almost half of all patients undergoing screening colonoscopy. In contrast, the ‘predict, resect, and discard’ strategy for diminutive and small colorectal polyps is a current topic especially in Western countries. ‘Is this an acceptable policy in Japan?’ Herein, we report the results of a questionnaire survey with regard to the management of diminutive colorectal polyps, including the thoughts of Japanese endoscopists regarding the ‘predict, resect, and discard’ strategy. At the moment, we propose that this strategy should be used by skilled endoscopists only.

The number of medical facilities that perform colorectal endoscopic submucosal dissection (ESD) has been growing, and its effectiveness has been increasingly reported in recent years. Indications approved by the Japanese government's medical insurance system are early colorectal cancers with a maximum tumor size of 2-5 cm. ESD was an effective procedure for treating noninvasive colorectal tumors difficult to resect en bloc by conventional EMR, resulting in a higher en bloc resection rate that is less invasive than surgery. Based on the excellent clinical results of colorectal ESDs, the Japanese health care insurance system has approved colorectal ESD for coverage.

Experts can accurately characterize the histology of diminutive polyps with narrow-band imaging (NBI). There are limited data on the performance of non-experts. To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts (in academics and community practice) by using video clips. Prospective, observational study. Academic and community practice. A total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in academic practice, and 5 non-experts in community practice. Participants reviewed a 20-minute, computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps. Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before (pretest) and after (posttest) reviewing the teaching module. Non-experts in academic practice showed a significant improvement in the sensitivity (54% vs 79%; P

Colonoscopy is the recommended method for diagnosis of colorectal diseases but the number of neoplastic lesions missed is not negligible. To reduce this it is necessary to achieve quality standards in colonoscopy, for example the extent of cecal intubation, adequate bowel cleansing, and appropriate withdrawal time. Conventional wisdom is that proper colonoscopy training is the most important aspect of detection of subtle lesions. Systematic examination, including careful inspection behind folds, removal of residual stools by lavage, and awareness of and an active search for subtle mucosal abnormalities, are key factors in increasing detection of neoplastic lesions. In addition, ancillary techniques might aid detection or better characterization of additional lesions. This review focuses on the requirements for a high quality colonoscopy and on the novel techniques that may improve detection of adenoma.

Background/Aims: This study aimed to analyze the endoscopic mucosal resection (EMR) with a novel uniquely shaped, double-loop snare (Dualoop, Medico's Hirata Inc., Tokyo, Japan) for colorectal polyps. Methods: This was a clinical trial conducted in two referral centers, Kyoto Prefectural University of Medicine and National Cancer Center Hospital in Japan. First, the firmness of various snares including ‘Dualoop' was experimentally analyzed with a pressure gauge. Five hundred and eighty nine consecutive polyps that underwent EMR with ‘Dualoop' were compared to 339 polyps with the standard round snare. Lesion characteristics, en bloc resection, and complications were analyzed. Results: ‘Dualoop' had the most firmness among the various snares. The average tumor size was 9.3 mm (5-30), and en bloc resection was achieved in 95.4%. The rate of en bloc resection for middle polyps 15-19 mm in diameter was significantly higher with the ‘Dualoop' than that with the round snare (97.9 vs. 80.0%, p < 0.05). The rate of en bloc resection was 64.7% for large polyps ≥20 mm in diameter using ‘Dualoop'. Higher age, larger tumor size, and superficial polyps were associated with the failure of en bloc resection. Conclusion: EMR with ‘Dualoop' was effective for resecting both middle and large polyps en-bloc.

Currently, several endoscopic resection (ER) methods for colorectal tumors are available, including polypectomy, conventional endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and modified ER. In the present review, we mainly focus on the current status of ER for colorectal tumors as well as the report from the Endoscopic Forum Japan (EFJ) 2016, which was held in Tokyo in August 2016. The proposed ER methods for colorectal tumors larger than 10 mm in diameter are as follows. (i) Pedunculated-type tumor is an indication for polypectomy, regardless of size. (ii) Non-pedunculated-type tumor larger than 20 mm in diameter is an indication for ESD in which en bloc resection using conventional EMR is difficult or impossible. (iii) Non-pedunculated-type tumor from 10 mm to 20 mm in diameter is an indication for conventional EMR. However, ESD or modified ER methods are acceptable according to the procedure and the condition of the tumor.

Summary Obesity induces lipotoxic cardiomyopathy, a condition in which lipid accumulation in cardiomyocytes causes cardiac dysfunction. Here, we show that glycogen synthase kinase-3α (GSK-3α) mediates lipid accumulation in the heart. Fatty acids (FAs) upregulate GSK-3α, which phosphorylates PPARα at Ser280 in the ligand-binding domain (LBD). This modification ligand independently enhances transcription of a subset of PPARα targets, selectively stimulating FA uptake and storage, but not oxidation, thereby promoting lipid accumulation. Constitutively active GSK-3α, but not GSK-3β, was sufficient to drive PPARα signaling, while cardiac-specific knockdown of GSK-3α, but not GSK-3β, or replacement of PPARα Ser280 with Ala conferred resistance to lipotoxicity in the heart. Fibrates, PPARα ligands, inhibited phosphorylation of PPARα at Ser280 by inhibiting the interaction of GSK-3α with the LBD of PPARα, thereby reversing lipotoxic cardiomyopathy. These results suggest that GSK-3α promotes lipid anabolism through PPARα-Ser280 phosphorylation, which underlies the development of lipotoxic cardiomyopathy in the context of obesity.

686 Background: dCRT with 5-FU/MMC is a standard treatment for cStage II/III SCCA. S-1 is an oral fluoropyrimidine and has a greater effect on radiosensitivity. We conducted this trial of dCRT with S-1/MMC to determine the recommended dose (RD) of S-1 in phase I part (P I) and to evaluate the efficacy and safety in phase II part (P II) for cStage II/III SCCA. When the primary endpoint in P II part is proven to be satisfactory, we can regard this combined treatment as the new standard treatment. Methods: Eligibility criteria included histologically proven SCCA, cStage II/III (UICC 6th), PS 0-1, and age 20-80 years. dCRT consisted of MMC (10 mg/m2 on days 1, 29) and S-1 (60 mg/m2/d in level 0 and 80 mg/m2/d in level 1 on days 1-14, 29-42) with concurrent 3-dimensional RT of 59.4 Gy/33fr. The P I adopted the 3+3 cohort design. The primary endpoint of P II was proportion of 3-year event-free survival (% 3-year-EFS). The sample size was 65 in the P II, with one-sided alpha of 5% and power of 80%, threshold and expected % 3-year EFS as 60% and 75%. Results: From Feb/2010 to Mar/2015, 69 pts (3 in level 0 and 66 [7 in P I and 59 in P II] in level 1) were enrolled. Pts’s backgrounds for level 1 were as follows: M/F, 12/54; Age, median 64 (range 33-80); cStage II/IIIA/IIIB, 29/9/28. Three in level 1 were ineligible and 63 eligible assigned to level 1 were included in efficacy analysis. In the P I, considering the details of DLTs, RD of S-1 was determined as 80 mg/m2/d. In the 63 eligible of level 1, %3-year EFS was 65.0% (90% CI 54.1-73.9%). % 3-year OS, PFS, and colostomy-free survival were 87.3% (95% CI 76.2-93.4%), 85.7% (74.3-92.3%), and 76.2% (63.7-84.9%), respectively. The complete response rate was 81% on central review. Among 65 pts receiving level 1 dCRT, common grade 3 or 4 acute toxicities were leukopenia (63.1%), neutropenia (40%), diarrhea (20%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). Only 6 (9.2%) showed grade 3 late toxicities. No treatment-related deaths were observed. Conclusions: Although dCRT with S-1/MMC showed acceptable toxicities and favorable 3-year survival, this study did not meet its primary endpoint. Clinical trial information: UMIN000003237.

Patients with submucosal invasive colorectal cancer (SM-CRC) treated with endoscopic resection who are at low risk of lymph node metastasis and local recurrence may be followed up with observation alone, while additional surgery is recommended for those with high risk features. However, the long-term outcomes that these strategies offer are still unclear. The objective of our study was to retrospectively evaluate the long-term outcomes of patients with SM-CRC managed with endoscopic resection.We retrospectively analyzed all patients with SM-CRC treated by endoscopic resection at six institutions between 2000 and 2007. SM-CRCs with (i) negative vertical margin, (ii) well or moderately differentiated adenocarcinoma, (iii) absence of lymphovascular invasion, and (iv) invasion depth1000 µm were classified as low risk. Patients with SM-CRCs without these characteristics were classified as high risk. Outcomes were assessed by 5-year recurrence-free survival (RFS) and recurrence rate.During the study period, 428 patients with SM-CRC (low risk, 126; high risk, 302) who underwent endoscopic resection as their first treatment were enrolled (median follow-up 61 months). Among the 120 patients with low risk features treated by endoscopic resection alone, the 5-year RFS and recurrence rates were 98 % and 0.8 %, respectively. Of the 302 patients with high risk features, 196 underwent additional surgery and 106 were managed with endoscopic resection alone. For those who underwent additional surgery, the 5-year RFS and recurrence rates were 97 % and 3.6 %, respectively. Among the 106 patients managed with endoscopic resection alone, RFS and recurrence rates were 89 % (P0.05 vs. low risk patients treated by endoscopic resection alone) and 6.6 % (P0.05), respectively.Endoscopic resection alone is adequate for the management of patients with SM-CRC and low risk features. However, in those patients with SM-CRC and high risk features, surgery should be considered in addition to endoscopic resection.

Submucosal invasive colorectal cancers (SM-CRC) have approximately a 10% chance of lymph node metastasis, which requires surgical resection including lymph node dissection for curative treatment. It is important to optimally survey patients after curative resection for SM-CRC in order to detect early recurrence. In the present report, we principally show the long-term outcomes after follow up of SM-CRC resected endoscopically based on a report of the literature and our experience in Japan. The long-term outcomes of low-risk SM-CRC endoscopically resected alone or high-risk SM-CRC with additional surgical resection with lymph node dissection are excellent. However, the risk of local recurrence of endoscopic resection alone in patients with high-risk submucosal invasive cancer was significantly higher in rectal cancer as compared to similar colonic cancer. Patients with submucosal rectal cancer showing high-risk pathological features are, therefore, strongly recommended to undergo additional treatment. We consider that longer follow up is required for patients with SM-CRC because recurrence occurred relatively later in SM-CRC compared to advanced colorectal cancer.

Little is known about the long-term outcomes of patients with submucosal invasive colorectal cancer who undergo endoscopic or surgical resection. We performed a retrospective analysis of long-term outcomes of patients treated for submucosal colon and rectal cancer.We collected data on 549 patients with submucosal colon cancer and 209 patients with submucosal rectal cancer who underwent endoscopic or surgical resection at 6 institutions over a median follow-up period of 60.5 months. Patients were classified into one of 3 groups: low-risk patients undergoing only endoscopic resection (group A), high-risk patients undergoing only endoscopic resection (group B), and high-risk patients undergoing surgical resection that included lymph node dissection (group C). We assessed recurrence rates, 5-year disease-free survival, and 5-year overall survival. Cox regression analysis was used to compare recurrences.The rates of recurrence, disease-free survival, and overall survival in group A for submucosal colon and rectal cancer were 0% versus 6.3% (P.05), 96% versus 90%, and 96% versus 89%, respectively. For group B, these values were 1.4% versus 16.2% (P.01), 96% versus 77% (P.01), and 98% versus 96%, respectively; local recurrence was observed in 5 patients (one with submucosal colon cancer and 4 with submucosal rectal cancer). Tumor location was the only factor that contributed significantly to disease recurrence and death (hazard ratio, 6.73; P = .045). For group C, these values were 1.9% versus 4.5%, 97% versus 95%, and 99% versus 97%, respectively.The risk for local recurrence was significantly higher in high-risk patients with submucosal rectal cancer than in patients with submucosal colon cancer when treated with only endoscopic resection. The addition of surgery is therefore recommended for patients with submucosal rectal cancer with pathologic features indicating a high risk of tumor progression; University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000008635.

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme ‘Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, ‘Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by ‘Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care.

Background and Aim Non-polypoid colorectal neoplasms are difficult to identify using conventional white light (WL) colonoscopy. The aim of the present pilot study was to compare an autofluorescence imaging (AFI) system with conventional WL colonoscopy for the identification of non-polypoid neoplasms by trainees in a colonoscopic observational situation. Methods We selected clear images with both AFI and WL in the same field taken by experts at the National Cancer Center Hospital, Tokyo, from December 2009 to November 2010. One hundred and eighty sets of images (137 non-polypoid neoplasms and 43 without neoplasm) were selected. The images were reviewed by two trainees without AFI experience. After attending a short educational lecture on the AFI system, the reviewers determined the presence of lesions in the randomly arranged images. The accuracy of AFI and WL for identifying non-polypoid neoplasms by trainees was assessed. Results The sensitivity and specificity for identifying non-polypoid neoplasms by trainees was not significantly different between AFI and WL. However, the specificity tended to be lower in AFI images than in WL images. Conclusions False-positive results tended to be more frequent for the AFI images than for the WL images. Further improvements in the technology and resolution are necessary for the AFI system to be useful for the detection of colorectal neoplasms. At present, clinical application of the AFI system may require more extensive structured training to improve its accuracy in the identification of non-polypoid colorectal neoplasms.

Although regular colonoscopy surveillance is recommended for patients with Lynch syndrome (LS) who underwent partial colectomy, the appropriate interval has not been determined. We report a case of colorectal cancer (CRC) detected by short-interval surveillance colonoscopy (SC) in a patient with LS having a past history of partial colectomy. A 65-year-old man underwent sigmoidectomy for advanced CRC. His family history revealed that his two younger brothers had CRC in their twenties and thirties, respectively, and the patient met with the criteria in the Revised Bethesda Guidelines. After confirming the loss of MSH2 protein expression in the primary tumor, subsequent genetic testing showed germline mutation with a large deletion of exon 7-14 in the MSH2 gene, indicating a diagnosis of LS. After the diagnosis of LS, the patient underwent annual SC. Three years after the initial surgery, superficial submucosal invasive cancer was detected. Subsequently, SC after a 6-month interval revealed a deep submucosal invasive cancer (7 mm in diameter). Although additional surgery was recommended, considering his comorbidities, regular SC rather than colectomy was selected. Even shorter-interval SC carried out within a year is not sufficient to detect endoscopically resectable tumors in some high-risk LS cases.

Background and study aims: The depth of invasion of the bowel wall influences the treatment of colorectal laterally spreading tumors (LSTs). The aim of this study was to evaluate the risk factors and patterns of submucosal invasion in a large series of LSTs that were removed en bloc. Patients and methods: Prospectively collected endoscopic and pathological data on a total of 822 LSTs, ≥ 10 mm in size and removed en block by endoscopic submucosal dissection (n = 670) or surgery (n = 152), were retrospectively analyzed. Results : In 414 LSTs of the granular type, submucosal invasion was detected in 80 cases (19 %; 95 % confidence interval [CI] 16 – 23) and was deep (≥ 1000 μm) in 79 % of cases. The invasion site was under a large (≥ 10 mm) nodule (56 %), depression (28 %), or was multifocal (16 %). Risk factors for deep submucosal invasion on multivariate analysis were the presence of a large nodule (odds ratio [OR] 12, 95 %CI 2 – 59), depression (OR 59, 95 %CI 9 – 387), and invasive pit pattern (OR 33, 95 %CI 12 – 88). The sensitivity and specificity of invasive pit pattern for detection of deep submucosal invasion were 52 % (95 %CI 40 % – 64 %) and 98 % (95 %CI 96 % – 99 %), respectively. In 408 LSTs of the nongranular type, submucosal invasion was detected in 159 cases (39 %; 95 %CI 34 – 44) and was deep in 54 % of cases. The invasion site was under a submucosal mass-like elevation (10 %), depression (45 %), or was multifocal (45 %). Risk factors for deep submucosal invasion were the presence of a submucosal mass-like elevation (OR 8, 95 %CI 1 – 61), depression (OR 28, 95 %CI 8 – 97), and invasive pit pattern (OR 79, 95 %CI 25 – 256). Conclusions : Because of a substantial risk of submucosal invasion and multifocal invasion, granular type LSTs with a large nodule or depression and nongranular type LSTs should be endoscopically removed en bloc.

Serrated lesions, especially sessile serrated adenoma/polyps (SSA/P) are considered one of the most important precursors of colorectal cancers. However, it is still difficult to endoscopically differentiate SSA/P from hyperplastic polyps. In the present review, we mainly focus on the current status and future perspectives of endoscopic diagnosis of colorectal serrated lesions based on the results of a questionnaire survey and report from the Endoscopic Forum Japan (EFJ) 2015 held in Tokyo in August 2015. The proposed diagnostic strategy recommended for colorectal serrated lesions is as follows. (i) For detection, use of an updated image-enhanced endoscopy system including autofluorescence imaging (AFI) and narrow-band imaging (NBI) may be promising. (ii) For differential diagnosis (hyperplastic polyp or SSA/P) of diminutive, small and large serrated lesions, NBI with magnification and magnifying chromoendoscopy using both indigocarmine and crystal violet should be applied, respectively. (iii) For differential diagnosis of SSA/P (with or without cytological dysplasia), magnifying chromoendoscopy, endocytoscopy and updated AFI system modalities might be promising.

Colonoscopy is considered the gold standard to detect and remove colorectal neoplasia. The efficacy of colonoscopy with polypectomy to reduce colorectal cancer incidence and mortality has been demonstrated. Recently, post-polypectomy surveillance colonoscopy has become a necessary intervention in daily practice not only in Western countries but also in the Asia-Pacific region. Therefore, it is crucial to establish new clinical practice guidelines to reduce the number of unnecessary surveillance colonoscopies in order to create space for screening colonoscopy. The Asia-Pacific Consensus group recommended that surveillance colonoscopy interval should be tailored according to risk level of index colonoscopy. However, precise guidelines on interval of surveillance cannot be given because of a lack of prospective data. According to Korean and Australian guidelines, surveillance intervals after index colonoscopy of 5 years for low-risk subjects and 3 years for high-risk subjects are recommended in Asia-Pacific regions at present. Prospective data including long-term outcomes from the Japan Polyp Study, which is a multicenter randomized control trial, would be useful to establish the Asia-Pacific consensus in the near future.

To assess the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the treatment of colorectal lesions.A literature search was conducted from January 2000 to May 2015. The main outcomes were: recurrence after "en bloc" and "piecemeal" resection; procedure related adverse events; the EMR endoscopic success rate and the completely eradicated resection rate (R0) after ESD.A total of 66 studies were included in the analysis. The total number of lesions was 17950 (EMR: 11.873; ESD: 6077). Recurrence rate was higher in the EMR than ESD group (765/7303l vs. 50/3910 OR 8.19, 95% CI 6.2-10.9 p0.0001). EMR-en bloc resection was achieved in 6793/10803 lesions (62.8%) while ESD-en bloc resection was obtained in 5500/6077 lesions (90.5%) (OR 0.18, p0.0001, 95% CI 0.16-0.2). Perforation occurred more frequently in ESD than in EMR group (p0.0001, OR 0.19, 95% CI 0.15-0.24).Endoscopic resection of large colorectal lesions is safe and effective. Compared with EMR, ESD results in higher "en bloc" resection rate and lower local recurrence rate, however ESD has high procedure-related complication rates.

Objective: Endoscopic resection techniques for treating colorectal tumors have advanced re-cently so that large colorectal tumors can now be treated endoscopically, although somepatients experience delayed bleeding after endoscopic resection. Our aim was to clarify therisk factors for delayed bleeding after endoscopic resection for colorectal tumors 20 mm indiameter. Endoscopic submucosal dissection cases were excluded because of the low inci-dence of delayed bleeding after such procedures.Methods: This was a retrospective study using a prospectively completed database andpatient medical records at a single, national cancer institution. A total of 403 colorectal endo-scopic resections were performed on 375 consecutive patients. We analyzed the database andretrospectively assessed patient age, gender, hypertension and current use of anticoagulant(warfarin) or antiplatelet drugs (e.g. aspirin, ticlopidine) as well as tumor location, size, macro-scopic type, histopathological findings, resection method and whether or not placement ofprophylactic clips was performed during the endoscopic resection.Results: The overall rate of delayed bleeding was 4.2% (17/403) and the median intervalbetween endoscopic resection and the onset of delayed bleeding was 2 days (range, 1–14days). All delayed bleeding cases were successfully controlled byendoscopic hemostasis involv-ing clipping and/orelectrocoagulation without the need for surgical interventions or blood transfu-sions. Based on our univariate analysis, the delayed bleeding rate was significantly higher inboth males (P ¼ 0.04) and those patients without prophylactic clip placement (P ¼ 0.04).Conclusions: Our study results indicated that prophylactic clip placement may be an effectivemethod for preventing delayed bleeding afterendoscopic resection for large colorectal tumors.Key words: colorectal tumors – endoscopic resection – delayed bleeding