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The Japan Gastroenterological Endoscopy Society published the second edition of the "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection" in 2019 to clarify the indications for colorectal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection and to ensure appropriate preoperative diagnoses as well as effective and safe endoscopic treatment in front-line clinical settings. Endoscopic resection with electrocautery, including polypectomy and EMR, is indicated for colorectal polyps. Recently, the number of facilities introducing and implementing cold polypectomy without electrocautery has increased. Herein, we establish supplementary guidelines for cold polypectomy. Considering that the level of evidence for each statement is limited, these supplementary guidelines must be verified in clinical practice.

Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation.A multicenter, large-scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015.ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra- and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%).This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first-line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136).

Colorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees’ skill acquisition. The differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018). A total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mm2/min vs. 15.9 mm2/min), en bloc resection rate (100% vs. 90%), and R0 resection rate (96% vs. 83%). The rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

Colorectal endoscopic submucosal dissection (ESD) is technically demanding while ensuring safety, especially in cases with fibrosis and/or poor maneuverability. To overcome such difficulties, we developed a novel method called the pocket-creation method with a traction device (PCM with TD). We then evaluated the effectiveness and safety of PCM with TD in colorectal ESD compared to other conventional methods. In total, 324 colorectal lesions treated with ESD from July 2018 to June 2019 were included. The following three treatment strategies were used: conventional ESD (CE), CE with TD, and PCM with TD. Patient backgrounds and treatment outcomes were retrospectively compared and analyzed. As ESD methods, CE, CE with TD, and PCM with TD account for 58% (187/324), 24% (78/324), and 18% (59/324), respectively. No significant difference was observed among the three groups in en bloc and R0 resection rates or adverse events. The rate of lesions with fibrosis and poor maneuverability was significantly higher in the PCM with TD group (CE group vs CE with TD group vs PCM with TD group: fibrosis, 24% vs 47% vs 64%, p

We prove a duality relation among multiple series with three parameters. As special case of it, we obtain some new identities for multiple Hurwitz zeta values, which are relations among extensions of the multiple Hurwitz zeta value.

It has been recently reported that deep invasive submucosal (T1b) colorectal cancer (CRC) without other pathological risk factors for lymph node metastasis has a low rate of lymph node metastasis, increasing the possibility of endoscopic submucosal dissection (ESD) in the future. However, ESD for T1b CRC is technically difficult, and some lesions cannot be resected en bloc. This study aimed to identify the risk factors associated with vertical incomplete ESD in T1b CRC.We retrospectively studied 140 pathological T1b CRC lesions that underwent initial ESD at our institution between January 2011 and October 2020, and categorized them into positive vertical margin (PVM) and negative vertical margin (NVM) groups. The risk factors for PVM were examined using univariate and multivariate analyses, and a subgroup analysis for T1b CRC with an obvious depressed surface was performed.Multivariate analysis revealed obvious depression (hazard ratio [HR]: 7.4; 95% confidence interval [CI]: 2.47-22.5) and severe fibrosis (HR: 11.4; 95% CI: 3.95-33.0) as significant risk factors for PVM. Length of depressed surface ≥12 mm (HR: 6.19; 95% CI: 1.56 -24.6) was identified as an independent predictor of PVM for T1b CRC with an obvious depression.Pathological T1b CRC cases with an obvious depression and severe fibrosis are at a high risk of vertical incomplete ESD.

Background/Aims: Endoscopic submucosal dissection (ESD) for residual or recurrent colorectal lesions after incomplete resection is challenging because of severe fibrosis. This study aimed to compare the efficacy of the pocket-creation method (PCM) with a traction device (TD) with that of conventional ESD for residual or recurrent colorectal lesions.Methods: We retrospectively studied 72 patients with residual or recurrent colorectal lesions resected using ESD. Overall, 31 and 41 lesions were resected using PCM with TD and conventional ESD methods, respectively. We compared patient background and treatment outcomes between the PCM with TD and conventional ESD groups, respectively. The primary endpoints were en bloc resection and R0 resection rates. The secondary endpoints were the dissection speed and incidence of adverse events.Results: En bloc resection was feasible in all cases with PCM with TD, but failed in 22% of cases of conventional ESD. The R0 resection rates for PCM with TD and conventional ESD were 97% and 66%, respectively. Dissection was significantly faster in the PCM with TD group (13.0 vs. 7.9 mm2/min). Perforation and postoperative bleeding were observed in one patient in each group.Conclusions: PCM with TD is an effective method for treating residual or recurrent colorectal lesions after incomplete resection.

Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also several types of precarcinomatous adenomas. It is important to establish practical guidelines wherein preoperative diagnosis of colorectal neoplasia and selection of endoscopic treatment procedures are appropriately outlined and to ensure that actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society compiled colorectal endoscopic submucosal dissection/endoscopic mucosal resection guidelines by using evidence-based methods in 2014. The first edition of these guidelines was published 5 years ago. Accordingly, we have published the second edition of these guidelines based on recent new knowledge and evidence.

Rectal multiple neuroendocrine tumors (M-NETs) are rare, with only few epidemiologic reports on the topic. Therefore, their clinicopathological features are not completely known, and the appropriate treatment strategy has not been established. This study aimed to compare the clinicopathological malignant potential (lymphatic or venous invasion-positive and lymph node metastasis rates) of M-NETs with that of solitary NETs (S-NETs). We retrospectively investigated 369 patients with NETs of the rectum. Patients who underwent colonoscopy at the Cancer Institute Hospital between January 1979 and 2016 and diagnosed with S-NETs were included, and S-NETs were found in 348 patients. Patients with M-NETs were classified into two groups as follows: patients with

Background and Aim Although colorectal laterally spreading tumors (LSTs) can be classified into four subtypes, the histopathological characteristics are known to differ among these subtypes. We therefore performed a logistic regression analysis to determine whether the risk of pathological T1 cancer of large colorectal LSTs can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. Methods In the main study, we assessed 1236 colorectal adenomas or early cancers that were classified as LSTs measuring 20 mm or more in diameter and treated endoscopically. Logistic regression analysis was performed to determine whether factors such as the subtype of LST could be used to predict the risk of pathological T1 cancer. A validation study of 356 large colorectal LSTs was conducted to confirm the validity of the results obtained in the main study. Results The locations and tumor diameter of the LSTs in the main study were found to differ significantly according to the LST subclassification (P, We performed a logistic regression analysis to determine whether the risk of invasive cancer of large colorectal laterally spreading tumors (LSTs) measuring 20 mm or greater and treated endoscopically can be predicted based on factors such as endoscopic findings in a large group of patients enrolled in a multicenter study in Japan. The locations and tumor diameters of the LSTs were found to differ significantly according to the LST subclassification. The risk of pathological T1 cancer was significantly associated with LST subclassification and tumor diameter.

Background and study aims Colorectal endoscopic submucosal dissection (ESD) is technically challenging owing to submucosal fibrosis and difficult endoscope manipulation. Therefore, various traction methods have been reported. We often use a simple looped nylon thread attached to a clip to assist with dissection. We assessed the feasibility of mentor-guided colorectal ESD using this traction device (TD). Patients and methods From December 2017 to March 2018, we retrospectively reviewed outcomes of 101 colorectal ESDs performed by two groups of endoscopists (A, 5 endoscopists with colorectal ESD experience of 300 cases). Group A was further divided into two subgroups that performed ESD with or without TD. Results No significant difference was observed in ESD completion rates (86.1 % [62/72] vs. 96.6 % [28/29]; odds ratio [OR], 0.22; 95 % confidence interval [CI], 0.005 – 1.71; P = 0.17) or procedure times (52.0 min vs. 40.0 min; P = 0.27) and adverse event rates between groups A and B. The rate of TD use was significantly higher in group A than in group B (44.4 % [32/72] vs. 20.7 % [6/29]; OR, 3.03; CI, 1.04 – 10.23; P = 0.03). The completion rate was not different between the two subgroups of group A (with vs. without TD) (81.2 % [26/32] vs. 90.0 % [36/40]; OR, 0.49; CI, 0.09 – 2.29; P = 0.32); however, the proportion of fibrosis cases was significantly higher in the TD-use group (46.8 % [15/32] vs. 22.5 % [9/40]; OR, 2.99; CI, 0.98 – 9.59; P = 0.03). Conclusion Mentor-guided colorectal ESD using TD was performed efficiently, safely, and in a manner comparable to that of experts.

Colorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees' skill acquisition.The differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018).A total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mmThe rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

Background Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. Methods A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. Results Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2–40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of Conclusions Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and

BACKGROUND Endoscopic assessment is crucial in diagnosing clinical complete response after neoadjuvant therapy in rectal cancer. OBJECTIVE The purpose of this research was to evaluate the benefits of adding narrow-band imaging endoscopy to conventional chromoendoscopy in predicting pathologic complete response in the surgical specimen. DESIGN This was a prospective nonrandomized study. SETTINGS This was an ad hoc study of a prospective phase II trial at a single comprehensive cancer center that evaluated oncologic outcomes of a neoadjuvant therapy for rectal cancer. PATIENTS Patients with high-risk stage II to III low rectal cancer who received neoadjuvant modified folinic acid, fluorouracil, and oxaliplatin plus bevacizumab followed by chemoradiotherapy and surgery were included. INTERVENTION Tumor response after neoadjuvant therapy was evaluated using conventional white light endoscopy plus chromoendoscopy then followed by using narrow-band imaging based on a predefined diagnostic protocol. MAIN OUTCOME MEASURES Diagnostic accuracy for predicting pathologic complete response and inter-rater agreement between an expert and trainee endoscopists were compared between the assessments using conventional white light endoscopy plus chromoendoscopy and the assessment adding narrow-band imaging. RESULTS In total, 61 patients were eligible for the study, and 19 had pathologic complete response (31.1%). Although the addition of narrow-band imaging correctly converted the diagnosis in 3 patients, overall diagnostic improvement in predicting pathologic complete response was limited (conventional chromoendoscopy vs adding narrow-band imaging: accuracy, 70.5% vs 75.4%; sensitivity, 63.2% vs 73.7%; specificity, 73.8% vs 76.2%; positive predictive value, 52.2% vs 58.3%; and negative predictive value, 81.6% vs 86.5%). A κ value for the inter-rater agreement improved from 0.599 to 0.756 by adding narrow-band imaging. LIMITATIONS This was a single-center study with a relatively small sample size. CONCLUSIONS Despite the limited improvement in diagnostic accuracy, adding narrow-band imaging to chromoendoscopy improved inter-rater agreement between the expert and nonexpert endoscopists. Narrow-band imaging is a reliable and promising modality for universal standardization of the diagnosis of clinical complete response. See Video Abstract at http://links.lww.com/DCR/B275. ADICION DE IMAGENES DE BANDA ESTRECHA A LA CROMOENDOSCOPIA PARA LA EVALUACION DE LA RESPUESTA TUMORAL A LA TERAPIA NEOADYUVANTE EN EL CANCER DE RECTO: La evaluacion endoscopica es fundamental para valorar la respuesta clinica completa despues de la terapia neoadyuvante en el cancer de recto.Evaluar los beneficios de agregar endoscopia de imagen de banda estrecha a la cromoendoscopia convencional para predecir la respuesta patologica completa en la muestra quirurgica.Estudio prospectivo no aleatorizado.Un estudio ad hoc de un ensayo prospectivo de fase II en un solo centro integral de cancer que evaluo los resultados oncologicos de una terapia neoadyuvante para el cancer rectal.Pacientes con cancer rectal bajo de alto riesgo en estadio II-III que recibieron acido folinico neoadyuvante modificado, fluorouracilo y oxaliplatino mas bevacizumab seguido de quimiorradioterapia y cirugia.La respuesta tumoral despues de la terapia neoadyuvante se evaluo mediante endoscopia de luz blanca convencional mas cromoendoscopia, seguido de imagenes de banda estrecha basadas en un protocolo de diagnostico predefinido.La precision diagnostica para predecir la respuesta patologica completa y el acuerdo entre evaluadores entre un experto y un endoscopista en entrenamiento se compararon entre las evaluaciones utilizando endoscopia de luz blanca convencional mas cromoendoscopia y la evaluacion agregando imagenes de banda estrecha.En total, 61 pacientes fueron elegibles para el estudio, y 19 tuvieron una respuesta patologica completa (31.1%). Aunque la adicion de imagenes de banda estrecha convirtio correctamente el diagnostico en 3 pacientes, la mejora diagnostica general en la prediccion de la respuesta patologica completa fue limitada (cromoendoscopia convencional versus adicion de imagenes de banda estrecha: precision, 70.5% versus 75.4%; sensibilidad, 63.2% versus 73.7%; especificidad, 73.8% versus 76.2%; valor predictivo positivo, 52.2% versus 58.3%; y valor predictivo negativo, 81.6% versus 86.5%). Un valor de kappa para el acuerdo entre evaluadores mejoro de 0.599 a 0.756 al agregar imagenes de banda estrecha.Un estudio de centro unico con un tamano de muestra relativamente pequeno.A pesar de la mejora limitada en la precision diagnostica, agregar imagenes de banda estrecha a la cromoendoscopia mejoro el acuerdo entre evaluadores entre los endoscopistas expertos y no expertos. La imagenologia de banda estrecha es una modalidad confiable y prometedora para la estandarizacion universal del diagnostico de respuesta clinica completa. Consulte Video Resumen en http://links.lww.com/DCR/B275.

ObjectiveTo assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs).DesignA prospective multicentre randomised controlled trial was conducted in 11 Japanese institutions. The enrolled participants underwent a two-round baseline colonoscopy (interval: 1 year) to remove all neoplastic lesions. Subsequently, they were randomly assigned to undergo follow-up colonoscopy at 1 and 3 years (2-examination group) or at 3 years only (1-examination group). The incidence of AN, defined as lesions with low-grade dysplasia ≥10 mm, high-grade dysplasia or invasive cancer, at follow-up colonoscopy was evaluated.ResultsA total of 3926 patients were enrolled in this study. The mean age was 57.3 (range: 40–69) years, and 2440 (62%) were male. Of these, 2166 patients were assigned to two groups (2-examination: 1087, 1-examination: 1079). Overall, we detected 29 AN in 28 patients at follow-up colonoscopy in both groups. On per-protocol analysis (701 in 2-examination vs 763 in 1-examination group), the incidence of AN was similar between the two groups (1.7% vs 2.1%, p=0.599). The results of the non-inferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat analysis). NP-CRNs composed of dominantly of the detected AN (62%, 18/29), and most of them were classified into laterally spreading tumour non-granular type (83%, 15/18).ConclusionAfter a two-round baseline colonoscopy, follow-up colonoscopy at 3 years detected AN, including NP-CRNs, as effectively as follow-up colonoscopies performed after 1 and 3 years.

Background and aims Precise endoscopic assessment of complete response to neoadjuvant chemoradiotherapy before surgery is important for optimizing surgical and non-surgical treatment. We prospectively evaluated the accuracy of the newly proposed endoscopic criteria to identify complete response, using magnifying chromoendoscopy. Methods New endoscopic criteria were created to define endoscopic complete response, near complete response and incomplete response, using magnifying chromoendoscopy. The criteria contained notable endoscopic findings, including shape of the scar, state of the ulcer, finding of white moss, presence of residual protruded nodules, regenerated pits of the scar, presence of neoplastic pit patterns, and extension of rectal wall. Seventy-nine patients with rectal cancer who received neoadjuvant chemoradiotherapy were prospectively evaluated 1–3 days before resection. Diagnostic accuracy to identify pathological complete response and interobserver agreement among a supervising colonoscopist and two trainees were investigated. Results Pathological complete response was obtained in 17 patients (21.5%). The diagnostic accuracy of endoscopic complete response was 85%, with a sensitivity of 47%, specificity of 97%, positive predictive value of 80% and negative predictive value of 77%. The kappa-value for interobserver agreement across 3 doctors was 0.57 (standard error, 0.74; 95% confidence interval, 0.39–0.76). Conclusion The newly proposed endoscopic criteria using magnifying chromoendoscopy achieved excellent diagnostic accuracy to determine good responders to neoadjuvant chemoradiotherapy in rectal cancer, with fair interobserver agreement. The criteria could be clinically useful to select patients for non-surgical management.

Background Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19–9 are used in clinical practice as tumor markers to diagnose or monitor colorectal cancer (CRC) patients, However, their specificities and sensitivities are not ideal, and novel alternatives are needed. In this study, mass spectrometry was used to search for screening markers, focusing on glycan alterations of glycoproteins in the sera of CRC patients. Methods Glycopeptides were prepared from serum glycoproteins separated from blood samples of 80 CRC patients and 50 healthy volunteers, and their levels were measured by liquid chromatography time-of flight mass spectrometry (LC–TOF–MS). Results Leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan (LRG–FTG) was identified as CRC marker after evaluating 30,000 candidate glycopeptide peaks. The average LRG–FTG level in CRC patients (1.25 ± 0.973 U/mL) was much higher than that in healthy volunteers (0.496 ± 0.433 U/mL, P

For the practical application of organic light emitting devices (OLEDs) based on thermally activated delayed fluorescence (TADF) for large area TV and solid state lighting, low power consumption as well as the operation lifetime at high brightness over 1000 cd m-2 must be improved. Here, we have developed a novel hexaphenylbenzene-based sterically bulky hole-transport layer named 4DBTHPB with deep ionization potential of 5.8 eV and high triplet energy of 2.7 eV. By using 4DBTHPB, we can realize a highly efficient and stable TADF OLED exhibiting external quantum efficiency of 21.6 % and power efficiency of 54.3 lm W-1 and operation lifetime at 50 % (LT50 ) of approximately 10 000 h at an initial luminance of 1000 cd m-2 . These performances are comparable to those of the state-of-the-art green phosphorescent OLEDs reported in the scientific literatures.

For decades, hyperbaric oxygen therapy has been considered a treatment option in patients with chronic radiation-induced proctitis after pelvic radiation therapy. Refractory cases of chronic radiation-induced proctitis include ulceration, stenosis, and intestinal fistulas with perforation. Appropriate treatment needs to be given. In the present study, we assessed the efficacy of hyperbaric oxygen therapy in five patients with radiation-induced rectal ulcers. Significant improvement and complete ulcer resolution were observed in all treated patients; no side-effects were reported. Hyperbaric oxygen therapy has a low toxicity profile and appears to be highly effective in patients with radiation-induced rectal ulcers. However, hyperbaric oxygen therapy alone failed to improve telangiectasia and easy bleeding in four of the five patients; these patients were further treated with argon plasma coagulation (APC). Although hyperbaric oxygen therapy may be effective in healing patients with ulcers, it seems inadequate in cases with easy bleeding. Altogether, these data suggest that combination therapy with hyperbaric oxygen therapy and APC may be an effective and safe treatment strategy in patients with radiation-induced rectal ulcers.

Colorectal endoscopic submucosal dissection (ESD) is technically demanding while ensuring safety, especially in cases with fibrosis and/or poor maneuverability. To overcome such difficulties, we developed a novel method called the pocket-creation method with a traction device (PCM with TD). We then evaluated the effectiveness and safety of PCM with TD in colorectal ESD compared to other conventional methods.In total, 324 colorectal lesions treated with ESD from July 2018 to June 2019 were included. The following three treatment strategies were used: conventional ESD (CE), CE with TD, and PCM with TD. Patient backgrounds and treatment outcomes were retrospectively compared and analyzed.As ESD methods, CE, CE with TD, and PCM with TD account for 58% (187/324), 24% (78/324), and 18% (59/324), respectively. No significant difference was observed among the three groups in en bloc and R0 resection rates or adverse events. The rate of lesions with fibrosis and poor maneuverability was significantly higher in the PCM with TD group (CE group vs CE with TD group vs PCM with TD group: fibrosis, 24% vs 47% vs 64%, p 0.001; poor maneuverability, 5.3% vs 13% vs 20%, p = 0.002). Dissection speed was significantly higher in the PCM with TD than in the CE with TD group (p = 0.003).PCM with TD can achieve a stable en bloc resection rate and R0 dissection rate without adverse events even in the hands of trainees, irrespective of the size and location of the lesion, presence of fibrosis, and under poor maneuverability conditions.

Objectives Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. Methods Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered as a separate sample. DNA was extracted from 177 samples of 60 lesions and amplified to screen for BRAF and K/NRAS mutations. Results Heterogeneous TSA samples were classified into four categories: sessile serrated lesion with TSA (SA-1); TSAs with microvesicular hyperplastic polyp (SA-2); TSAs with unclassified adenoma, characterized by tubulo-serrated histology (SA-3); and TSAs with conventional adenomas (SA-4). On endoscopy, SA-1 lesions had sessile-elevated morphology with the small reddish elevations; SA-2 lesions had a pedunculated appearance with a whitish mucosal component at the stalk; SA-3 lesions had a sessile-elevated component surrounded by flat spreading margins; and SA-4 lesions had mixed adenomatous morphology. Eighteen of the 19 category SA-1 and -2 lesions (95%) had BRAF mutations, and all of the SA-3 and -4 lesions had K/NRAS mutations. Conclusions Traditional serrated adenomas were classified into two phenotypes according to their molecular characteristics: microvesicular serrated subtypes with BRAF mutations (SA-1 and -2 lesions) and subtypes containing tubulo-serrated/conventional adenoma with K/NRAS mutations (SA-3 and -4 lesions). Each subtype had characteristic macroscopic and microscopic morphologies and was distinct on endoscopy.

Background & AimsA random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC.MethodsWe performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups.ResultsThe mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679–2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P

Owing to increased awareness and use of narrow-band imaging, there are more opportunities to treat superficial pharyngeal cancer (SPC). The present study aimed to describe the short- and long-term outcomes of endoscopic resection (ER) for SPC.This study included 166 consecutive SPC in 113 patients treated during 2006 to 2013 at one referral cancer center. In the first period, we treated patients using endoscopic mucosal resection (EMR), in the second period using conventional ESD (cESD) and in the recent period using double-scope ESD (dsESD), which involves a second thin endoscope for assistance to produce traction. Median follow-up period was 30 months.All lesions were diagnosed as squamous cell carcinoma. Complete resection rate of cESD and dsESD procedures was 56.4% and 82.3% (P 0.01), and local recurrence rate was 2.6% and 0.0%, respectively. Procedure duration was significantly shorter for dsESD than for cESD (P 0.05). Four cases of recurrent lymph node (LN) metastasis were observed; however, all patients with LN metastases survived to a 48-month median interval after neck dissection. Risk factors for LN metastasis included subepithelium invasion, tumor thickness1000 μm, droplet infiltration, and lymphovascular invasion. Overall survival rate after 5 years was 79.5%; no patients died of SPC. Cumulative rate of metachronous SPC after 5 years was 46.5%.ER for SPC is a feasible and effective treatment, although metachronous SPC occurred frequently. For the technique of ER, dsESD was effective.

The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) in undifferentiated-type early gastric cancers (UD-type EGCs) is unclear. This study investigated the accuracy of ME-NBI in the diagnostic demarcation. Among UD-type EGCs that were initially surgically resected between June 2011 and August 2014 in this hospital, 74 lesions were studied that were preoperatively diagnosed with white-light imaging (WLI) or endoscopic ultrasonography as lesions for which endoscopic treatment was not indicated and found to be early gastric cancers by postoperative pathology. The demarcation line was marked on the most oral and anal sides with argon plasma coagulation using WLI and ME-NBI, and the diagnostic demarcation of cancer was defined as correct, if consistent with the results of postoperative pathology. The length of extension into the proliferative zone, distance between crypts and inflammatory cell infiltration (updated Sydney classification: USC) were compared between the correctly diagnosed and the misdiagnosed cases. The diagnosis was correct in 62 cases (83.8 %). The average distance between crypts in correctly diagnosed and misdiagnosed cases was approximately 1.9 and 1.3 times, respectively, that in normal mucosa (p

The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46–79 years), gender (male, 6; female, 15), clinical stage (I, 20; II 1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6–39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4–109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum.

Background and Aim In the present study, we investigated the advantages of narrow-band imaging (NBI) for efficient diagnosis of sessile serrated adenoma/polyp (SSA/P). The main objective of this study was to analyze the characteristic features of cancer coexisting with serrated lesion by carrying out NBI. Methods We evaluated 264 non-malignant serrated lesions by using three modalities (conventional white light colonoscopy, magnifying chromoendoscopy, and magnifying NBI). Of the evaluated cancer cases with serrated lesions, 37 fulfilled the inclusion criteria. Results In diagnosing non-malignant SSA/P, an expanded crypt opening (ECO) under magnifying NBI is a useful sign. One hundred and twenty-five lesions (87%) of observed ECO were, at the same time, detected to have type II open pit pattern, which is known to be a valuable indicator when using magnifying chromoendoscopy. ECO had high sensitivity of 80% for identifying SSA/P, with 62% specificity and 83% positive predictive value (PPV). In detecting the cancer with SSA/P, irregular vessels under magnifying NBI were frequently observed with 100% sensitivity and 99% specificity, 86% PPV and 100% negative predictive value. Conclusions A focus on irregular vessels in serrated lesions might be useful for identification of cancer with SSA/P. This is an advantage of carrying out magnifying NBI in addition to being used simultaneously with other modalities by switching, and observations can be made by using wash-in water alone. We can carry out advanced examinations for selected lesions with irregular vessels. To confirm cancerous demarcation and invasion depth, a combination of all three aforementioned modalities should be done.

Determining the depth of invasion of early stage colorectal cancer has been emphasized as a means of improving endoscopic diagnostic accuracy. Recent studies have focused on other pathological risk factors for lymph node metastasis (LNM). We investigated the significance of depth of invasion and predictive properties of other endoscopic findings. We retrospectively investigated 846 patients with submucosal invasive (T1) colorectal cancer who received an accurate pathological diagnosis and were treated between January 2005 and December 2016. Pathological risk factors associated with LNM were reviewed. We divided patients into groups: low-risk T1 colorectal cancer (LRC; no risk factors) and high-risk T1 colorectal cancer (HRC; exhibiting lymphovascular invasion, tumor budding grade of 2/3, and/or poor differentiation) and studied predictive endoscopic factors for HRC. Significant risk factors for LNM in multivariate analysis were lymphovascular invasion [odds ratio (OR) 8.09; 95% confidence interval (CI) 3.84–17.1], tumor budding (OR 1.89; 95% CI 1.09–3.29), and histological differentiation (OR 2.09; 95% CI 1.12–3.89). The LNM-positive rate with only deep submucosal invasion was 1.6%. Significant predictive factors for HRC in multivariate analysis identified rectal tumor location (OR 1.92; 95% CI 1.35 –2.72, depression (OR 2.73; 95% CI 1.96 –3.80), protuberance within the depression (OR 2.58; 95% CI 1.39– 4.78), expansiveness (OR 2.39; 95% CI 1.27– 4.50), and loss of mucosal patterns (OR 1.90; 95% CI 1.20 –3.01) as significant factors. Rectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

Three different sized zinc oxide (ZnO) nanoparticles were synthesized as spherical ZnO (S-ZnO), rodlike ZnO (R-ZnO), and intermediate shape and size ZnO (I-ZnO) by controlling the reaction time. The average sizes of the ZnO nanoparticles were 4.2 nm × 3.4 nm for S-ZnO, 9.8 nm × 4.5 nm for I-ZnO, and 20.6 nm × 6.2 nm for R-ZnO. Organic light-emitting devices (OLEDs) with these ZnO nanoparticles as the electron injection layer (EIL) were fabricated. The device with I-ZnO showed lower driving voltage and higher power efficiency than those with S-ZnO and R-ZnO. The superiority of I-ZnO makes it very effective as an EIL for various types of OLEDs regardless of the deposition order or method of fabricating the organic layer, the ZnO layer, and the electrode.

Background and Aim Endoscopic submucosal dissection (ESD) is useful as a minimally invasive treatment option for early gastric cancer. ESD is also used in the management of postoperative remnant gastric cancers in the stomach and gastric tube cancers. Perforation and delayed bleeding have been the main complications of ESD reported in the management of gastric tube cancer. However, in the current literature, there is no description of precordial skin burns caused by electrical coagulation. Methods While we treated 22 patients with gastric tube cancers by ESD from 2005 to 2014, we experienced five skin burns in four patients after ESD. We retrospectively analyzed clinical characteristics of precordial skin burn as a complication of ESD. Results All skin burns occurred in patients reconstructed using a presternal route, whose incidence of precordial skin burn was 55.6%. In all cases, lesions were located in the upper or middle third of gastric tubes irrespective of their direction. Skin burn developed on postoperative day (POD) 1 or POD 2, taking 4–7 days to heal and was accompanied by high fever in 60% of cases. Conclusion The present study suggests that when carrying out ESD for gastric tube cancer using the presternal route, it is necessary to consider the occurrence of a precordial skin burn as a possible complication.

Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions and eradication therapy. However, some reports have described cases of H. pylori-negative gastric cancers (HpNGC), and the prevalence was 0.42–5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD-type) is more frequent than the differentiated type (D-type). The UD-type is mainly signet ring-cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D-type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor-like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patient's quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.

Purpose: In 1977, the Japanese Society for Cancer of the Colon and Rectum (JSCCR) published the first edition of the general guidelines that described how to record clinical and histopathological findings of colorectal carcinomas (CRCs) and how to treat these cancers, and since then, the guidelines were revised several times. The aim of this study was to examine the impact of the revisions of the JSCCR guidelines on the treatment of submucosal CRCs (T1-CRCs) in Japanese clinical settings. Methods: Questionnaires were sent to all 391 member institutions of the JSCCR. The questionnaires consisted of 2 parts: details of the institutions and treatment strategies for T1-CRCs. Results: 73 (19 %) institutions responded to the survey. The number of treated T1-CRCs has increased year by year, and the rate of endoscopic resection for T1-CRCs has significantly increased with revisions of the guidelines (1417 [47 %] of 2985 T1-CRCs in 2003 – 2005, 2110 [50 %] of 4212 in 2006 – 2008, and 2546 [54 %] of 4686 in 2009 – 2011, P Conclusion: The revisions of the JSCCR guidelines have influenced the treatment of T1-CRCs in Japanese clinical settings. There is room to revise the criteria for curative endoscopic resection to avoid unnecessary surgeries.

The management of rectal cancer is a significant oncologic challenge because rectal cancer has a poor prognosis among the various types of colorectal cancer. There have been several recent reports on a nonoperative approach for advanced lower rectal cancer, and this may be best for local disease control. However, objective evaluation of tumor response after preoperative chemoradiotherapy has not been standardized. The purpose of this study is to evaluate our method of endoscopic evaluation of complete response. This is a retrospective chart review. All patients received a long course of preoperative chemoradiotherapy (5-fluorouracil-based chemotherapy and 45–50.4 Gy) followed by radical surgical resection from May 2005 to March 2012 in The Cancer Institute Hospital of Japanese Foundation for Cancer Research. One hundred fifty-seven patients were reviewed consecutively. Criteria for endoscopic complete response were defined with a focus on the degree of ulcer healing and pit pattern without magnification. Endoscopic CR (E-CR) evaluation with our definitions reflected histopathologic response evaluation with an accuracy of 91.7 %, sensitivity of 27.8 %, specificity of 100 %, positive predictive value (PPV) of 100 %, and negative predictive value (NPV) of 91.4 % (p

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.

BACKGROUND AND AIM Anticoagulants are used to prevent thromboembolic events. Direct oral anticoagulants (DOAC) are our new choice; however, their effect on bleeding risk for endoscopic treatment has not been reported. We aimed to assess the clinical effect of DOAC compared to warfarin for gastric endoscopic submucosal dissection (ESD). METHODS We retrospectively studied 97 patients on anticoagulants and treated 108 gastric neoplasms with ESD in three referral institutes. Twenty-four patients were taking DOAC, including dabigatran (12), rivaroxaban (11), and apixaban (one) and 73 were taking warfarin. RESULTS In the DOAC group, delayed bleeding rate was significantly higher in patients on rivaroxaban than in patients on dabigatran (45% vs 0%, P

A 72-year-old male with nausea and heartburn was found to have early pharyngeal squamous cell carcinoma, superficial and advanced esophageal squamous cell carcinoma and early esophageal adenocarcinoma by esophagogastroduodenoscopy. Computerized tomography demonstrated left cardiac lymph node swellings. We prioritized the treatment for esophageal squamous cell carcinoma, as this was the most advanced cancer among the triple primaries. The patient underwent neoadjuvant chemotherapy for esophageal squamous cell carcinoma followed by esophagectomy. Four months after esophagectomy, endoscopic submucosal dissection for pharyngeal squamous cell carcinoma was performed. This is a first report of pharyngeal squamous cell carcinoma, esophageal squamous cell carcinoma and esophageal adenocarcinoma occurring as triple primary cancers in a single patient. Smoking-induced tumor formation through DNA methylation is a common risk factor for patients with triple primary malignancies, being an example of epigenetic field cancerization induced by exposure to carcinogenic factors.

Conventional endoscopic resection (CER) includes polypectomy and endoscopic mucosal resection. The most common complications related to these techniques are post procedure bleeding and perforation. The aim of this study was to evaluate the outcomes of CER for colorectal neoplasms ≧20 mm and to clarify predictive factors for complications. We conducted a multicenter prospective study at 18 specialized institutes. From October 2007 to December 2010, 1,029 CERs were performed at participating institutes. We collected the data prospectively and analyzed gender, age, tumor size, gross appearance, mode of resection, etc. The mean size of polyps resected was 26.4 ± 8.6 mm (range 20–120 mm). The final pathology was Vienna classification category 1 or 2 in 24, category 3 in 502, and category 4 or 5 in 503 lesions. Post procedure bleeding and intra procedure perforation occurred, respectively, in 16 (1.6 %) and 8 cases (0.78 %). The overall complication rate was 2.3 %. Risk factors for bleeding in multivariate analysis were only patients under 60 years of age. Risk factors for perforation in multivariate analysis were en bloc resection and Vienna classification category 4–5. The difference of complication rate was not statistically significant regarding gender, size, tumor location, gross appearance, treatment method, and kind of insufflation. CER is a safe, efficient, and effective minimally invasive therapy for large colorectal lesions. However, care should be taken for post procedure bleeding in patients under 60 years of age and for perforation in cases of Vienna classification category 4–5 or when an en bloc resection is tried.

Colorectal endoscopic submucosal dissection (C-ESD) is a promising but challenging procedure. We aimed to evaluate the factors associated with technical difficulties (failure of en bloc resection and procedure time, ≥2 h) and adverse events (perforation and bleeding) of C-ESD. We conducted a retrospective exploratory factor analysis of a prospectively collected cohort in 15 institutions. Eight-hundred sixteen colorectal neoplasms larger than 20 mm from patients who underwent C-ESD were included. We assessed the outcomes of C-ESD and risk factors for technical difficulties and adverse events. Of the 816 lesions, 767 (94 %) were resected en bloc, with a median procedure time of 78 min. Perforation occurred in 2.1 % and bleeding in 2.2 %. Independent factors associated with failure of en bloc resection were low-volume center (