Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Performance evaluation of a computer-aided polyp detection system with artificial intelligence for colonoscopy.

OBJECTIVES: A computer-aided detection (CAD) system was developed to support the detection of colorectal lesions by deep learning using video images of lesions and normal mucosa recorded during colonoscopy. The study's purpose was to evaluate the stand-alone performance of this device under blinded conditions. METHODS: This multicenter prospective observational study was conducted at four Japanese institutions. We used 326 videos of colonoscopies recorded with patient consent at institutions in which the Ethics Committees approved the study. The sensitivity of successful detection of the CAD system was calculated using the target lesions, which were detected by adjudicators from two facilities for each lesion appearance frame; inconsistencies were settled by consensus. Successful detection was defined as display of the detection flag on the lesion for more than 0.5 s within 3 s of appearance. RESULTS: Of the 556 target lesions from 185 cases, detection success sensitivity was 97.5% (95% confidence interval [CI] 95.8-98.5%). The "successful detection sensitivity per colonoscopy" was 93% (95% CI 88.3-95.8%). For the frame-based sensitivity, specificity, positive predictive value, and negative predictive value were 86.6% (95% CI 84.8-88.4%), 84.7% (95% CI 83.8-85.6%), 34.9% (95% CI 32.3-37.4%), and 98.2% (95% CI 97.8-98.5%), respectively. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000044622).

Development of lightweight and high-strength hollow titanium-plated denture material using three-dimensional printing.

Owing to its desirable ability to fabricate complex shapes, three-dimensional printing is preferred over casting for manufacturing dentures. Furthermore, titanium is widely used in dental implants and dentures because of its high corrosion resistance, biocompatibility, strength, and low density. In this study, we aimed to develop a new metal denture material from three-dimensional-printed (3DP) to achieve lighter weight and greater strength than those of PMMA dentures. Hollow (3DP-H) structure and solid (3DP-S) structure titanium plate specimens of 0.5, 1.0, and 3.0 mm in thickness were used. Casted Ti, casted Co-Cr, and PMMA plates were fabricated for comparison. Elastic modulus, density, thermal conductivity, hardness, and proof stress of the specimens were measured and plotted on a radar chart to enable multifaceted evaluation. The results indicated that the density of the 3DP-H plates reduced by 28-36% compared with those of 3DP-S and cast Ti plates. The weight of the metal-denture-equivalent section of the 0.5-mm-thick 3DP-H titanium-plated denture reduced to two-thirds that of the 2.0-mm-thick PMMA denture. The proof stress of the 0.5-mm-thick 3DP-H plate increased to about 3 times that of the 2.0-mm-thick PMMA plate. The total value of the 0.5-mm-thick 3DP-H titanium plates was higher than it of the 1.0-mm-thick PMMA plates. This study suggests that it is possible to produce 3DP-H titanium plate dentures exhibiting not only extremely lightweight compared to conventional PMMA dentures but also sufficient strength.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection of deep invasive submucosal colorectal cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Pathological T1b CRC cases with an obvious depression and severe fibrosis are at a high risk of vertical incomplete ESD.

Training program using a traction device improves trainees' learning curve of colorectal endoscopic submucosal dissection.

BACKGROUND: 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. METHODS: 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). RESULTS: 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%). CONCLUSIONS: 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.

Guidelines for Colorectal Cold Polypectomy (supplement to "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection").

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.

Outcomes of endoscopic submucosal dissection for colorectal neoplasms: Prospective, multicenter, cohort trial.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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).

Adding Narrow-Band Imaging to Chromoendoscopy for the Evaluation of Tumor Response to Neoadjuvant Therapy in Rectal Cancer.

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. ADICIÓN DE IMÁGENES DE BANDA ESTRECHA A LA CROMOENDOSCOPÍA PARA LA EVALUACIÓN DE LA RESPUESTA TUMORAL A LA TERAPIA NEOADYUVANTE EN EL CÁNCER DE RECTO: La evaluación endoscópica es fundamental para valorar la respuesta clínica completa después de la terapia neoadyuvante en el cáncer de recto.Evaluar los beneficios de agregar endoscopia de imagen de banda estrecha a la cromoendoscopía convencional para predecir la respuesta patológica completa en la muestra quirúrgica.Estudio prospectivo no aleatorizado.Un estudio ad hoc de un ensayo prospectivo de fase II en un solo centro integral de cáncer que evaluó los resultados oncológicos de una terapia neoadyuvante para el cáncer rectal.Pacientes con cáncer rectal bajo de alto riesgo en estadio II-III que recibieron ácido folínico neoadyuvante modificado, fluorouracilo y oxaliplatino más bevacizumab seguido de quimiorradioterapia y cirugía.La respuesta tumoral después de la terapia neoadyuvante se evaluó mediante endoscopia de luz blanca convencional más cromoendoscopía, seguido de imágenes de banda estrecha basadas en un protocolo de diagnóstico predefinido.La precisión diagnóstica para predecir la respuesta patológica 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 más cromoendoscopía y la evaluación agregando imágenes de banda estrecha.En total, 61 pacientes fueron elegibles para el estudio, y 19 tuvieron una respuesta patológica completa (31.1%). Aunque la adición de imágenes de banda estrecha convirtió correctamente el diagnóstico en 3 pacientes, la mejora diagnóstica general en la predicción de la respuesta patológica completa fue limitada (cromoendoscopía convencional versus adición de imágenes de banda estrecha: precisión, 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 mejoró de 0.599 a 0.756 al agregar imágenes de banda estrecha.Un estudio de centro único con un tamaño de muestra relativamente pequeño.A pesar de la mejora limitada en la precisión diagnóstica, agregar imágenes de banda estrecha a la cromoendoscopía mejoró el acuerdo entre evaluadores entre los endoscopistas expertos y no expertos. La imagenología de banda estrecha es una modalidad confiable y prometedora para la estandarización universal del diagnóstico de respuesta clínica completa. Consulte Video Resumen en http://links.lww.com/DCR/B275.

Malignant potential of colorectal neoplasms in Lynch syndrome: an analysis of 325 lesions endoscopically treated at a single institute.

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 <5, ≥5 and <10, ≥10 and <20, and ≥20 mm, respectively. The frequencies of advanced neoplasms in the proximal colon, distal colon and rectum did not significantly differ (36, 35 and 41%, respectively). 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 <10 mm and most of those ≥10 mm were advanced neoplasms, we recommend that in Lynch syndrome patients, careful colonoscopic surveillance should be performed throughout the colon, and all neoplastic lesions, regardless of the size, should be subjected to detailed endoscopic examination, complete resection and detailed pathological examination.

Clinical utility of the pocket-creation method with a traction device for colorectal endoscopic submucosal dissection.

BACKGROUND: 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. 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. RESULTS: 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). CONCLUSIONS: 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.

Randomised comparison of postpolypectomy surveillance intervals following a two-round baseline colonoscopy: the Japan Polyp Study Workgroup.

OBJECTIVE: To 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). DESIGN: A 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. RESULTS: A 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). CONCLUSION: After 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.

Macroscopic and microscopic morphology and molecular profiling to distinguish heterogeneous traditional serrated adenomas of the colorectum.

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.

Japan Gastroenterological Endoscopy Society guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal 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.

Clinicopathological characteristics and frequency of multiple rectal neuroendocrine tumors: a single-center retrospective study.

BACKGROUND: 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. PURPOSE: 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). METHODS: 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 < 8 tumors (several (S) group, n = 21) and those with ≥ 8 tumors (numerous (N) group, n = 3). RESULTS: The overall frequency of M-NETs was 5.7% and that of the N group was 0.8%. The mean tumor diameter in the N group was 6.0 mm (range, 4-8 mm). The lymphatic invasion rates of the S-NETs, and S and N groups of the M-NETs were 8.9%, 5.6%, and 66.7%, respectively. Moreover, the lymph node metastasis rates were 9.2%, 11.1%, and 33.3, respectively. CONCLUSIONS: While M-NETs in the S and N groups had different characteristics, they were rarer in the N group. The N group may have higher rates of lymphatic invasion and lymph node metastasis regardless of tumor size.

A Novel Sterically Bulky Hole Transporter to Remarkably Improve the Lifetime of Thermally Activated Delayed Fluorescent OLEDs at High Brightness.

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.

Serum leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan: a novel colorectal cancer marker.

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 < 10- 10), and its sensitivity and specificity exceeded those of CA19-9. The combination of CEA and LRG-FTG showed a complementary effect and had better sensitivity (84%), specificity (90%), and AUC (0.91 by ROC analysis) than each marker alone or any other previously reported marker. LRG-FTG alone or combined with CEA also corresponded well with patient response to treatment. CONCLUSIONS: We identified LRG-FTG as a new CRC marker, with a sensitivity and specificity exceeding CA19-9. The combination of LRG-FTG and CEA showed much higher sensitivity and specificity than each marker alone. Further validation beyond this initial exploratory cohort is warranted.

Comparison of Targeted vs Random Biopsies for Surveillance of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND & AIMS: A 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. METHODS: We 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. RESULTS: The 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 < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation. CONCLUSIONS: In a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608.

Clinicopathological features of Siewert type II adenocarcinoma: comparison of gastric cardia adenocarcinoma and Barrett's esophageal adenocarcinoma following endoscopic submucosal dissection.

OBJECTIVES: Siewert type II esophagogastric junction adenocarcinoma encompasses both gastric cardia adenocarcinoma (GCA) and Barrett's esophageal adenocarcinoma (BEA) due to short-segment Barrett's esophagus. We compared these two types of Siewert type II esophagogastric junction adenocarcinoma in terms of background factors and clinical outcomes of endoscopic submucosal dissection (ESD). METHODS: We enrolled 139 patients (142 lesions) who underwent ESD from 2006 to 2014 at our institution. Background factors evaluated were age, sex, body mass index, hypertension, hyperlipidemia, hyperuricemia, diabetes mellitus, smoking, drinking, double cancer, and endoscopic findings. Clinical outcomes evaluated were procedure time, en bloc resection rate, curative resection rate, and adverse events. RESULTS: There were 87 GCA lesions (61.2%) and 55 BEA lesions. Features of BEA [55 lesions (38.8%)] included a younger age, small diameter, and a protruding type, along with a high frequency of esophageal hiatal hernia and less mucosal atrophy. There were no significant differences in lifestyle-related background factors between the GCA and BEA groups. Curative resection rate was greater for GCA (81%) than for BEA (66%) (P = 0.01). There were no serious adverse events in either group. Among the factors for noncurative resection, lymphovascular invasion and depth of invasion were greater for BEA (33.3 vs. 7 and 20.7 vs. 8.2%, respectively (P < 0.01). Of the noncured patients, 70% underwent additional surgery and none had postoperative lymph node metastasis. CONCLUSIONS: Siewert type II adenocarcinoma encompasses two types of cancers with different etiologies: GCA and BEA. Although there are no significant differences in lifestyle-related background factors between GCA and BEA, BEA is a risk factor for noncurative resection via ESD.

Accuracy of diagnostic demarcation of undifferentiated-type early gastric cancer for magnifying endoscopy with narrow-band imaging: surgical cases.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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 < 0.0001). The accuracy of diagnosis was higher when atrophy and neutrophil and monocyte infiltration were mild according to the USC (p < 0.05). The additional use of ME-NBI improved the accuracy of diagnosis by 36.5 % compared with the use of WLI alone. CONCLUSION: The use of ME-NBI in the preoperative diagnosis of the demarcation of cancer is useful to prevent postoperative positive surgical margins.