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OBJECTIVES Data on the long-term outcomes of endoscopic submucosal dissection (ESD) performed in elderly patients with early colorectal cancer (CRC) are limited. We analyzed the prognosis of elderly CRC patients, not only from the viewpoint of treatment curability but also from the patients' baseline physical condition assessed by several indexes. METHODS A retrospective analysis of 729 patients aged ≥75 years who underwent ESD for Tis/T1 CRC in 16 institutions was conducted. The patients were classified into three groups based on curability: curative ESD (Group A, n = 582), non-curative ESD with additional surgery (Group B, n = 60), and non-curative ESD without additional surgery (Group C, n = 87). Overall survival (OS) was compared among the groups, and factors associated with reduced OS were investigated. RESULTS The median follow-up periods in Groups A, B, and C were 41, 49, and 46 months, respectively (P = 0.62), during which 92 patients died. Two patients (0.3%) in Group A, none (0%) in Group B, and three (3.4%) in Group C died of CRC. Three-year OS rates in Groups A, B, and C were 93.9%, 96.1%, and 90.1%, respectively, without a significant difference (P = 0.07). Multivariate analysis indicated low (

We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study.We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative,2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C).Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS.ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Although molecular bromine (Br2) is a useful brominating reagent, it is not easy to handle. Herein, we describe the preparation of a novel air-stable bromine complex prepared from 1,3-dimethyl-2-imidazolidinone (DMI) and Br2, which was identified to be (DMI)2HBr3 by spectral and X-ray techniques. This complex was then used to brominate olefins, carbonyl compounds, and aromatics, as well as in the Hofmann rearrangement. Yields of reaction products using this complex were almost the same or superior to those using other bromine alternatives.

Background and study aims A post-endoscopic submucosal dissection (ESD) scar is expected to look homogeneous, however, some patients develop benign polypoid nodule scar (PNS). Incidence of PNS is unknown, yet these scars have direct clinical implications because they may render evaluation of post-ESD neoplastic recurrence difficult. Therefore, we reviewed the clinical experience of 5 ESD referral centers and evaluated their PNS incidence and clinical management. Patients and methods This was a retrospective multicenter case series enrolling patients that underwent R0, curative gastric ESD from 2003 to 2015 in 5 academic centers. PNS was defined as ESD site nodularity with hyperplastic or regenerative tissue histology. Results A total of 2275 patients underwent gastric ESD with endoscopy control and 28 patients (18 men/10 women) developed PNS for overall incidence of 1.2 %. Incidence of PNS ranged from 0.15 % to 11.4 % between centers. All patients that developed PNS had primary neoplastic lesions located in the distal stomach. Considering only lesions situated in the antrum (n = 912), incidence of PNS was 3.1 %. After mean follow-up of 43 months (range 6 – 192), no malignant recurrence in the PNS has been identified. In five patients (17.8 %) PNS disappeared after a mean of 18 months. Conclusion PNS occurs exclusively after ESD in the distal stomach in approximately 3.1 % of patients. Although PNS appearance can be concerning, no malignant recurrence was observed after curative R0 resection. Therefore, PNS should be viewed as a benign alteration that does not require any type of intervention, other than endoscopic surveillance.

Background Musculocontractural Ehlers-Danlos syndrome is a new and rare subtype of Ehlers-Danlos syndrome in which anesthetic considerations for airway and respiratory management, prevention of skin injuries and joint dislocations, and hemostatic management for severe perioperative bleeding are required. Case presentation A 19-year-old woman with musculocontractural Ehlers-Danlos syndrome was scheduled to undergo posterior spinal fusion from the 4th thoracic to the 4th lumbar vertebrae under general anesthesia. Her trachea was easily intubated with a videolaryngoscope despite a small mouth and micrognathia. Pressure-controlled ventilation with limited peak inspiratory pressure was performed for prevention of pneumothorax. Skin damage and joint luxation were prevented by using a low rebounding mattress, terpolymer-based barrier film, and careful patient positioning. Blood transfusion was effectively performed on the basis of point-of-care viscoelastic hemostatic assay monitoring. She had an uneventful postoperative course without any complications. Conclusions We safely managed a patient with musculocontractural Ehlers-Danlos syndrome undergoing scoliosis surgery.

Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD. We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin. Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding. The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.

BACKGROUND AND AIM Prophylactic clipping (PC) after polypectomy has the potential to prevent post-polypectomy bleeding (PPB). We aimed to evaluate the effectiveness of PC in preventing PPB for

Objectives Differentiation between gastric adenocarcinoma and low-grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aimed to clarify the incidence of carcinoma in specimens—obtained via endoscopic resection (ER)—from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy. Methods In this multi-center, prospective, observational study, patients with gastric adenoma (Vienna category 3 or 4.1) diagnosed on endoscopic forceps biopsy were enrolled. All the specimens were subjected to histopathological central review. Primary endpoint was the incidence of carcinoma (Vienna category 4.2 or over) among the biopsy-proven gastric LGA. Secondary endpoints were the histological findings of resected specimens, clinicopathological features of carcinoma, and short-term outcomes of all ER cases. Results Ninety-five patients with 104 lesions diagnosed as gastric adenoma were enrolled. After central review of the biopsy specimens, 47 lesions were diagnosed as LGA and 7 lesions (15%) as adenocarcinoma (95% confidence interval, 7.6–28%). Carcinoma was detected in lesions that had a minimum size of 6 mm; the incidence of carcinoma was higher in the larger lesions. There was a histological discrepancy between biopsy and ER material in more than 60% of the cases. Conclusions A substantial proportion of biopsy-proven gastric LGA specimens were diagnosed as adenocarcinoma after ER. This indicated the histological discrepancy between biopsy-proven gastric LGA and histology of the resected material. This article is protected by copyright. All rights reserved.

Background and study aims It remains unclear whether the experience of endoscopists affects clinical outcomes for acute lower gastrointestinal bleeding (ALGIB). We aimed to determine the feasibility and safety of colonoscopies performed by nonexperts using secondary data from a randomized controlled trial for ALGIB. Patients and methods We analyzed clinical outcomes in 159 patients with ALGIB who underwent colonoscopies performed by two groups of endoscopists: experts and nonexperts. We compared endoscopy outcomes, including identification of stigmata of recent hemorrhage (SRH), successful endoscopic treatment, adverse events (AEs), and clinical outcomes between the two groups, including 30-day rebleeding, transfusion, length of stay, thrombotic events, and 30-day mortality. Results Expert endoscopists alone performed colonoscopies in 96 patients, and nonexperts performed colonoscopies in 63 patients. The use of antiplatelets and warfarin was significantly higher in the expert group. The SRH identification rate (24.0 and 17.5 %), successful endoscopic treatment rate (95.0 and 100 %), rate of AEs during colonoscopy (0 and 0 %), transfusion rate (6.3 and 4.8 %), length of stay (8.0 and 6.4 days), rate of thrombotic events (0 and 1.8 %), and mortality (0 and 0 %) were not different between the expert and nonexpert groups. Rebleeding within 30 days occurred more often in the expert group than in the nonexpert group (14.3 vs. 5.4 % P = 0.0914). Conclusions The performance of colonoscopies for ALGIB by nonexperts did not result in worse clinical outcomes, suggesting that its use could be feasible for nonexperts for diagnosis and treatment of ALGIB.

Endoscopic submucosal dissection (ESD) is widely practiced in Japan and the Eastern World and is rapidly expanding in western countries for the management of early malignancies of the upper and lower gastrointestinal tube. In addition, novel therapeutic applications deriving from ESD have emerged including the treatment of achalasia, of submucosal tumors, of diverticula, of strictures and of reflux disease. An ESD procedure necessitates not only skills and specific training, but also familiarization with a vast spectrum of devices (endoscopes, high-frequency generators and their settings, endoknives, hoods, irrigation devices) and techniques (such as countertraction, artificial ulcer closure), that render the procedure faster, more efficient and safer. This technological article gives an overview on current and novel equipment for an ESD and associated techniques.

Background and Aims Diagnosing esophageal squamous cell carcinoma (SCC) depends on individual physician expertise and may be subject to interobserver variability. Therefore, we developed a computerized image-analysis system to detect and differentiate esophageal SCC. Methods A total of 9591 nonmagnified endoscopy (non-ME) and 7844 ME images of pathologically confirmed superficial esophageal SCCs and 1692 non-ME and 3435 ME images from noncancerous lesions or normal esophagus were used as training image data. Validation was performed using 255 non-ME white-light images, 268 non-ME narrow-band images/blue-laser images, and 204 ME narrow-band images/blue-laser images from 135 patients. The same validation test data were diagnosed by 15 board-certified specialists (experienced endoscopists). Results Regarding diagnosis by non-ME with narrow-band imaging/blue-laser imaging, the sensitivity, specificity, and accuracy were 100%, 63%, and 77%, respectively, for the artificial intelligence (AI) system and 92%, 69%, and 78%, respectively, for the experienced endoscopists. Regarding diagnosis by non-ME with white-light imaging, the sensitivity, specificity, and accuracy were 90%, 76%, and 81%, respectively, for the AI system and 87%, 67%, and 75%, respectively, for the experienced endoscopists. Regarding diagnosis by ME, the sensitivity, specificity, and accuracy were 98%, 56%, and 77%, respectively, for the AI system and 83%, 70%, and 76%, respectively, for the experienced endoscopists. There was no significant difference in the diagnostic performance between the AI system and the experienced endoscopists. Conclusions Our AI system showed high sensitivity for detecting SCC by non-ME and high accuracy for differentiating SCC from noncancerous lesions by ME.

Bone cancer pain is a complex pain state involving ongoing pain and movement-related pain, which are thought to be caused by different mechanisms. Transient receptor potential vanilloid subfamily 1 (TRPV1) is involved in ongoing pain but not movement-related pain. The purpose of this study was to investigate the role of transient receptor potential vanilloid subfamily 2 (TRPV2) in bone cancer pain. Proportions of TRPV1- and TRPV2-immunoreactive neurons in lumbar dorsal root ganglia innervating the femurs of male mice were examined by using Fluoro-Gold. Mice were intrathecally injected with small interfering RNA (siRNA) against TRPV2 or scrambled siRNA for three consecutive days from day 14 after sarcoma injection into the left femur. In the mice with bone cancer, the number of spontaneous flinches was quantified for assessment of ongoing pain, and limb use and weight bearing were assessed as indications of movement-related pain. Changes in TRPV2 protein levels in dorsal root ganglion were evaluated by Western blotting. We also examined the effects of intrathecal administration of siRNA against TRPV2 or scrambled siRNA on thermal and mechanical sensitivities in normal mice without tumors. The proportions of TRPV1-immunoreactive and TRPV2-immunoreactive neurons were 21% and 22% of neurons in dorsal root ganglia innervating the femur, respectively. Tumor-bearing mice exhibited an increased number of spontaneous flinches and impaired limb use and weight bearing at day 13 after sarcoma injection. TRPV2 protein level in dorsal root ganglia at day 13 was comparable to that at baseline. siRNA against TRPV2 significantly improved limb use and weight bearing but did not affect the number of spontaneous flinches compared to those in the group treated with scrambled siRNA. siRNA against TRPV2 did not affect thermal or mechanical sensitivity in normal mice. The results suggest that TRPV2 is involved in movement-related pain but not ongoing pain in mice with bone cancer.

We report a case of severe laryngeal edema devel- oped after the trachea intubation for 10 days. A 78- year-old woman presented with pulmonary edema due to fluid administration for acute pancreatitis. Endotra- cheal intubation and mechanical ventilation therapy were required for 10 days. The cuff pressures and endotracheal tube positions were routinely checked. A light level of sedation was maintained during mechani- cal ventilation. Ten days later, her trachea was extu- bated. One hour after extubation, she was observed to have inspiratory stridor and she complained of respira- tory distress. Fiberoptic examination revealed laryngeal edema and ulceration of the tracheal mucosa, consis- tent with the lesion where the endotracheal tube cuff had been attached. To maintain the airway, re-intuba- tion and elective tracheostomy were performed. Light sedation during mechanical ventilation may predispose the patient to tracheal injury.

Background The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)–expressing afferents. Methods A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg−1 h−1, n = 5) administration of QX-314 on both bone cancer pain–related behaviors and phosphorylated cyclic adenosine monophosphate response element–binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain–related behaviors (n = 10). Results The numbers of flinches indicative of ongoing pain in QX-314–treated mice were smaller than those in vehicle-treated mice at 10 min (3 mg/kg, 4 ± 3; 1 mg/kg, 5 ± 3 vs. 12 ± 3; P < 0.001; n = 8 to 9), 24 h (3 ± 2 vs. 13 ± 3, P < 0.001), and 48 h (4 ± 1 vs. 12 ± 2, P < 0.001; n = 5 in each group) after QX-314 administration, but impaired limb use, weight-bearing including that examined by the CatWalk system, and rotarod performance indicative of movement-evoked pain were comparable. QX-314 selectively inhibited the increase in phosphorylated cyclic adenosine monophosphate response element–binding protein expression in TRPV1-positive, but not in TRPV1-negative, dorsal root ganglion neurons compared to that in the case of vehicle administration (32.2 ± 3.0% vs. 52.6 ± 5.9%, P < 0.001; n = 6 in each group). Ablation of TRPV1-expressing afferents mimicked the effects of QX-314. Conclusion This study showed that systemic administration of QX-314 in mice inhibits some behavioral aspects of bone cancer pain through selective inhibition of TRPV1-expressing afferents without coadministration of TRPV1 agonists.

Background and study aims: Sessile serrated adenoma/polyps (SSA/Ps) have a different potential than traditional adenomatous polyps for developing into malignant colorectal cancer. However, little is known about the coexistent cancer rate. Here, we evaluate the frequency of carcinoma in serrated polyps removed by endoscopic resection (ER). Patients and methods: This was a retrospective single-center cohort study of consecutive patients with colorectal polyps who underwent ER from March 2003 to October 2014. We determined the frequency of serrated polyps among all resected colorectal polyps and analyzed the clinicopathological findings as well as the frequency and characteristics of coexistent carcinoma in the serrated polyps resected by ER based on pathology reports. Results: A total of 21,048 polyps from 15,326 patients were identified, including 15,984 traditional adenomatous polyps (75.9 %), 621 SSA/Ps (3.0 %), 136 traditional serrated adenomas (TSAs) (0.6 %), 1,121 hyperplastic polyps (5.3 %), and 3,186 polyps of other types (15.1 %). The clinical and endoscopic findings of SSA/Ps revealed a male predominance (68.6 %), with 61.7 % of the polyps located in the proximal colon. Males accounted for 77.2 % of all patients with TSAs, and 77.2 % of these polyps were located in the distal colon. The mean sizes of the SSA/Ps and TSAs were 8.8 and 10.7 mm, respectively. Among the SSA/Ps, 8 (1.3 %) cases had coexistent carcinoma, and 1 (0.7 %) patient with TSA showed coexistent carcinoma. In the patients with SSA/Ps, female sex and a tumor size ≥ 10 mm were predictive factors for coexistent carcinoma. Conclusions: The frequency of SSA/Ps with carcinoma was lower than that for traditional adenoma. Female sex and tumor size ≥ 10 mm were significant predictive factors for coexistent carcinoma.

Background & Aims We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). Methods We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24–96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. Results SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective colonoscopy group (difference, 0.3; 95% confidence interval, –12.5 to 13.0; P = .967). Rebleeding within 30 days of hospital admission occurred in 15.3% of patients in the early colonoscopy group and 6.7% of patients in the elective colonoscopy group (difference, 8.6; 95% confidence interval, –1.4 to 18.7); there were no significant differences between groups in successful endoscopic treatment rate, transfusion rate, length of stay, thrombotic events, or death within 30 days. The adverse event of hemorrhagic shock occurred during bowel preparation in no patient in the early group vs 2 patients (2.5%) in the elective colonoscopy group. Conclusions In a randomized controlled study, we found that colonoscopy within 24 hours after hospital admission did not increase SRH or reduce rebleeding compared with colonoscopy at 24–96 hours in patients with ALGIB. ClinicalTrials.gov, Numbers: UMIN000021129 and NCT03098173

Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P Conclusion DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.

Background and study aims A 70-year-old-man underwent an esophagectomy and posterior mediastinal reconstruction for esophageal cancer that was curatively resected. Although the patient was allowed to eat after surgery, he repeatedly vomited after drinking water or eating meals and required continuous hospitalization. An upper gastrointestinal series and endoscopic examination revealed an obstruction due to the flexure of the gastric conduit, which was repeatedly treated with endoscopic balloon dilation. Endoscopic balloon dilation was completely ineffective, however, because the obstruction was not due to a small lumen diameter, but rather to severe flexure. We hypothesized that the power of contraction provided by ulcer scar formation after mucosal resection could straighten the flexure, and thus removed a piece of the mucosa 8 cm in diameter on the oral side of the flexure by endoscopic submucosal dissection (ESD) 4 months after the esophagectomy. Endoscopic examination on post-ESD Day 10 revealed that the gastric conduit flexure was straightened due to ulcer scarring, and obstruction at the flexure opened over time. Meals were restarted and the patient could eat without vomiting. He was discharged from the hospital 5 weeks after ESD. This is the first case report of obstruction due to flexure of the gastric conduit after esophagectomy that was successfully treated with mucosectomy using ESD. Mucosectomy using ESD may be an effective treatment option for obstruction due to flexure of the gastric conduit after esophagectomy.

Background The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. Methods This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. Discussion This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. Trial registration UMIN-CTR Identifier, UMIN000021129. Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173. Registered on 24 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2558-y) contains supplementary material, which is available to authorized users.

Background and study aims : Endoscopic submucosal dissection (ESD) is technically difficult because of poor visualization and instability in the cutting area. Although mucosal flap formation improves visualization of the cutting area, it is difficult to achieve, especially in colorectal ESD. To facilitate mucosal flap formation, we developed the “clip-flap method” by substituting an endoclip for the mucosal flap until it is formed. Patients and methods: The clip-flap method was applied to 114 of 119 large superficial colorectal tumors being treated by ESD. Therapeutic efficacy and safety were assessed. Results: Mean tumor diameter, resected specimen diameter, and procedure time were 32.5 mm, 38.9 mm, and 82.0 minutes, respectively. The en bloc resection rate was 97.5 %. Intraoperative perforation occurred in one patient who was treated conservatively. A single endoclip was used for 92 lesions and improved visualization of the cutting area. A cross pattern of endoclips was used for 22 lesions and further stabilized the visual field, especially near the lateral side. Conclusions: The clip-flap method is a simple, safe, and effective option for ESD of large superficial colorectal tumors.

Gastric cancer and liver cirrhosis (LC) are often comorbid. However, little is known about the clinical outcomes of gastric endoscopic submucosal dissection (ESD) in patients with comorbid LC. This case–control study used a multicentre retrospective cohort. We identified 69 LC patients from the cohort of patients with early gastric cancer, who underwent gastric ESD at 12 hospitals from March 2003 to November 2010. Using the propensity score matching method, 69 patients without LC were used to compare the short- and long-term outcomes of ESD. Among the 69 LC patients, 53 (77 %) were Child-Pugh grade A (CP-A) and 16 (28 %) had past or present histories of hepatocellular carcinoma (HCC). Short-term outcomes did not differ between the LC patients and controls or between the CP-A and CP-B/C patients. Although the LC patients had significantly worse long-term outcomes than the controls (the 5-year overall survival rates were 60 vs. 91 %, respectively), patients with CP-A liver function without HCC histories had an overall survival almost equivalent to that of patients without LC (controls). LC patients appear to be good candidates for ESD if they have CP-A liver function and no history of HCC. Although their short-term outcomes were not inferior, the patients with Child-Pugh grades B/C or with histories of HCC benefited less from ESD.

The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85–1.25) for the area under plasma concentration–time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.