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Introduction The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia. Methods This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia. Results Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and postendoscopy bleeding. More interventional radiology procedures were needed for diverticulosis and small bowel bleeding. Etiologies with favorable outcomes and low procedure rates were ischemic colitis and infectious colitis. Higher rates of painless hematochezia at presentation were significantly associated with multiple diseases, such as rectal ulcer, hemorrhoids, angioectasia, radiation colitis, and diverticulosis. The same was true in cases of hematochezia with diarrhea, fever, and hemodynamic instability. Discussion This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.

BACKGROUND AND AIM This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS We retrospectively reviewed 10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Objective Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. Design This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. Results A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). Conclusions In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

Outcomes of acute lower gastrointestinal bleeding have not been compared according to hospital capacity. We aimed to perform a propensity score-matched cohort study with path and mediation analyses for acute hematochezia patients. Hospitals were divided into high- versus low-volume hospitals for emergency medical services. Rebleeding and death within 30 days were compared. Computed tomography, early colonoscopy (colonoscopy performed within 24 h), and endoscopic therapies were included as mediators. A total of 2644 matched pairs were yielded. The rebleeding rate within 30 days was not significant between high- and low-volume hospitals (16% vs. 17%, P = 0.44). The mortality rate within 30 days was significantly higher in the high-volume cohort than in the low-volume cohort (1.7% vs. 0.8%, P = 0.003). Treatment at high-volume hospitals was not a significant factor for rebleeding (odds ratio [OR] = 0.91; 95% confidence interval [CI], 0.79–1.06; P = 0.23), but was significant for death within 30 days (OR = 2.03; 95% CI, 1.17–3.52; P = 0.012) on multivariate logistic regression after adjusting for patients’ characteristics. Mediation effects were not observed, except for rebleeding within 30 days in high-volume hospitals through early colonoscopy. However, the direct effect of high-volume hospitals on rebleeding was not significant. High-volume hospitals did not improve the outcomes of acute hematochezia patients.

Direct and indirect clipping treatments are used worldwide to treat colonic diverticular bleeding (CDB), but their effectiveness has not been examined in multicenter studies with more than 100 cases.We sought to determine the short- and long-term effectiveness of direct versus indirect clipping for CDB in a nationwide cohort.We studied 1041 patients with CDB who underwent direct clipping (n = 360) or indirect clipping (n = 681) at 49 hospitals across Japan (CODE BLUE-J Study).Multivariate analysis adjusted for age, sex, and important confounding factors revealed that, compared with indirect clipping, direct clipping was independently associated with reduced risk of early rebleeding (30 days; adjusted odds ratio [AOR] 0.592, p = 0.002), late rebleeding (1 year; AOR 0.707, p = 0.018), and blood transfusion requirement (AOR 0.741, p = 0.047). No significant difference in initial hemostasis rates was observed between the two groups. Propensity-score matching to balance baseline characteristics also showed significant reductions in the early and late rebleeding rates with direct clipping. In subgroup analysis, direct clipping was associated with significantly lower rates of early and late rebleeding and blood transfusion need in cases of stigmata of recent hemorrhage with non-active bleeding on colonoscopy, right-sided diverticula, and early colonoscopy, but not with active bleeding on colonoscopy, left-sided diverticula, or elective colonoscopy.Our large nationwide study highlights the use of direct clipping for CDB treatment whenever possible. Differences in bleeding pattern and colonic location can also be considered when deciding which clipping options to use.

Introduction:As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years., Methods:We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years., Results:The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003)., Discussion:This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years.

Background and study aims: Light-emitting diodes (LEDs) are used widely for their high luminous efficiency and durability. We developed a novel prototype high definition endoscope with white LEDs and evaluated the image quality it produced against a commercial endoscope with conventional light source. Patients and methods: The specifications of both colonoscopes were identical, except for the LED light source at the tip of the prototype. We examined 20 patients with rectal or sigmoid colon lesions and the image quality was evaluated in 40 images (one image from the LED colonoscope and one from the conventional colonoscope for each lesion) by three endoscopists. We additionally evaluated the 17 videos recorded with the LED colonoscope that were available. Image quality, mucosal and vascular color, and luminous distribution and intensity were scored on a 5-point scale. Results: The mean score for vascular color given by one evaluator was significantly higher using the LED colonoscope than using the conventional colonoscope. The mean scores for mucosal color and luminous intensity from another evaluator were significantly lower with the LED colonoscope than with the conventional colonoscope. There were no significant differences in the luminous distribution scores for any of the evaluators. The image quality of the videos was evaluated as being similar with both colonoscopes. Conclusions: Image quality from the LED and conventional colonoscopes were similar, although the luminous intensity of the LEDs is inferior to that of the conventional light source at the present time.

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

The frequencies of DNA methylation of certain tumor-related genes are higher in Epstein-Barr virus (EBV)-associated gastric carcinomas than in EBV-negative gastric carcinomas. EBV-associated gastric carcinomas have distinct clinicopathological features; however, there are no case-control studies comparing methylation frequency between EBV-associated gastric carcinomas and controls that have been adjusted according to the clinicopathological features of EBV-associated gastric carcinomas. This study evaluated 25 EBV-associated gastric carcinomas that were positive for EBV-encoded small RNA 1 (EBER-1) by in situ hybridization and 50 EBV-negative gastric carcinomas that were matched with the EBV-associated gastric carcinomas by age, sex, histology, depth of tumor invasion, and stage. Methylation status of 16 loci associated with tumor-related genes was analyzed by methylation-specific polymerase chain reaction (PCR) to identify genes in which DNA methylation specifically occurred in EBV-associated gastric carcinomas. Methylation frequencies of 12 of the 16 genes were higher in EBV-associated gastric carcinomas than in EBV-negative controls, and the frequency of methylation of 6 specific loci (MINT2, MINT31, p14, p16, p73, and RUNX3) was significantly higher in EBV-associated gastric carcinomas than in EBV-negative controls. There were no significant differences in the methylation frequencies of the other genes. The mean methylation index in EBV-associated gastric carcinomas was significantly higher than that in EBV-negative controls. DNA methylation of tumor suppressor genes that regulate the cell cycle and apoptosis specifically occurred in EBV-associated gastric carcinomas. Aberrant DNA methylation might lead to the development and progression of EBV-associated gastric carcinoma.

Aim of this study is to find subgroup of early gastric cancer with lymph node metastasis for which successive further surgical operation is needed after endoscopic resection.A total of 559 lesions of early gastric cancer, which had undergone curative gastrectomy, were enrolled in this study. We retrospectively investigated 10 clinicopathological factors predictive of lymph node metastasis by univariate and multivariate analysis. We showed the frequency of lymph node metastasis of subgroups in combination of independent factors selected by multivariate analysis.Lymph node metastases were detected in 57 lesions (10.2%). Univariate analysis revealed that lesion size30 mm, undifferentiated components, sm massive invasion, lymphatic invasion and venous invasion were factors significantly correlated with lymph node metastasis. By multivariate analysis, risk factors for lymph node metastasis were lesion size30 mm, undifferentiated components, sm massive invasion, and lymphatic invasion, with odds ratios of 2.17, 2.30, 5.88 and 8.24, respectively. In lesions with undifferentiated components, LNM were found in all subgroups.When we treat early gastric cancers contained undifferentiated components, even if they are predominantly differentiated-type intramucosal lesions, an additional surgical procedure should be considered or careful follow-up is required.

BACKGROUND/AIMS The introduction of endoscopic submucosal dissection for the treatment of early gastric cancer has enabled en bloc resection of lesions that cannot be treated with conventional endoscopic mucosal resection. Despite expansion of indications for endoscopic treatment, a considerable number of patients still require additional treatment. The objective of this study was to summarize the outcomes of endoscopic submucosal dissection performed on patients with early gastric cancer and to identify factors associated with incomplete resection and non-curative resection. METHODOLOGY This study examined 605 lesions in 533 patients with early gastric cancer who underwent endoscopic submucosal dissection. Evaluation of treatment outcome was based on the rates of complete resection and curative resection. Factors associated with incomplete resection and non-curative resection were retrospectively identified. RESULTS Of the 605 lesions, 562 (92.9%) and 510 (84.3%) were diagnosed as complete resection and curative resection, respectively. Factors identified as associated with incomplete resection were tumor size ≥30 mm, location in the U region, undifferentiated carcinoma, sm2 invasion and ulceration. Factors identified as associated with non-curative resection were tumor size ≥30 mm, location in the U region and ulceration. CONCLUSIONS Incomplete and non-curative resection appears to be associated with preoperative diagnosis of lesions and technical difficulty.

Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD.This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital. We analyzed risk factors for delayed bleeding from ESD in relation to various clinical and pathological factors.En bloc resection rate was 95.4% (519/544), and curative resection rate was 87.8% (477/544). Delayed bleeding occurred in 7.0% (38/544) and perforation occurred in 1.8% (10/544) of patients. Univariate analysis revealed platelet count (Plt)15 × 10⁴/μl (p = 0.013), prothrombin time (PT)70% (p = 0.044), resected size ≥ 50 mm (p = 0.038), and positive/indeterminate lateral margin (p = 0.012) to be risk factors for delayed bleeding. Multivariate analysis showed that Plt15 × 10⁴/μl (odds ratio [OR], 2.62; 95% confidence interval [CI]: 1.17-5.53, p = 0.020) and positive/indeterminate lateral margin (OR, 5.45; 95% CI: 1.39-17.95, p = 0.018) were independent risk factors for delayed bleeding.Low Plt, low PT, large resected size, and positive/indeterminate lateral margin were significant risk factors for delayed bleeding from ESD. Patients with these risk factors must be carefully observed for signs of delayed bleeding.

Magnifying endoscopy with narrow-band imaging (ME-NBI) enhances images of the irregular mucosal structures and microvessels of gastric carcinoma, and could be useful for determining the margin between cancerous and non-cancerous mucosa. We evaluated the usefulness of ME-NBI for determining the tumor margin compared with indigocarmine chromoendoscopy (ICC).The subjects were 110 patients (with 118 lesions) who underwent endoscopic submucosal dissection for gastric tumors. They were randomized into ME-NBI and ICC groups. Marking was carried out by electrocautery with the tip of a high-frequency snare at the tumor margins determined by each observation. The distance from the marking dots to the tumor margin was measured histopathologically in the resected specimens. Marking was diagnosed as accurate if the distance was less than 1 mm.Of the 118 gastric lesions, 55 were allocated to the ME-NBI group, and 63 to the ICC group. Seventeen lesions in the ME-NBI group and 18 lesions in the ICC group were excluded because the distance from the marking dots to the tumor margin was immeasurable histopathologically. Thirty-eight lesions in the ME-NBI group and 45 lesions in the ICC group were evaluated. The rate of accurate marking of the ME-NBI group was significantly higher than that of the ICC group (97.4% vs 77.8%, respectively; P-value = 0.009).Magnifying endoscopy with narrow-band imaging can identify gastric tumor margins more clearly than ICC.

Strip biopsy and endoscopic submucosal dissection (ESD) have been developed as a local treatment for early gastric cancer (EGC). However, the lesion criteria for the use of ESD, rather than strip biopsy, remain to be elucidated.On the basis of reviews of literature and our observations concerning the outcome of strip biopsy, we set the criteria for selecting strip biopsy and ESD as follows. The indications for strip biopsy were lesions less than 10 mm in size and located in the anterior wall or greater curvature of the lower and middle stomach. ESD was indicated for all other lesions. The validity of the criteria was then analyzed prospectively in 156 patients. The rate of en bloc R0 resection and local recurrence were evaluated.Subsequently, 156 lesions were divided according to the criteria and were endoscopically resected by strip biopsy (n = 13) or ESD (n = 143). The en bloc R0 resection rates for the whole group and the strip biopsy and ESD groups was 93.5% (146/156), 92.3% (12/13), and 93.7% (134/143), respectively. None of the patients had suffered from local recurrence in either the strip biopsy or ESD groups.The validity of our criteria for selecting strip biopsy and ESD was verified. Our criteria exploit the advantages of both procedures and obtain better endoscopic therapy outcomes for EGC.

We performed a photodynamic therapy for local recurrence after chemoradiotherapy for esophageal cancer. The patient was a 60s man, who presented dysphasia. Esophagoscopy, CT and FDG-PET revealed an advanced esophageal cancer with mediastinal lymph node metastasis. He rejected a surgical treatment and underwent chemoradiotherapy, then achieved CR once. Subsequent FDG-PET, however, showed slightly FDG uptake at primary focus of the esophagus. Endoscopic biopsy specimen from Lugol's unstained lesion of the esophagus revealed squamous cell carcinoma, and he was diagnosed as a recurrence of the esophageal cancer. He underwent chemotherapy again, but the recurrent lesion enlarged. Because the control of the metastatic lesion was excellent and the recurrent lesion was considered as a superficial cancer, he was performed photodynamic therapy. Two months after photodynamic therapy, the esophagoscopy and FDG-PET showed no findings of the recurrence of the esophageal cancer. It was suggested that photodynamic therapy for local recurrence after definitive chemotherapy for esophageal cancer was effective and relatively safe.

Hyperspectral imaging (HSI) is a new technology that obtains spectroscopic information and renders it in image form. This study examined the difference in the spectral reflectance (SR) of gastric tumors and normal mucosa recorded with a hyperspectral camera equipped with HSI technology and attempted to determine the specific wavelength that is useful for the diagnosis of gastric cancer. A total of 104 gastric tumors removed by endoscopic submucosal dissection from 96 patients at Yamaguchi University Hospital were recorded using a hyperspectral camera. We determined the optimal wavelength and the cut-off value for differentiating tumors from normal mucosa to establish a diagnostic algorithm. We also attempted to highlight tumors by image processing using the hyperspectral camera's analysis software. A wavelength of 770 nm and a cut-off value of 1/4 the corrected SR were selected as the respective optimal wavelength and cut-off values. The rates of sensitivity, specificity, and accuracy of the algorithm's diagnostic capability were 71%, 98%, and 85%, respectively. It was possible to enhance tumors by image processing at the 770-nm wavelength. HSI can be used to measure the SR in gastric tumors and to differentiate between tumorous and normal mucosa.