Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial.

BACKGROUND: Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. Clinically, SP/MC has a slower post-dose defaecation response than PEG and is perceived as less cleansing; therefore, it is not currently used for major bowel cancer screening preparation. The standard formulation for bowel preparation is PEG; however, a large dose is required, and it has a distinctive flavour that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical trials have shown that SP/MC is superior to PEG in terms of acceptability. We aim to compare the novel bowel cleansing method (test group) comprising SP/MC with elobixibat hydrate and the standard bowel cleansing method comprising PEG plus ascorbic acid (standard group) for patients preparing for outpatient colonoscopy. METHODS: This phase III, multicentre, single-blind, noninferiority, randomised, controlled, trial has not yet been completed. Patients aged 40-69 years will be included as participants. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction will be excluded. The target number of research participants is 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint is the degree of bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥ 6). The secondary endpoints are patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to the BBPS (BBPS score ≥ 8), degree of bowel cleansing according to the Aronchik scale, and bowel cleansing time. DISCUSSION: This trial aims to develop a "patient-first" colon cleansing regimen without the risk of inadequate bowel preparation by using both elobixibat hydrate and SP/MC. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; no. s041210067; 9 September 2021; https://jrct.niph.go.jp/ ), protocol version 1.5 (May 1, 2023).

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Curative Management After Endoscopic Resection for Esophageal Squamous Cell Carcinoma Invading Muscularis Mucosa or Shallow Submucosal Layer-Multicenter Real-World Survey in Japan.

INTRODUCTION: Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS: We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS: A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION: pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Endoscopic causes and characteristics of missed gastric cancers after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Because endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) preserves the entire stomach, missed gastric cancers (MGCs) are often found in the remaining gastric mucosa. However, the endoscopic causes of MGCs remain unclear. Therefore, we aimed to elucidate the endoscopic causes and characteristics of MGCs after ESD. METHODS: From January 2009 to December 2018, all patients undergoing ESD for initially detected EGC were enrolled. According to a review of EGD images before ESD, we identified the endoscopic causes (perceptual, exposure, sampling errors, and inadequate preparation) and characteristics of MGC in each endoscopic cause. RESULTS: Of 2208 patients who underwent ESD for initial EGC, 82 patients (3.7%) had 100 MGCs. The breakdown of endoscopic causes of MGCs was as follows: 69 (69%) perceptual errors, 23 (23%) exposure errors, 7 (7%) sampling errors, and 1 (1%) inadequate preparation. Logistic regression analysis showed that the risk factors for perceptual error were male sex (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.16-5.18), isochromatic coloration (OR, 3.17; 95% CI, 1.47-6.84), greater curvature (OR, 2.31; 95% CI, 1.121-4.40), and lesion size ≤12 mm (OR, 1.74; 95% CI, 1.07-2.84). The sites of exposure errors were around the incisura angularis (11 [48%]), posterior wall of the gastric body (6 [26%]), and antrum (5 [21%]). CONCLUSIONS: We identified MGCs in 4 categories and clarified their characteristics. Quality improvements in EGD observation, with attention to the risks of perceptual and site of exposure errors, can potentially prevent missing EGCs.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

Diagnostic performance of endoscopy for subsquamous extension of superficial adenocarcinoma of the esophagogastric junction.

OBJECTIVES: Extension of adenocarcinoma of the esophagogastric junction under the squamous epithelium may lead to errors when determining lateral margins. However, the characteristics of subsquamous extension are unclear. Herein, we evaluated the prevalence and characteristics of subsquamous extension of adenocarcinoma of the esophagogastric junction and the diagnostic performance of endoscopy for this condition. METHODS: Eighty-nine consecutive patients with superficial adenocarcinoma of the esophagogastric junction who underwent endoscopic or surgical resection at a tertiary cancer center between January 2010 and December 2017 were retrospectively evaluated. Endoscopic subsquamous extension was defined as a submucosal tumor-like elevation covered by squamous epithelium and/or a brownish area with abnormal microvessels on the squamous epithelium observed using narrow-band imaging. The diagnostic performance of endoscopy for subsquamous extension was evaluated using histological subsquamous extension as gold standard. RESULTS: Thirty-nine patients (44%) had histological subsquamous extension. Proton pump inhibitor use was significantly associated with histological subsquamous extension [odds ratio: 4.65; 95% confidence interval (CI): 1.77-12.2]. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endoscopic subsquamous extension were 56% (95% CI: 40-72%), 96% (86-99%), 92% (73-99%), 74% (62-84%) and 79% (69-87%), respectively. The median length difference between histological and endoscopic subsquamous extension was 2 mm (range: -6 to 9 mm). CONCLUSIONS: The sensitivity of endoscopic diagnosis of subsquamous extension was unsatisfactory. The endoscopic length of subsquamous extension tended to be underestimated. An oral safety margin of one centimeter is reasonable during endoscopic resection of adenocarcinoma of the esophagogastric junction.IMPACT STATEMENT This study will contribute significantly to the literature because this is the first study to determine the difference between the lengths of subsquamous extension detected endoscopically and histologically. This study determines the prevalence of subsquamous extension and identifies characteristics associated with subsquamous extension. An understanding of the risk of subsquamous extension is important when choosing a treatment strategy and planning the resection margins in patients with adenocarcinoma of the esophagogastric junction. This study provides patients with subsquamous extension characteristics and suggests a method for accurately diagnosing this condition.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Tip-in EMR as an alternative to endoscopic submucosal dissection for 20- to 30-mm nonpedunculated colorectal neoplasms.

BACKGROUND AND AIMS: Tip-in EMR, which includes anchoring the snare tip, has recently shown a favorable en-bloc and R0 resection rate for colorectal neoplasms. Thus, Tip-in EMR may be an alternative to endoscopic submucosal dissection (ESD). We aimed to compare clinical outcomes between Tip-in EMR and ESD for large colorectal neoplasms. METHODS: This retrospective study evaluated consecutive patients who underwent Tip-in EMR or ESD for 20- to 30-mm nonpedunculated colorectal neoplasms at a Japanese tertiary cancer center between January 2014 and December 2019. Baseline characteristics, treatment results, and long-term outcomes were analyzed using 1:1 propensity score matching. RESULTS: Seven hundred nine lesions were evaluated. The Tip-in EMR group included 1 lesion with a nonlifting sign but no lesions with fold convergence. After propensity score matching, each group included 140 lesions. The ESD group showed significantly higher en-bloc resection rates (99.3% vs 85.0%) and R0 resection rates (90.7% vs 62.9%). Procedure time was significantly shorter in the Tip-in EMR group (8 minutes vs 60 minutes). The Tip-in EMR and ESD groups did not differ significantly with respect to local recurrence rate (2.1% vs 0%). CONCLUSIONS: Tip-in EMR is comparable with ESD with respect to the local recurrence rate but has a shorter procedure time, despite the lower en-bloc and R0 resection rates for 20- to 30-mm nonpedunculated colorectal neoplasms without fold convergence or nonlifting sign. Thus, Tip-in EMR could be a feasible alternative to ESD in these lesions.

Biliary obstruction and pancreatitis after duodenal stent placement in the descending duodenum: a retrospective study.

BACKGROUND: Metallic stents placed in the descending duodenum can cause compression of the major duodenal papilla, resulting in biliary obstruction and pancreatitis. These are notable early adverse events of duodenal stent placement; however, they have been rarely examined. This study aimed to assess the incidence of and risk factors for biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum. METHODS: We retrospectively reviewed data of consecutive patients who underwent metallic stent placement in the descending duodenum for malignant gastric outlet obstruction at a tertiary referral cancer center between April 2014 and December 2019. Risk factors for biliary obstruction and/or pancreatitis were analyzed using a logistic regression model. RESULTS: Sixty-five patients were included. Biliary obstruction and/or pancreatitis occurred in 12 patients (18%): 8 with biliary obstruction, 2 with pancreatitis, and 2 with both biliary obstruction and pancreatitis. Multivariate analysis indicated that female sex (odds ratio: 9.2, 95% confidence interval: 1.4-58.6, P = 0.02), absence of biliary stents (odds ratio: 12.9, 95% confidence interval: 1.8-90.2, P = 0.01), and tumor invasion to the major duodenal papilla (odds ratio: 25.8, 95% confidence interval: 2.0-340.0, P = 0.01) were significant independent risk factors for biliary obstruction and/or pancreatitis. CONCLUSIONS: The incidence of biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum was non-negligible. Female sex, absence of biliary stents, and tumor invasion to the major duodenal papilla were the primary risk factors. Risk stratification can allow endoscopists to better identify patients at significant risk and permit detailed informed consent.

Risk Factors for Non-Ampullary Duodenal Adenocarcinoma: A Systematic Review.

INTRODUCTION: An increase in the incidence of duodenal adenocarcinoma has been recently reported. However, little is known about the risk factors for duodenal adenocarcinoma, which are important for screening purposes. We, therefore, aimed to conduct a systematic review to identify risk factors for non-ampullary duodenal adenocarcinoma. METHODS: A medical literature search was performed using electronic databases, including PubMed, Cochrane Library, Japan Medical Abstracts Society, and Web of Science. Studies that assessed the association between dietary habits, lifestyle behaviors, comorbidities, and non-ampullary duodenal adenocarcinoma were extracted. The Newcastle-Ottawa Scale was used to assess the risk of bias in individual studies, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the quality of evidence across studies included in this review. RESULTS: Out of 1,244 screened articles, 10 were finally selected for qualitative synthesis. In the general population, no consistent risk factors were identified except for Helicobacter pylori positivity, which was considered a risk factor in 2 studies, but the quality of evidence was considered very low because of the high risk of bias. In patients with familial adenomatous polyposis (FAP), Spigelman stage IV at initial endoscopy was considered a consistent risk factor in 3 studies. CONCLUSIONS: There are currently limited data regarding risk factors for non-ampullary duodenal adenocarcinoma, and no conclusive risk factors were identified in the general population. However, in patients with FAP, Spigelman stage IV was identified as a consistent risk factor. Further studies are needed to improve diagnosis and support effective clinical management of this malignancy.

Predicting the depth of superficial adenocarcinoma of the esophagogastric junction.

BACKGROUND AND AIM: Preoperative determination of the invasion depth of superficial adenocarcinoma of the esophagogastric junction is important for appropriate endoscopic or surgical resection. There are no objective criteria regarding this; therefore, we investigated the factors associated with the invasion depth of superficial adenocarcinoma of the esophagogastric junction. METHODS: This retrospective study evaluated patients with superficial adenocarcinoma of the esophagogastric junction who had undergone endoscopic or surgical resection at a Japanese tertiary cancer center between April 2004 and December 2017. We analyzed endoscopic features of intramucosal to slight submucosal (M-SM1; < 500 µm) and deep submucosal (SM2; ≥ 500 µm) adenocarcinoma of the esophagogastric junction and extracted significant factors associated with and assessed the diagnostic performance of endoscopic features for SM2 lesion. RESULTS: A total of 106 cases were included in this study. Multivariate analysis indicated that depressed or protruded type (odds ratio [OR], 11.1), lesion size ≥ 15 mm (OR, 3.11), uneven surface (OR, 6.31), and subsquamous extension (OR, 5.41) were significantly associated with SM2 adenocarcinomas of the esophagogastric junction. When the macroscopic type was depressed or protruded, high sensitivity (97%) but fair specificity (46%) were observed for SM2 adenocarcinoma of the esophagogastric junction, whereas uneven surface and subsquamous extension showed high specificity (96% and 87%) but fair sensitivity (36% and 46%). CONCLUSIONS: Depressed or protruded type, lesion size ≥ 15 mm, uneven surface, and subsquamous extension were significantly associated with the invasion depth of superficial adenocarcinoma of the esophagogastric junction. These endoscopic features are useful in determining the treatment method preoperatively.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

BACKGROUND AND AIM: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS: There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS: Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.

Circularity Is a Potential Noninvasive Diagnostic Indicator to Differentiate Gastric Submucosal Tumors.

BACKGROUND AND AIMS: Noninvasive, imaging diagnosis of gastrointestinal mesenchymal tumors (GIMTs) is still difficult. This study aimed to develop a novel diagnostic method of GIMTs via endoscopic ultrasonography (EUS) using circularity. METHODS: In a derivation series, we retrospectively collected 50 GIMTs 2-5 cm in diameter of two institutions. After selecting one EUS still image showing the maximal area per lesion, two endoscopists who were blind to the histological diagnosis assessed circularity, a surrogate indicator of roundness (range, 0-1; 1 = a true circle), with an image-analyzing software. Median circularity of three types of GIMT was compared, and the cutoff value to differentiate a group from other groups was presented by drawing a receiver operating characteristic curve. Subsequently, we assessed the diagnostic ability of circularity in 91 GIMTs which were retrospectively collected from the other two institutions by using the optimal cutoff value presented in the derivation series. RESULTS: The circularity in leiomyomas indicated 0.70 and was significantly lower than that of gastrointestinal stromal tumors (0.89), schwannomas (0.90), and their combined group. When leiomyomas were diagnosed as the circularity of <0.8305, which was presented as the optimal cutoff value, the diagnostic accuracy, sensitivity, and specificity in the validation series were 73.6%, 80.0%, and 72.4%, respectively. CONCLUSION: The data demonstrated that leiomyomas significantly exhibited more distortion than other GIMTs. That implies that the difference in shape, which is objectively determined as circularity, is useful to noninvasively discriminate leiomyomas from other GIMTs.

Bleeding following Endoscopic Submucosal Dissection for Early Gastric Cancer in Surgically Altered Stomach.

INTRODUCTION: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). METHODS: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. RESULTS: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87-2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00-28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21-19.14). DISCUSSION/CONCLUSION: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.

Cold snare polypectomy for superficial non-ampullary duodenal epithelial tumor: a prospective clinical trial (pilot study).

BACKGOUND: Cold snare polypectomy (CSP) can minimize the risk of adverse events and has become a standard treatment for small colorectal polyps. CSP might also be suitable for small superficial non-ampullary duodenal epithelial tumors (SNADETs). This study aimed to evaluate the safety of CSP for SNADETs. METHODS: The major indication criteria were as follows: (1) endoscopically diagnosed SNADET, (2) ≤ 10 mm, and (3) a single primary lesion. CSP was performed using an electrosurgical snare without electrocautery. Follow-up endoscopy and scar biopsy were performed 3 months after CSP. The primary endpoint was the delayed adverse events rate. RESULTS: In total, 21 patients were enrolled. Two and 19 lesions were located in the duodenal bulb and 2nd portion, respectively; the median lesion size was 8 mm. CSP was attempted for all lesions; three lesions could not be resected without electrocautery and were removed by conventional endoscopic mucosal resection (EMR). The rate of spurting bleeding after CSP was 0%. The median procedure time was 12 min, the median resected specimen size was 12 mm, and the rate of en bloc resection was 81% (17/21). No adverse events were observed intraoperatively, with no delayed adverse events after CSP. Histopathology revealed 15 adenomas, 4 cancers (intramucosal), and 2 non-neoplastic lesions. The horizontal margins were negative/positive/undetermined in 9, 1, and 11 cases, respectively. All vertical margins were negative. Only one recurrence was detected by follow-up endoscopy 3 months after CSP. CONCLUSIONS: CSP can be performed safely for small SNADETs. CLINICAL TRIAL REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm ), and the registration number is UMIN000019157.

Influence of hospital volume on bleeding after endoscopic submucosal dissection for early gastric cancer in Japan: a multicenter propensity score-matched analysis.

BACKGROUND: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume. METHODS: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching. RESULTS: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups. CONCLUSIONS: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.

Diagnostic ability of magnification endoscope with narrow-band imaging in screening esophagogastroduodenoscopy.

OBJECTIVES: Magnifying endoscopy with narrow-band imaging (M-NBI) is useful for the optical diagnosis of gastrointestinal neoplasms. However, the utility of M-NBI in screening esophagogastroduodenoscopy (EGD) is unclear. We aimed to evaluate the diagnostic ability of the magnification endoscope (ME) in screening EGD for a population with a low prevalence of upper gastrointestinal cancers. METHODS: Overall, 4887 asymptomatic examinees without a history of laryngopharyngeal and/or upper gastrointestinal neoplasms who underwent opportunistic screening EGD between April 2011 and December 2017 were enrolled in this retrospective study. The examinees were categorized into two groups depending on whether screening EGD was performed using ME (ME group) or not (non-ME group). Using a propensity score-matched analysis, the diagnostic ability of EGD was compared between the two groups. RESULTS: In total, 1482 examinees (30%) were allocated to the ME group and 3405 (70%) to the non-ME group. Thirty-five epithelial neoplasms were detected in 30 examinees (0.6%). The groups were matched for baseline characteristics (1481 pairs). Both groups showed no significant difference in the epithelial neoplasm detection rate (0.8% vs. 0.3%; P = 0.14). The biopsy rate was significantly lower in the ME group than in the non-ME group (12% vs. 15%; P = 0.003). The positive predictive value (PPV) for biopsy was significantly higher in the ME group than in the non-ME group (6.6% vs. 2.8%; P = 0.048). CONCLUSIONS: Using an ME for screening EGD in an apparently healthy, asymptomatic population could reduce unnecessary biopsies by improving PPV for biopsy without decreasing the epithelial neoplasm detection rate.

Endoscopic submucosal dissection versus surgery in elderly patients with early gastric cancer of relative indication for endoscopic resection.

OBJECTIVES: Surgery is recommended for early gastric cancer (EGC) beyond the endoscopic resection (ER)-indication for the risk of lymph node metastasis; however, ER may be chosen as a "relative ER-indication" considering age and comorbidities. This study aimed to compare outcomes of endoscopic submucosal dissection (ESD) only and surgery (primary surgery and additional surgery after non-curative ESD) among elderly patients with relative ER-indication EGC and to further assess prognostic factors. METHODS: Outcomes of ESD and surgery (417 cases; 114 ESD, 303 surgery) in elderly patients (≥75 years) with relative ER-indication EGC were retrospectively analyzed. Prognostic factors were also examined. RESULTS: During the observation period (median; ESD, 34 months; surgery, 61 months), 29% of ESD and 35% of surgery patients died, including 4% and 5% from gastric cancer (GC), respectively. ESD showed lower overall survival (OS) than surgery (P = 0.027) but comparable disease-free survival (P = 0.916). OS-associated factors were age and prognostic nutritional index (PNI) in males (age ≥79, hazard ratio [HR] 2.21, P = 0.001; PNI <45, HR 2.06, P = 0.031) and age in females (age ≥82, HR 4.06, P = 0.004). Treatment was not a prognostic factor in either subgroup. Pathological category ≥pT1b2 (submucosal invasion ≥500 µm) and lymphovascular invasion (LVI) were significantly associated with GC death (mortality: ≥pT1b2, 7.7%, P = 0.002; LVI, 10.1%, P < 0.001). CONCLUSIONS: In elderly patients with relative ER-indication EGC, ESD may have comparable long-term efficacy to surgery, and treatment selection had a minor contribution to OS. For patients with poor preoperative prognostic factors, diagnostic ESD may be performed first, followed by additional surgery based on pathological results.

Tip-in Endoscopic Mucosal Resection for 15- to 25-mm Colorectal Adenomas: A Single-Center, Randomized Controlled Trial (STAR Trial).

INTRODUCTION: One-piece endoscopic mucosal resection (EMR) for lesions >15 mm is still unsatisfactory, and attempted 1-piece EMR for lesions >25 mm can increase perforation risk. Therefore, modifications to ensure 1-piece EMR of 15- to 25-mm lesions would be beneficial. The aim of this study was to investigate whether Tip-in EMR, which anchors the snare tip within the submucosal layer, increases en bloc resection for 15- to 25-mm colorectal lesions compared with EMR. METHODS: In this prospective randomized controlled trial, patients with nonpolypoid colorectal neoplasms of 15-25 mm in size were recruited and randomly assigned in a 1:1 ratio to undergo Tip-in EMR or standard EMR, stratified by age, sex, tumor size category, and tumor location. The primary endpoint was the odds ratio of en bloc resection adjusted by location and size category. Adverse events and procedure time were also evaluated. RESULTS: We analyzed 41 lesions in the Tip-in EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2%) patients undergoing Tip-in EMR and 30 (73.1%) who had EMR. The adjusted odds ratio of en bloc resection in Tip-in EMR vs EMR was 3.46 (95% confidence interval: 1.06-13.6, P = 0.040). The Tip-in EMR and EMR groups did not differ significantly in adverse event rates (0% vs 4.8%) or median procedure times (7 vs 5 minutes). DISCUSSION: In this single-center randomized controlled trial, we found that Tip-in EMR significantly improved the en bloc resection rate for nonpolypoid lesions 15-25 mm in size, with no increase in adverse events or procedure time.