Traction-assisted endoscopic submucosal dissection for a previously tattooed colonic laterally spreading tumor.

Video 1Traction-assisted colorectal endoscopic submucosal dissection using the multiloop method for a previously tattooed laterally spreading tumor in the sigmoid colon.

Histopathologic features and fragmentation of polyps with cold snare defect protrusions.

BACKGROUND AND AIMS: Cold snare defect protrusions (CSDPs) include muscularis mucosa (MM) and submucosa tissue. CSDPs are thought to result from fragmentation of the specimen during shallow excision. Our aim in this study was to clarify whether CSDPs are associated with polyp fragmentation. METHODS: We retrospectively analyzed 1026 neoplastic colorectal polyps resected by cold snare polypectomy for which the presence or absence of CSDPs was assessed from the endoscopic image. All prepared specimens were reviewed and assessed for the presence or absence of polyp fragmentation, and the proportion of MM on the stump was measured. In addition, the risk factors for CSDP occurrence were evaluated. RESULTS: CSDPs occurred in 116 of the 1026 polyps (11.3%). Polyp fragmentation was significantly associated with the occurrence of CSDP on univariate analysis (odds ratio [OR], 3.74; P < .001) and multivariate analysis (OR, 3.13; P < .001). The proportion of MM >50% was significantly lower in the CSDP group than in the non-CSDP group (51.5% vs 70.9%, P < .001). CSDPs were significantly associated with a large polyp size (OR, 1.32; P = .007) and a large specimen size (OR, 1.24; P < .001) on multivariate analysis. CONCLUSIONS: The occurrence of CSDP was associated with less MM on the stump and fragmentation of the specimen. Clinically, the presence of CSDP is a good indicator of polyp fragmentation.

Predicting a rapid response to adalimumab treatment and favorable short-term outcomes through the high platelet count in patients with ulcerative colitis: A multicenter retrospective cohort study.

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 10/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.

Comparison of dissection speed during colorectal ESD between the novel Multiloop (M-loop) traction method and ESD methods without traction.

Background and study aims We previously reported on a novel traction method called Multiloop (M-loop) for faster colorectal endoscopic submucosal dissection (ESD). In this study, we retrospectively compared the difference in submucosal dissection time (SDT), and submucosal dissection speed (SDS) between groups of patients who were treated using traction with the M-loop method, and with non-traction methods of colorectal ESD. Patients and methods We reviewed and timed duration of colorectal ESD by the non-traction method from videos recorded between June 2016 and December 2017. From January 2018 onward, we used the M-loop method during all colorectal ESDs and timed it until August 2018. Outcomes of colorectal ESD with the M-loop method and non-traction methods were compared. The study involved two experts and eight non-experts and was carried out at a tertiary endoscopic center in Japan. Results The study included 50 patients who treated with the M-loop method and 115 patients treated with the non-traction method. Submucosal dissection time (SDT) was not significantly different (M-loop group, 42.1  ±â€Šâ€Š4.2 min, non-traction ESD group, 51.9 ±â€Š3.3 min) ( P  = 0.098), but submucosal dissection speed (SDS) was significantly greater (M-loop group, 28.0 ±â€Š2.9 mm 2  /min, non-traction ESD group, 19.9 ±â€Š2.0 mm 2 /min) ( P  = 0.0014) in the M-loop method group. Multivariate analysis showed that the M-loop method increased SDS by odds ratio of 1.46 ( P  = 0.001) when compared to the non-traction ESD method. A significant difference was also observed for SDT and SDS when the two methods were compared after propensity score matching ( P  = 0.001). No differences in unfavorable outcomes were observed. Conclusions The M-loop method improved SDS compared to non-traction methods of ESD. The method is an effective tool to assist colorectal ESD.

Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Traction methods have been reported to speed up endoscopic submucosal dissection (ESD). We used the multiloop (M-loop) method as a traction method for colorectal ESD and recorded the submucosal dissection time (SDT) and submucosal dissection speed (SDS). METHODS: From January to August 2018, we used the M-loop method for colorectal ESD procedures and timed the duration and recorded the outcomes. Two experts and eight nonexperts performed the procedures, which were carried out at a tertiary endoscopic center in Japan. RESULTS: A total of 50 patients were treated by colorectal ESD using the M-loop method. The mean SDT was 42.1 ± 4.16 minutes and the mean SDS was 28.0 ± 2.89 mm2/minutes. The mean SDS was 38.9 ± 6.9 mm2/minutes for experts and 25.3 ± 3.1 mm2/minutes for nonexperts. En bloc resection was achieved in 100% of cases. There were 3 adverse events and unfavorable outcomes. CONCLUSIONS: Traction by the M-loop method improved SDS in colorectal ESD. The method can be an effective tool to assist colorectal ESD. Further evaluation of the usefulness of the M-loop method is required in direct comparison with conventional ESD.

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

Background: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). Objective: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. Design: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). Setting: 30 Japanese institutions. Patients: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. Intervention: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. Measurements: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). Results: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. Limitation: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. Conclusion: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. Primary Funding Source: Japanese Gastroenterological Association.

Multicenter prospective study on the histological diagnosis of gastric cancer by narrow band imaging-magnified endoscopy with and without acetic acid.

Background and study aims The usefulness of endoscopy for diagnosing histological type remains unclear. This study aimed to examine the diagnostic accuracy of white light endoscopy (WLE), magnified endoscopy with narrow band imaging (NBI-ME), and NBI-ME with acetic acid enhancement (NBI-AA) for histological type of gastric cancer. Patients and methods Patients with depressed-type gastric cancers resected by endoscopic submucosal dissection were prospectively enrolled, and 221 cases were analyzed. Histological type was diagnosed by WLE, followed by NBI-ME and NBI-AA. Histological type was classified into differentiated adenocarcinoma and undifferentiated adenocarcinoma. Histological type was diagnosed based on lesion color in WLE, surface patterns (pit, villi, and unclear) and vascular irregularities in NBI-ME, and surface patterns in NBI-AA. Results Histological types of target areas were differentiated adenocarcinoma and undifferentiated adenocarcinoma in 206 and 15 cases, respectively. Diagnostic accuracy of WLE, NBI-ME, and NBI-AA for the histological type was 96.4 % (213/221), 96.8 % (214/221), and 95.5 % (211/221), respectively. No significant differences were observed among modalities. Positive predictive value based on endoscopic findings in NBI-ME was 98.0 % (149/152) for the villi pattern, 100 % (19/19) for the irregular pit pattern, 100 % (9/9) for the unclear surface pattern with a vascular network, 90.3 % (28/31) for the unclear surface pattern with mild vascular irregularity, and 88.9 % (8/9) for the unclear surface pattern with severe vascular irregularity. Conclusions NBI-ME and NBI-AA did not show any advantages over WLE for diagnostic accuracy. Villi pattern, irregular pit pattern, and vascular network may be useful for identifying differentiated adenocarcinoma.

Endoscopic gastric mucosal atrophy distinguishes the characteristics of superficial esophagogastric junction adenocarcinoma.

BACKGROUND AND AIM: Western studies have suggested two distinct etiologies of esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma. The present study investigated whether endoscopic gastric mucosal atrophy can distinguish between these two types of EGJ adenocarcinoma. METHODS: Data were collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent endoscopic or surgical resection at eight Japanese institutions in 2010-2015. Clinicopathological characteristics of EGJ cancers with and without endoscopic gastric mucosal atrophy were compared. EGJ was defined as the lower end of the palisade vein and/or the top of the gastric folds. RESULTS: Of the 229 patients identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter group was younger (64 vs 70 years, P = 0.000); had a higher proportion of patients negative for H. pylori (90% vs 47%, P < 0.0001); and had higher rates of gastroesophageal reflux disease symptoms (43% vs 12%, P = 0.017), mucosal breaks (25% vs 15%, P = 0.009), Barrett's esophagus (BE, 78% vs 42%, P < 0.0001), and tumors above the EGJ (81% vs 19%, P < 0.0001) and on the upper-right side (74% vs 38%, P < 0.0001) than the former group. Multivariate analysis showed that H. pylori positivity (odds ratio [OR] = 13.0, P < 0.001), long-segment BE (OR = 0.025, P = 0.033), and longitudinal (OR = 8.6, P = 0.001) and circumferential (OR = 4.7, P = 0.006) tumor locations were independently associated with gastric mucosal atrophy. CONCLUSION: Two distinct types of EGJ cancer were identified, with and without endoscopic gastric mucosal atrophy. These types were associated with different tumor locations.

MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer.

Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.

Basic principles and practice of gastric cancer screening using high-definition white-light gastroscopy: Eyes can only see what the brain knows.

Endoscopic diagnosis of gastrointestinal tumors consists of the following processes: (i) detection; (ii) differential diagnosis; and (iii) quantitative diagnosis (size and depth) of a lesion. Although detection is the first step to make a diagnosis of the tumor, the lesion can be overlooked if an endoscopist has no knowledge of what an early-stage 'superficial lesion' looks like. In recent years, image-enhanced endoscopy has become common, but white-light endoscopy (WLI) is still the first step for detection and characterization of lesions in general clinical practice. Settings and practice of routine esophagogastroduodenoscopy (EGD) such as use of antispasmodics, number of endoscopic images taken, and observational procedure are customarily decided in each facility in each country and are not well standardized. Therefore, in the present article, we attempted to outline currently available evidence and actual Japanese practice on gastric cancer screening using WLI, and provide tips for detecting EGC during routine EGD which could become the basis of future research.

Differences in routine esophagogastroduodenoscopy between Japanese and international facilities: A questionnaire survey.

BACKGROUND AND AIM: The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good-quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries. METHODS: To clarify the differences in routine EGD, a questionnaire survey was conducted in 98 Japanese and 53 international institutions. RESULTS: Prevalence of screening examination among routine EGD was higher in Japanese than in international institutions. Japanese endoscopists noted that endoscopic mucosal atrophy was the most significant risk factor for GC, whereas international endoscopists paid more attention to clinical information such as age, symptoms and family history. Antispasmodics, mucolytics and defoaming agents were used more frequently in Japanese institutions. The examination time was similar (mostly 5-10 min) between Japanese and international institutions. Japanese endoscopists took more pictures (>20 in almost all institutions) than international endoscopists (≤20 in two-thirds of institutions). In Japanese institutions, biopsy specimens were more frequently taken from areas of mucosal discoloration, unevenness or spontaneous bleeding rather than from obvious endoscopic lesions such as ulceration or polyps. In most Japanese institutions, one or two biopsy specimens were taken per lesion, compared with ≥three in international institutions. CONCLUSION: There were some discrepancies between Japanese and international institutions for routine EGD. Thus, standardization is required for adequate risk assessment, proper techniques, and knowledge of endoscopic diagnosis of EGC.

The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway.

Polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that correlates with the regulation of invasion and metastasis and is overexpressed in human cancers such as colorectal cancer. MicroRNA-31 (miR-31) plays an oncogenic role and is associated with BRAF mutation and poor prognosis in colorectal cancer. EZH2 is functionally considered to suppress miR-31 expression in human cancers; however, no study has reported its relationship with colon cancer. We therefore evaluated EZH2 expression using immunohistochemistry and assessed miR-31 and epigenetic alterations using 301 colorectal carcinomas and 207 premalignant lesions. Functional analysis was performed to identify the association between EZH2 and miR-31 using cancer cell lines. In the current study, negative, weak, moderate, and strong EZH2 expressions were observed in 15%, 19%, 25%, and 41% of colorectal cancers, respectively. EZH2 was inversely associated with miR-31 (P < 0.0001), independent of clinicopathological and molecular features. In a multivariate stage-stratified analysis, high EZH2 expression was related to favorable prognosis (P = 0.0022). Regarding premalignant lesions, negative EZH2 expression was frequently detected in sessile serrated adenomas/polyps (SSA/Ps) (76%; P < 0.0001) compared with hyperplastic polyps, traditional serrated adenomas, and non-serrated adenomas (25-36%). Functional analysis demonstrated that the knockdown of EZH2 increased miR-31 expression. In conclusion, an inverse association was identified between EZH2 and miR-31 in colorectal cancers. Our data also showed that upregulation of EZH2 expression may be rare in SSA/Ps. These results suggest that EZH2 suppresses miR-31 in colorectal cancer and may correlate with differentiation and evolution of serrated pathway.

Current status of transnasal endoscopy worldwide using ultrathin videoscope for upper gastrointestinal tract.

Transnasal endoscopy with an ultrathin endoscope has been reported to be highly acceptable even without any sedative measures. Poor image quality and complex manipulation have been reported as shortcomings of this type of endoscopy compared with standard transoral endoscopy. However, image quality has improved markedly with the latest ultrathin endoscopes. To investigate the status of clinical use of endoscopes, we recently conducted a questionnaire survey involving 149 facilities (98 in Japan and 51 overseas). In Japan, transnasal endoscopes were being used primarily in clinics (34% in clinics and 9% in hospitals). Overseas, however, transnasal endoscopes were seldom used (1% in hospitals and 0% in clinics). This may be attributable to the complex pretreatment and more challenging manipulation required for transnasal endoscopes. However, it is evident that transnasal endoscopes are highly acceptable for patients. If the pretreatment required is simplified and healthcare physicians improve their skills and understanding, this type of endoscopy will have high potential for common use.

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK).

BACKGROUND: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. METHODS: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with all-stage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. RESULTS: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p = 0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. CONCLUSIONS: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.