Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Intensive Frequent Granulocyte Adsorptive Apheresis Therapy for Acute Fulminant Ulcerative Colitis: Two Consecutive Case Reports.

Granulocyte/monocyte adsorptive apheresis (GMA) therapy is a treatment method for ulcerative colitis (UC). Twice-weekly GMA regimens are usually administered to treat severe UC. Although GMA efficacy is considered frequency-dependent, there is no uniformly accepted optimal GMA regimen, and there is insufficient evidence regarding optimal GMA therapy frequency for acute fulminant UC. Case 1 was of a 33-year-old man, and case 2 was of a 20-year-old woman. They were diagnosed with acute fulminant UC and treated with steroid therapy, but exhibited exacerbated UC, and their conditions worsened. We, therefore, initiated intensive frequent GMA therapy (conducted 10-11 times during a 13-day period). In both cases, remission was achieved within two weeks of therapy induction. Herein, we describe two consecutive cases in which rapid remission of acute fulminant UC was achieved without adverse events using intensive frequent GMA therapy. These cases suggest that intensive frequent GMA therapy might induce rapid remission in acute fulminant UC cases and may be more effective than twice-weekly GMA regimens.

Clinical outcomes of permanent stenting with endoscopic ultrasound gallbladder drainage.

BACKGROUND/AIMS: Endoscopic ultrasound gallbladder drainage (EUS-GBD) is gaining attention as a treatment method for cholecystitis. However, only a few studies have assessed the outcomes of permanent stenting with EUS-GBD. Therefore, we evaluated the clinical outcomes of permanent stenting using EUS-GBD. METHODS: This was a retrospective, single-center cohort study. The criteria for EUS-GBD at our institution are a high risk for surgery, inability to perform surgery owing to poor performance status, and inability to obtain consent for emergency surgery. EUS-GBD was performed using a 7-Fr double-pigtail plastic stent with a dilating device. The primary outcomes were the recurrence-free rate of cholecystitis and the late-stage complication-avoidance rate. Secondary outcomes were technical success, clinical success, and procedural adverse events. RESULTS: A total of 41 patients were included in the analysis. The median follow-up period was 168 (range, 10-1,238) days. The recurrence-free and late-stage complication-avoidance rates during the follow-up period were 95% (38 cases) and 90% (36 cases), respectively. There were only two cases of cholecystitis recurrence during the study period. CONCLUSION: EUS-GBD using double-pigtail plastic stent was safe and effective with few complications, even in the long term, in patients with acute cholecystitis.

Endoscopic submucosal dissection using an ultrathin endoscope for superficial pharyngeal cancer: a prospective feasibility study (with video).

Background and study aims Endoscopic submucosal dissection (ESD) of pharyngeal cancers with conventional endoscopes often is difficult, not only because of the narrow working space, but also because endoscope maneuverability in the pharynx is poor due to interference from the endotracheal tube and/or hyoid bone. However, we hypothesized that those problems could possibly be resolved by use of an ultrathin endoscope for ESD of superficial pharyngeal cancer. The aim of this prospective interventional study was to investigate the feasibility of ESD for superficial pharyngeal cancer using an ultrathin endoscope. Patients and methods This feasibility study was conducted at NTT Medical Center Tokyo between June 2020 and September 2021, and data from a total of 20 consecutively superficial pharyngeal cancers were analyzed. The primary outcome measure was the R0 resection rate. The ESD completion rate, en bloc resection rate, procedure time, and frequency of intraoperative and postoperative adverse events (AEs) were also evaluated as secondary outcome measures. Results Data from 16 patients with 20 lesions were included in the analysis. All of the lesions were successfully resected by ultrathin endoscope ESD, and the en bloc and R0 resection rates were 100 % and 85.0 % (17/20), respectively; the procedure time was 37.8 ±â€Š28.2 minutes. No intraoperative or postoperative AEs were encountered in any cases. Conclusions ESD using an ultrathin endoscope is feasible for superficial pharyngeal cancers and has potential to be a safe and effective treatment option for these cancers.

Causal effect of anxiety and depression status on the symptoms of gastroesophageal reflux disease and functional dyspepsia during proton pump inhibitor therapy.

BACKGROUND: Although anxiety and depression status is considered related to gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) symptoms, ambiguity primarily arises from the difficulty in determining their cause-effect relationships. We aimed to examine the longitudinal reciprocal causation between anxiety/depression status and GERD/FD symptoms among symptomatic adult patients with GERD. METHODS: Adult (≥ 20 years) patients with GERD symptoms received PPI treatment for 4 weeks after endoscopy. GERD and FD symptom subscales (GERD-SS/FD-SS) were evaluated using the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST). Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS). A cross-lagged analysis using structural equation modeling was conducted to examine causal relationships among psychiatric bias (anxiety and depression scores) and upper gastrointestinal symptoms (GERD-SS and FD-SS scores) over time. RESULTS: A total of 182 patients with GERD (men: 120; age: 57.1 ± 12.8 years; body mass index: 24.2 ± 4.1 kg/m2; nonerosive reflux disease/erosive reflux disease: 61/121) were eligible before (T1) and after 4 weeks (T2) of PPI therapy. The cross-lagged effect model indicated that anxiety at T1 contributed to the FD-SS at T2 (ß = 0.18*) and depression at T1 contributed to the GERD-SS at T2 (ß = 0.23*) (*p < 0.05). CONCLUSION: Psychiatric bias was a risk factor for refractory GERD and FD. Anxiety and depression status reduced the therapeutic effect of PPIs on GERD and FD symptoms. Therefore, attention is required to detect the anxiety/depression status of patients with GERD/FD symptoms to treat patients appropriately and optimize therapeutic outcomes.

A single-sided trans-nasal catheter for smooth and efficient oxygen delivery can improve the safety in patients undergoing pancreato-biliary endoscopy under intravenous sedation: A randomized trial.

Background: Pancreato-biliary endoscopic procedures often need to be performed under deep intravenous sedation. The patients are at an increased risk of respiratory depression influenced by the anatomical dead space of the upper respiratory system. We aimed to evaluate the benefit of oxygen delivery through a single-sided trans-nasal catheter (TC) for patients undergoing pancreato-biliary endoscopy. Methods: Oxygen supplementation during the procedure was provided either by insertion of a single-sided TC or insertion of a conventional nasal catheter (NC). A prospective, single-blind, randomized controlled study was conducted in two groups. Results: The number of patients who indicated a decrease in the peripheral transcutaneous oxygen saturation (SpO2; desaturation) was significantly lower in the TC group than in the counterpart (8/58; 13.8% vs. 26/58; 44.8% p < 0.001). The efficient oxygen delivery in the safe range was better conserved in the TC group than in the NC one. There was no adverse effect on both groups. The maximum SpO2 while the endoscopic procedure was significantly higher in the TC group (99.7% vs. 99.3% p = 0.016) and the minimum SpO2 was also significantly higher in the same group (97.7% vs. 94.1% p < 0.0001), which meant that the efficient oxygen delivery was better maintained in TC group than the NC group. Conclusions: A single-sided TC placed in the pharynx in patients undergoing pancreato-biliary endoscopy prepares a superior condition of the patients for venous sedation, maintained hyper-oxygen saturation and a relatively higher SpO2 level to be maintained in limited conditions to reduce the dead space with acceptable tolerance, as compared to the placement of a conventional NC.

Integrated environmental, lifestyle, and epigenetic risk prediction of primary gastric neoplasia using the longitudinally monitored cohorts.

BACKGROUND: DNA methylation accumulates in non-malignant gastric mucosa after exposure to pathogens. To elucidate how environmental, methylation, and lifestyle factors interplay to influence primary gastric neoplasia (GN) risk, we analyzed longitudinally monitored cohorts in Japan and Singapore. METHODS: Asymptomatic subjects who underwent a gastric mucosal biopsy on the health check-up were enrolled. We analyzed the association between clinical factors and GN development using Cox hazard models. We further conducted comprehensive methylation analysis on selected tissues, including (i) mucosae from subjects developing GN later, (ii) mucosae from subjects not developing GN later, and (iii) GN tissues and surrounding mucosae. We also use the methylation data of mucosa collected in Singapore. The association between methylation and GN risk, as well as lifestyle and methylation, were analyzed. FINDINGS: Among 4234 subjects, GN was developed in 77 subjects. GN incidence was correlated with age, drinking, smoking, and Helicobacter pylori (HP) status. Accumulation of methylation in biopsied gastric mucosae was predictive of higher future GN risk and shorter duration to GN incidence. Whereas methylation levels were associated with HP positivity, lifestyle, and morphological alterations, DNA methylation remained an independent GN risk factor through multivariable analyses. Pro-carcinogenic epigenetic alterations initiated by HP exposure were amplified by unfavorable but modifiable lifestyle choices. Adding DNA methylation to the model with clinical factors improved the predictive ability for the GN risk. INTERPRETATION: The integration of environmental, lifestyle, and epigenetic information can provide increased resolution in the stratification of primary GN risk. FUNDING: The funds are listed in Acknowledgements section.

Comparison of the effects of individual symptoms of gastroesophageal reflux disease co-existing functional dyspepsia on patients' daily lives: A prospective, observational study.

Background and Aim: Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods: We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD-TEST], Hospital Anxiety and Depression Scale [HADS], and 8-item Short-Form Health Survey [SF-8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD-TEST, anxiety and depression score of HADS, and physical and mental component summary of SF-8. Results: Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD-EPS/FD-PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS-symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life-SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD-SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion: Dealing with co-existing FD symptoms without overlooking them may be important in the management of GERD.

Two independent modes of kidney stone suppression achieved by AIM/CD5L and KIM-1.

The prevalence of kidney stones is increasing and its recurrence rate within the first 5 years is over 50%. No treatments that prevent the occurrence/recurrence of stones have reached the clinic. Here, we show that AIM (also called CD5L) suppresses stone development and improves stone-associated physical damages. The N-terminal domain of AIM associates with calcium oxalate crystals via charge-based interaction to impede the development of stones, whereas the 2nd and C-terminal domains capture the inflammatory DAMPs to promote their phagocytic removal. Accordingly, when stones were induced by glyoxylate in mice, recombinant AIM (rAIM) injection dramatically reduced stone development. Expression of injury molecules and inflammatory cytokines in the kidney and overall renal dysfunction were abrogated by rAIM. Among various negatively charged substances, rAIM was most effective in stone prevention due to its high binding affinity to crystals. Furthermore, only AIM was effective in improving the physical complaints including bodyweight-loss through its DAMPs removal effect. We also found that tubular KIM-1 may remove developed stones. Our results could be the basis for the development of a comprehensive therapy against kidney stone disease.

Successful endoscopic submucosal dissection for a tumor located completely within a colonic diverticulum after inversion of the diverticulum using a traction device.

Video 1Successful endoscopic submucosal dissection for a tumor completely located within a colonic diverticulum after inversion of the diverticulum using a traction device. After reconfirming that the diverticulum could be inverted into the lumen with forceps, the first endoclip grasping a ring-thread made of dental floss was fixed on the mucosa in the diverticulum. Immediately afterward, a second endoclip was used to grasp the ring-thread and fix it to the opposite colonic wall. By insufflating with air, the lesion within the inverted diverticulum was pulled out of the diverticulum into the colonic lumen, establishing a good field of view for dissection. After local injection of hyaluronic acid, a circumferential incision and dissection were performed using a DualKnife, and the lesion was promptly removed en bloc. The wound was completely closed with endoclips, along with the diverticulum. The total procedure time was 10 minutes, and there were no adverse events.

A new classification for the diagnosis of superficial non-ampullary duodenal epithelial tumors using endocytoscopy: A prospective study.

BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).

Endoscopic and histological features of Helicobacter pylori-negative differentiated gastric adenocarcinoma arising in the antrum.

BACKGROUND AND AIM: With the increasing prevalence of persons without Helicobacter pylori (HP) infection, cases of HP-negative gastric cancer are increasing. Although rare, cases of differentiated adenocarcinoma of the antrum have been reported in HP-negative patients. We collected cases with such lesions and investigated their endoscopic and histological features. METHODS: Of 1965 consecutive patients with early gastric cancer who underwent endoscopic resection between January 2009 and December 2017, we extracted 9 cases of HP-negative differentiated adenocarcinoma located in the antrum (HPN-DAA). The clinical data, endoscopic findings, and histopathological findings were reviewed. RESULTS: Of the nine patients with HPN-DAA, seven were male, and the median age was 53.8 years. The tumor arose from the pyloric gland mucosa in all cases. According to the endoscopic findings, the lesions were flat-elevated or depressed, mimicking varioliform gastritis. Magnifying endoscopy with narrow-band imaging showed the absence of a clear demarcation line or an irregular microvessel/surface pattern. As for the histopathological findings, eight of the nine lesions were diagnosed as high-grade dysplasia/intraepithelial neoplasia, while the remaining case was diagnosed as tubular adenocarcinoma with submucosal infiltration. The findings of immunohistochemistry confirmed that three cases were of the intestinal mucin phenotype and six were of the mixed gastric and intestinal mucin phenotype. CONCLUSION: HPN-DAA is a very rarely occurring cancer that had never been recognized earlier. They belong to the new category of HP-negative cancers, and there seems to be a certain number of such cases.

Palisade technique as an effective endoscopic submucosal dissection tool for large colorectal tumors.

Background and study aims Endoscopic submucosal dissection (ESD) has become the standard treatment for colorectal ESD, but large colorectal tumors remain difficult to remove. We developed a new method, called the palisade technique, by modifying the multiple tunneling technique. In this method, a palisade of submucosal tissue is left beneath the tumor to anchor a dissected specimen, maintaining effective submucosal traction. Patients and methods The study included 11 patients with large colorectal tumors that were over half the circumference of the colorectal lumen which were treated using the palisade technique from August 2017 to October 2019. Overall resection outcomes were assessed. Results All 11 lesions were removed en bloc. The R0 resection rate was 45.6 % because of marginal burning of the specimen, but no local recurrence was found after a median observation period of 31 months. The median submucosal dissection time (SDT) and submucosal dissection speed (SDS) were 170 minutes and 23.1 mm 2 /min, respectively. One case of post-ESD hemorrhage was successfully managed endoscopically, and two cases of post-colorectal ESD coagulation syndrome were managed conservatively. Conclusion The palisade technique can be an effective and safe technique for treating large colorectal tumors that extend over half the luminal circumference.

Clinical features and therapeutic responses to proton pump inhibitor in patients with severe reflux esophagitis: A multicenter prospective observational study.

BACKGROUND AND AIM: In patients with severe erosive reflux disease (ERD; Los Angeles classification grade C/D) who do not undergo endoscopic examination, insufficient strength and duration of proton pump inhibitor (PPI) therapy may lead to complications such as esophageal bleeding and stenosis. Therefore, to provide a safe and effective treatment for gastroesophageal reflux disease (GERD), we investigated the clinical features of patients with severe ERD and their responses to PPI therapy. METHODS: Patients with GERD symptoms received PPI therapy for 4 weeks after endoscopic examination. The patients completed the Gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaire before and 2 or 4 weeks after PPI treatment. Patient characteristics, presence/absence of coexisting atrophic gastritis (AG) and hiatus hernia (HH), and responses to PPI therapy were compared in patients with GERD among three groups (nonerosive reflux disease, mild ERD [grade A/B], and severe ERD). RESULTS: The severe ERD group had a significantly higher proportion of males, higher body mass index, and longer duration of GERD morbidity. Furthermore, the severe ERD group also had a significantly lower incidence of coexisting AG and higher incidence of HH. There was no difference in the severity of GERD before PPI treatment among the three groups. Unexpectedly, the response to PPI therapy was the best in the severe ERD group. CONCLUSION: Sufficient strength and period of PPI therapy are required, even if the symptoms show early improvement, when treating GERD patients without performing endoscopy, considering the possibility of severe ERD.

Evaluation of colorectal endoscopic submucosal dissection using a multifunctional snare: a prospective clinical feasibility study (with videos).

BACKGROUND AND AIMS: The number of colorectal endoscopic submucosal dissections (ESDs) for early colorectal cancer is expected to increase in the future; therefore, cost reduction is a clinically important issue. The SOUTEN snare (Kaneka Medics, Tokyo, Japan) is a novel multifunctional snare developed for hybrid ESD at a low price. If ESD can be performed safely using the SOUTEN snare, the same therapeutic effect can be obtained as with conventional ESD at a lower cost. The aim of this prospective, pilot, clinical feasibility study was to evaluate the safety and efficacy of ESD using the SOUTEN snare (SOUTEN-ESD). METHODS: From October 2018 to January 2019, 119 consecutive patients (121 ESD procedures, 137 colorectal neoplasms) were prospectively enrolled and treated by SOUTEN-ESD at NTT Medical Center Tokyo and Omori Red Cross Hospital. The outcomes of SOUTEN-ESD were evaluated. RESULTS: Among 137 neoplasms, SOUTEN-ESD was completed in all cases. No cases required conversion to hybrid ESD or to a dedicated ESD device. The mean procedure time was 26.1 ± 14.3 minutes. Both the en-bloc resection rate and R0 resection rate were 100%. The rate of perforation was 0%, the rate of delayed bleeding was 2.2%, and the rate of post-ESD coagulation syndrome was 2.9%. CONCLUSIONS: SOUTEN-ESD was safe and had good outcomes. Although further studies are required to examine indications for SOUTEN-ESD and confirm the results of this study, effective ESD with this novel knife is feasible. The SOUTEN snare is a realistic option for colorectal ESD. (Clinical trial registration number: UMIN 000034299.).

Endoscopic submucosal dissection for colorectal neoplasms in proximity or extending to a diverticulum.

BACKGROUND AND AIMS: At specialized facilities, endoscopic submucosal dissection (ESD) has currently been performed even for difficult cases such as tumors extending to a diverticulum that previously required surgery. This study aims to classify the type of lesion according to the degree of infiltration to a diverticulum and assessed the safety and efficacy of ESD for each type of lesion. METHODS: We retrospectively reviewed ESD for lesions at NTT Medical Center Tokyo between January 2014 and April 2019. Lesions were classified as follows: Type 1: lesions in contact with or within 3 mm of the edge of a diverticulum; Type 2: lesions that partially infiltrated into a diverticulum; and Type 3: lesions that infiltrated into and completely covered the diverticulum. Furthermore, ESD strategies were divided into A and B, which indicates that a lesion was resected separately from the diverticulum and along the entire diverticulum, respectively. The clinicopathological characteristics and clinical outcomes were analyzed according to the strategy. RESULTS: A total of 47 lesions satisfied inclusion criteria (19 Type 1, 12 Type 2, and 16 Type 3 lesions). 19 Type 1 and 8 Type 2 lesions were resected using Strategy A, while 4 Type 2 and 16 Type 3 lesions were resected using Strategy B. En bloc resection was achieved in all cases. In Strategy A, the R0 resection rate was 96.3% and the curative resection rate was 88.9%. On the contrary, in Strategy B, the R0 resection rate was 95.0% and the curative resection rate was 90.0%. In Strategy B, one of the patients developed post-operative bleeding that required endoscopic hemostasis; another patient developed delayed perforation that required emergency surgery. CONCLUSIONS: ESD for colorectal neoplasms in proximity or extending to a diverticulum is challenging, but this procedure can be a safe and effective therapeutic option.

Simple scoring system for the diagnosis of superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIMS: Differentiating superficial non-ampullary duodenal epithelial tumors (SNADETs) that harbor malignant potential is important. We developed a simple scoring system and investigated whether it enables the differentiation of low-grade adenoma and high-grade adenoma/adenocarcinoma. PATIENTS AND METHODS: We retrospectively enrolled 197 consecutive patients with 207 SNADETs who underwent endoscopic resection at NTT Medical Center Tokyo between March 2016 and May 2019. Endoscopic findings were compared between Vienna Classification (VCL) C3 and C4/5 lesions. A multivariate logistic regression analysis was performed to develop a scoring system to identify VCL C4/5 lesions. The efficacy of our scoring system was elucidated among five novice and five expert endoscopists. RESULTS: Of 207 SNADETs, 66 and 141 lesions were pathologically diagnosed as VCL C3 and C4/5. A multivariate logistic regression analysis identified a tumor diameter of 10-19 mm (OR, 3.81; 95% CI, 1.02-14.2; P = 0.04), a tumor diameter ≥20 mm (OR, 95.2; 95% CI, 10.4-871.0; P < 0.001), a red color (OR, 14.5; 95% CI, 3.55-59.6; P < 0.001), the presence of irregular surface pattern (OR, 12.4; 95% CI, 3.00-51.4; P < 0.001), and the presence of irregular vessel pattern (OR, 13.7; 95% CI, 4.03-46.6; P < 0.001) as independent significant predictors of VCL C4/5. Considering these results, we developed a scoring system. Using an appropriate cutoff value, the diagnostic accuracy, sensitivity and specificity were calculated as 92%, 95% and 93%. The average diagnostic accuracy did not differ between novice and expert endoscopists (86% vs 87%, P = 0.76). CONCLUSIONS: Our scoring system was useful for differentiating VCL C3 and C4/5 lesions. UMIN Clinical Trials (No. 000039063).