Usefulness of virtual scale endoscope for early gastrointestinal lesions.

Objectives: For early gastrointestinal lesions, size is an important factor in the selection of treatment. Virtual scale endoscope (VSE) is a newly developed endoscope that can measure size more accurately than visual measurement. This study aimed to investigate whether VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies. Methods: This study prospectively enrolled patients with early gastrointestinal lesions ≤20 mm in size visually. Lesion sizes were measured in the gastrointestinal tract visually, on endoscopic resection specimens with VSE, and finally on endoscopic resection specimens using a ruler. The primary endpoint was the normalized difference (ND) of VSE measurement. The secondary endpoints were the ND of visual measurement and the variation between NDs of VSE and visual measurements. ND was calculated as (100 × [measured size - true size] / true size) (%). True size was defined as size measured using a ruler. Results: This study included 60 lesions from April 2022 to December 2022, with 20 each in the esophagus, stomach, and colon. The lesion size was 14.0 ± 6.3 mm (mean ± standard deviation). Morphologies were protruded, slightly elevated, and flat or slightly depressed type in 8, 24, and 28 lesions, respectively. The primary endpoint was 0.3 ± 8.8%. In the secondary endpoints, the ND of visual measurement was -1.7 ± 29.3%, and the variability was significantly smaller in the ND of VSE measurement than in that of visual measurement (p < 0.001, F-test). Conclusions: VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies.

Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Smartphone application for artificial intelligence-based evaluation of stool state during bowel preparation before colonoscopy.

OBJECTIVES: Colonoscopy (CS) is an important screening method for the early detection and removal of precancerous lesions. The stool state during bowel preparation (BP) should be properly evaluated to perform CS with sufficient quality. This study aimed to develop a smartphone application (app) with an artificial intelligence (AI) model for stool state evaluation during BP and to investigate whether the use of the app could maintain an adequate quality of CS. METHODS: First, stool images were collected in our hospital to develop the AI model and were categorized into grade 1 (solid or muddy stools), grade 2 (cloudy watery stools), and grade 3 (clear watery stools). The AI model for stool state evaluation (grades 1-3) was constructed and internally verified using the cross-validation method. Second, a prospective study was conducted on the quality of CS using the app in our hospital. The primary end-point was the proportion of patients who achieved Boston Bowel Preparation Scale (BBPS) ≥6 among those who successfully used the app. RESULTS: The AI model showed mean accuracy rates of 90.2%, 65.0%, and 89.3 for grades 1, 2, and 3, respectively. The prospective study enrolled 106 patients and revealed that 99.0% (95% confidence interval 95.3-99.9%) of patients achieved a BBPS ≥6. CONCLUSION: The proportion of patients with BBPS ≥6 during CS using the developed app exceeded the set expected value. This app could contribute to the performance of high-quality CS in clinical practice.

Tumor thickness as a novel risk factor for lymph node metastasis by superficial squamous cell carcinoma of head and neck.

Narrow-band imaging combined with magnified endoscopy has enabled the detection of superficial squamous cell carcinoma of the head and neck (SSCCHN) that has been resected with minimally invasive treatment, preserving vocalization and swallowing functions. However, risk factors of lymph node metastasis (LNM) must be identified, as some patients with LNM have a poor prognosis. From an initial 599 patients with 700 lesions who underwent trans-oral surgery in 27 Japanese hospitals (a nationwide registration survey), we enrolled 541 patients with 633 SSCCHNs, as indicated by central pathological diagnoses. All pathological specimens for each patient were examined using 20 pathological factors that are thought to affect the LNM of SSCCHN. In all, 24 (4.4%) of the 568 SSCCHNs exhibited LNM, and all 24 had at least one solitary nest of epithelial neoplastic cells present in the stroma, clearly separated from the intraepithelial carcinoma. Multivariate analysis also showed that tumor thickness (p = 0.0132, RR: 7.85, 95% confidence interval [CI]: 1.54-40.02), and an INFc pattern classified as infiltrating growth (INF) with unclear boundaries between tumor and non-tumor tissues (p = 0.0003, RR: 14.47, 3.46-60.46), and tumor budding (p = 0.0019, RR: 4.35, CI: 1.72-11.01) were significantly associated with LNM. Solitary nests may be indicative of LNM. In addition, tumor thickness was revealed to be a risk factor for LNM in SSCCHNs using pT factors that do not include an invasion depth element because of the anatomical absence of the muscularis mucosae.

Biologic therapy for ulcerative colitis associated with immune thrombocytopenia.

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, occasionally manifests with extraintestinal manifestations. We present a 51-year-old male with refractory UC and immune thrombocytopenia (ITP) resistant to conventional treatments. The introduction of biologics, ustekinumab or adalimumab, resulted in clinical remission of colitis and improvements in platelet count. This case underscores the efficacy of biologics in managing refractory UC associated with ITP, emphasizing their potential to control intestinal inflammation and address concurrent thrombocytopenia, potentially avoiding surgical intervention.

Factors affecting complete stone removal and bile duct stone recurrence in patients with surgically altered anatomy treated by double-balloon endoscopy-assisted endoscopic retrograde cholangiography.

OBJECTIVES: This study assessed factors influencing the complete removal and recurrence of bile duct stones in patients with surgically altered anatomy (SAA) undergoing double-balloon endoscopy-assisted endoscopic retrograde cholangiography (DBERC). METHODS: A retrospective analysis of 289 patients with SAA treated for biliary stones with DBERC at Jichi Medical University Hospital (January 2007 to December 2022) was conducted. Evaluation of factors impacting complete stone removal was performed in 257 patients with successful bile duct cannulation. Logistic and Cox proportional hazards regression models were used to compute the odds ratios (ORs) and hazard ratios (HRs) at 95% confidence intervals (CIs). RESULTS: Of 257 patients, 139 (54.0%) and 209 (81.3%) achieved initial and complete removal, respectively. Recurrence occurred in 55 (21.4%) patients. Factors associated with initial complete stone removal included cholangitis (P < 0.01, OR 0.48, 95% CI 0.27-0.83), number of stones (P < 0.01, OR 0.31, 95% CI 0.18-0.54), and largest stone diameter (P < 0.01, OR 0.37, 95% CI 0.20-0.67). The size of the largest stone was associated with complete removal (P = 0.01, OR 0.24, 95% CI 0.13-0.76). Recurrence was associated with cholangitis (P = 0.046, HR 0.54, 95% CI 0.29-0.99), congenital biliary dilatation (P = 0.01, HR 2.65, 95% CI 1.21-5.80), and number of stones (P = 0.02, HR 1.96, 95% CI 1.12-3.41). CONCLUSIONS: Successful complete bile stone removal in patients with SAA depends on the stone diameter and number. Stone recurrence is influenced by the number of stones and history of congenital biliary dilatation.

Endoscopic Diagnosis of Small Bowel Tumor.

Recent technological advances, including capsule endoscopy (CE) and balloon-assisted endoscopy (BAE), have revealed that small intestinal disease is more common than previously thought. CE has advantages, including a high diagnostic yield, discomfort-free, outpatient basis, and physiological images. BAE enabled endoscopic diagnosis and treatment in the deep small bowel. Computed tomography (CT) enterography with negative oral contrast can evaluate masses, wall thickening, and narrowing of the small intestine. In addition, enhanced CT can detect abnormalities outside the gastrointestinal tract that endoscopy cannot evaluate. Each modality has its advantages and disadvantages, and a good combination of multiple modalities leads to an accurate diagnosis. As a first-line modality, three-phase enhanced CT is preferred. If CT shows a mass, stenosis, or wall thickening, a BAE should be selected. If there are no abnormal findings on CT and no obstructive symptoms, CE should be selected. If there are significant findings in the CE, determine the indication for BAE and its insertion route based on these findings. Early diagnosis of small intestinal tumors is essential for favorable outcomes. For early diagnosis, the possibility of small bowel lesions should be considered in patients with unexplained symptoms and signs after examination of the upper and lower gastrointestinal tract.

Comparison of Effective Imaging Modalities for Detecting Gastric Neoplasms: A Randomized 3-Arm Phase II Trial.

INTRODUCTION: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI. METHODS: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%. RESULTS: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively. DISCUSSION: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection.

Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment. METHODS: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC. RESULTS: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8+ T cells and conventional CD4+ T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1+CD8+ T cells in the tumor after CRT could predict a confirmed complete response and favorable survival. CONCLUSIONS: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1+CD8+ T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment.

The presence of hiatal hernia is a significant predictor for symptomatic recurrence after cessation of vonoprazan therapy for gastroesophageal reflux disease: a long-term observational study.

BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms frequently recur after cessation of acid blockers. The presence of a hiatal hernia may worsen GERD symptoms and increase the risk of esophageal malignancy. The aim of this study is to clarify the timing and predictors for recurrence of GERD symptoms after cessation of vonoprazan (VPZ) therapy. METHODS: A retrospective observational study involved 86 patients who underwent cessation of VPZ therapy for symptomatic GERD. Collated data from medical record review included the endoscopic findings and Izumo scale score. RESULTS: The mean duration of continuous VPZ therapy before cessation was 7.9 months. GERD symptoms requiring the resumption of VPZ therapy recurred in 66 of 86 patients (77%). Kaplan-Meier analysis showed that overall recurrence-free rates at 6 months, one and two years after VPZ cessation were 44%, 32% and 23%, respectively. Alcohol use, the presence of a hiatal hernia and long-term therapy for more than six months were identified as significant positive predictors for symptomatic recurrence. Notably, hiatal hernia had the highest hazard ratio in both univariate and multivariate analyses. The recurrence-free rate in patients with a hiatal hernia was much lower at 6 months than in patients without a hiatal hernia (15% and 51%, respectively p = 0.002). After the symptomatic recurrence, GERD symptoms improved significantly after one-month VPZ therapy. CONCLUSION: The rate of symptomatic recurrence after VPZ cessation in patients with GERD is considerable. Cessation of acid suppression therapy should be cautious in patients with both a hiatal hernia and GERD.

Advanced diagnostic endoscopy in the upper gastrointestinal tract: Review of the Japan Gastroenterological Endoscopic Society core sessions.

The Japan Gastroenterological Endoscopy Society (JGES) held four serial symposia between 2021 and 2022 on state-of-the-art issues related to advanced diagnostic endoscopy of the upper gastrointestinal tract. This review summarizes the four core sessions and presents them as a conference report. Eleven studies were discussed in the 101st JGES Core Session, which addressed the challenges and prospects of upper gastroenterological endoscopy. Ten studies were also explored in the 102nd JGES Core Session on advanced upper gastrointestinal endoscopic diagnosis for decision-making regarding therapeutic strategies. Moreover, eight studies were presented during the 103rd JGES Core Session on the development and evaluation of endoscopic artificial intelligence in the field of upper gastrointestinal endoscopy. Twelve studies were also discussed in the 104th JGES Core Session, which focused on the evidence and new developments related to the upper gastrointestinal tract. The endoscopic diagnosis of upper gastrointestinal diseases using image-enhanced endoscopy and AI is one of the most recent topics and has received considerable attention. These four core sessions enabled us to grasp the current state-of-the-art in upper gastrointestinal endoscopic diagnostics and identify future challenges. Based on these studies, we hope that an endoscopic diagnostic system useful in clinical practice is established for each field of upper gastrointestinal endoscopy.

Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Novel gastric endoscopic submucosal dissection training model enhances the endoscopic submucosal dissection skills of trainees: a multicenter comparative study.

BACKGROUND: Endoscopic submucosal dissection (ESD) requires high endoscopic technical skills, and trainees should develop effective training methods. In collaboration with KOTOBUKI Medical, we developed the G-Master, which is a non-animal training model that can simulate various parts of gastric ESD. We aimed to clarify the usefulness of the G-Master for inexperienced ESD trainees. METHODS: We collected data from the first 5 gastric ESD cases conducted by 15 inexperienced ESD trainees at 5 participating centers between 2018 and 2022. The participants were divided into two groups: the G-Master training and non-G-Master training groups. Outcome measurements, such as procedural speed, perforation rate, self-completion rate, and en bloc resection rate, were compared between the two groups retrospectively. RESULTS: A total of 75 gastric ESD cases were included in this study. The G-Master training group included 25 cases performed by 5 trainees, whereas the non-G-Master training group included 50 cases performed by 10 trainees. The median procedural speed for all cases was significantly faster in the G-Master training group than in the non-G-Master training group. Moreover, the procedural speed was linearly improved from the initial to the last cases in the lower location in the G-Master training group compared with the non-G-Master training group. In addition, although there was no significant difference, the G-Master training group showed lower rates of perforation and a lesser need to transition to expert operators than the non-G-Master training group. CONCLUSION: The G-Master could improve the ESD skills of inexperienced ESD trainees.

Outcomes of repeated endoscopic submucosal dissection for superficial Esophageal squamous cell carcinoma on endoscopic resection scar.

BACKGROUND: Endoscopic submucosal dissection (ESD) can be performed for superficial esophageal cancer. However, performing ESD for superficial esophageal cancer on a previous endoscopic resection scar may be difficult. METHODS: We compared the outcomes between ESD for superficial esophageal cancers on previous endoscopic resection scar (group A) and that for naïve lesions (group B). The study included outcomes of ESD, cumulative incidence of local failure, and predictors of the occurrence of local failure in ESD patients with squamous cell carcinoma (SCC). The outcome variables evaluated were en bloc resection rates, procedure times, adverse events, and overall survival rates. RESULTS: Overall, 220 lesions were extracted (groups A and B: 23 and 197 lesions, respectively). In groups A and B, the complete resection rates were 60.9 and 92.9% (P < 0.001), and the mean procedure times were 79 and 68 min (P = 0.15), respectively. The perforation rates in groups A and B were 4.3 and 1% (P = 0.28). The 1-year cumulative local failure rates were 22 and 1% (P < 0.001), respectively. In the multivariate Cox proportional hazards analysis, superficial esophageal SCC on a previous endoscopic resection scar was a strong predictor of local failure (hazard ratio = 21.95 [3.99-120.80], P < 0.001). The 3-year overall survival rates in groups A and B were 95 and 93% (P = 0.99), respectively. CONCLUSIONS: Repeated ESD on scar is an option for treating superficial esophageal SCC with an acceptable rate of adverse events. Because of the low complete resection rate and high local failure compared with conventional ESD, strict endoscopic follow-up is required after repeated esophageal ESD.

Prospective multicenter trial of the cryoballoon ablation system for superficial esophageal squamous cell carcinoma on the post-endoscopic resection scar. A CRYO-SCAR study (EPOC1902).

BACKGROUND AND AIMS: Endoscopic resection (ER) is a minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). Post-ER scars complicate en bloc resection, even with advanced techniques, such as endoscopic submucosal dissection. The cryoballoon ablation system (CBAS) effectively manages Barrett's esophagus but has limited evidence in SESCC treatment, particularly on post-ER scars. This study aimed to evaluate the efficacy and safety of the CBAS for treating SESCC on post-ER scars. METHODS: This prospective study was conducted at two tertiary referral centers in Japan in patients endoscopically diagnosed with T1a SESCC on the post-ER scar. Focal CBAS was used for cryoablation, with specific criteria for lesion selection and treatment method. The primary endpoint was local complete response (L-CR) rate of the primary lesion 48 weeks after the first cryoablation as evaluated by an independent central evaluation committee. RESULTS: From October 2020 to October 2021, 15 patients with 17 lesions underwent cryoablation, with two requiring repeat cryoablation. The L-CR rate for primary and all lesions evaluated by the central evaluation committee was 100%. The endoscopist's evaluation was consistent with these results. The median procedure time was 9 min. Eight patients experienced no pain, and the highest pain score reported on a numeric 1-10 rating scale was 3. The technical success rate was 94.7% (18/19). Throughout the median follow-up period of 14.3 months, recurrences, deaths, or severe treatment-related adverse events were not reported. CONCLUSIONS: CBAS is a potentially safe and effective approach for SESCC on post-ER scars and represents an encouraging alternative to traditional endoscopic treatments.

Impact of Flagging/Risk Stratification System on Complications in Hospitalist Hip Fracture Co-management: Retrospective Cohort Study.

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications. Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis. Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31-0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03-10.84). Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT.

Near-Infrared Fluorescence Imaging Sensor with Laser Diffuser for Visualizing Photoimmunotherapy Effects under Endoscopy.

The drug efficacy evaluation of tumor-selective photosensitive substances was expected to be enabled by imaging the fluorescence intensity in the tumor area. However, fluorescence observation is difficult during treatments that are performed during gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port. This device was employed to demonstrate that a laser diffuser with an NIR fluorescence imaging sensor could be delivered through a 3.2 mm diameter port. In addition, fluorescence images of Cetuximab-IR700 were successfully observed in two mice, and the fluorescence intensity confirmed that the fluorescence decayed within 330 s. This device is expected to have practical application as a tool to identify the optimal irradiation dose for tumor-selective photosensitive substances under endoscopy.