Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake.

BACKGROUND/AIMS: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. METHODS: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. RESULTS: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). CONCLUSION: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

Effectiveness of endoscopic resection for colorectal neoplasms in ulcerative colitis: a multicenter registration study.

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at risk of developing colorectal cancer. The feasibility of endoscopic resection (ER) for UC-associated neoplasia has been suggested, but its efficacy and safety remain unclear. We aimed to assess the efficacy and safety of ER for colorectal neoplasms in patients with UC. METHODS: This was a retrospective, multicenter cohort study of patients with UC who initially underwent ER or surgery for colorectal neoplasms between April 2015 and March 2021. Patients who had prior colorectal neoplastic lesions were excluded. RESULTS: Among 213 men and 123 women analyzed, the mean age at UC onset was 41.6 years, and the mean age at neoplasia diagnosis was 56.1 years for 240 cases of total colitis, 59 cases of left-sided colitis, 31 cases of proctitis, and 6 cases of segmental colitis. EMR was performed for 142 lesions, and endoscopic submucosal dissection (ESD) was performed for 96 lesions. The perforation rate was 2.5% for all 238 lesions removed by ER and 6.3% for the 96 lesions removed by ESD. Among 146 ER lesions followed up with endoscopy, the local recurrence rate was 2.7%. The incidence of metachronous neoplasia after ER was 6.1%. All patients were followed a median of 34.7 months after initial treatment, and 5 died (all surgical cases). Overall survival was significantly higher in the ER group than in the surgery group (P = .0085). CONCLUSIONS: ER for colorectal neoplasms in UC may be acceptable in selected cases, although follow-up for metachronous lesions is necessary.

Computer-aided diagnosis of early-stage colorectal cancer using nonmagnified endoscopic white-light images (with videos).

BACKGROUND AND AIMS: Differentiation of colorectal cancers (CRCs) with deep submucosal invasion (T1b) from CRCs with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer-aided diagnosis (CADx) system to establish the diagnosis of early-stage cancers using nonmagnified endoscopic white-light images alone. METHODS: From 5108 images, 1513 lesions (Tis, 1074; T1a, 145; T1b, 294) were collected from 1470 patients at 10 academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Oversampling and focal loss were used to compensate class imbalance of the invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and 2 trainees read the identical testing dataset. RESULTS: At a 90% cutoff for the per-lesion score, CADx showed the highest specificity of 94.4% (95% confidence interval [CI], 91.3-96.6), with 59.8% (95% CI, 48.3-70.4) sensitivity and 87.3% (95% CI, 83.7-90.4) accuracy. The area under the characteristic curve was 85.1% (95% CI, 79.9-90.4) for CADx, 88.2% (95% CI, 83.7-92.8) for expert 1, 85.9% (95% CI, 80.9-90.9) for expert 2, 77.0% (95% CI, 71.5-82.4) for trainee 1 (vs CADx; P = .0076), and 66.2% (95% CI, 60.6-71.9) for trainee 2 (P < .0001). The function was also confirmed on 9 short videos. CONCLUSIONS: A CADx system developed with endoscopic white-light images showed excellent per-lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (Clinical trial registration number: UMIN000037053.).

Anxiety and behavioral changes in Japanese patients with inflammatory bowel disease due to COVID-19 pandemic: a national survey.

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.

Efficacy of endoscopy under general anesthesia for the detection of synchronous lesions in oro-hypopharyngeal cancer.

BACKGROUND/AIMS: Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. METHODS: This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. RESULTS: Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. CONCLUSION: Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

Small and large intestinal cancer in patients with Crohn's disease studied by surgeons.

PURPOSE: The current study summarized the clinical course and treatment outcomes of intestinal cancer in CD seen in our department and explored the steps to take in the future. METHODS: Subjects were patients who had been diagnosed with CD at our hospital and who underwent surgery in our department from 1985 to 2020. RESULTS: Thirty-one patients had CD and intestinal cancer, including 6 with cancer of the small intestine and 25 with cancer of the large intestine. In all six patients with cancer of the small intestine, the site where cancer or a tumor developed was at or near the site of the anastomosis made at a previous surgery. Of the 25 patients with cancer of the large intestine, 22 developed cancer in the rectum or anal region. CONCLUSION: Many of the patients with cancer of the small intestine had previously undergone surgery, and the cancer developed at or near the site of the anastomosis. In patients who have previously undergone resection of the small intestine, the small intestine needs to be examined regularly. Cancer of the large intestine often developed in the rectum or anal region of our patients, so a detailed examination of the same site needs to be performed.

Thiopurine naivety at tacrolimus induction is a predictor of long-term remission in patients with intractable ulcerative colitis who responded to tacrolimus.

BACKGROUND: The short-term efficacy of tacrolimus (Tac) for steroid-dependent and steroid-resistant refractory ulcerative colitis (UC) has been demonstrated; however, its long-term outcomes have not been well documented. Thus, this study aimed to clarify the long-term outcomes of patients who achieved Tac-induced remission and identify its predictors. METHODS: This study included patients with moderate-to-severe active UC who started receiving Tac at our hospital between July 2004 and December 2016. Short-term treatment response was assessed using the Lichtiger index 3 months after starting Tac, and responding patients were further followed up to assess long-term outcomes. The primary endpoint was the relapse-free survival after Tac-induced remission, and the secondary endpoint was the identification of factors associated with relapse after Tac-induced remission. RESULTS: The cumulative relapse-free survival rate at 10 years after Tac-induced remission was 33.2%. Multivariate analysis revealed that being thiopurine naïve at Tac induction was associated with the absence of relapse (hazard ratio: 0.45; 95% confidence interval: 0.22-0.92). CONCLUSIONS: Approximately one-third of patients who achieved Tac-induced remission maintained long-term remission. Being thiopurine naïve at Tac induction was a predictor of the absence of relapse.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

A review on the current status and definitions of activity indices in inflammatory bowel disease: how to use indices for precise evaluation.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn's disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Clinicopathological characteristics of colorectal serrated polyposis syndrome (SPS): results of a multicenter study by the SPS Study Group in Japan.

BACKGROUND: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan. METHODS: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria. RESULTS: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II. CONCLUSIONS: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.

Guidelines for Colorectal Cold Polypectomy (supplement to "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection").

The Japan Gastroenterological Endoscopy Society published the second edition of the "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection" in 2019 to clarify the indications for colorectal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection and to ensure appropriate preoperative diagnoses as well as effective and safe endoscopic treatment in front-line clinical settings. Endoscopic resection with electrocautery, including polypectomy and EMR, is indicated for colorectal polyps. Recently, the number of facilities introducing and implementing cold polypectomy without electrocautery has increased. Herein, we establish supplementary guidelines for cold polypectomy. Considering that the level of evidence for each statement is limited, these supplementary guidelines must be verified in clinical practice.

Long-term outcomes of endoscopic balloon dilation for intestinal strictures in patients with Crohn's disease during maintenance treatment with anti-tumor necrosis factor alpha antibodies.

BACKGROUND AND AIMS: Efficacy of endoscopic balloon dilation (EBD) for intestinal strictures in patients with Crohn's disease (CD) receiving anti-tumor necrosis factor alpha antibodies (anti-TNF) as maintenance therapy is unclear. We investigated the long-term efficacy and safety of EBD for intestinal strictures in patients with CD receiving anti-TNF. METHODS: We retrospectively analyzed data from patients with CD who received anti-TNF as maintenance therapy from 2008 to 2017, underwent EBD, and were followed up for ≥6 months. The primary endpoint was the cumulative surgery-free rate. The main secondary endpoints were technical success, repeat EBD rate, risk factors affecting surgical outcomes, and safety. RESULTS: Seventy-two patients with CD were assessed. The median observation period after EBD was 50 months. The technical success rate was 67%. The 3- and 5-year cumulative surgery-free rates were 81.1% and 73.5%, respectively. The repeat EBD rate was 74%. Multivariable analyses showed that risk factors affecting surgical outcomes were age at disease onset ≤16 years (hazard ratio 3.69; 95% confidence interval 1.36-10.01; P = 0.011). Serious complications requiring surgery developed in three patients. CONCLUSIONS: Endoscopic balloon dilation was an effective and safe short-term treatment and a useful long-term treatment for CD patients with intestinal strictures receiving anti-TNF as maintenance therapy.

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Background and study aims A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms. Patients and methods We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium. Results In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group ( P  < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells. Conclusions This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.

Erratum: Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

[This corrects the article DOI: 10.1055/a-1452-9669.].

Usefulness of vessel plus surface classification system for the diagnosis of early gastric cancer after Helicobacter pylori eradication.

BACKGROUND: It has been reported that it is sometimes difficult to make a diagnosis of gastric cancer detected after Helicobacter pylori (H. pylori) eradication. Therefore, we conducted a study to determine the usefulness of magnifying endoscopy using vessel plus surface classification system for making a diagnosis of early gastric cancer after H. pylori eradication. METHOD: Usefulness of the markers of the vessel plus surface classification system for diagnosing gastric cancer using magnifying endoscopy with narrow-band imaging was investigated for gastric cancer detected after H. pylori eradication (H. pylori-eradicated group) vs. H. pylori-positive gastric cancer (H. pylori-positive group). RESULTS: 85 lesions were included in this study. The H. pylori-eradicated group comprised 27 lesions, whereas the H. pylori-positive group comprised 58 lesions. As for magnified endoscopic findings based on the vessel plus surface classification system, the respective positivity rates in the H. pylori-eradicated group vs. those in the H. pylori-positive group were as follows: demarcation line, 100% (27/27) vs. 100% (58/58); irregular microvascular pattern, 100% (27/27) vs. 100% (58/58); and irregular microsurface pattern, 78% (21/27) vs. 95% (55/58). There was no significant difference in the positivity rates of the demarcation line and irregular microvascular pattern between the groups. The positivity rate of the irregular microsurface pattern was significantly lower in the H. pylori-eradicated group than in the H. pylori-positive group (P=0.03). CONCLUSION: We presume that the microvascular pattern is more useful than the microsurface pattern as a diagnostic marker in cases of gastric cancer detected after H. pylori eradication.

Possible Earlier Diagnosis of Ulcerative Colitis-Associated Neoplasia: A Retrospective Analysis of Interval Cases during Surveillance.

BACKGROUND: Early detection of ulcerative colitis-associated neoplasia (UCAN) is often difficult. The aim of this study was to clarify the morphology of initial UCAN. METHODS: White-light colonoscopy images obtained within the 2 years before UCAN diagnosis were retrospectively reviewed. The primary endpoint was the frequency of visible or invisible neoplasia on the endoscopic images before UCAN diagnosis. The secondary endpoints were comparisons of (1) visible or invisible neoplasia on initial endoscopic images of early-stage and advanced cancers, (2) the clinical backgrounds of patients in whom neoplasia was visible or invisible on initial endoscopic images, and (3) the clinical backgrounds of patients with distinct and indistinct UCAN borders. RESULTS: Of the 27 UCAN lesions (11 early-stage; 16 advanced-stage), 25.9% (n = 7) were initially visible and 74.1% (n = 20) were invisible. The mean interval between the last surveillance colonoscopy and UCAN diagnosis was 14.5 ± 6.7 months. Of early-stage cancers, 18.2% (n = 2) were visible and 81.8% (n = 9) were invisible. Of advanced-stage cancers, 31.3% (n = 5) were visible and 68.8% (n = 11) were invisible. Invisible lesions were significantly more common in the rectum (p = 0.011) and tended to be more common in patients with inflammation and left-sided colitis (p = 0.084, p = 0.068, respectively). Patients with indistinct UCAN borders were significantly more likely to present with inflammation than those with distinct UCAN borders (p = 0.021). CONCLUSION: More careful surveillance is needed because rectum lesions and inflammation are difficult to identify as neoplasia even within the 2 years before a UCAN diagnosis.

Gastric metaplasia of the duodenal mucosa in Crohn's disease: novel histological and endoscopic findings.

Background and study aims Upper gastrointestinal endoscopy and biopsy are useful for differential diagnosis of Crohn's disease (CD) of the large intestine and ulcerative colitis (UC). We aimed to identify novel histopathological and endoscopic findings in the upper gastrointestinal tract in patients with CD who did not have Helicobacter pylori infection. Patients and methods Upper gastrointestinal endoscopy was performed on patients with CD and UC. Mucosal lesions detected were subsequently observed using magnifying endoscopy with narrow-band imaging (M-NBI), following which biopsy was performed. When no mucosal lesion was detected on conventional endoscopy, M-NBI and biopsy were performed on four sites: the gastric body, gastric antrum, duodenal bulb, and second portion of the duodenum. Results The prevalences of gastric metaplasia (GM) were 48 % (24/50) and 16 % (8/50) in the CD and UC groups, showing a significant difference ( P  = 0.001). In 23 of 24 patients with histologically proven GM in the CD group, mucosal lesions were detected using conventional white-light imaging (C-WLI). In 22 of 24 patients with histologically proven GM in the CD group, disappearance of normal villous structure and the presence of curved marginal crypt epithelium were noted using magnifying endoscopic findings characteristic of GM (M-GM). A combination of C-WLI and M-NBI yielded a significantly increased specificity ( P  = 0.004) and accuracy ( P  = 0.039). Conclusions The prevalence of GM in the duodenal mucosa was significantly higher in patients with CD than in controls. The identified endoscopic findings may be useful as novel indicators for the histological diagnosis of GM in the duodenum.