Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

BACKGROUND: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. METHODS: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. RESULTS: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). CONCLUSIONS: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

Risk factors for the development of second primary esophageal squamous-cell carcinoma after endoscopic resection for esophageal squamous-cell carcinoma according to genetic polymorphisms related to alcohol and nicotine metabolism.

BACKGROUND: Multiple development of esophageal squamous-cell carcinoma is explained by field cancerization and is associated with alcohol consumption and smoking. We investigated the association between the development of second primary esophageal squamous-cell carcinoma after endoscopic resection for esophageal squamous-cell carcinoma and genetic polymorphisms related to alcohol and nicotine metabolism. METHODS: The study group comprised 56 patients with esophageal squamous-cell carcinoma after endoscopic resection. The main variables were the following: (i) cumulative incidence and total number of second primary esophageal squamous-cell carcinoma according to genetic polymorphisms in alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6; and (ii) risk factors of second primary esophageal squamous-cell carcinoma identified using a multivariate Cox proportional-hazards model. The frequencies of alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and cytochrome P450 2A6 genetic polymorphisms in the buccal mucosa were analyzed. RESULTS: The median follow-up was 92.8 months (range: 2.7-134.2). Slow-metabolizing alcohol dehydrogenase 1B was associated with a higher 7-year cumulative incidence of second primary esophageal squamous-cell carcinoma (fast-metabolizing alcohol dehydrogenase 1B vs slow-metabolizing alcohol dehydrogenase 1B: 20.5% vs 71.4%, P = 0.006). Slow-metabolizing alcohol dehydrogenase 1B (relative risk [95% confidence interval]: 3.17 [1.49-6.73]), inactive aldehyde dehydrogenase 2 (2.17 [1.01-4.63]) and poorly-metabolizing cytochrome P450 2A6 (4.63 [1.74-12.33]) had a significantly higher total number of second primary esophageal squamous-cell carcinoma per 100 person-years. In the multivariate Cox proportional-hazards model, slow-metabolizing alcohol dehydrogenase 1B was a significant risk factor of the development of second primary esophageal squamous-cell carcinoma (hazard ratio 9.92, 95% confidence interval: 2.35-41.98, P = 0.0018). CONCLUSIONS: Slow-metabolizing alcohol dehydrogenase 1B may be a significant risk factor for the development of second primary esophageal squamous-cell carcinoma. In addition, inactive aldehyde dehydrogenase 2 and poorly-metabolizing cytochrome P450 2A6 may be important factors.

Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.

BACKGROUND: Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. METHODS: This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. RESULTS: ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%). CONCLUSIONS: ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

Evaluation of the risk of metachronous multiple squamous cell carcinoma of the head and neck after transoral surgery based on the genetic polymorphisms of alcohol dehydrogenase 1B and aldehyde dehydrogenase 2.

Patients with superficial head and neck squamous cell carcinoma (HNSCC) can be completely treated by techniques of transoral surgery (TOS). The aim of this study was to evaluate the risk of metachronous multiple HNSCC arising after TOS based on alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2). We registered patients who underwent TOS for superficial HNSCC. Buccal cell samples were obtained by using a cotton swab to examine two single nucleotide polymorphisms in ADH1B and ALDH2 genotyping. We used Cox proportional hazards models to examine the risk of metachronous HNSCC. A total of 198 patients who underwent TOS for HNSCC were evaluated. In multivariate analysis, risks for second HNSCC were ADH1B*1/*1 [hazard ratio (HR), 1.88; 95% confidence interval (CI), 1.11-3.19; P = 0.02], ALDH2*1/*2 (HR, 2.11; 95% CI, 1.00-5.16; P = 0.048) and alcohol consumption before TOS (HR, 1.17; 95% CI, 1.06-1.27; P = 0.01). The 5-year incidence rates of second primary HNSCC in the temperance group and the non-temperance group were 20.8 and 46.5%, respectively (HR, 0.54; 95% CI, 0.31-0.92; P = 0.02). Cumulative development rates of third HNSCC in the temperance group and non-temperance group at 10 years were 11.3 and 36.1%, respectively (HR, 0.19; 95% CI, 0.03-0.65; P = 0.006). ADH1B*1/*1, ALDH2*1/*2 and moderate or heavy alcohol consumption before treatment are independent risk factors of metachronous HNSCC. Since it was shown that temperance decreased the incidences of second and third metachronous HNSCC, advice to discontinue alcohol drinking is necessary.

Eradication of Helicobacter pylori may improve dyspepsia in the elderly for the long term.

BACKGROUND: Therapy for eradication of Helicobacter pylori (H. pylori) improves symptoms of H. pylori-associated dyspepsia (HPD), but the effects of eradication in elderly patients are unclear. The aim of our study was to investigate dyspepsia symptoms and long-term effects of eradication in elderly patients. METHODS: This retrospective study included 496 patients who received H. pylori eradication therapy. The patients were divided into a group of elderly patients (group E: ≧ 65 years old) and a group of non-elderly patients (group N: < 65 years old). Abdominal symptoms were evaluated using a questionnaire about abdominal symptoms before eradication and after eradication (1-2 months and more than one year). Dyspepsia was defined as a score of 4 points or more for at least one of 4 items (postprandial fullness, early satiety, epigastric pain, and hunger pain). Improvement of symptoms was defined on the basis of changes in Global Overall Systems scores. RESULTS: There were no differences in abdominal symptoms before eradication between the two groups. Successful eradication improved symptoms in patients with dyspepsia within 2 months (in 75.6% (56/74) of the patients in group N and in 64.5% (20/31) of the patients in group E). The questionnaire showed that 80% (32/40) of the patients in group N and 60% (12/20) of the patients in group E had long-term relief of dyspepsia. The scores for abdominal symptoms in group E continued to improve for a mean period of 54.8 months after eradication. CONCLUSIONS: Eradication of H. pylori age-independently improved dyspepsia symptoms for the long term.

The Alcohol Use Disorders Identification Test and the risk of metachronous cancer after endoscopic resection of esophageal cancer.

Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8-14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0-7, 1.2 for 8-14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC [multivariate hazard ratio (95% confidence interval) = 6.98 (1.31-37.09) and 3.19 (1.19-8.54), respectively]. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676.

Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV.

BACKGROUND: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). METHODS: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. RESULTS: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. CONCLUSIONS: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.

AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

BACKGROUND: Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. METHODS: Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. RESULTS: 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. CONCLUSIONS: Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.

Effectiveness of planned surveillance for detecting second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma.

BACKGROUND: Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients' outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. METHODS: We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3-6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter. RESULTS: During the median follow-up period of 49.4 months (1.3-81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. CONCLUSIONS: Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.

Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. OBJECTIVES: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. METHODS: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. RESULTS: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. CONCLUSIONS: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.

Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions.

This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC.

Association between macrocytosis and metachronous squamous cell carcinoma of the esophagus after endoscopic resection in men with early esophageal squamous cell carcinoma.

BACKGROUND: Macrocytosis is associated with an increased risk of squamous cell carcinoma (SCC) arising in the esophagus in men. The aim of this study was to evaluate the association between macrocytosis and metachronous SCC of the esophagus after endoscopic resection (ER) of early esophageal SCC in men. METHODS: The study group comprised 278 men with early esophageal SCC after ER. The main study variables were as follows: (1) cumulative incidence and total number of metachronous SCC of the esophagus according to the presence or absence of macrocytosis (mean corpuscular volume ≥ 106 fl) and (2) predictors of metachronous SCC of the esophagus as assessed with a multivariate Cox proportional-hazards model. RESULTS: The median follow-up was 50.3 months. Macrocytosis was associated with a higher 2-year cumulative incidence of metachronous SCC of the esophagus (without macrocytosis vs. with macrocytosis: 11.4% vs. 38.1%, p = 0.002). Macrocytosis was also associated with a higher total number of metachronous SCC of the esophagus per 100 person-years (without macrocytosis vs. with macrocytosis: 7.7 vs. 31.5 per 100 person-years, p < 0.0001). In addition, macrocytosis was a significant predictor of metachronous SCC of the esophagus on multivariate Cox proportional-hazards analysis (relative risk 2.23). CONCLUSION: Macrocytosis is a useful predictor of the risk of metachronous SCC of the esophagus after ER of early esophageal SCC in men.

Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection.

BACKGROUND: Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR. METHODS: From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding. RESULTS: A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs. CONCLUSIONS: The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test.

Vonoprazan, a potassium-competitive acid blocker, is a new class of acid-suppressing agent. The acid-inhibitory effect of vonoprazan has been well-documented. However, there is no report on the extent to which the amount of gastric acid secretion is suppressed, not pH measurement, by the use of vonoprazan. The aim of this study was to evaluate this suppression effect. This was a single-arm, interventional pilot study involving 7 healthy Japanese men. The subjects were administered 20 mg vonoprazan for 6 days. The amount of gastric acid secretion was determined using the calcium carbonate breath test. The acid outputs were defined as the maximum Δ13C‰ (Δ13C max) and area under the curve (AUC) during the 30 min sampling period. The Δ13C max and AUC values significantly decreased on the administration of 20 mg vonoprazan. The AUC dropped by approximately 78% on day 1 and by 84% on day 6 and subsequently returned to the control level after cessation of vonoprazan therapy (reduction by 68% on day 7 and by 42% on day 8). In conclusion, the amount of gastric acid secretion rapidly decreased by the administration of vonoprazan; this inhibitory effect was found to be potent and long-lasting. (UMIN ID: UMIN000025469).

Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Although graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV) reactivation also occurs in patients after allo-HSCT and these conditions often clinically overlap. The aim of this study was to determine reliable endoscopic findings of CMV colitis in patients with gastrointestinal graft-versus-host-disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to have GI-GVHD with or without CMV colitis and patients with an immunosuppressive condition were retrospectively analyzed. We divided the patients into three groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group B), and CMV colitis without undergoing allo-HSCT (group C). From medical records, the involved colorectal areas and endoscopic findings according to the groups were compared. A total of 70 patients were divided into three groups (group A: n = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C frequently occurred in the cecum including ileocecal valves. On the other hand, there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer lesions were more frequently observed in groups A and C than in group B (p < 0.001). The sensitivity and specificity of mucosal injuries in the cecum for prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in the cecum are reliable endoscopic findings for CMV colitis in patients with GI-GVHD after allo-HSCT.

Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether colorectal luminal stricture develops after circumferential endoscopic submucosal dissection (ESD) in the colorectum, and whether the development of luminal stricture could be prevented by using MSC-CS enema. METHODS: In the first experiment, we performed circumferential ESD in the rectums or distal colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured the degree of luminal stricture. In the second experiment, we performed circumferential ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3 in each group) to measure the degree of luminal stricture, and performed histological analysis. RESULTS: Severe luminal stricture was observed in the rectum but not in the distal colon. Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria were observed in the rectum but not in the distal colon. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria on Day 22, and reduced inflammatory cell infiltration on Day 8. CONCLUSIONS: Luminal stricture after ESD developed only in the rectum because of the difference in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.

Lavender Color in Linked Color Imaging Enables Noninvasive Detection of Gastric Intestinal Metaplasia.

BACKGROUND AND AIMS: Recently, there have been some reports that image-enhanced endoscopy may improve detection of gastric intestinal metaplasia (GIM). Our aim was to determine the usefulness of linked color imaging (LCI) for detection of GIM. METHODS: In prospectively recruited patients, the whole antrum was observed by white light imaging (WLI) followed by LCI. When a whitish flat elevation (WFE) in WLI and a lavender color sign (LCS) in LCI were detected, target biopsies were performed after LCI. Random biopsies were performed in patients who had neither WFE nor LCS. The primary endpoint was the diagnostic accuracy of GIM per patient in WLI and LCI and the secondary endpoints were that of GIM per biopsy and interobserver agreement. RESULTS: Data from 128 patients were analyzed and 58 patients (45.3%) had histological GIM in the antrum. The per-patient yields of WLI and LCI to detect GIM were 19.0% (11/58) and 91.4% (53/58) respectively. Diagnostic accuracies of target biopsies for GIM were 23.7% in WLI and 84.2% in LCI. Kappa values among 3 doctors were 0.60 for WFE and 0.78 for LCS respectively. CONCLUSION: LCI could be a new diagnostic tool for detecting GIM during routine endoscopy.

Endoscopic Modified Medial Maxillectomy for Fungal Ball of the Hypoplastic Maxillary Sinus With Bony Hypertrophy.

Sinus fungal ball is defined as noninvasive chronic rhino-sinusitis with a clump of mold in the paranasal sinuses, typically affecting the maxillary sinus. Fairly good outcomes of endoscopic surgery have been reported where the ball is removed through the antrostomy. However, the affected sinus tends to have a smaller cavity and thicker bony walls. As such, it is often challenging to maintain a window size that is sufficient to control possible recurrence. The endoscopic modified medial maxillectomy procedure was applied to a 61-year old and a 70-year old female patient with maxillary sinus fungal ball. Using this method, we created a much larger inferior meatal antrostomy without difficulty. The window provided us with an endoscopic view of the whole sinus and complete eradication of the lesion. Endoscopic modified medial maxillectomy is useful as a surgical procedure for maxillary sinus fungal ball and should be considered for better outcomes.