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.

Combination of artificial intelligence-based endoscopy and miR148a methylation for gastric indefinite dysplasia diagnosis.

BACKGROUND AND AIM: Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN). METHODS: We compared the accuracy of physician-performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)-based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR-148a, miR-124a-3, NKX6-1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty-two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions. RESULTS: The board-certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588). CONCLUSION: AI with miR148s DNA methylation-based diagnosis is a potential modality for diagnosing GIN.

Clinical usefulness of red dichromatic imaging in hemostatic treatment during endoscopic submucosal dissection: First report from a multicenter, open-label, randomized controlled trial.

OBJECTIVES: To verify the efficacy and safety of red dichromatic imaging (RDI) in hemostatic procedures during endoscopic submucosal dissection (ESD). METHODS: This is a multicenter randomized controlled trial of 404 patients who underwent ESD of the esophagus, stomach, colorectum. Patients who received hemostatic treatments by RDI during ESD were defined as the RDI group (n = 204), and those who received hemostatic treatments by white light imaging (WLI) were defined as the WLI group (n = 200). The primary endpoint was a shortening of the hemostasis time. The secondary endpoints were a reduction of the psychological stress experienced by the endoscopist during the hemostatic treatment, a shortened treatment time, and a non-inferior perforation rate, in RDI versus WLI. RESULTS: The mean hemostasis time in RDI (n = 860) was not significantly shorter than that in WLI (n = 1049) (62.3 ± 108.1 vs. 56.2 ± 74.6 s; P = 0.921). The median hemostasis time was significantly longer in RDI than in WLI (36.0 [18.0-71.0] vs. 28.0 [14.0-66.0] s; P = 0.001) in a sensitivity analysis. The psychological stress was significantly lower in RDI than in WLI (1.71 ± 0.935 vs. 2.03 ± 1.038; P < 0.001). There was no significant difference in the ESD treatment time between RDI (n = 161) and WLI (n = 168) (58.0 [35.0-86.0] vs. 60.0 [38.0-88.5] min; P = 0.855). Four perforations were observed, but none of them took place during the hemostatic treatment. CONCLUSIONS: Hemostatic treatment using RDI does not shorten the hemostasis time. RDI, however, is safe to use for hemostatic procedures and reduces the psychological stress experienced by endoscopists when they perform hemostatic treatment during ESD. UMIN000025134.

Tip-in endoscopic mucosal resection for large colorectal sessile polyps.

BACKGROUND: Tip-in endoscopic mucosal resection (EMR) is a modified EMR technique using which en bloc resection of large colorectal sessile polyps can be performed; however, its usefulness for colorectal sessile polyps of > 20 mm has not been reported. This study examined treatment outcomes of tip-in and conventional EMR for large colorectal sessile polyps of ≥ 20 mm. METHODS: This was a retrospective case-control study conducted at a single tertiary center in Japan. Subjects included those with large colorectal sessile polyps of ≥ 20 mm, excluding pedunculated-type polyps, who underwent endoscopic resection between January 2010 and January 2019. The primary outcome was endoscopic treatment outcomes when using tip-in and conventional EMR, and the secondary outcome was the local recurrence rate after endoscopic treatment. RESULTS: Forty-three colorectal lesions were treated using tip-in EMR and 83 using conventional EMR. Tip-in EMR had a significantly higher en bloc resection rate (90.7% vs. 69.8.%), and significantly shorter treatment duration (6.64 ± 0.64 min vs. 10.47 ± 0.81 min) than conventional EMR. However, for lesions > 30 mm, en bloc resection rate was 50.0% and 52.6% for tip-in and conventional EMR, respectively, indicating no significant difference. Perforation rates with tip-in and conventional EMR were 4.6% and 3.6%, respectively, indicating no significant difference. Local recurrence was examined in 80 cases who were followed up for > 6 months after endoscopic resection; recurrence rate was 0% and 7.0% in tip-in and conventional EMR cases, respectively, without significance difference. CONCLUSIONS: Tip-in EMR showed high en-block resection rate, particularly in polyps of < 30 mm, and no residual tumor was found. This technique is a potential endoscopic treatment alternative for large colorectal sessile polyps of ≥ 20 mm.

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.

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.

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.

[Detection of early gastric cancer facilitated by surveillance for a pyogenic liver abscess caused by Streptococcus intermedius].

We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess.

Safety, efficacy, and long-term outcomes for endoscopic submucosal dissection of early esophagogastric junction cancer.

BACKGROUND: Early esophagogastric junction (EGJ) cancer is currently being treated in the same way as early gastric cancer, by endoscopic submucosal dissection (ESD), but long-term outcomes are still unknown. Our aim was to retrospectively evaluate the safety and efficacy of ESD in treating early EGJ cancer and compare risk factors in curative and non-curative resection cases. METHODS: Forty-four cases of early EGJ cancer, defined as a Siewert's type II tumor, in 44 patients with a mean age of 70.0 years and a male/female ratio of 90.9:9.1 % were treated by ESD between January 2004 and June 2010. There were 30 standard indication cases; the remaining 14 cases were expanded indication cases. RESULTS: Mean resected specimen and tumor sizes were 35 and 17 mm, respectively, and median procedure time was 121 min, with no bleeding or perforation complications. All cases were resected en bloc with an 84.1 % curative resection rate (37/44). The curative resection rates in the standard and expanded indication cases were 90.0 % (27/30) and 71.4 % (10/14), respectively. There were no significant differences in tumor location, tumor morphology, tumor size, histology of biopsy specimens, or standard versus expanded indication cases with regard to risk factors for curative and non-curative resections. However, submucosal invasion, positive tumor margins, lymphovascular invasion, and some components of poorly differentiated adenocarcinomas in just the submucosal layer were significantly more common in the non-curative resection cases. CONCLUSIONS: ESD was a safe, effective, and minimally invasive treatment for early EGJ cancer. For tumors without any submucosal invasion findings, therefore, ESD is an acceptable treatment option, in addition to also being suitable for diagnostic purposes in evaluating the need for surgery.

Diagnosis of laterally spreading tumors (LST) in the rectum and selection of treatment: characteristics of each of the subclassifications of LST in the rectum.

BACKGROUND: In recent years, endoscopic submucosal dissection (ESD) has often been used for the treatment of laterally spreading tumors (LST) of the rectum. The present study was carried out with the aim of clarifying the characteristics of each of the subtypes of LST in the rectum that are often treated by ESD. PATIENTS AND METHODS: This study involved 141 rectal LST that were initially treated at our hospital between March 2005 and December 2010 and whose endoscopic images and histopathological specimens could be re-examined. The LST were divided into LST-G-H (homogeneous type), LST-G-MIX (nodular mixed type), LST-NG-F (flat type) and LST-NG-PD (pseudo-depressed type) type lesions, and tumor diameter and depth of invasion of each of these tumor types were investigated. RESULTS: Regarding the depth of invasion, the proportion of submucosa-massive (SM-m) lesions was high in the LST-NG-PDtumors, even among tumors measuring <20 mm in diameter; both the rate of cancer and proportion of SM-m lesions were significantly higher in the LST-NG-PD tumors than in the LST-NG-F tumors (P < 0.05). In both LST-NG-MIX and LST-NG-PD tumors, the proportion of SM-m lesions was significantly higher in the lower rectum than in the upper rectum (P < 0.05). CONCLUSION: For LST of the rectum (particularly of the lower rectum), it is necessary to carefully select the treatment considering LST subclass and tumor diameter from the standpoint of the presence of malignancy, quality of life, and prognosis of patients.

Visceral disseminated varicella-zoster virus infection in an immunocompetent host.

Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas.

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study.

Background and Aims: Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients' quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods: This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1-9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results: LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0-57.2 and 13.3%, 95% CI = 8.1-21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26-0.85 and 0.49, 95% CI = 0.26-0.91, respectively). Conclusion: Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Efficient Colonoscopic Identification of Colonic Bleeding Diverticulum Using Intradiverticular Water Injection with a Nontraumatic Tube.

OBJECTIVES: The colonoscopic identification of stigmata of recent hemorrhage (SRH) in patients with colonic diverticular bleeding (CDB) is difficult. Factors that influence the identification of SRH in the diagnosis of CDB were investigated. METHODS: This was a retrospective study of 487 early colonoscopy patients with acute lower gastrointestinal bleeding who were diagnosed with CDB. Comorbidities, medications, bowel preparation, use of a transparent cap, use of a water-jet scope, colonoscopy by an expert colonoscopist, and use of a nontraumatic (NT) tube were assessed. A multivariate analysis was used to estimate the odds ratio and 95% confidence interval. RESULTS: Of the 487 colonoscopy patients diagnosed with CDB, 191 (39%) were definitively identified with SRH. The use of a transparent cap, a water-jet scope, an expert colonoscopist, and an NT tube were independent predictive factors for SRH on univariate analysis. A multivariable logistic regression model showed that colonoscopy by an expert colonoscopist and the use of an NT tube were predictive factors for SRH. CONCLUSIONS: Intradiverticular water injection with an NT tube by an expert colonoscopist is useful in identifying CDB, and may help achieve effective endoscopic hemostasis.

A novel mask to prevent aerosolized droplet dispersion in endoscopic procedures during the coronavirus disease pandemic.

ABSTRACT: Endoscopic procedures increase the risk of transmission of severe acute respiratory syndrome coronavirus 2 to medical staff, because aerosols are generated during upper gastrointestinal endoscopy. There have been several reported studies on devices for infection prevention; however, few reports have validated them. Therefore, we developed a novel mask to prevent the diffusion of aerosol droplets from patients undergoing endoscopy.We compared microdroplet dispersion during coughing episodes when using the novel mask with microdroplet dispersion when using the conventional mouthpiece alone.The mean number of microdroplets was significantly smaller in the group that used the novel mask (57.9 ±â€Š122.91 vs 933.6 ±â€Š119.80 droplets; P = .01).The novel mask may aid in reducing the degree of exposure of medical personnel to microdroplets and the risk of subsequent infection.

Risk Factors for Late Rebleeding of Colonic Diverticular Bleeding in Elderly Individuals.

OBJECTIVES: This study aimed to examine the clinical characteristics of colonic diverticular bleeding (CDB) in elderly individuals. METHODS: This retrospective case-control study was conducted at a single tertiary center. A total of 519 patients (356 men and 163 women; mean age of 73.1 ± 12.5 years) with CDB and hospitalized between January 2004 and May 2019 were analyzed. The subjects were divided into two groups: the elderly (274 individuals aged ≥75 years; mean age, 82.1 ± 5.3 years) and non-elderly (245 individuals aged <75 years; mean age, 63.0 ± 10.3 years) groups. Primary outcomes were early and late rebleeding rates, and secondary outcomes were the risk factors for late rebleeding in elderly individuals. Rebleeding occurring within 30 days of hospitalization was defined as early rebleeding, whereas rebleeding occurring after 31 days was defined as late rebleeding. RESULTS: The early rebleeding rates were 30.6% and 33.1% (p = 0.557) in the elderly and non-elderly groups, respectively. The late rebleeding rates were 42.3% and 30.6% (p = 0.005) in the elderly and non-elderly groups, respectively. The 3-year recurrence-free survival was 63.6% in the elderly group and 75.6% in the non-elderly group (log-rank test: p < 0.001). Multivariate analysis revealed the use of non-steroidal anti-inflammatory drugs (NSAIDs) [odds ratio (OR), 3.55], chronic kidney disease (OR, 2.89), and presence of bilateral diverticula (OR, 1.83) as the independent risk factors for late rebleeding in elderly individuals. CONCLUSIONS: Elderly individuals with CDB require careful follow-up even after discharge. Furthermore, it is important to consider discontinuing NSAIDs to prevent rebleeding.

Risk factors of interventional radiology/surgery for colonic diverticular bleeding.

BACKGROUND AND AIM: Colonic diverticular bleeding (CDB) stops spontaneously, but sometimes, excessive bleeding does not allow hemostasis and requires interventional radiology (IR)/surgery. We examined risk factors in patients who required IR/surgery for CDB and late recurrent bleeding rate after IR/surgery. METHODS: This retrospective case-control study was conducted at a tertiary center. We included 608 patients who required hospitalization for CDB. Patients were investigated for risk factors using logistic regression analysis. We also investigated early and late recurrent bleeding rates following IR/surgery. RESULTS: In 261 patients (42.9%), the bleeding source was identified, and endoscopic hemostasis was performed; 23 (3.8%) required IR/surgery. In multivariate analysis, shock state with a blood pressure of ≤90 mmHg (P < 0.001; odds ratio [OR], 20.1; 95% confidence interval [CI], 5.08-79.5), positive extravasation on contrast-enhanced computed tomography (P < 0.001; OR 9.5, 95% CI 2.85-31.4), two or more early recurrent bleeding episodes (P = 0.002; OR 7.4, 95% CI 2.14-25.4), and right colon as the source of bleeding (P = 0.023; OR 4.1, 95% CI 1.25-14.0) were independent risk factors requiring IR/surgery. Early recurrent bleeding was observed in 0% and 28.0% patients (P < 0.001) in the IR/surgery and no IR/surgery groups, respectively, whereas late recurrent bleeding rate was observed in 43.4% and 30.7% patients (P = 0.203) in the IR/surgery and no IR/surgery groups, respectively. Four patients who required surgery experienced late recurrent bleeding at a site different from the initial CDB. CONCLUSIONS: Although IR/surgery is an effective hemostatic treatment wherein endoscopic treatment is unsuccessful, late recurrent bleeding cannot be prevented.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. METHODS: One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. RESULTS: GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. CONCLUSIONS: We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Intra-abdominal bleeding as a rare complication after colonic endoscopic mucosal resection in a patient taking direct oral anticoagulants.

We describe the case of an 84-year old female who was taking rivaroxaban 30 mg/day and had a medical history of atrial fibrillation. She underwent endoscopic mucosal resection of a 5-mm adenoma located in the hepatic flexure of the transverse colon. Following the procedure, she developed gradually intensifying abdominal pain, with the appearance of small amount of blood in the feces. For that reason, she visited our facility on the 5th day post-endoscopic mucosal resection. At the time of the visit, contrast-enhanced abdominal computed tomography revealed no extravasation or free air; however, bloody ascites was confirmed in the peritoneal cavity. Thus, the patient was diagnosed with post-endoscopic mucosal resection intra-abdominal hemorrhage and hospitalized the same day. After admission, rivaroxaban was discontinued and patient condition monitored. Because subsequent abdominal computed tomography revealed no distinct increase in bloody ascites, no interventional radiological or surgical procedure was performed, and the patient was discharged after providing only conservative treatment. While hemorrhage and perforation are the main complications after colonic endoscopic mucosal resection, so far, there have been a few reports on the occurrence of intra-abdominal hemorrhage following endoscopic mucosal resection. Emergency treatment is sometimes required in patients with intra-abdominal hemorrhage. It is important to keep in mind that this complication, although very rare, may occur, particularly in patients taking anticoagulants.

Delayed perforation after endoscopic band ligation for colonic diverticular hemorrhage.

A 77-year-old woman presented with the chief complaint of large amounts of hematochezia. Contrast-enhanced computed tomography (CT) revealed extravasation of contrast medium from the diverticula in the sigmoid colon; therefore, upon diagnosis of sigmoid colonic diverticular hemorrhage, she was immediately admitted to our hospital. Emergency colonoscopy revealed active bleeding from the diverticula in the sigmoid colon; hemostasis was achieved with endoscopic band ligation (EBL). However, 4 days later, she suddenly developed severe abdominal pain while defecation, prompting the requirement for obtaining a CT scan, which revealed intraabdominal free air, and delayed perforation after EBL was diagnosed. Emergency surgery was immediately performed; the perforation site was closed with sutures. EBL is useful in achieving hemostasis for colonic diverticular hemorrhage; however, it carries the risk of serious complications, such as delayed perforation, which require surgery. Although EBL is useful to achieve hemostasis for diverticular hemorrhage in the colon, it is preferable to carefully judge its indication owing to the risk of serious complications.