A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening.

The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

Characteristics, outcomes, and risk factors of surgery for acute lower gastrointestinal bleeding: nationwide cohort study of 10,342 hematochezia cases.

BACKGROUND: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited. METHODS: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed. RESULTS: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis. CONCLUSIONS: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB.

Early feeding reduces length of hospital stay in patients with acute lower gastrointestinal bleeding: A large multicentre cohort study.

AIM: No studies have compared the clinical outcomes of early and delayed feeding in patients with acute lower gastrointestinal bleeding (ALGIB). This study aimed to evaluate the benefits and risks of early feeding in a nationwide cohort of patients with ALGIB in whom haemostasis was achieved. METHODS: We reviewed data for 5910 patients with ALGIB in whom haemostasis was achieved and feeding was resumed within 3 days after colonoscopy at 49 hospitals across Japan (CODE BLUE-J Study). Patients were divided into an early feeding group (≤1 day, n = 3324) and a delayed feeding group (2-3 days, n = 2586). Clinical outcomes were compared between the groups by propensity matching analysis of 1508 pairs. RESULTS: There was no significant difference between the early and delayed feeding groups in the rebleeding rate within 7 days after colonoscopy (9.4% vs. 8.0%; p = 0.196) or in the rebleeding rate within 30 days (11.4% vs. 11.5%; p = 0.909). There was also no significant between-group difference in the need for interventional radiology or surgery or in mortality. However, the median length of hospital stay after colonoscopy was significantly shorter in the early feeding group (5 vs. 7 days; p < 0.001). These results were unchanged when subgroups of presumptive and definitive colonic diverticular bleeding were compared. CONCLUSION: The findings of this nationwide study suggest that early feeding after haemostasis can shorten the hospital stay in patients with ALGIB without increasing the risk of rebleeding.

Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan.

INTRODUCTION: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes. METHODS: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated. RESULTS: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785-2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084-1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471-0.609; p < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p < 0.001). CONCLUSION: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

INTRODUCTION: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). METHODS: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. RESULTS: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. CONCLUSIONS: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Multicenter propensity score-matched analysis comparing short versus long cap-assisted colonoscopy for acute hematochezia.

Background and Aim: While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods: We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE-J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results: A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P < 0.001). The rate of SRH with active bleeding was significantly higher in long cap users (P < 0.001). Other clinical outcomes did not differ significantly. Conclusion: Compared to that with short caps, long cap-assisted colonoscopy is superior for the diagnosis of acute hematochezia, especially CDB, and the identification of active bleeding.

Long-term Risks of Recurrence After Hospital Discharge for Acute Lower Gastrointestinal Bleeding: A Large Nationwide Cohort Study.

BACKGROUND & AIMS: Currently, large, nationwide, long-term follow-up data on acute lower gastrointestinal bleeding (ALGIB) are scarce. We investigated long-term risks of recurrence after hospital discharge for ALGIB using a large multicenter dataset. METHODS: We retrospectively analyzed 5048 patients who were urgently hospitalized for ALGIB at 49 hospitals across Japan (CODE BLUE-J study). Risk factors for the long-term recurrence of ALGIB were analyzed by using competing risk analysis, treating death without rebleeding as a competing risk. RESULTS: Rebleeding occurred in 1304 patients (25.8%) during a mean follow-up period of 31 months. The cumulative incidences of rebleeding at 1 and 5 years were 15.1% and 25.1%, respectively. The mortality risk was significantly higher in patients with out-of-hospital rebleeding episodes than in those without (hazard ratio, 1.42). Of the 30 factors, multivariate analysis showed that shock index ≥1 (subdistribution hazard ratio [SHR], 1.25), blood transfusion (SHR, 1.26), in-hospital rebleeding (SHR, 1.26), colonic diverticular bleeding (SHR, 2.38), and thienopyridine use (SHR, 1.24) were significantly associated with increased rebleeding risk. Multivariate analysis of colonic diverticular bleeding patients showed that blood transfusion (SHR, 1.20), in-hospital rebleeding (SHR, 1.30), and thienopyridine use (SHR, 1.32) were significantly associated with increased rebleeding risk, whereas endoscopic hemostasis (SHR, 0.83) significantly decreased the risk. CONCLUSIONS: These large, nationwide follow-up data highlighted the importance of endoscopic diagnosis and treatment during hospitalization and the assessment of the need for ongoing thienopyridine use to reduce the risk of out-of-hospital rebleeding. This information also aids in the identification of patients at high risk of rebleeding.

Outcomes and recurrent bleeding risks of detachable snare and band ligation for colonic diverticular bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Ligation therapy, including endoscopic detachable snare ligation (EDSL) and endoscopic band ligation (EBL), has emerged as an endoscopic treatment for colonic diverticular bleeding (CDB); its comparative effectiveness and risk of recurrent bleeding remain unclear, however. Our goal was to compare the outcomes of EDSL and EBL in treating CDB and identify risk factors for recurrent bleeding after ligation therapy. METHODS: We reviewed data of 518 patients with CDB who underwent EDSL (n = 77) or EBL (n = 441) in a multicenter cohort study named the Colonic Diverticular Bleeding Leaders Update Evidence From Multicenter Japanese Study (CODE BLUE-J Study). Outcomes were compared by using propensity score matching. Logistic and Cox regression analyses were performed for recurrent bleeding risk, and a competing risk analysis was used to treat death without recurrent bleeding as a competing risk. RESULTS: No significant differences were found between the 2 groups in terms of initial hemostasis, 30-day recurrent bleeding, interventional radiology or surgery requirements, 30-day mortality, blood transfusion volume, length of hospital stay, and adverse events. Sigmoid colon involvement was an independent risk factor for 30-day recurrent bleeding (odds ratio, 1.87; 95% confidence interval, 1.02-3.40; P = .042). History of acute lower GI bleeding (ALGIB) was a significant long-term recurrent bleeding risk factor on Cox regression analysis. A performance status score of 3/4 and history of ALGIB were long-term recurrent bleeding factors on competing risk regression analysis. CONCLUSIONS: There were no significant differences in outcomes between EDSL and EBL for CDB. After ligation therapy, careful follow-up is required, especially in the treatment of sigmoid diverticular bleeding during admission. History of ALGIB and performance status at admission are important risk factors for long-term recurrent bleeding after discharge.

Development and validation of a novel model for predicting stigmata of recent hemorrhage in acute lower gastrointestinal bleeding: Multicenter nationwide study.

OBJECTIVES: Stigmata of recent hemorrhage (SRH) directly indicate a need for endoscopic therapy in acute lower gastrointestinal bleeding (LGIB). Colonoscopy would be prioritized for patients with highly suspected SRH, but the predictors of colonic SRH remain unclear. We aimed to construct a predictive model for the efficient detection of SRH using a nationwide cohort. METHODS: We retrospectively analyzed 8360 patients admitted through hospital emergency departments for acute LGIB in the CODE BLUE-J Study (49 hospitals throughout Japan). All patients underwent inpatient colonoscopy. To develop an SRH predictive model, 4863 patients were analyzed. Baseline characteristics, colonoscopic factors (timing, preparation, and devices), and computed tomography (CT) extravasation were extensively assessed. The performance of the model was externally validated in 3497 patients. RESULTS: Colonic SRH was detected in 28% of patients. A novel predictive model for detecting SRH (CS-NEED score: ColonoScopic factors, No abdominal pain, Elevated PT-INR, Extravasation on CT, and DOAC use) showed high performance (area under the receiver operating characteristic curve [AUC] 0.74 for derivation and 0.73 for external validation). This score was also highly predictive of active bleeding (AUC 0.73 for derivation and 0.76 for external validation). Patients with low (0-6), intermediate (7-8), and high (9-12) scores in the external validation cohort had SRH identification rates of 20%, 31%, and 64%, respectively (P < 0.001 for trend). CONCLUSIONS: A novel predictive model for colonic SRH identification (CS-NEED score) can specify colonoscopies likely to achieve endoscopic therapy in acute LGIB. Using the model during initial management would contribute to finding and treating SRH efficiently.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

Timing of colonoscopy in acute lower GI bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: We aimed to determine the optimal timing of colonoscopy and factors that benefit patients who undergo early colonoscopy for acute lower GI bleeding. METHODS: We identified 10,342 patients with acute hematochezia (CODE BLUE-J study) admitted to 49 hospitals in Japan. Of these, 6270 patients who underwent a colonoscopy within 120 hours were included in this study. The inverse probability of treatment weighting method was used to adjust for baseline characteristics among early (≤24 hours, n = 4133), elective (24-48 hours, n = 1137), and late (48-120 hours, n = 1000) colonoscopy. The average treatment effect was evaluated for outcomes. The primary outcome was 30-day rebleeding rate. RESULTS: The early group had a significantly higher rate of stigmata of recent hemorrhage (SRH) identification and a shorter length of stay than the elective and late groups. However, the 30-day rebleeding rate was significantly higher in the early group than in the elective and late groups. Interventional radiology (IVR) or surgery requirement and 30-day mortality did not significantly differ among groups. The interaction with heterogeneity of effects was observed between early and late colonoscopy and shock index (shock index <1, odds ratio [OR], 2.097; shock index ≥1, OR, 1.095; P for interaction = .038) and performance status (0-2, OR, 2.481; ≥3, OR, .458; P for interaction = .022) for 30-day rebleeding. Early colonoscopy had a significantly lower IVR or surgery requirement in the shock index ≥1 cohort (OR, .267; 95% confidence interval, .099-.721) compared with late colonoscopy. CONCLUSIONS: Early colonoscopy increased the rate of SRH identification and shortened the length of stay but involved an increased risk of rebleeding and did not improve mortality and IVR or surgery requirement. Early colonoscopy particularly benefited patients with a shock index ≥1 or performance status ≥3 at presentation.

Nationwide cohort study identifies clinical outcomes of angioectasia in patients with acute hematochezia.

BACKGROUND: While angioectasia is an important cause of acute hematochezia, relevant clinical features remain unclear. This study aims to reveal risk factors, clinical outcomes, and the effectiveness of therapeutic endoscopy for patients with acute hematochezia due to angioectasia. METHODS: This retrospective cohort study was conducted at 49 Japanese hospitals between January 2010 and December 2019, enrolling patients hospitalized for acute hematochezia (CODE BLUE-J study). Baseline factors and clinical outcomes for angioectasia were analyzed. RESULTS: Among 10,342 patients with acute hematochezia, 129 patients (1.2%) were diagnosed with angioectasia by colonoscopy. The following factors were significantly associated with angioectasia: chronic kidney disease, liver disease, female, body mass index < 25, and anticoagulant use. Patients with angioectasia were at a significant increased risk of blood transfusions compared to those without angioectasia (odds ratio [OR] 2.61; 95% confidence interval [CI] 1.69-4.02). Among patients with angioectasia, 36 patients (28%) experienced rebleeding during 1-year follow-up. The 1-year cumulative rebleeding rates were 37.0% in the endoscopic clipping group, 14.3% in the coagulation group, and 32.8% in the conservative management group. Compared to conservative management, coagulation therapy significantly reduced rebleeding risk (P = 0.038), while clipping did not (P = 0.81). Multivariate analysis showed coagulation therapy was an independent factor for reducing rebleeding risk (hazard ratio [HR] 0.40; 95% CI 0.16-0.96). CONCLUSIONS: Our data showed patients with angioectasia had a greater comorbidity burden and needed more blood transfusions in comparison with those without angioectasia. To reduce rebleeding risk, coagulation therapy can be superior for controlling hematochezia secondary to angioectasia.

Bleeding following Endoscopic Submucosal Dissection for Early Gastric Cancer in Surgically Altered Stomach.

INTRODUCTION: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). METHODS: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. RESULTS: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87-2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00-28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21-19.14). DISCUSSION/CONCLUSION: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.

Utility of red dichromatic imaging for identifying the bleeding point in endoscopic hemostasis of colonic diverticular bleeding.

Video 1Endoscopic hemostasis of colonic diverticular bleeding using red dichromatic imaging to identify the bleeding point.

The Optimal Cut-off of the Latex Immunoassay (LZ Test) for Helicobacter pylori Infection Based on the Stool Antigen Test and Helicobacter pylori-associated Gastritis.

Objective Helicobacter pylori antibody kits using the latex immunoassay (LIA) are widely used in Japan. However, the optimal cut-off of the LIA remains unclear. This study clarified the optimal cut-off of the LIA for assessing the current infection status of patients (currently infected, never infected, spontaneously eradicated) in clinical practice. Methods In total, 482 subjects with no history of H. pylori eradication therapy who underwent a medical examination at our hospital were enrolled. The infection status was ascertained using a stool antigen test, and the endoscopic findings of H. pylori-associated gastritis. H. pylori antibody levels were measured using the LIA. Results In total, 414, 38, and 30 subjects were categorized into the never-infected, currently infected, and spontaneously eradicated groups. The optimal cut-off based on receiver operating characteristic curve analysis was 4 U/mL, whereas the area under the curve, sensitivity, and specificity for differentiating never-infected and currently infected subjects were 0.95, 92.1%, and 94.7%, respectively. When applying the cut-off of 4 U/mL to the judgment of current infection in all subjects, the sensitivity and specificity were 92.1% and 92.6%, respectively. Conclusion Our findings suggest that 4 U/mL was the optimal cut-off for differentiating current infection from no prior infection, and the value may be stable because of the exclusion of subjects with spontaneous eradication. The cut-off may be useful in initial screening for current H. pylori infection.

Anal Intraepithelial Neoplasia: Precursor of Anal Squamous Cell Carcinoma.

Anal squamous cell carcinoma (SCC) is rare, but it has been commonly detected as an invasive cancer. The standard treatment for anal SCC was surgical resection. However, recent medical advances have enabled the standard treatment to be chemoradiotherapy. Anal intraepithelial neoplasia (AIN) is a premalignant lesion of SCC. The screening test for AIN and human papilloma virus vaccine are important for the following high-risk patients: patients positive for human immunodeficiency virus and men who have sexual intercourse with men. Although cytology can be easily applied for a screening test, the false-negative rate for AIN is high. Instead, high-resolution anoscopy (HRA) has been gaining attention as a promising screening method for high-risk patients. Investigations comparing characteristic findings of HRA with the histology of AIN have demonstrated that HRA is a highly specific test for AIN. Magnifying or image-enhanced endoscopies are also routinely used for colonoscopy, as they allow detailed observations at higher magnifications than those of HRA. Hence, these endoscopic modalities can be applied for assessing AIN. Ablation therapies or topical medications are available as the local treatment for AIN. Although endoscopic submucosal dissection is considered to be feasible to remove AIN, it has a technical difficulty to approach endoscopically invisible areas. Hence, this technique may be useful to resect AIN localized in the endoscopically visible areas, when the localization is confirmed via targeted biopsy.

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.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

BACKGROUND AND AIM: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS: There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS: Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.