The International Bleeding Risk Score: A New Risk Score that can Accurately Predict Mortality in Patients with Upper GI-Bleeding

AGA Abstracts

89-100%) in the validation cohort, as compared to 61% and 84%, respectively, for cyst fluid CEA and cytology (p<0.001 and p=0.02). Furthermore, CEA and cytology gave a high proportion of inconclusive results (29 and 16%), whereas the low cyst fluid requirements for proteomics allowed for the analysis of all lesions. For the detection of manifest malignancy in a pancreatic cystic lesion, the best combination was MUC5AC and prostate stem cell antigen PSCA (cut-off 12.0 fmol/µl), with an overall accuracy of 96% (95% CI: 90-99%). This panel detected 95% of malignancies, as compared to 35% for CEA (p<0.001) and 50% for cytology (p=0.003). Conclusion A panel of three cyst fluid protein biomarkers accurately identified cystic forms and precursors of pancreatic cancer, comparing favourably to currently available diagnostic tests. Thus, clinical implementation of this analysis is expected to facilitate timely intervention and prevention of pancreatic cancer.

671 THE INCIDENCE AND RISK FACTOR FOR PANCREATIC CANCER IN PATIENTS WITH PANCREATIC CYSTIC LESIONS Teppei Yoshioka, Minoru Shigekawa, Tomohide Tatsumi, Hironari Sueyoshi, Takuo Yamai, Takahiro Suda, Tadashi Kegasawa, Kenji Ikezawa, Ryotaro Sakamori, Tetsuo Takehara Background and aim: Intraductal papillary mucinous neoplasia (IPMN) is a well-known risk factor for pancreatic cancer (PC) and it is important to survey IPMN patients to detect malignancy. However, the incidence of PC is low and there are so many IPMN patients. Therefore, it is not realistic to examine all IPMN patients permanently and it is recommended to stop surveillance at 5 years from initial diagnosis in the AGA guideline. In this study, we investigate the incidence of PC in patients suspected IPMN and clarify what types of cysts are susceptible to be PC and how long the observation period should be. Patients and methods: From Jan 2005 to Dec 2015, we enrolled 947 patients with pancreatic cystic lesions (PCLs), retrospectively. After excluding patients observed within 6 months or suspected of other cystic lesions, we diagnosed 605 patients as PCLs presumed to be IPMN by MRCP or contrast enhanced CT, except plain CT and transabdominal US. By imaging studies at initial diagnosis, high-risk group (H group) was defined as patients with worrisome features (WF) or high-risk stigmata (HRS) according to the international consensus guideline 2012. Low-risk group (L group) was defined as patients other than H group. Kaplan-Meier method and Cox proportional hazard model were applied to assess the frequency and risk factors for PC. Results: In H group/L group, the numbers of patients were 47/558, mean observation periods were 54.5±41.7 months/67.1±43.1 months, PC occurred in 8 patients/28 patients and 5-year incidence of PC were 17.4%/3.4%, respectively. In H group, IPMN derived PC occurred in all 8 patients, while IPMN concomitant PC occurred in 13 patients of L group (46.4%; 13/28). The risk factors for PC in L group were age (over 70-year-old), sex (male), cyst size (over 20mm), MPD diameter (over 3mm), and multilocular formation by univariate analysis. Among these factors, age (over 70-year-old) was an independent risk factor for PC by multivariate analysis (HR; 2.34, P=0.03). Of 558 patients in L group, after we excluded 290 patients whose observation periods were less than 5 years and 35 patients who changed to WF or HRS (33 to WF and 2 to HRS), we assessed the incidence of PC in remaining 233 patients without progression after 5-year observation. Among this cohort, PC occurred in 9 patients and 1-, 2-, 3-, 4- and 5-year incidences of PC (that is 6-, 7-, 8-, 9- and 10year from initial diagnosis) were 1.9%, 1.9%, 3.5%, 4.5% and 5.8%, respectively. Conclusion: In patients with PCLs presumed to be IPMN, it is inappropriate to quit surveillance at 5 years from initial diagnosis because PC occurred after 5-year observation even in Low-risk group. Age over 70-year-old can be the candidate to narrow down high-risk group of PC, however, further investigations are needed for more efficient surveillance of malignancy focused on high-risk group.

673 THE INTERNATIONAL BLEEDING RISK SCORE: A NEW RISK SCORE THAT CAN ACCURATELY PREDICT MORTALITY IN PATIENTS WITH UPPER GI-BLEEDING Stig B. Laursen, Loren Laine, Harry Dalton, Iain A. Murray, Michael Schultz, Jing Hieng Ngu, Adrian J. Stanley Objectives: Several risk scores have been developed for prediction of mortality in patients with upper gastrointestinal bleeding (UGIB). A recent international multicentre study has shown that none of the existing risk scores (Rockall, AIMS65, PNED, Glasgow Blatchford score (GBS)) have satisfactory ability to predict this endpoint. Based on data from an international multicentre study we aimed to develop a new risk score for prediction of 30day mortality in patients with UGIB. Methods: Consecutive patients presenting with UGIB at six large international centres located in United States, Scotland, England, Denmark, Singapore, and New Zealand were prospectively included over 12 months. Data regarding patients' characteristics, bleeding characteristics, findings at endoscopy, treatment, and outcome at day 30 were registered. Using logistic regression analysis we developed a preendoscopy risk score for prediction of 30-day mortality and compared the discriminative abilities with the performance of Rockall, AIMS65, GBS, and PNED scores at traditional cut-offs. Results: A total of 3012 patients were included. Median age was 65 years and 58% were male. A weighted risk score based on age, comorbidities, and blood tests (see table 1) had higher discriminative abilities for prediction of mortality than existing scores when evaluated by area under receiving operator characteristic curves (AUROC) (0.863 vs 0.6920.793; p<0.001). Sensitivity and specificity compared with existing risk scores are presented in table 2. Patients with a score of ≤3 (56%) had a very low risk of death of 0.7%. Patients with a score of 4-7 (34%) had a mortality rate of 9.3% and patients with a score of ≥8 (10%) had a very high mortality rate of 34%. The proposed risk score classified more patients as low-risk patients than Admission Rockall score and GBS (56% versus 19-30%; p<0.001) and classified low-risk patients had similar mortality rates (0.7% vs 0.4-1.3%; P=NS). Classified low-risk patients using the proposed risk score had lower mortality than those classified low-risk with PNED and AIMS65 (0.7 vs 3.4%; p<0.001). The proposed risk score performed equally well at all sites (AUROC: 0.850-0.953; p=NS). Conclusion: The International Bleeding Risk Score seems better than existing risk scores in predicting 30day mortality among patients presenting with UGIB. This score can be calculated shortly after hospitalization because it does not require findings at endoscopy. Using this it is possible to identify patients at high risk of death allowing targeted management and interventions that may improve outcome. Furthermore, it also enables early identification of more than 50% of all patients at very low risk of death (<1%). Future studies validating the performance of the proposed score are needed.

672 A DOUBLE-BLIND, RANDOMIZED TRIAL OF MISOPROSTOL FOR HEALING OF SMALL BOWEL BLEEDING ULCERS IN PATIENTS ON CONTINUOUS ASPIRIN Francis K. Chan, Koji Otani, Akira Higashimori, Carmen Kee, Jessica Ching, Yee Kit Tse, Raymond S Tang, Angeline Lo, Heyson Chan, Long Yan K. Lam, Rashid Lui, Tetsuo Arakawa, Siew C. Ng, Yasuhiro Fujiwara, Justin C. Wu, Toshio Watanabe Background To date, there is no effective pharmacological treatment for small bowel ulcers. We assessed the efficacy of misoprostol for healing of small bowel ulcers in patients with gastrointestinal (GI) bleeding who received continuous aspirin therapy. Method This was an 8-week, double-blind, randomized, placebo-controlled trial of misoprostol for healing of small bowel ulcers. Patients were eligible if they had: 1. been on regular aspirin ≤160 mg per day for established cardiothrombotic diseases; 2. overt bleeding or anemia of small bowel in origin; 3. no bleeding source on gastroscopy and colonoscopy; and 4. an agreed score of 3 (>4 erosions) or 4 (large erosion or ulcer) confirmed by capsule endoscopy [Graham DY et al. 2005]. We excluded patients who had: a high risk of capsule retention, difficulty in swallowing a video capsule or terminal illness. Patients were randomly assigned to receive either 200 mg misoprostol four times daily or an identical-appearing placebo for 8 weeks. All patients continued aspirin 80 mg per day for the duration of the trial. Concomitant nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, sucralfate, rebamepide, antibiotics, corticosteroids, or iron supplement were prohibited during the trial. Follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing. All capsule images were evaluated by a panel of blinded adjudicators. Any discrepancy was resolved by consensus. The primary endpoint was complete healing of small bowel ulcers/erosions at 8 weeks. Results The intention-to-treat population included all patients who took at least one dose of study drug and returned for follow-up capsule endoscopy (N=72; 35 misoprostol, 37 placebo). Their demographic characteristics were shown in the Table. Twelve patients (34.3%) receiving misoprostol and four (10.8%) receiving placebo had complete healing at 8 weeks (P=0.017). Conclusion Among patients with small bowel bleeding who receive continuous aspirin therapy, misoprostol is superior to placebo in healing small bowel ulcers. This study was supported by a competitive grant of the Research Grant Council of Hong Kong (CUHK460811)

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AGA Abstracts

factors, along with proper discharge planning are essential to reduce mortality and morbidity from GIB.

AGA Abstracts

Table 1. International risk score for prediction of 30-day mortality

ASA: American Society of Anaesthesiologists Table 2. Predictive abilities for identification of patients in low or high risk of mortality

675 EFFECT OF VONOPRAZAN ON THE ANTI-PLATELET FUNCTION OF CLOPIDOGREL OR PRASUGREL IN RELATION TO CYP2C19 GENOTYPE Takuma Kagami, Mihoko Yamade, Hitomi Ichikawa, Takahiro Uotani, Shu Sahara, Yasushi Hamaya, Moriya Iwaizumi, Satoshi Osawa, Ken Sugimoto, Hiroaki Miyajima, Takahisa Furuta

ARS: Admission Rockall score GBS: Glasgow Blatchford Score NPV: Negative Predictive Values PNED: Progetto Nazionale Emorragia Digestive PPV: Positive Predictive Values

Background and aim: Anti-platelet therapy is commonly given to patients with coronary heart disease, stroke, and peripheral artery disease. Gastrointestinal hemorrhage is a common serious complication of long-term anti-platelet therapy. To prevent such bleeding, an acid inhibitor such as a proton pump inhibitor (PPI) is often co-administered. Vonoprazan belongs to a new class of gastric acid inhibitors that function as potassium-competitive acid blockers. It is predominantly inactivated by CYP3A4, and partially by CYP2C19. Plasma concentrations and gastric acid inhibitory actions are therefore less affected by polymorphisms of drugmetabolizing enzymes, such as CYP2C19, than those of other PPIs. Although CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel and esomeprazole, drugdrug interactions between vonoprazan and clopidogrel or prasugrel are yet to be elucidated. The aim of this study was to compare the effects of vonoprazan and esomeprazole on the anti-platelet functions of clopidogrel or prasugrel in relation to CYP2C19 genotypes. Methods: Thirty-one healthy Japanese volunteers [14 CYP2C19 rapid (RMs), 9 intermediate (IMs), and 8 poor metabolizers (PMs)] received six different single daily regimens in random order: (i) clopidogrel 75 mg alone, (ii) clopidogrel+esomeprazole 20 mg, (iii) clopidogrel+vonoprazan 10 mg, (iv) prasugrel 3.75 mg alone, (v) prasugrel+esomeprazole, and (vi) prasugrel+vonoprazan. Each dosage was administered at 8:30 a.m. (1 hour before breakfast). On day 7 of each regimen, the P2Y12 assay was performed at 8:30 a.m. Results: For all genotypes, the median inhibition of platelet aggregation (IPA) values for clopidogrel alone, clopidogrel+esomeprazole, clopidogrel+vonoprazan, prasugrel al on e, prasugrel+esomeprazole, and prasugrel+vonoprazan were 34%, 33%, 14%, 59%, 47%, and 37%, respectively. Vonoprazan attenuated the anti-platelet functions of clopidogrel and prasugrel more potently than esomeprazole, at 14% vs. 33% (p<0.001) and 37% vs. 47% (p=0.011), respectively. The effects of esomeprazole and vonoprazan on clopidogrel differed when stratified by CYP2C19 genotype groups [21% for clopidogrel+vonoprazan vs. 40% for clopidogrel+esomeprazole (p=0.004) in RMs, 20% vs. 36% (p=0.033) in IMs, and 2% vs. 14% (p=0.043) in PMs]. The same tendencies were observed for prasugrel [35% for prasugrel+vonoprazan vs. 48% for prasugrel+esomeprazole (p=0.017) in RMs, 35% vs. 43% (n.s.; not significant) in IMs, and 37% vs. 50% (n.s.) in PMs] Conclusion: This is the first study to show that vonoprazan attenuates the anti-platelet function of clopidogrel and prasugrel. Interestingly, vonoprazan attenuated the anti-platelet function of clopidogrel and prasugrel more potently than esomeprazole, while esomeprazole affected the anti-platelet function of prasugrel less potently, irrespective of CYP2C19 genotype. (UMIN000019901)

674 PREDICTORS FOR IN-HOSPITAL MORTALITY AND 30-DAY READMISSION IN PATIENTS PRESENTING WITH GASTROINTESTINAL BLEEDING IN THE UNITED STATES Satish Munigala, Jason Bill, Chien-Huan Chen, Thomas Burroughs, C. Prakash Gyawali Background: Gastrointestinal bleeding (GIB) is associated with higher costs and healthcare utilization due to need for endoscopy and other invasive interventions. However, population based data on risk factors for in-hospital mortality and 30-day readmission are limited. Methods: The Nationwide Readmission Database (NRD) was interrogated to identify patients discharged with a primary diagnosis of GIB in 2013. Age< 18 years, pregnancy & delivery status, missing mortality information, and discharge against medical advice were exclusions. Death during index hospitalization, discharge in December 2013 and missing length of stay data were exclusions for readmission analysis. Diagnosis codes were scrutinized for evidence of invasive diagnostic and therapeutic procedures performed. The final data set included demographics, comorbidities, insurance status, median income, hospital location and size, time of admission, interventions and discharge type. Multivariate logistic regression analysis was performed to identify independent predictors for mortality and readmission risk. Results: After exclusions, 594,362 patients with GIB were identified (mean age 53.0 ±17 years, 51% F). Overall in-hospital mortality rate was 2.5%; mortality rate for upper GIB (2.0%) was lower than that for lower GIB (2.3%) and obscure GIB (4.2%), p<0.001 across groups. 16.1% (85,346/531,139) were readmitted within 30 days (median: 11 days); readmission rate for lower GIB (14.1%) was lower than that for upper GIB (16.8%) and obscure GIB (18.0%). Both mortality and readmission rates increased with age, with highest mortality (4.2%) and readmission rates (15.2%) in patients >85 years (Figure). On multivariate analysis, odds ratio (OR) for mortality in this age group was 6.13 (95% confidence intervals 5.337.05). Mortality was higher with lower GIB (OR 1.55, p<0.001) and obscure GIB (OR 2.26, p<0.001) compared to upper GIB. Other independent predictors for mortality included age, male gender, Medicare and Medicaid insurance status, comorbidities (especially cardiovascular failure, acute kidney injury and respiratory failure), cirrhosis, weekend admissions and interventions other than endoscopy or surgery (Table). Both mortality and readmission rates were lower when upper endoscopy and colonoscopy were performed. Weekend admissions (OR 0.96) and lower GIB (OR 0.89) had lower risk of 30 day readmission, while surgical/ other interventions and patients discharged to extended care facilities were associated with increased risk of readmission (Table). Conclusions: The most vulnerable patients with GIB are the elderly, those with Medicare or Medicaid coverage, obscure GIB, and comorbidities, where mortality and 30-day readmissions are highest. Identifying and addressing these

AGA Abstracts

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