Stig Borbjerg Laursen

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study

Objective To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. Design International multicentre prospective study. Setting Six large hospitals in Europe, North America, Asia, and Oceania. Participants 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. Main outcome measures Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. Results The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. Conclusions The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited. Trial registration Current Controlled Trials ISRCTN16235737.

Supplementary arteriel embolization an option in high-risk ulcer bleeding – a randomized study

Abstract Objective. One of the major challenges in peptic ulcer bleeding (PUB) is rebleeding which is associated with up to a fivefold increase in mortality. We examined if supplementary transcatheter arterial embolization (STAE) performed after achieved endoscopic hemostasis improves outcome in patients with high-risk ulcers. Material and methods. The study was designed as a non-blinded, parallel group, randomized-controlled trial and performed in a university hospital setting. Patients admitted with PUB from Forrest Ia – IIb ulcers controlled by endoscopic therapy were randomized (1:1 ratio) to STAE of the bleeding artery within 24 h or continued standard treatment. Randomization was stratified according to stigmata of hemorrhage. Patients were followed for 30 days. Primary outcome was a composite endpoint where patients were classified into five groups based on transfusion requirement, development of rebleeding, need of hemostatic intervention and mortality. Secondary outcomes were rebleeding, number of blood transfusions received, duration of admission and mortality. Results. Totally 105 patients were included. Of the 49 patients allocated to STAE 31 underwent successful STAE. There was no difference in composite endpoint. Two versus eight patients re-bled in the STAE and control group, respectively (Intention-to-treat analysis; p = .10). After adjustment for possible imbalances a strong trend was noted between STAE and rate of rebleeding (p = .079). Conclusions. STAE is potentially useful for preventing rebleeding in high-risk PUB. STAE can safely be performed in selected cases with high risk of rebleeding. Further studies are needed in order to confirm these findings; ClincialTrials.gov number, NCT01125852.

The excess long-term mortality in peptic ulcer bleeding is explained by nonspecific comorbidity

Abstract Objective. Previous studies have concluded that peptic ulcer bleeding (PUB) is associated with increased long-term mortality. The underlying mechanism of this excess mortality is poorly understood. The aim of the present study was to examine if PUB patients have an increased long-term mortality compared to a matched control group when adjusting for comorbidity and socioeconomic status. Additionally, we identified predictive factors for mortality and examined causes of death. Material and methods. We performed an observational study, comparing consecutive patients admitted with PUB with a matched control cohort from the source population. Predictors of mortality were identified using proportional hazards models. Causes of death were retrieved from death certificates. Long-term mortality was analyzed with adjustment for Charlson comorbidity index (CCI) and average income in residence municipality using proportional hazards models. Results. We included 455 PUB cases and 2224 control subjects. Median follow up was 9.7 years, and median survival for the PUB and control cohorts was 7 and 12 years, respectively (p < 0.001). PUB patients had a higher level of comorbidity (mean CCI: 0.92 vs. 0.49; p < 0.0001). After adjustments, PUB patients had an excess mortality lasting at least 10 years after presentation. Age, comorbidity, male sex, anemia, and smoking were predictors for long-term mortality. The distribution of causes of death was similar in the two cohorts. Conclusion. PUB patients have an increased long-term mortality that is explained by nonspecific comorbidity.

Transcatheter arterial embolization is the first-line therapy of choice in peptic ulcer bleeding not responding to endoscopic therapy

Abstract Objective. In 5–10% of patients with peptic ulcer bleeding (PUB) it is impossible to achieve endoscopic hemostasis because of severe bleeding. These patients have traditionally been treated surgically. Transcatheter arterial embolization (TAE) may, however, be associated with a better outcome because of the less-invasive nature of the procedure. The aim of the present study was to identify the treatment of choice in endoscopy-refractory PUB. Materials and methods. A retrospective study. Consecutive patients treated with surgery or TAE for endoscopy-refractory PUB during a period of 16 years at a university hospital were included. Primary hemostasis, rebleeding rate, mortality, and complications were assessed. Mortality was compared between groups after adjustment for age, comorbidity, and anemia using logistic regression analyses. Comorbidity was quantified using the Charlson comorbidity index (CCI). Results. One hundred and eighteen patients were included. Patients treated with TAE had a higher CCI (mean: 2.33 vs 1.42; p = .003), and more severe anemia (mean: 6.8 vs 7.9 g/dl; p = .007) compared with patients treated with surgery. Surgery was associated with a higher rate of primary hemostasis (100% vs 91%; p = .007), lower rate of rebleeding (15% vs 40%; p = .004) but also higher rate of complications (60% vs 38%; p = .02) than TAE. Surgery was associated with an increased mortality (Odds ratio: 3.05; p = .033) when adjusting for confounding factors and excluding patients (n = 3) who were not candidates for both interventions. Conclusions. We propose use of TAE as first-line therapy in these patients as it may be associated with lower mortality and lower rate of complications compared with surgery.

Severity and outcomes of upper gastrointestinal bleeding with bloody vs. coffee-grounds hematemesis

Objectives:Numerous reviews indicate bloody hematemesis signifies more severe bleeding than coffee-grounds hematemesis. We assessed severity and outcomes related to bleeding symptoms in a prospective study.Methods:Consecutive patients presenting with hematemesis or melena were categorized as bloody emesis (N=1209), coffee-grounds emesis without bloody emesis (N=701), or melena without hematemesis (N=1069). We assessed bleeding severity (pulse, blood pressure) and predictors of outcome (hemoglobin, risk stratification scores) at presentation, and outcomes of bleeding episodes. The primary outcome was a composite of transfusion, intervention, or mortality.Results:Bloody and coffee-grounds emesis were similar in pulse ≥100 beats/min (35 vs. 37%), systolic blood pressure ≤100 mm Hg (12 vs. 12%), and hemoglobin ≤100 g/l (25 vs. 27%). Risk stratification scores were lower with bloody emesis. The composite end point was 34.7 vs. 38.2% for bloody vs. coffee-grounds emesis; mortality was 6.6 vs. 9.3%. Hemostatic intervention was more common (19.4 vs. 14.4%) with bloody emesis (due to a higher frequency of varices necessitating endoscopic therapy), as was rebleeding (7.8 vs. 4.5%). Outcomes were worse with hematemesis plus melena vs. isolated hematemesis for bloody (composite: 62.4 vs. 25.6%; hemostatic intervention: 36.5 vs. 13.8%) and coffee-grounds emesis (composite: 59.1 vs. 27.1%; hemostatic intervention: 26.4 vs. 8.1%).Conclusions:Bloody emesis is not associated with more severe bleeding episodes at presentation or higher mortality than coffee-grounds emesis, but is associated with modestly higher rates of hemostatic intervention and rebleeding. Outcomes with hematemesis are worsened with concurrent melena. The presence of bloody emesis plus melena potentially could be considered in decisions regarding timing of endoscopy.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one‐third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment.

926 Supplementary Transcatheter Arterial Embolization After Successful Endoscopic Hemostasis Prevents Rebleeding in Peptic Ulcer Bleeding

of early EAC patients undergoing EET was noted. Overall, 79% and 47% of patients had at least 2–years and 5–years of follow-up, respectively. There was no difference in the 2– year (EET: 93.5% vs. Surgery: 89.6%, p=0.12).and 5–year (EET: 69.3% vs. 75.8%, p=0.23) EC-free survival rates between the two groups Patients in the EET group had higher mortality due to non-EAC causes [2 years: EET 12.8% vs. Surgery 5.7%, p ,0.001; 5 years: EET 34.8% vs. Surgery 12.9%, p,0.001] (Table 1). Cox proportional hazards model showed no difference in EC-specific mortality in the EET compared to surgery group [Hazard ration (HR): 1.02 (95% CI 0.6–1.6), p=0.92]. Variables associated with mortality were older age, stage T1a (compared to T0), year of diagnosis and receipt of radiation therapy (Table 2).Conclusions:Results of this population-based study demonstrate comparable mid and long-term (2 and 5–year) EC-free survival in patients with early EAC undergoing EET and surgical resection. The significant differences in non-EAC related mortality between these two treatment modalities highlight the selection bias in therapies offered to patients with early EAC. Table 1: Comparison of baseline characteristics and survival between patients with early esophageal adenocarcinoma limited to Stage T0 and T1a undergoing endoscopic eradication and surgery

Risk Factors for Rebleeding in Peptic Ulcer Bleeding: A Second Look at Second-Look Endoscopy.

Rebleeding, which occurs in 10–15 % of patients with peptic ulcer bleeding (PUB) [1], is associated with a twoto fivefold mortality increase, depending on the presence of other risk factors [2]. Therefore, identification of the predictors of rebleeding seems meaningful in order to identify high-risk patients needing close observation and rapid treatment in case of the development of rebleeding. According to previous studies, hemodynamic shock, usually defined as a systolic blood pressure \100 mmHg, often combined with tachycardia [100 beats/min, is the most powerful pre-endoscopic predictor of rebleeding [3, 4]. In a meta-analysis, hemodynamic shock was associated with an odds ratio (OR) of rebleeding of 3.3 [3]. Conversely, studies on the association between anemia and rebleeding have found conflicting results: Some of the existing data indicate that hemoglobin \10 g/L may be associated with an increased risk of rebleeding [3]. Data concerning the risks of transfusion are even more confounded by differing study protocols (e.g., preor postendoscopic transfusion, different categorization of volume) to the point that the rebleeding risk of pre-endoscopic transfusion is unknown. Regarding endoscopic predictors, active bleeding at endoscopy (OR 1.7), ulcer size [2 cm (OR 2.8), posterior duodenal ulcer location (OR 3.8), and high lesser gastric curvature ulcer location (OR 2.9) all predict rebleeding in a meta-analysis [3]. The type of endoscopic treatment applied does also affect the risk of rebleeding. A Cochrane analysis reported that combination of epinephrine injection with a second endoscopic treatment modality reduces the relative risk (RR) of rebleeding or persistent bleeding (RR 0.57) compared to endoscopic treatment with epinephrine alone [5]. Therefore, endoscopic monotherapy with injection of epinephrine should be avoided. In a meta-analysis based on eight randomized controlled trials (RCTs) published from 1994 to 2006, performance of second-look endoscopy within 16–48 h was associated with a significant reduction in rebleeding rate (OR 0.55) [6]. Generalization of this finding to current practice standards can be questioned because only one of the included studies used endoscopic combination therapy combined with high-dose infusion of proton-pump inhibitors [7]. Furthermore, detailed review of the fully published component studies revealed that a significant reduction in rebleeding was only evident in two studies that included patients with a very high risk of rebleeding (up to 47 % of included patients had hemodynamic shock) [6]. When these two trials were excluded from the meta-analysis, the association between performance of second-look endoscopy and rebleeding became statistically insignificant [6]. In a cost-effectiveness analysis, performance of secondlook endoscopy was only cost-effective after therapeutic endoscopy if the risk of rebleeding was greater than 31 % [8]. In this issue of Digestive Diseases and Sciences, Kim et al. [9] published a prospective multicenter study of risk factors for rebleeding among 699 patients with PUB from Forrest classification [10] Ia–IIb ulcers. Using multivariate logistic regression analysis, the authors reported that performance of second-look endoscopy was associated with a lower risk (OR 0.269) of rebleeding. High transfusion volume (above 5 units) and use of nonsteroidal anti-inflammatory drugs (NSAIDs) were both associated with a fourfold increase in risk of rebleeding. The authors & Stig Borbjerg Laursen Stig.laursen@rsyd.dk

Previous Use of Antithrombotic Agents Reduces Mortality and Length of Hospital Stay in Patients With High-risk Upper Gastrointestinal Bleeding

Background & Aims Anti‐thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti‐thrombotic agents on outcomes of patients with high‐risk UGIB. Methods We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee‐ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti‐thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow‐Blatchford Score, and full Rockall scores. We also collected and analyzed data on co‐morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. Results Of the 619 patients who required endoscopic therapy, data on use of anti‐thrombotic agents was available for 568; 253 of these patients (44%) used anti‐thrombotic agents. Compared to patients not taking anti‐thrombotic agents, patients treated with anti‐thrombotics were older (P < .001), had a higher mean American Society of Anesthesiologists classification score (P < .0001), had a higher mean Rockall score (P < .0001), a higher mean AIMS65 score (P < .0001), and more frequently bled from ulcers (P < .001). There were no differences between groups in sex, systolic blood pressure, level of hemoglobin at hospital admission, frequency of malignancies, Glasgow‐Blatchford Score, need for surgery or interventional radiology, number of rebleeding events, or requirement for transfusion. All‐cause mortality was lower in patients who took anti‐thrombotic drugs (11 deaths, 4%) than in patients who did not (37 deaths, 12%) (P = .002); this was due to lower bleeding‐related mortality in patients taking anti‐thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) (P = .003). Patients taking anti‐thrombotic drugs had mean hospital stays of 6.9 days (95% CI, 2–23 days) compared to 7.9 days for non‐users of anti‐thrombotic agents (95% CI, 2–26 days) (P = .04). Conclusions Despite being older, with higher American Society of Anesthesiologists classification, AIMS65, and Rockall scores, patients who have UGIB that requires endoscopic therapy and take anti‐thrombotic drugs have lower mortality due to GI bleeding and shorter hospital stays, with similar rates of rebleeding, surgery, and transfusions, compared with those not taking anti‐thrombotic drugs.

Wireless Capsule Endoscopy as a tool in diagnosing Autoimmune Enteropathy

Autoimmune enteropathy (AE) is an immune mediated illness of the intestinal mucosa. The cause is unknown, and the diagnosis is based on typical characteristics displayed. There is no gold standard for treatment. We present two adult cases of AE and demonstrate the challenges in establishing the diagnosis. The extensive diagnostic work up excluded other more common causes of protracted diarrhoea. Wireless capsule endoscopy (WCE) displayed universal small intestinal mucosal damage with shortened villi that led to the suspicion of AE in both patients. The diagnosis was confirmed with microscopy, showing shortened villi, villous blunting and hyperplasia of crypts in both patients. In one patient, deep crypt lymphocytosis with minimal intraepithelial lymphocytosis was found as well. Both patients were successfully treated with high-dose immunosuppressant therapy to induce and maintain remission. Use of WCE as a diagnostic tool was invaluable in establishing the diagnosis of AE.