Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Doppler-Guided Second-Look Endoscopy in Peptic Ulcer Bleeding: A Randomised Controlled Trial.

BACKGROUND: Endoscopic treatment guided by Doppler endoscopic probes (DEPs) during index endoscopy may be associated with improved outcome in patients with peptic ulcer bleeding (PUB). As competencies for DEP evaluation are not always available for index endoscopy, we examined the outcome associated with DEP evaluation at second-look endoscopy. METHODS: The study was designed as a non-blinded, parallel group, randomised controlled trial. Patients admitted with PUB from Forrest Ia-IIb ulcers, controlled by endoscopic therapy, were randomised (1:1 ratio) to second-look endoscopy <24 h with DEP evaluation of the bleeding ulcer or continued standard treatment. Patients were followed up for 30 days. The primary outcome was rebleeding. Secondary outcomes included the number of transfusions, length of hospital stay, and 30-day mortality. RESULTS: A total of 62 patients were included. At second-look endoscopy, 91% (29/32) of patients had a positive DEP signal at the ulcer base and were treated with contact thermal therapy (n = 29), injection of diluted adrenaline (n = 23), and haemoclips (n = 7). Among the 32 patients treated with DEP evaluation, only one rebled (3%) compared to four patients (13%) in the control group (p = 0.20). There were no differences in the secondary outcomes between groups, and there were no complications related to DEP evaluation. CONCLUSIONS: Second-look endoscopy with DEP-guided evaluation and treatment is safe and associated with a very low risk of rebleeding (3%) in patients with PUB. Second-look endoscopy with DEP evaluation may be considered in selected PUB patients at high risk of rebleeding, and may represent an alternative to the use of DEP for index endoscopy. Nevertheless, we did not find that second-look endoscopy with DEP evaluation significantly improved patient outcome compared to standard treatment.

Endoscopic treatment of gastric antral vascular ectasia.

Gastric antral vascular ectasia is characterized endoscopically by stripes of dilated blood vessels in the antrum. It is a well-known cause of gastrointestinal blood loss, anaemia, and recurrent need for blood transfusion. The treatment may be challenging, and an overview is given in this review. Pharmacological treatment has not been effective, endoscopic treatment is more tolerable than abdominal surgery. The endoscopic modalities, including argon plasma coagulation, endoscopic band ligation, and radiofrequency ablation are safe and relative efficient. Comparative studies are sparse but indicate the modalities as equally effective.

Hypotension develops one to two hours before other symptoms in peptic ulcer rebleeding; a matched cohort study.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB) and is associated with increased mortality. Blood pressure and heart rate are two easy non-invasive measurements to evaluate the hemodynamics and therefore a standard observation during hospitalization. OBJECTIVE: We aimed to investigate the dynamics of systolic blood pressure and heart rate up to time of peptic ulcer rebleeding. DESIGN: Retrospective matched cohort study. Hemodynamics in patients with peptic ulcer rebleeding was compared to hemodynamics in a matched control group consisting of patients with PUB without rebleeding. Blood pressure and heart rate in the six hours up to diagnosis of rebleeding was compared with baseline in the case cohort as well as with the matched control group. RESULTS: Thirty-eight patients with peptic ulcer rebleeding and 66 controls were included. Mean age was 75 years, 62% were males and 30-day mortality was 23%. Baseline systolic blood pressure in cases was 114 mmHg. Compared to baseline, we found significant decrease in systolic blood pressure two hours before rebleeding (4 mmHg; p = 0.041) and one hour before rebleeding (14 mmHg; p = 0.0002). Mean systolic blood pressure 30 min before rebleeding was 89 mmHg. No significant change was found in heart rate (p = 0.99). In the control group no change was found in systolic blood pressure or heart rate. CONCLUSION: In patients with peptic ulcer rebleeding, hypotension develops 1-2 h before other symptoms of rebleeding. Thus, close monitoring of blood pressure is needed in order to ensure early identification of rebleeding in high-risk patients.

[Risk scoring systems for assessment of patients with upper gastrointestinal bleeding].

Many scoring systems have been developed to predict various outcomes in patients with upper gastrointestinal bleeding (UGIB) including need-for-intervention, endoscopy, transfusion and/or death. This review summarises the present knowledge of the various scoring systems. It has been impossible to develop one score to predict all outcomes of interest. Glasgow-Blatchford Score (GBS) is shown to be superior to predict hospital-based intervention or death. For mortality, the newly developed ABC score seems promising. International guidelines recommend routine use of GBS to assess patients with UGIB, which is shown to reduce hospital admissions, length-of-stay and cost utilisation.

Analysis of patterns of bacteremia and 30-day mortality in patients with acute cholangitis over a 25-year period.

INTRODUCTION: Acute cholangitis (AC) is a condition of bacterial infection in the biliary tract with a high mortality rate of around 10%. Direct association between presence of bacteremia and 30-day mortality among AC patients is sparsely investigated and remains unclear. AIMS AND METHODS: Our aim was to investigate association between bacteremia and 30-day mortality among patients with AC included over a period of 25 years. All AC patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) at Odense University Hospital, between 1 January 1990 and 31 October 2015, were identified using a prospective ERCP database. Blood culture results from the patients along with antimicrobial resistance patterns were collected from a bacteremia research database. RESULTS: During the study period, 775 consecutive AC patients underwent ERCP and blood cultures were collected from 528 patients. Among these patients 48% (n = 260) had bacteremia. Overall, 30-day mortality in patients with blood cultures performed was 13% (n = 69). In patients with bacteremia, 30-day mortality was 19% (n = 49), compared to 7% (n = 20) in patients without bacteremia (p < .01). Presence of bacteremia was associated with increased 30-day mortality (OR [95% CI]: 3.43 [1.92-6.13]; p < .01) following adjustment for confounding factors. Among the species, bacteremia with Enterobacter cloacae was significantly associated with increased 30-day mortality (OR [95% CI]: 2.97 [1.16-7.62]; p = .02). CONCLUSION: Our results indicate that presence of bacteremia was associated with a nearly fourfold increase in 30-day mortality among AC patients.

ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study.

OBJECTIVES: Existing scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB. DESIGN AND SETTING: International cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score's performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk. PARTICIPANTS AND RESULTS: We included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81-84) than existing scores (AUROCs: 0.65-0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4-7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; p<0.001). In LGIB, patients with low, medium and high ABC scores had in-hospital mortality rates of 0.6%, 6.3% and 18%, respectively. CONCLUSIONS: In contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.

Unchanged mortality in patients with acute cholangitis despite an increase in malignant etiologies - a 25-year epidemiological study.

Background and aims: Acute cholangitis (AC) is a rare but serious condition, with an incidence of 7.0 per 10,000 people and mortality rates up to 10%. The aim of this study was to describe changes in obstruction etiology, comorbidities, clinical factors, and mortality among AC patients during a 25-year period. Methods: Using a database of 11,563 consecutive ERCP-procedures performed from 1990-2015 at Odense University Hospital, we identified all AC cases during that period. Clinical and epidemiological data were collected from the database and the Danish Patient Registry. Association with 30-day mortality was investigated using multiple logistic regression analysis with adjustment for confounding factors. Results: In total, 775 consecutive and individual cases of AC were included. Among cases, 42% (n = 326) were of malignant etiology, with an increasing incidence over time (regression coefficient [95% CI]: 0.03 [0.01-0.04] per year; p = .01). Mean Charlson Comorbidity Index was 1.4, with an increase over time (regression coefficient [95% CI]: 0.04 [0.03-0.05] per year; p < .01). Malignant obstruction etiology was associated with 30-day mortality (OR [95% CI]: 1.11 [1.04-1.18]; p < .01). Overall 30-day mortality was 12% (n = 91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time (OR [95% CI]: 1 [1-1.00]; p = .91 per year). Conclusion: Significant increases in the incidence of malignant obstruction etiology and severity of comorbidities among AC patients were observed during the study period. Despite those findings, 30-day mortality remained unchanged, potentially reflecting a general improvement in the management of AC.

[Timing of endoscopic retrograde cholangiopancreatography in patients with acute cholangitis].

The optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis (AC) remains unclear. The aim of this review is to clarify associations between timing of ERCP and clinical outcomes in patients with AC by discussing the current literature. Briefly, it is shown that ERCP before 72 and 48 hours of hospital admission is associated with reduced incidences of composite adverse outcomes and organ failure, respectively. ERCP before 24 hours seems to be associated with reduced 30-day mortality. Thus, performance of ERCP with biliary decompression within 24 hours from time of hospital admission is recommended in patients with AC.

Arterial lactate does not predict outcome better than existing risk scores in upper gastrointestinal bleeding.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a frequent medical emergency and several scoring systems are developed to help risk-stratify patients. We aimed to investigate if elevated arterial lactate (AL) was associated with 30-day mortality, need for hospital-based intervention, or rebleeding. Furthermore, we compared the performance of AL with existing scoring systems and examined if incorporation of AL could improve their predictive ability. MATERIALS AND METHODS: Retrospective cohort study of 331 consecutive patients admitted with UGIB during a one-year period. Multivariate analyses were performed to evaluate the association between AL and outcomes. Receiver operating characteristic curves were used to compare AL with existing scoring systems and to test if incorporation of AL could significantly increase their performance. RESULTS: AL was significantly associated with mortality (p = .001), need for hospital-based intervention (p = .005), and rebleeding (p = .031). In predicting mortality and rebleeding, AL performed equally to existing scoring systems, however, inferior to all, in predicting need for intervention. Two of the scoring systems were marginally improved in predicting mortality if AL was included. CONCLUSIONS: AL is associated with adverse outcomes in patients with UGIB, but has only similar or inferior ability to predict relevant clinical outcomes compared to existing scoring systems. Although AL could enhance performance of two scorings systems in predicting mortality, it does not have an apparent clinical significance. Thus, our data does not support routine measurement of AL in patients with UGIB.

[Peroral cholangioscopy].

Peroral cholangioscopy has been used since the 1970'es and provides direct visualization of the biliary tree, possibility of electrohydraulic or laser lithotripsy and visually guided biopsies. This paper presents an overview of the existing literature focusing on the Spyglass single-operator cholangioscopy system. Several studies indicate that cholangioscopy can improve therapy of difficult accessible biliary stones and histological diagnosis in patients with indeterminate bile duct stenoses.

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.

Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding.

A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women < 40 years of age. Small intestine investigation (capsule endoscopy, CT, or MRI enterography) is not recommended routinely after negative bidirectional endoscopy but should be conducted if there are red flags indicating malignant or inflammatory small bowel disease (e.g., involuntary weight loss, abdominal pain or increased CRP). Targeted treatment of any cause of anemia with iron deficiency found on diagnostic assessment should be initiated. In addition, iron supplementation should be administered, with the goal of normalizing hemoglobin levels and replenishing iron stores. Oral treatment with a 100-200 mg daily dose of elemental iron is recommended (lower dose if side effects), but 3-6 months of oral iron therapy is often required to achieve therapeutic goals. Intravenous iron therapy is used if oral treatment lacks efficacy or causes side effects or in the presence of intestinal malabsorption or prolonged inflammation. Three algorithms are given for the following conditions: a) the paraclinical diagnosis of anemia with iron deficiency; b) the diagnostic work-up for unexplained anemia with iron deficiency without overt bleeding; and c) how to proceed after negative bidirectional endoscopy of the gastrointestinal tract.

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

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.

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

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.

National consensus on management of peptic ulcer bleeding in Denmark 2014.

DESCRIPTION: The Danish Society of Gastroenterology and Hepatology have compiled a national guideline for the management of peptic ulcer bleeding. Sources of data included published studies up to June 2014. Quality of evidence and strength of recommendations have been graded. The guideline was approved by the Danish Society of Gastroenterology and Hepatology September 4, 2011. The current version is revised June 2014. RECOMMENDATIONS: RECOMMENDATIONS emphasize the importance of early and efficient resuscitation. Use of a restrictive blood transfusion policy is recommended in haemodynamically stable patients without serious ischaemic disease. Endoscopy should generally be performed within 24 hours, reducing operation rate, rebleeding rate and duration of in-patient stay. When serious ulcer bleeding is suspected and blood found in gastric aspirate, endoscopy within 12 hours will result in faster discharge and reduced need for transfusions. Endoscopic hemostasis remains indicated for high-risk lesions. Hemoclips, thermocoagulation, and epinephrine injection are effective in achieving endoscopic hemostasis. Use of endoscopic monotherapy with epinephrine injection is not recommended. Intravenous high-dose proton pump inhibitor (PPI) therapy for 72 hours after successful endoscopic hemostasis is recommended even though the evidence is questionable. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least three days after endoscopic hemostasis. Patients with peptic ulcer bleeding who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) within 24 hours from primary endoscopy. Patients in need of continued treatment with ASA or a nonsteroidal anti-inflammatory drug should be put on prophylactic treatment with PPI at standard dosage. The combination of 75 mg ASA and PPI should be preferred to monotherapy with clopidogrel in patients needing anti-platelet therapy on the basis of indications other than coronary stents. Low-risk patients without clinical suspicion of peptic ulcer bleeding who have a Glasgow Blatchford score ≤ 1 can be offered out-patient care, unless hospital admission is required for other reasons.

[Proton pump inhibitors in peptic ulcer bleeding].

Treatment with proton pump inhibitors (PPI) is shown to improve the outcome of peptic ulcer bleeding (PUB). A recent Cochrane review evaluated different regimes of PPI-treatment in the management of PUB. The current evidence suggests that treatment with high-dose PPI (cumulative PPI-dose > 600 mg for the first 72 hours) is not associated with an improved outcome compared to treatment with a lower dose of PPI. The available studies are, however, characterized by high risk of bias, insufficient blinding, and a low event rate. Therefore, the existing data are insufficient to conclude that lower doses of PPI are equally efficacious to high-dose treatment. As the current evidence is strongest for high-dose treatment for patients with serious PUB it is recommended to use high-dose PPI treatment in patients treated with endoscopic therapy. This is in line with the national recommendations in Denmark.

Sexual function and body image are similar after laparoscopy-assisted and open ileal pouch-anal anastomosis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is performed in patients with ulcerative colitis and familial adenomatous polyposis where the majority of patients are sexually active. Laparoscopic surgery is becoming the preferred technique for most colorectal interventions, and we examined postoperative sexual function and body image compared to those after open surgery IPAA. METHODS: Patients treated with IPAA in the period from October 2008 to March 2012 were included. Evaluation of sexual function, body image, and quality of life was performed using the Female Sexual Function Index (FSFI), the International Index of Erectile Function (IIEF), the Body Image Questionnaire (BIQ), and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). RESULTS: We included 72 patients (38 laparoscopy-assisted and 34 open). Response rate was 74 %. There were no differences in demographics, functional outcome, quality of life (SIBDQ score: 53 vs. 53), or time of follow-up (637 vs. 803 days). All women and men showed scores above the cutoff line of normal sexual function. There was no significant difference in sexual function between the laparoscopic and open groups. We found no differences in BIQ between open and laparoscopic IPAA; however, there was a tendency toward lower postoperative self-esteem among women compared to men (p = 0.07). We also found a tendency toward a better body image among laparoscopy-treated women compared to open-treated women (p = 0.07). CONCLUSIONS: Although there might be a tendency toward better body image among laparoscopy-treated women, the two surgical techniques seem equal with respect to postoperative sexual function.