LONG-TERM NATURAL HISTORY OF PRESUMPTIVE DIVERTICULAR HEMORRHAGE.

OBJECTIVES: The natural history of patients with well-documented presumptive diverticular hemorrhage (TICH) is unknown. Our aims are to report: 1) rebleeding rates and clinical outcomes of presumptive TICH patients with and without rebleeding, 2) conversion to definitive TICH during long-term follow-up (F/U), and 3) risk factors for presumptive TIC rebleeding. METHODS: This was a retrospective cohort study of prospectively collected results of presumptive TICH patients from 1994 to 2023. Presumptive TICH was diagnosed for patients with TIC's without stigmata of recent hemorrhage and no other cause of bleeding found on anoscopy, enteroscopy, capsule endoscopy, computerized tomography angiography, or tagged red blood cell scan. Patients with ≤ 6 months of F/U were excluded. RESULTS: Of 139 patients with presumptive TICH, 104 were males and 35 females. Median age was 76 years. There were no significant differences in baseline demographics of rebleeders and non-rebleeders. During long-term median F/U of 73 months, 24.5% (34/139) rebled. 56% (19/34) of rebleeders were diagnosed as definitive TICH and they had significantly higher rates of readmission (p<0.001), reintervention (p<0.001), and surgery (p<0.001). During F/U, there were significantly higher rates of newly diagnosed hypertension (HTN) and/or atherosclerotic cardiovascular disease (ASCVD) in rebleeders (p = 0.033 from logistic model). All-cause mortality was 42.8%, but none was from TICH. CONCLUSIONS: For presumptive TICH during long-term F/U: 1) 75.5% did not rebleed and 24.5% rebled. 2) 56% of rebleeders were diagnosed as definitive TICH. 3) New development of HTN and ASCVD were risk factors for TIC rebleeding.

Endoscopic Diagnosis and Treatment of Colonic Diverticular Bleeding.

This is a description and critical analysis of current diagnosis and treatment of diverticular hemorrhage. The focus is on colonoscopy for identification and treatment of stigmata of recent hemorrhage (SRH) in diverticula. A classification of definitive, presumptive, and incidental diverticular hemorrhage is reviewed and recommended. The approach to definitive diagnosis with urgent colonoscopy is put into perspective of other management strategies including angiography (of different types), nuclear medicine scans, surgery, and medical treatment. Advancements in diagnosis, risk stratification, and colonoscopic hemostasis are described including those that obliterate arterial blood flow underneath SRH and prevent diverticular rebleeding. Recent innovations are discussed.

Patient Outcomes of Definitive Diverticular Hemorrhage After Colonoscopic, Medical, Surgical, or Embolization Treatment.

BACKGROUND: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH). AIMS: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment. METHODS: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan-Meier analysis was for time-to-first diverticular rebleed. RESULTS: 162 patients with DDH were stratified based on their final treatment before discharge-104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow-Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications. CONCLUSIONS: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

The Importance of Arterial Blood Flow Detection for Risk Stratification and Eradication to Achieve Definitive Hemostasis of Severe Non-Variceal UGI Hemorrhage.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common medical problem worldwide. Independent endoscopic risk factors for rebleeding and mortality of NVUGIB that are treatable are stigmata of recent hemorrhage (SRH) and arterial blood flow underneath SRH. The specific aims of this paper are to describe the importance of arterial blood flow detection for risk stratification and as a guide to definitive hemostasis of severe NVUGIB. METHODS: This is a review of randomized controlled trials and prospective cohort study methodologies and results which utilized a Doppler endoscopic probe (DEP) for the detection of arterial blood underneath SRH, for risk stratification, and as a guide to definitive hemostasis. The results are compared to visually guided hemostasis based upon SRH. RESULTS: Although SRH have been utilized to guide endoscopic hemostasis of NVUGIB for 50 years, when most visually guided treatments are applied to lesions with major SRH, arterial blood flow underneath SRH is not obliterated in 25-30% of patients and results in rebleeding. Definitive hemostasis, significantly lower rebleeding rates, and improvements in other clinical outcomes resulted when DEP was used for risk stratification and as a guide to obliteration of arterial blood flow underneath SRH. CONCLUSIONS: DEP-guided endoscopic hemostasis is a very effective and safe new method to improve patient outcomes for NVUGIB.

Ischemic colitis as a cause of severe hematochezia: A mini review.

Ischemic colitis (IC) is a common cause of severe lower gastrointestinal bleeding (LGIB) in the elderly. There are very few studies of patients with IC as a cause of severe LGIB in the literature. This article aims to review diagnosis, colonoscopic findings, medical treatment, and outcomes of patients with IC as a cause of severe hematochezia. The majority of IC patients with severe hematochezia can be successfully managed with medical treatment. Colonoscopic hemostasis with hemoclips is safe and feasible in treating major stigmata of recent hemorrhage in focal ischemic ulcers. Colon surgery is indicated in patients who fail medical treatment and/or have severe ongoing bleeding, clinical deterioration, or peritoneal signs. Overall, the morbidity rates in patients with IC range from 10% to 79%. Clinical outcomes in patients who need colon surgery for IC are worse than those treated with medical management. Patients who develop hematochezia from IC during hospitalization for other medical conditions have worse clinical outcomes than those with an outpatient start of bleeding. Further research is warranted for the prevention, early diagnosis, and treatment of patients with severe hematochezia from IC.

Outcomes of patients with ischemic colitis causing severe hematochezia managed medically or surgically.

PURPOSE: To compare short- and long-term outcomes of hospitalized patients with ischemic colitis (IC) presenting with severe hematochezia and treated medically or colectomy and also those with inpatient vs. outpatient start of hematochezia. METHODS: A retrospective analysis of prospectively collected data for IC patients hospitalized for severe hematochezia from two teaching hospitals was done from 1994 to 2020, with the diagnosis of IC made colonoscopically and confirmed histologically. RESULTS: Ninety-seven patients initially all had medical management for IC. Seventy-two (74.2%) were stable and had no further bleeding; 17 (17.5%) had colon resection; and 8 were critically ill and not surgical candidates. Surgical patients and non-surgical candidate had higher comorbidity scores; received more red blood cell (RBC) transfusion (median (IQR) 5 (3-10) vs. 4.5 (3-6.5) vs. 1 (0-4) units, p < 0.001); had significantly longer hospital and ICU days; had higher severe complication rates (35.3% vs. 100%. vs. 5.6%, p < 0.001); and had higher 30-day all-cause mortality rates (23.5% vs. 87.5% vs. 0, p < 0.001). Inpatients developing IC hemorrhage had more RBC transfusions, more complications, longer hospital stays, and higher mortality than patients whose IC bleeding started as outpatients. CONCLUSIONS: The majority of IC patients hospitalized for severe hematochezia were successfully treated medically. Patients who were not surgical candidate had the highest rates of severe complications and mortality. Surgical patients and those who were not surgical candidate had worse outcomes than the medical group. Patients with inpatient start of bleeding from IC had significantly worse outcomes than those with outpatient start of bleeding.

Severe Upper Gastrointestinal Hemorrhage Caused by Reflux Esophagitis.

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.

Acute gastrointestinal bleeding: proposed study outcomes for new randomised controlled trials.

BACKGROUND: Acute gastrointestinal bleeding (GIB) remains a common cause of hospitalisation. However, interpretation and comparisons of published studies in GIB have been hampered by disparate study methodology. AIMS: To make recommendations about outcome measures to be used in future randomised controlled trials (RCTs) of patients with acute bleeding from any GI source (nonvariceal UGI, variceal, small bowel, or colon) and suggest new RCTs in acute GIB for future peer-reviewed funding. METHODS: As part of a National Institutes of Health conference entitled "Hemostatic Outcomes in Clinical Trials", a group of GIB experts performed targeted critical reviews of available evidence with the goal of proposing a bleeding outcome that could potentially be applied to different disciplines. In addition, the panel sought to develop a clinically meaningful primary endpoint specifically for acute GIB, potentially allowing a more contemporary regrouping of clinically relevant outcomes. RESULTS: The primary endpoint proposed was a composite outcome of further bleeding within 30 days after randomisation leading to red blood cell transfusion, urgent intervention (repeat endoscopy; interventional radiology or surgery), or death. Secondary outcomes may include the individual components of the primary outcome, length of hospitalisation, serious adverse events, and health care resource utilisation. CONCLUSION: The proposed endpoint may help move the GIB field forward by focusing on the most clinically relevant outcomes for patients with acute GIB of all types and informing study design and importance of sample size determination for future RCTs in GIB.

Recommended primary outcomes for clinical trials evaluating hemostatic blood products and agents in patients with bleeding: Proceedings of a National Heart Lung and Blood Institute and US Department of Defense Consensus Conference.

ABSTRACT: High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.

Randomized Controlled Trial of Over-the-Scope Clip as Initial Treatment of Severe Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe NVUGIB. This was our study aim. METHODS: Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of hemorrhage - SRH (active spurting bleeding, visible vessel, or clot) - or lesser SRH (oozing bleeding or flat spots - with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation - MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30 day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician. RESULTS: 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC vs. Standard groups in rates of rebleeding (4% vs. 28.6%; p = .017; relative risk 0.10, 95% confidence intervals 0.01, 0.91; number needed to treat 4); severe complications (0 % vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH. CONCLUSION: 1. OTSC significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not. (ClinicalTrials.gov, Number: NCT03065465).

Varices: Esophageal, Gastric, and Rectal.

Gastrointestinal varices are associated with cirrhosis and portal hypertension. Variceal hemorrhage is a substantial cause of morbidity and mortality, with esophageal and gastric varices the most common source and rectal varices a much less common cause of severe gastrointestinal bleeding. The goals of managing variceal hemorrhage are control of active bleeding and prevention of rebleeding. This article focuses on reviewing the current management strategies, including optimal medical, endoscopic, and angiographic interventions and their clinical outcomes to achieve these goals. Evidence based discussion is used with current references as much as possible.

The Cutting Edge: Doppler Probe in Guiding Endoscopic Hemostasis.

This article examines use of the Doppler endoscopic probe (DEP) for risk stratification and as a guide to definitive hemostasis of nonvariceal upper gastrointestinal (NVUGI) bleeding and colonic diverticular hemorrhage. Studies report that lesions with high-risk stigmata of recent hemorrhage (SRH) have a higher rate of a positive DEP signal compared with those without such SRH. Lesions with a persistently positive DEP signal after endoscopic hemostasis have a higher 30-day rebleeding rate. Studies document arterial blood flow underneath stigmata of recent hemorrhage as a risk factor for rebleeding of focal nonvariceal gastrointestinal lesions. With DEP probe as a guide, rates of definitive endoscopic hemostasis and clinical outcomes are improved compared with standard visually guided treatment.

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

Laparotomy and intraoperative enteroscopy for obscure gastrointestinal bleeding before and after the era of video capsule endoscopy and deep enteroscopy: A tertiary center experience.

BACKGROUND: To evaluate roles of intraoperative endoscopy (IOE) in management of severe obscure GI bleeding (OGIB) before vs. after introduction of video capsule endoscopy (VCE) and deep enteroscopy (DE). METHODS: We retrospectively reviewed prospectively collected data of patients undergoing IOE for severe OGIB in a tertiary referral center. RESULTS: 52 patients had laparotomy/IOE for OGIB, 11 pre and 41 post VCE/DE eras. In the pre VCE/DE era, 36.4% (4/11) had preoperative presumptive diagnoses while in the post VCE/DE era presumptive diagnoses were made in 48.8% (20/41) (p = 0.18). Preoperative evaluation led to correct diagnoses in 18.2% (2/11) in the pre and 51.2% (21/41) in the post VCE/DE era (p = 0.09). Vascular lesions and ulcers were the most common diagnoses, but rebleeding was common. No rebleeding was found among patients with tumors, Meckel's diverticulum, and aortoenteric fistula. CONCLUSIONS: Presumptive diagnoses in the post VCE/DE era were usually accurate. If VCE or DE are negative, the probability of negative IOE is high. Patients with tumors and Meckel's diverticulum were the best candidates for IOE.

What Does Lesion Blood Flow Tell Us About Risk Stratification and Successful Management of Non-variceal UGI Bleeding?

PURPOSE OF REVIEW: There has been a decline in mortality associated with upper gastrointestinal (UGI) hemorrhage as the use of urgent endoscopy has increased. This review will examine endoscopic risk stratification of non-variceal UGI bleeding (e.g., ulcers, Dieulafoy lesions, and Mallory-Weiss tears), including the use of the Doppler endoscopic probe (DEP). RECENT FINDINGS: Prospective studies evaluating the use of DEP in non-variceal UGI hemorrhage showed that lesions with high-risk stigmata of recent hemorrhage (SRH) have a higher rate of a positive DEP signal compared to those with intermediate-risk SRH. Additionally, lesions with a persistently positive DEP signal after endoscopic hemostasis were seen with high-risk SRH and had a higher 30-day rebleeding rate. Residual arterial blood flow underneath ulcers is a significant risk factor for rebleeding. However, if more endoscopic treatment is applied, clinical outcomes for patients with severe non-variceal UGI hemorrhage are improved, as documented by a recent CURE Hemostasis randomized controlled trial (RCT).