Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding.

BACKGROUND & AIMS: Hemostatic powders have been clinically used in the treatment of gastrointestinal bleeding. We investigated the non-inferiority of a polysaccharide hemostatic powder (PHP), compared with conventional endoscopic treatments, for peptic ulcer bleeding (PUB). METHODS: This study was a prospective multi-center, randomized, open-label, controlled trial at 4 referral institutions. We consecutively enrolled patients who had undergone emergency endoscopy for PUB. The patients were randomly assigned to either a PHP or conventional treatment group. In the PHP group, diluted epinephrine was injected, and the powder was applied as a spray. Conventional endoscopic treatment included the use of electrical coagulation or hemoclipping after injection of diluted epinephrine. RESULTS: Between July 2017 and May 2021, 216 patients were enrolled in this study (PHP group, 105; control group, 111). Initial hemostasis was achieved in 92 of 105 patients (87.6%) in the PHP group and 96 of 111 patients (86.5%) in the conventional treatment group. Re-bleeding did not differ between the 2 groups. In subgroup analysis, the initial hemostasis failure rate in the conventional treatment group was 13.6% for Forrest IIa cases; however, there was no initial hemostasis failure in the PHP group (P = .023). Large ulcer size (≥15 mm) and chronic kidney disease with dialysis were independent risk factors for re-bleeding at 30 days. No adverse events were associated with PHP use. CONCLUSIONS: PHP is not inferior to conventional treatments and could be useful in initial endoscopic treatment for PUB. Further studies are needed to confirm the re-bleeding rate of PHP. CLINICALTRIALS: gov, Number: NCT02717416).

Epinephrine injection monotherapy shows similar hemostatic efficacy to epinephrine injection combined therapy in high-risk patients (Forrest Ib) with bleeding ulcers.

BACKGROUND: Whether combination therapy has higher hemostatic efficacy than epinephrine injection monotherapy in different Forrest classifications is not clear. This study aimed to compare hemostatic efficacy between epinephrine injection monotherapy (MT) and combination therapy (CT) based on different Forrest classifications. METHODS: We retrospectively analyzed peptic ulcer bleeding (PUB) patients who underwent endoscopic epinephrine injections or epinephrine injections combined with a second therapy between March 2014 and June 2022 in our center, and the patients were divided into MT group or CT group. Subsequently, a propensity score matching analysis (PSM) was performed and rebleeding rates were calculated according to Forrest classifications via a stratified analysis. RESULTS: Overall, 605 patients who met the inclusion criteria were included, and after PSM, 173 patients in each of the CT and MT groups were included. For PUB patients with nonbleeding visible vessels (FIIa), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 8.8%, 17.5%, 19.3%, and 19.3% in the MT group, respectively, and rates were 0%, 4.1%, 5.5%, and 5.5% in the CT group, respectively, with significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.015, P = 0.011, P = 0.014, and P = 0.014, respectively). However, for PUB patients with oozing bleeding (FIb), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 14.9%, 16.2%, 17.6%, and 17.6% in the MT group, respectively, and rates were 13.2%, 14.7%, 14.7%, and 16.2% in the CT group, respectively, with no significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.78, P = 0.804, P = 0.644 and P = 0.825). CONCLUSION: Combined therapy has higher hemostatic efficacy than epinephrine injection monotherapy for PUB patients with visible blood vessel (FIIa) ulcers. However, epinephrine injection monotherapy is equally as effective as combined therapy for PUB patients with oozing blood (FIb) ulcers.

Endoscopic Versus Conservative Therapy for Bleeding Peptic Ulcer with Adherent Clot: A Comprehensive Systematic Review and Meta-Analysis.

INTRODUCTION: Peptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots. METHODS: We systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively. RESULTS: Eleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22-0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21-0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23-0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21-0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21-0.95, P = 0.04), and LOS (MD - 3.17 days, 95% CI - 4.14, - 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24-2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17-1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08-0.96, P = 0.04) with endoscopic therapy compared to conservative therapy. CONCLUSIONS: Our meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.

Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding.

BACKGROUND AND AIMS: The aim of this study was to evaluate the safety and effectiveness of Hemospray (Cook Medical, Winston-Salem, NC, USA), a hemostatic powder, as monotherapy for active peptic ulcer bleeding. METHODS: In this prospective, multicenter, single-arm study, patients with Forrest Ia or Ib peptic ulcers underwent endoscopic application of Hemospray as treatment of first intent. Effectiveness endpoints were successful hemostasis at the end of the index endoscopy, recurrent bleeding within 72 hours and from 72 hours to 30 days, adverse events requiring reintervention or resulting in morbidity or mortality, and 30-day mortality. RESULTS: Hemospray was successfully administered in 98.5% of patients (66/67). Hemostasis was achieved at the index endoscopy in 90.9% of patients (60/66) with Hemospray alone and in an additional 4 patients treated with additional modalities, yielding an overall hemostasis rate of 97.0% (64/66). Rebleeding occurred in 13.3% of patients (8/60), 5 within 72 hours and 3 between 72 hours and 30 days. Two cases of perforation and 2 patient deaths occurred during the study, but none of these cases or any other adverse events were attributed to the use of Hemospray. The rate of early rebleeding was significantly higher in patients with Forrest Ia ulcers compared with patients with Forrest Ib ulcers. Higher rates of early bleeding in patients with Forrest Ia ulcers is consistent with results from studies where Hemospray was used as rescue after failure of conventional methods. CONCLUSIONS: Hemospray is an effective initial treatment for patients with active peptic ulcer bleeding, but care should be taken to monitor for recurrent bleeding. (Clinical trial registration number: NCT01306864.).

Nomogram for predicting rebleeding after initial endoscopic epinephrine injection monotherapy hemostasis in patients with peptic ulcer bleeding: a retrospective cohort study.

BACKGROUND: Although the current guidelines recommend endoscopic combination therapy, endoscopic epinephrine injection (EI) monotherapy is still a simple, common and effective modality for treating peptic ulcer bleeding (PUB). However, the rebleeding risk after EI monotherapy is still high, and identifying rebleeding patients after EI monotherapy is unclear, which is highly important in clinical practice. This study aimed to identify risk factors and constructed a predictive nomogram related to rebleeding after EI monotherapy. METHODS: We consecutively and retrospectively analyzed 360 PUB patients who underwent EI monotherapy between March 2014 and July 2021 in our center. Then we identified independent risk factors associated with rebleeding after initial endoscopic EI monotherapy by multivariate logistic regression. A predictive nomogram was developed and validated based on the above predictors. RESULTS: Among all PUB patients enrolled, 51 (14.2%) had recurrent hemorrhage within 30 days after endoscopic EI monotherapy. After multivariate logistic regression, shock [odds ratio (OR) = 12.691, 95% confidence interval (CI) 5.129-31.399, p < 0.001], Rockall score (OR = 1.877, 95% CI 1.250-2.820, p = 0.002), tachycardia (heart rate > 100 beats/min) (OR = 2.610, 95% CI 1.098-6.203, p = 0.030), prolonged prothrombin time (PT > 13 s) (OR = 2.387, 95% CI 1.019-5.588, p = 0.045) and gastric ulcer (OR = 2.258, 95% CI 1.003-5.084, p = 0.049) were associated with an increased risk of rebleeding after an initial EI monotherapy treatment. A nomogram incorporating these independent high-risk factors showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.876 (95% CI 0.817-0.934) (p < 0.001). CONCLUSIONS: We developed a predictive nomogram of rebleeding after EI monotherapy, which had excellent prediction accuracy. This predictive nomogram can be conveniently used to identify low-risk rebleeding patients after EI monotherapy, allowing for decision-making in a clinical setting.

An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding.

BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Efficacy of hemostatic powders as monotherapy or rescue therapy in gastrointestinal bleeding related to neoplastic or non-neoplastic lesions.

BACKGROUND: Hemostatic powder (HP) in gastrointestinal bleeding (GIB) is mainly used as rescue therapy after failure of conventional hemostatic procedures (CHP). AIM: To define the best field of application and the efficacy of HP as first choice monotherapy or rescue therapy. METHODS: We compared the efficacy of HP monotherapy, HP rescue therapy, and CHP in the management of active GIB due to neoplastic and non-neoplastic lesions. RESULTS: A total of 108 patients, 43 treated with HP as either first choice or rescue therapy and 65 with CHP, were included in the study. The most frequent sources of bleeding were peptic ulcer and malignancy. Immediate hemostasis rates were: HP monotherapy = 100% in peptic ulcer and 100% in malignancy; HP rescue therapy = 93.2% in peptic ulcer and 85.7% in malignancy; CHP = 77.9% in peptic ulcer and 41.7 in malignancy. Definitive hemostasis rates were: HP monotherapy = 50% in peptic ulcer and 45.5% in malignancy; HP rescue therapy = 73.3% in peptic ulcer and 85.7% in malignancy; CHP = 69.1% in peptic ulcer and 33.3% in malignancy. No difference was found in terms of additional intervention between the three groups. CONCLUSIONS: HP is highly effective as monotherapy and rescue therapy in GIB. GIB related to malignancy may be the best field of application of HP, but confirmatory studies are necessary.

Giant Gastric Ulcers: An Unusual Culprit.

Mycophenolate Mofetil (MMF) is routinely used immunosuppressant in solid organ transplantation is commonly associated with several gastrointestinal (GI) side effects. Here we present a case of giant gastric ulcer of 5 cm from MMF use post cardiac transplant. CASE DESCRIPTION: A 56-year-old male with history of severe ischemic cardiomyopathy post heart transplant was on immunosuppression with MMF, tacrolimus and prednisone for 5 months. He presented with severe epigastric pain and intermittent episodes of melena for 1 month. His pain radiated to back that is worsened with eating. Associated with loss of appetite, vomiting and 16-pound weight loss in 3 months. He never smoked, drank alcohol or used over the counter pain medications. He was profoundly anemic requiring blood transfusions. EGD performed demonstrated very large clean-based ulcer of 5 cm diameter in the body, smaller ulcer of 8 mm diameter in pre-pyloric region and 5-10 small aphthous ulcers in the gastric body and fundus. Gastric biopsies taken from the ulcer were negative for Helicobacter pylori, cytomegalovirus and malignancy. Flexible sigmoidoscopy revealed non-bleeding inflamed internal hemorrhoids. Consequently, MMF was discontinued and switched to azathioprine. He was treated with twice daily proton pump inhibitor therapy with resolution of abdominal pain, improved appetite and weight gain. DISCUSSION: MMF is well known for common GI side-effects such as nausea, diarrhea, vomiting, ulcers, abdominal pain and rarely gastrointestinal bleeding. Few studies reported 3 to 8% incidence of ulcer perforation and GI bleeding within 6 months. Risk of gastroduodenal erosions is nearly 1.83 times for MMF, with the highest lesions associated with MMF-tacrolimus-corticosteroid combination treatment as seen in our patient. Hypothesis is that GI tract is vulnerable because of dependence of enterocytes on de novo synthesis of purines, which is disrupted by MMF. Typically, upper GI mucosal injuries of mucosal irritation leading to esophagitis, gastritis and/or ulcers are seen. Endoscopy is both diagnostic and therapeutic if bleeding gastric ulcers are noted. Minor complications improve with reduction of drug dose or use of enteric coated preparation if feasible. Discontinuation of the drug is main stay in the management of MMF related ulcer disease. Simple medical treatment with either H2-receptor antagonists, proton-pump inhibitors, coating agents, prostaglandins or combination has proven effective in most cases. Considering excellent results with medical management of ulcer, role of surgery is limited.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Hemostatic spray powder TC-325 for GI bleeding in a nationwide study: survival and predictors of failure via competing risks analysis.

BACKGROUND AND AIMS: TC-325 (Hemospray, Cook Medical, Winston-Salem, NC) is an inorganic hemostatic powder recently approved by the U.S. Food and Drug Administration. This study aimed to examine the effectiveness, safety, and predictors of TC-325 failure in a large real-life cohort. METHODS: This was a retrospective study conducted at 21 Spanish centers. All patients treated with TC-325 until September 2018 were included. The primary outcome was treatment failure, defined as failed intraprocedural hemostasis or recurrent bleeding within the first 30 postprocedural days. Secondary outcomes included safety and survival. Risk and predictors of failure were assessed via competing-risk models. RESULTS: The cohort comprised 261 patients, of whom 219 (83.9%) presented with upper gastrointestinal bleeding (GIB). The most common causes were peptic ulcer (28%), malignancy (18.4%), and therapeutic endoscopy-related GIB (17.6%). TC-325 was used as rescue therapy in 191 (73.2%) patients. The rate of intraprocedural hemostasis was 93.5% (95% confidence interval [CI], 90%-96%). Risks of TC-325 failure at postprocedural days 3, 7, and 30 were 21.1%, 24.6%, and 27.4%, respectively. On multivariate analysis, spurting bleeding (P = .004), use of vasoactive drugs (P = .02), and hypotension (P = .008) were independent predictors of failure. Overall 30-day survival was 81.9% (95% CI, 76%-86%) and intraprocedural hemostasis was associated with a better prognosis (adjusted hazard ratio, 0.29; P = .006). Two severe adverse events were noted. CONCLUSION: TC-325 was safe and effective for intraprocedural hemostasis in more than 90% of patients, regardless of the cause or site of bleeding and its use as rescue therapy. In this high-risk cohort treated with TC-325, the 30-day failure rate exceeded 25% and was highest with spurting bleeding or hemodynamic instability.

Using Hemospray Improves the Cost-effectiveness Ratio in the Management of Upper Gastrointestinal Nonvariceal Bleeding.

GOALS: We compared the cost-effectiveness of traditional recommended endoscopic hemostatic therapies and Hemospray alone or in combination when treating nonvariceal upper gastrointestinal bleeding (NVUGIB). BACKGROUND: Hemospray (TC-325) is a novel endoscopic hemostatic powder, achieving hemostasis through adherence to actively bleeding biological surfaces. STUDY: A decision tree of patients with NVUGIB assessed 4 possible treatment strategies: traditional therapy alone (T), Hemospray alone (H), traditional therapy completed by Hemospray if needed (T+H), or Hemospray completed by traditional therapy if needed (H+T). Using published probabilities, effectiveness was the likelihood of avoiding rebleeding over 30 days. Costs in 2014 US$ were based on the US National Inpatient Sample. A third-party payer perspective was adopted. Sensitivity and subgroup analyses were performed. RESULTS: For all patients, T+H was more efficacious (97% avoiding rebleeding) and less expensive (average cost per patient of US$9150) than all other approaches. The second most cost-effective approach was H+T (5.57% less effective and US$635 more per patient). Sensitivity analyses showed T+H followed by a strategy of H+T remained more cost-effective than H or T alone when varying all probability assumptions across plausible ranges. Subgroup analysis showed that the inclusion of H (especially alone) was least adapted for ulcers and was more cost-effective when treating lesions at low risk of delayed rebleeding. CONCLUSIONS: Hemospray improves the effectiveness of traditional hemostasis, being less costly in most NVUGIB patient populations. A Hemospray first approach is most cost-effective for nonulcer bleeding lesions at low risk of delayed hemorrhage.

CEGP-003 Spray Has a Similar Hemostatic Effect to Epinephrine Injection in Cases of Acute Upper Gastrointestinal Bleeding.

BACKGROUND: Endoscopically applicable hemostatic agents have been demonstrated to have high initial hemostasis rates in cases of upper gastrointestinal bleeding (UGIB). AIMS: The authors developed a new hemostatic powder (CEGP-003) and evaluated its hemostatic and ulcer healing effects in UGIB. METHODS: Patients with peptic ulcer or post-endoscopic resection bleeding were randomly assigned to be treated by epinephrine injection or CEGP-003 spray. All patients were placed under observation for 3 days and underwent second-look endoscopy. The primary outcome was initial hemostasis rate, and the secondary outcomes were rebleeding rate and ulcer healing effect. RESULTS: Seventy-two patients with UGIB were enrolled in this study. Causes of bleeding were peptic ulcer (15, 20.5%), post-endoscopic mucosal resection (11, 15.1%), and post-endoscopic submucosal dissection bleeding (47, 64.4%). Initial hemostasis was achieved in 89.2% (34/37) of patients in the epinephrine group and in 100% (35/35) in the CEGP-003 group (p = 0.115). Rebleeding occurred in 2.7% (1/37) and 8.6% (3/35) in the epinephrine and CEGP-003 groups, respectively (p = 0.35). Three days after endoscopic hemostasis, the ulcer healing effects of epinephrine and CEGP-003 were similar (p = 0.79). CONCLUSION: This study shows that CEGP-003 spray has a hemostatic effect similar to epinephrine in terms of initial hemostasis and rebleeding rates. The authors consider CEGP-003 a potential therapeutic tool for UGIB as a definitive or bridge therapy and that it is particularly useful for oozing lesions after endoscopic resection.

Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

BACKGROUND/PURPOSE: Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. METHODS: The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding. RESULTS: The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05). CONCLUSION: Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083).

Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high-dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta-analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management. METHODS: A literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30-day mortality. RESULTS: There were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) -0.03, 95% CI -0.26, 0.19; P = 0.76], duration of hospital stay (MD -0.61, 95% CI -1.45, 0.23; P = 0.16) or 30-day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration. CONCLUSIONS: Oral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs.

Value of Oral Proton Pump Inhibitors in Acute, Nonvariceal Upper Gastrointestinal Bleeding: A Network Meta-Analysis.

BACKGROUND: Intravenous (IV) proton pump inhibitors (PPI) are the standard medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB). Optimal route of PPI delivery has been questioned. AIM: The aim was to perform a systematic review and network meta-analysis for the endpoints of risk of rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of blood transfused (UBT) among trials evaluating acid suppressive medications in ANVGIB. METHODS: A total of 39 studies using IV PPI drip, IV scheduled PPI, oral PPI, H2-receptor antagonists, and placebo were identified. Network meta-analysis was used for indirect comparisons and Bayesian Markov Chain Monte Carlo methods for calculation of probability superiority. RESULTS: No difference was observed between IV PPI drip and scheduled IV PPI for mortality (relative risk=1.11; 95% credibility interval, 0.56-2.21), LOS (0.04, -0.49 to 0.44), ROS (1.27, 0.64-2.35) and risk of rebleeding within 72 hours, 1 week, and 1 month [(0.98, 0.48-1.95), (0.59, 0.13-2.03), (0.82, 0.28-2.16)]. Oral PPIs were as effective as IV scheduled PPIs and IV PPI drip for LOS (0.22, -0.61 to 0.79 and 0.16, -0.56 to 0.80) and UBT (-0.25, -1.23 to 0.65 and -0.06, -0.71 to 0.65) and superior to IV PPI drip for ROS (0.30, 0.10 to 0.78). CONCLUSION: Scheduled IV PPIs were as effective as IV PPI drip for most outcomes. Oral PPIs were comparable to scheduled IV for LOS and UBT and superior to IV PPI drip for ROS. Conclusions should be tempered by low frequency endpoints such as ROS, but question the need for IV PPI drip in ANVGIB.

Comparison of hemostatic forceps with soft coagulation versus argon plasma coagulation for bleeding peptic ulcer--a randomized trial.

BACKGROUND AND STUDY AIMS: Endoscopic high-frequency soft coagulation is used to manage visible bleeding or nonbleeding vessels during endoscopic submucosal dissection. The aim of the present study was to compare the efficacy of hemostasis by soft coagulation (using hemostatic forceps) with argon plasma coagulation (APC), in a prospective randomized trial. PATIENTS AND METHODS: From January 2013 to June 2014, 276 patients were randomly assigned into two groups: epinephrine injection plus APC (the APC group); or epinephrine injection plus soft coagulation using hemostatic forceps (the HFSC group). As the primary outcome we compared recurrent bleeding rates within 30 days after initial hemostasis in a noninferiority design. RESULTS: After exclusion, 75 patients in the APC group and 76 in the HFSC group were finally evaluated. In the APC group 72 patients (96 %) were successfully treated with the assigned treatment alone vs. 73 (96 %) in the HFSC group. Initial endoscopic hemostasis using a single or combined modality was achieved in all patients. Recurrent bleeding within 30 days was experienced by five patients (6.7 %) and seven patients (9.2 %) in the AFC and HFSC groups, respectively (P = 0.563), and within 7 days by three patients (4.0 %) and five patients (6.6 %), respectively (P = 0.719). We found no significant difference in the rates of adverse events (1.3 % vs. 2.6 %) or mortality (2.7 % vs. 2.6 %) between the groups. CONCLUSIONS: The efficacy and safety of soft coagulation using endoscopic hemostatic forceps is not inferior to APC when used to treat patients with bleeding peptic ulcers. Clinicaltrials.gov NCT02020603.

Increasing biopsy number and sampling from gastric body improve the sensitivity of rapid urease test in patients with peptic ulcer bleeding.

BACKGROUND: Previous studies demonstrated that the sensitivity of rapid urease test (RUT) for diagnosis of Helicobacter pylori infection decreased during peptic ulcer bleeding. AIM: We designed this study and tried to find a better method to improve the detection rate of H. pylori infection at the same session of endoscopic diagnosis of peptic ulcer bleeding. METHODS: We prospectively enrolled 116 patients with peptic ulcer bleeding. These patients received intravenous proton pump inhibitor and then received upper gastrointestinal endoscopy within 24 h after arrival. We took one piece of biopsy from gastric antrum (Group 1), four pieces from gastric antrum (Group 2), and one piece from the gastric body (Group 3) for three separate RUTs, respectively. (13)C-urease breath test was used as gold standard for diagnosis of H. pylori infection. RESULTS: There were 74 patients (64 %) with positive (13)C-urease breath test. Among these 74 patients, 45 patients had positive RUT (sensitivity: 61 %) in Group 1; 55 patients had positive RUT (sensitivity: 74 %) in Group 2; 54 patients had positive RUT (sensitivity: 73 %) in Group 3. There were significant differences between Group 1 and Group 2 (p = 0.02) and between Group 1 and Group 3 (p = 0.022). CONCLUSIONS: The sensitivity of RUT was 61 % during peptic ulcer bleeding. The sensitivity of RUT can be increased significantly by increased biopsy number from gastric antrum or biopsy from gastric body.