Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.

BACKGROUND & AIMS: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

Prevalence and outcomes of upper gastrointestinal bleeding in COVID-19: A systematic review and meta-analysis.

Upper gastrointestinal bleeding (UGIB) in COVID-19 presents challenges in patient management. Existing studies lack comprehensive review due to varied designs, samples, and demographics. A meta-analysis can provide valuable insights into the incidence, features, and outcomes of UGIB in COVID-19. A comprehensive literature search was carried out using several databases. We considered all appropriate observational studies from all over the world. Mantel-Haenszel odds ratios and associated 95% confidence intervals (CIs) were produced to report the overall effect size using random effect models. Besides, Random effects models were used to calculate the overall pooled prevalence. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 21 articles consisting of 26,933 COVID-19 patients were considered. The pooled estimate of UGIB prevalence in patients admitted with COVID-19 across studies was 2.10% (95% CI, 1.23-3.13). Similarly, the overall pooled estimate for severity, mortality, and rebleeding in COVID-19 patients with UGIB was 55% (95% CI, 37.01-72.68), 29% (95% CI, 19.26-40.20) and 12.7% (95% CI, 7.88-18.42) respectively. Further, UGIB in COVID-19 patients was associated with increased odds of severity (OR = 3.52, 95% CI 1.80-6.88, P = 0.001) and mortality (OR = 2.16, 95% CI 1.33-3.51, P = 0.002) compared with patients without UGIB. No significant publication bias was evident in the meta-analysis. The results of our study indicate that UGIB in individuals with COVID-19 is linked to negative outcomes such as severe illness, higher mortality rates, and an increased risk of re-bleeding. These findings highlight the significance of identifying UGIB as a significant complication in COVID-19 cases and emphasise the importance of timely clinical assessment and proper treatment.

Nonvariceal upper gastrointestinal bleeding in COVID-19 patients: insights from the National Inpatient Sample.

BACKGROUND: This retrospective study, conducted using the U.S. National Inpatient Sample (NIS), examines the outcomes and management of nonvariceal upper gastrointestinal bleeding (NVUGIB) in COVID-19 patients and identifies predictive factors to enhance patient prognosis. METHODS: We analyzed the 2020 U.S. NIS data involving adult patients (≥18 years) admitted with NVUGIB and categorized them based on the presence of COVID-19. Primary and secondary outcomes, NVUGIB-related procedures, and predictive factors were evaluated. RESULTS: Of 184,885 adult patients admitted with NVUGIB, 1.6% (2990) had COVID-19. Patients with NVUGIB and COVID-19 showed higher inpatient mortality, acute kidney injury, need for intensive care, and resource utilization metrics. Notably, there was a lower rate of early esophagogastroduodenoscopy (EGD). Multivariate logistic regression revealed conditions like peptic ulcer disease, mechanical ventilation, and alcohol abuse as significant positive predictors for NVUGIB in COVID-19 patients, whereas female gender and smoking were negative predictors. CONCLUSION: Our findings suggest that COVID-19 significantly increases the risk of mortality and complications in NVUGIB patients. The observed decrease in early EGD interventions, potentially contributing to higher mortality rates, calls for a review of treatment strategies. Further multicenter, prospective studies are needed to validate these results and improve patient care strategies.

Proton pump inhibitor therapy after transcatheter angiography in refractory nonvariceal acute upper gastrointestinal bleeding patients: a cohort study.

BACKGROUND: Transcatheter angiography (TA) could help to diagnose and treat refractory nonvariceal upper gastrointestinal bleeding (NVUGIB). Proton pump inhibitors (PPIs) are the key medication for reducing the rebleeding rate and mortality and are usually continued after TA. It is unknown whether high-dose PPIs after TA are more effective than the standard regimen. METHODS: We retrospectively collected data from patients who received TA because of refractory NVUGIB from 2010 to 2020 at West China Hospital. 244 patients were included and divided into two groups based on the first 3 days of PPIs treatment. All baseline characteristics were balanced using the inverse probability of treatment weighting method. The 30-day all-cause mortality, rebleeding rate and other outcomes were compared. The propensity score matching method was also used to verify the results. RESULTS: There were 86 patients in the high-dose group and 158 in the standard group. The average daily doses of PPI were 192.1 ± 17.9 mg and 77.8 ± 32.0 mg, respectively. Cox regression analysis showed no difference in the 30-day all-cause mortality (aHR 1.464, 95% CI 0.829 to 2.584) or rebleeding rate (aHR 1.020, 95% CI 0.693 to 1.501). There were no differences found in red blood cell transfusion, hospital stay length and further interventions, including endoscopy, repeating TA, surgery and ICU admission. The results were consistent in the subgroup analysis of patients with transcatheter arterial embolization. CONCLUSION: In refractory NVUGIB patients who received TA, regardless of whether embolization was performed, high-dose PPI treatment did not provide additional benefits compared with the standard regimen.

Diagnosis Value of the Blood Urea Nitrogen-to-Creatinine Ratio in Determining the Need for Intervention of Acute Upper Gastrointestinal Bleeding.

INTRODUCTION: The blood urea nitrogen (BUN)-to-creatinine (Cr) ratio (BUN/Cr ratio) may be used to evaluate the need for intervention of acute upper gastrointestinal bleeding (AUGIB). This study aimed to explore the predictive value of the BUN/Cr ratio in the need for intervention of AUGIB. METHODS: This retrospective observational study included patients with AUGIB in the hospital's emergency department between August 2019 and May 2023. The patients were grouped according to whether they underwent an intervention for AUGIB. Patients treated between August 2019 and May 2022 were selected as the training set and the others as the validation set. RESULTS: A total of 466 patients (328 males, 138 females) with AUGIB were enrolled in the intervention group (n = 167) and the no-intervention group (n = 299). In the training set, multivariable logistic regression showed that the BUN/Cr ratio (odds ratio [OR]: 1.013, 95% confidence interval [CI]: 1.003-1.023, p = 0.009), hemoglobin (OR: 0.989, 95% CI: 0.981-0.997, p = 0.010), and a previous history of esophageal variceal bleeding (OR: 6.898, 95% CI: 3.989-11.929, p < 0.001) were independently associated with intervention for AUGIB. The area under receiver operating characteristic curve of BUN/Cr ratio and the prediction model based on logistic regression to predict the need for intervention of AUGIB were 0.604 (95% CI: 0.544-0.664) and 0.759 (95% CI: 0.706-0.812) in the training set and 0.634 (95% CI: 0.529, 0.740) and 0.708 (95% CI: 0.609, 0.806) in the validation set, respectively. CONCLUSION: The BUN/Cr ratio was associated with the need for AUGIB intervention. Combining it with other parameters might improve its diagnostic value to predict the need for intervention of AUGIB.

Mucormycosis mimicking portal hypertensive haemorrhage as a complication of alcoholic liver cirrhosis: a case report.

Mucor is a rare cause of gastrointestinal ulcers. This case describes a case of mucormycosis that occurred in a patient with liver cirrhosis who was hospitalized to accept a splenectomy for traumatic splenic rupture. During the perioperative period, the patient developed upper gastrointestinal bleeding(UGIB), which was diagnosed as mucormycosis-related gastric ulcer according to gastroscopy. Patients with liver cirrhosis often get UGIB for Portal hypertension, but they also can develop UGIB for multiple other reasons, including infectious ulcers for immunosuppression. The case emphasizes the importance of excluding fungal-induced ulcer haemorrhage before diagnosing Portal hypertensive-induced variceal haemorrhage in patients with liver cirrhosis.

Systematic review and meta-analysis of endoscopic versus medical management of peptic ulcers with adherent clots.

Peptic ulcer disease is an important cause of upper gastrointestinal bleeding. Current guidelines recommend endoscopic treatment for ulcers with active bleeding or non-bleeding visible vessels, but the optimal management of ulcers with adherent clots is unclear. We performed a systematic review of the efficacy of endoscopic versus medical management of peptic ulcers with adherent clots. A systematic literature search was performed through September 2022 (MEDLINE, Embase, and CENTRAL). Randomized controlled trials (RCTs) comparing the effect of endoscopic versus medical management alone for peptic ulcers with adherent clots on the outcome of recurrent bleeding were incuded. A random-effects meta-analysis was performed to estimate the overall treatment effect. We included seven RCTs reporting on the endoscopic versus medical management of peptic ulcers with adherent clots. The pooled cohort comprised 268 patients with a mean age of 62.8 years and a mean follow up of 20 days. There was a significant reduction in the risk of recurrent bleeding with endoscopic hemostatic treatment for peptic ulcers with adherent clots, compared with medical management alone (risk ratio [RR] = 0.40, 95% confidence interval [CI] 0.16-0.95, 268 participants). However, there was no difference in mortality (RR = 0.90, 95% CI 0.23-3.59, 52 participants) or need for ulcer surgery (RR = 0.48, 95% CI 0.10-2.28, 52 participants) between endoscopic and medical management groups. In summary, there was evidence for a reduction in recurrent bleeding from peptic ulcers with adherent clots treated with endoscopic hemostatic techniques compared with medical management alone but no difference in rates of mortality or need for surgery.

Inferior vena cava collapsibility index and stroke volume as predictors of blood transfusion in upper gastrointestinal bleeding in the emergency department.

BACKGROUND AND AIM: This study investigates the effectiveness of bedside ultrasonography in predicting blood transfusion requirements in patients with upper gastrointestinal bleeding (UGIB). It focuses on evaluating the inferior vena cava (IVC) diameter, IVC collapsibility index (CI), and stroke volume (SV) as ultrasonographic measures. METHODS: A hundred adult patients enrolled in this prospective clinical study. The patients were divided into two groups (group 1: only saline administered group, group 2: saline and blood administered group). IVC diameter, IVC CI, and SV were measured at the time of admission and after treatment. RESULTS: At the initial admission, group 1 exhibited an IVC CI of 20.4% and an SV of 65.0 mL, whereas group 2 displayed an IVC CI of 26.6% and an SV of 58.0 mL. Upon analyzing the relationship between the Glasgow-Blatchford score (GBS) and SV, we identified a significant negative correlation (r = -0.7350; P < 0.001). Similarly, a weak negative correlation was observed between the Rockall score (RS) and SV (r = -0.4718; P < 0.001). It is worth noting that patients with UGIB require blood transfusion if their SV falls below 62.5 mL, with an area under the curve (AUC) of 89.1% and a 95% confidence interval (CI) ranging from 82.8% to 95.4%. CONCLUSION: IVC CI and SV can be used as parameters to predict the need for blood transfusion in the ED in patients with UGIB.

Sepsis as a Potential Risk Factor for Upper Gastrointestinal Bleeding in Critically Ill Patients: A Systematic Review and Meta-analysis.

Purpose: Sepsis is a common and critical condition in intensive care units (ICUs) known to complicate patient outcomes. Previous studies have indicated an association between sepsis and various ICU morbidities, including upper gastrointestinal bleeding (UGIB). However, the extent of this relationship and its implications in ICU settings remain inadequately quantified. This study aims to elucidate the association between sepsis and the risk of UGIB in ICU patients. Methods: A comprehensive meta-analysis was conducted, encompassing nine studies with a total of nearly 9000 participants. These studies reported events for both sepsis and nonsepsis patients separately. Pooled odds ratios (ORs) were calculated to assess the risk of UGIB in septic versus nonseptic ICU patients. Subgroup analyses were conducted based on age and study design, and both unadjusted and adjusted ORs were examined. Results: The pooled OR indicated a significant association between sepsis and UGIB (OR = 3.276, 95% CI: 1.931 to 5.557). Moderate heterogeneity was observed (I² = 43.9%). The association was significant in adults (pooled OR = 4.083) but not in children. No difference in association was found based on the study design. Unadjusted and adjusted ORs differed slightly, indicating the influence of confounding factors. Conclusion: This meta-analysis reveals a significant association between sepsis and an increased risk of UGIB in ICU patients, particularly in adults. These findings highlight the need for vigilant monitoring and proactive management of septic ICU patients to mitigate the risk of UGIB. Future research should focus on understanding the underlying mechanisms and developing tailored preventive strategies.

Acute Nonvariceal Upper Gastrointestinal Bleeding in Patients Using Anticoagulants: Does the Timing of Endoscopy Affect Outcomes?

BACKGROUND: In patients with acute nonvariceal upper gastrointestinal bleeding (NVUGIB), early (≤ 24 h) endoscopy is recommended following hemodynamic resuscitation. Nevertheless, scarce data exist on the optimal timing of endoscopy in patients with NVUGIB receiving anticoagulants. OBJECTIVE: To analyze how the timing of endoscopy may influence outcomes in anticoagulants users admitted with NVUGIB. METHODS: Retrospective cohort study which consecutively included all adult patients using anticoagulants presenting with NVUGIB between January 2011 and June 2020. Time from presentation to endoscopy was assessed and defined as early (≤ 24 h) and delayed (> 24 h). The outcomes considered were endoscopic or surgical treatment, length of hospital stay, intermediate/intensive care unit admission, recurrent bleeding, and 30-day mortality. RESULTS: From 636 patients presenting with NVUGIB, 138 (21.7%) were taking anticoagulants. Vitamin K antagonists were the most frequent anticoagulants used (63.8%, n = 88). After adjusting for confounders, patients who underwent early endoscopy (59.4%, n = 82) received endoscopic therapy more frequently (OR 2.4; 95% CI 1.1-5.4; P = 0.034), had shorter length of hospital stay [7 (IQR 6) vs 9 (IQR 7) days, P = 0.042] and higher rate of intermediate/intensive care unit admission (OR 2.7; 95% CI 1.3 - 5.9; P = 0.010) than patients having delayed endoscopy. Surgical treatment, recurrent bleeding, and 30-day mortality did not differ significantly between groups. CONCLUSION: Early endoscopy (≤ 24 h) in anticoagulant users admitted with acute nonvariceal upper gastrointestinal bleeding is associated with higher rate of endoscopic treatment, shorter hospital stay, and higher intermediate/intensive care unit admission. The timing of endoscopy did not influence the need for surgical intervention, recurrent bleeding, and 30-day mortality.

The efficacy of sclerotherapy as the initial treatment in patients with bleeding from Dieulafoy's lesion of the upper gastrointestinal tract.

BACKGROUND: Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL). METHODS: Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist. RESULTS: In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30 days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0 days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5 days, p = 0.005) compared to sclerotherapy alone. CONCLUSION: Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL.

Emergency medicine updates: Upper gastrointestinal bleeding.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a condition commonly seen in the emergency department (ED). Therefore, it is important for emergency clinicians to be aware of the current evidence regarding the diagnosis and management of this disease. OBJECTIVE: This paper evaluates key evidence-based updates concerning UGIB for the emergency clinician. DISCUSSION: UGIB most frequently presents with hematemesis. There are numerous causes, with the most common peptic ulcer disease, though variceal bleeding in particular can be severe. Nasogastric tube lavage for diagnosis is not recommended based on the current evidence. A hemoglobin transfusion threshold of 7 g/dL is recommended (8 g/dL in those with myocardial ischemia), but patients with severe bleeding and hemodynamic instability require emergent transfusion regardless of their level. Medications that may be used in UGIB include proton pump inhibitors, prokinetic agents, and vasoactive medications. Antibiotics are recommended for those with cirrhosis and suspected variceal bleeding. Endoscopy is the diagnostic and therapeutic modality of choice and should be performed within 24 h of presentation in non-variceal bleeding after resuscitation, though patients with variceal bleeding may require endoscopy within 12 h. Transcatheter arterial embolization or surgical intervention may be necessary. Intubation should be avoided if possible. If intubation is necessary, several considerations are required, including resuscitation prior to induction, utilizing preoxygenation and appropriate suction, and administering a prokinetic agent. There are a variety of tools available for risk stratification, including the Glasgow Blatchford Score. CONCLUSIONS: An understanding of literature updates can improve the ED care of patients with UGIB.

Three Simple Parameters on Admission to the Emergency Department are Predictors for Endoscopic Intervention in Patients with Suspected Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND: A considerable number of patients with nonvariceal upper gastrointestinal bleeding (UGIB) need endoscopic intervention. OBJECTIVE: The aim of this study was to determine factors that predict the need for endoscopic intervention at the time of admission to the emergency department. METHODS: Consecutive patients with International Classification of Diseases, Tenth Revision diagnosis code K92.2 (gastrointestinal hemorrhage) who underwent upper endoscopy between February 2019 and February 2022, including patients diagnosed with nonvariceal UGIB in the emergency department in the study were reviewed retrospectively. The patients were divided into two groups: those treated endoscopically and those not treated endoscopically. These two groups were compared according to clinical and laboratory findings at admission and independent predictors for endoscopic intervention were determined using multivariate regression analysis. RESULTS: Although 123 patients (30.3%) were treated endoscopically, endoscopic treatment was not required in 283 (69.7%) patients. Syncope, mean arterial pressure (MAP), and blood urea nitrogen (BUN) at admission were independent predictors for endoscopic intervention in the multivariate analysis, after adjusting for endoscopy time. The area under the curve of the syncope+MAP+BUN combination for endoscopic intervention was 0.648 (95% CI 0.588-0.708). Although the syncope+MAP+BUN combination predicted the need for intervention significantly better than pre-endoscopy Rockall and AIMS65 scores (p = 0.010 and p < 0.001, respectively), there was no significant difference in its comparison with the Glasgow-Blatchford score (p = 0.103). CONCLUSIONS: Syncope, MAP, and BUN at admission were independent predictors for endoscopic therapy in patients with nonvariceal UGIB. Rather than using complicated scores, it would be more practical and easier to predict the need for endoscopic intervention with these three simple parameters, which are included in the Glasgow-Blatchford score.

Efficacy and safety of proton pump inhibitors on cardiovascular events and inflammatory factors in patients with upper gastrointestinal bleeding undergoing dual antiplatelet therapy.

BACKGROUND: This work evaluated the effects of proton pump inhibitors (PPIs) on cardiovascular events (CVEs) and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Clinical data from these patients were analysis, intending to provide relevant theoretical evidence for clinical practice. MATERIALS AND METHODS: Data of 166 patients who underwent percutaneous coronary intervention and developed UGIB while on DAPT at The First People' Hospital of Linping District from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, PPI and non-PPI group, respectively. Furthermore, occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed. RESULTS: In patients with UGIB, melena is a common presentation. The incidence of CVE in the PPI group showed no statistically significant difference compared to the control group, and there was no significant variance observed in the distribution of CVE incidence among different PPIs. However, levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were significantly lower in the PPI group compared to the non-PPI group (P < 0.05). CONCLUSION: Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients.

National trends in hospitalizations for gastrointestinal bleeding in Japan.

Gastrointestinal bleeding (GIB) is a significant public health concern, predominantly associated with high morbidity. However, there have been no reports investigating the trends of GIB in Japan using nationwide data. This study aims to identify current trends and issues in the management of GIB by assessing Japan's national data. We analyzed National Database sampling data from 2012 to 2019, evaluating annual hospitalization rates for major six types of GIB including hemorrhagic gastric ulcers, duodenal ulcers, esophageal variceal bleeding, colonic diverticular bleeding, ischemic colitis, and rectal ulcers. In this study, hospitalization rates per 100,000 indicated a marked decline in hemorrhagic gastric ulcers, approximately two-thirds from 41.5 to 27.9, whereas rates for colonic diverticular bleeding more than doubled, escalating from 15.1 to 34.0. Ischemic colitis rates increased 1.6 times, from 20.8 to 34.9. In 2017, the hospitalization rate per 100,000 for colonic diverticular bleeding and ischemic colitis surpassed those for hemorrhagic gastric ulcers (31.1, 31.3, and 31.0, respectively). No significant changes were observed for duodenal ulcers, esophageal variceal bleeding, or rectal ulcers. The findings of this study underscore a pivotal shift in hospitalization frequencies from upper GIB to lower GIB in 2017, indicating a potential shift in clinical focus and resource allocation.

Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports.

Background and Objectives: Variceal bleeding (VB) is the most concerning condition that is difficult to treat after atezolizumab/bevacizumab in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: We would like to introduce the cases of two patients who underwent bevacizumab reduction or discontinuation when VB occurred after atezolizumab/bevacizumab. Results: VB occurred in two patients who showed good tumor response after atezolizumab/bevacizumab treatment, and all VBs were successfully treated with endoscopic variceal ligations. In the first patient, VB did not occur as the tumor response decreased after a 50% reduction in bevacizumab. In the second patient, VB occurred again after a 50% bevacizumab reduction, so bevacizumab was discontinued and treatment with atezolizumab alone has been successfully maintained. Conclusions: Accordingly, we would like to suggest that considering bevacizumab dose reduction instead of changing to tyrosine kinase inhibitor may be a good clinical choice in atezolizumab/bevacizumab patients who develop VB.

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).

Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease.

The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Efficacy of endoscopic therapy and long-term outcomes of upper gastrointestinal tumor bleeding in patients with esophageal cancer.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) from malignancies is associated with a poor outcome. Only a small number of studies on gastrointestinal tumor bleeding have been published so far, focusing mainly on bleeding from gastric cancer. Since the information on patients with UGIB from esophageal cancer appears insufficient, this study aimed to present clinical and endoscopic findings, treatment options as well as clinical outcomes such as rebleeding and survival of those patients. METHODS: This retrospective analysis included all patients admitted with UGIB from esophageal cancer at our university hospital during a 10-year period. RESULTS: 45 patients were analyzed of whom 26 (57.8%) already had cancer stage IV at index bleeding. 22 (48.9%) patients presented with hemodynamic instability and 30 (66.7%) patients received blood transfusions. Active bleeding was present in 24 (53.3%) patients, of whom 20 (83.3%) received endoscopic therapy. Successful hemostasis was achieved in 18 (90%) of 20 patients with Argon plasma coagulation used most frequently (52.4%). Early and delayed rebleeding occurred in 5 (12.5%) and 11 (27.5%) of all inoperable patients, respectively. Intake of anticoagulation or anti-platelet drugs were risk factors for delayed rebleeding and the median overall survival after index bleeding was 1.2 months. CONCLUSION: UGIB from esophageal cancer occurred most frequently in advanced tumor stages and was associated with significant blood loss. Even though initial endoscopic therapy was effective, rebleeding occurred in a significant number of patients. Those taking anticoagulants or anti-platelet drugs should be closely monitored for rebleeding. The overall survival after index bleeding was poor.