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).

Endoscopic Diagnosis, Grading, and Treatment of Bleeding Peptic Ulcer Disease.

Peptic ulcer bleeding is a major cause for hospital admissions and has a significant mortality. Endoscopic interventions reduce the risk of rebleeding in high-risk patients and several options are available including injection therapies, thermal therapies, mechanical clips, hemostatic sprays, and endoscopic suturing. Proton-pump inhibitors and Helicobacter pylori treatment are important adjuncts to endoscopic therapy. Endoscopic therapy is indicated in Forrest 1a, 1b, and 2a lesions. Patients with Forrest 2b lesions may do well with proton-pump inhibitor therapy alone but can also be managed by removal of the clot and targeting endoscopic therapy to the underlying lesion.

Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

Comparison and validation of the Japanese score and other scoring systems in patients with peptic ulcer bleeding: A retrospective study.

Acute upper gastrointestinal bleeding (UGIB) is one of the most urgent medical conditions, with peptic ulcer bleeding (PUB) accounting for most gastrointestinal bleeding cases. The Japanese scoring system was developed to predict the probability of intervention in patients with UGIB, and it is more effective than other scoring systems, according to several studies. This study aimed to verify whether the Japanese scoring system is better than other scoring systems in predicting the probability of intervention when limited to PUB in patients with UGIB. We enrolled patients who presented with symptoms of UGIB and were diagnosed with peptic ulcers using endoscopy. The performances of the scoring systems in predicting patient outcomes were validated and compared using the receiver-operating characteristic curve analysis. Additionally, we used the chi-square test, Fisher exact test, and the t test to analyze the association between the patients characteristics and clinical outcomes. Of the 1228 patients diagnosed with peptic ulcers, 90.6% underwent endoscopy. rebleeding occurred in 12.5% of the patients, and 2.5% of the patients died within 30 days. The Japanese score was the most effective in predicting the need for endoscopic intervention for PUB. Sex, systolic blood pressure, hematemesis, syncope, blood urea nitrogen level, and the American Society of Anesthesiologists score were predictive factors for the probability of endoscopic intervention in patients with PUB. The Japanese score is an effective predictor of the probability of endoscopic intervention in patients with PUB.

Urea Breath Testing to Detect Helicobacter pylori in Patients with Peptic Ulcer Bleeding During Proton Pump Inhibitor Treatment.

This was a descriptive study carried out from January to December 2021, at Quanzhou First Hospital, an affiliated hospital of Fujian Medical University, to investigate the efficacy of the urea breath test in detecting Helicobacter pylori infection in patients with peptic ulcer bleeding affected with proton pump inhibitors. A total of 77 patients with peptic ulcer bleeding, who underwent urea breath testing after active bleeding, were divided into two groups. The Helicobacter pylori infection positivity rate in patients with peptic ulcer bleeding was 66.2%. The time from bleeding to detection and from admission to detection was not significantly different between the Helicobacter pylori-positive and -negative groups (p=0.840 and 0.285, respectively). Even with high-dose proton pump inhibitor treatment, a urea breath test can be performed after peptic ulcer bleeding ceases and results in an acceptable positivity rate. There was no significant difference in the accuracy of Helicobacter pylori detection between the time from bleeding to testing and from admission to testing. Key Words: Peptic ulcer, Helicobacter pylori, Upper gastrointestinal bleeding, Urea breath test, Proton pump inhibitor.

A prospective, open-labeled, and randomized trial for assessing safety and clinical utility of gastric biopsies during emergency gastroscopy for patients with bleeding gastric ulcers.

OBJECTIVE: There is no consensus on whether a gastroscopic biopsy is necessary during the emergency treatment of gastrointestinal (GI) diseases such as gastric ulcer bleeding. In this study, we examined the clinical utility and safety of an emergency gastroscopic biopsy for the assessment of gastric ulcer bleeding. METHODS: We enrolled 150 patients with a single bleeding gastric ulcer after emergency gastroscopy (EG) from April 2020 to April 2022. The patients were randomly divided into the biopsy and no biopsy groups, and they were followed-up until June 2022 to examine whether recurrent gastric ulcer bleeding had occurred. RESULTS: Re-bleeding occurred in 15 out of 150 (10%) patients. We diagnosed malignancies in 17 (11.3%) patients and validated 14 (9.3%) of them during the initial gastroscopy procedure. Factors that could predict the occurrence of gastric ulcer re-bleeding with biopsy during EG included an absence of ischemic heart disease (odds ratio [OR] = 0.395, confidence interval [CI]: 0.24-0.65, p ≤ .005), renal disease (OR = 1.74, CI: 0.77-1.59, p ≤ .005), and using warfarin or oral anticoagulants (OR = 11.953, CI: 3.494-39.460, p ≤ .005). No significant differences were observed in 60-day bleeding (p = .077) and the duration of hospitalization (p = .700) between the two groups. CONCLUSIONS: Patients undergoing biopsy during EG did not exhibit an increased risk of re-bleeding compared with those who did not undergo a biopsy. An early biopsy facilitates an early pathologic diagnosis, early clinical intervention, safe discharge of low-risk patients, and improved outcomes in high-risk patients.

Clinical Outcomes of Patients with Benign Peptic Ulcer Bleeding After an Emergency Endoscopy Based on Patient Location.

BACKGROUND AND AIMS: In the efforts toward reducing bleeding-related mortality, it is crucial to determine the risk factors for rebleeding after endoscopic hemostasis in benign peptic ulcer (BPU). METHODS: Between 2013 and 2017, the medical records of 864 BPU patients were selected from 5076 who had undergone emergency endoscopy for suspected upper gastrointestinal bleeding. Patients who visited the emergency room or were hospitalized for other illnesses were selected. The primary end point was rebleeding within 30 days after initial endoscopy. The risk factors of rebleeding and subgroup analyses according to patient location were evaluated. RESULTS: Among 864 BPU bleeding patients, rebleeding after completion of BPU bleeding occurred in 140 (16.2%). Initial indicators of hypotension (OR 1.878, p = 0.005) and Forrest classes Ia (OR 25.53, p < 0.001), Ib (OR 27.91, p = 0.005), IIa (OR 21.41, p < 0.001), and IIb (OR 23.74, p < 0.001) were independent risk factors of rebleeding compared to Forrest class III, and being inpatients (OR 1.75, p = 0.01). Compared to the outpatients, the inpatients showed significantly higher rebleeding rates (25.6% vs 13.8%, p < 0.001), predictive bleeding scores, red blood transfusion counts, proportion of Forrest classes Ia, Ib, and IIb (p < 0.001), and overall mortality rates (68.8% vs 34.0%, p < 0.001). CONCLUSIONS: Patient location was a novel predictive factor of BPU rebleeding. Particularly, being an inpatient correlated with increased rebleeding. Furthermore, Forrest classes Ia, Ib, IIa, and IIb were predictive of rebleeding not only the included BPUs, but also in the inpatient or outpatient groups.

Scoring systems for predicting clinical outcomes in peptic ulcer bleeding.

Few studies have focused on assessing the usefulness of scoring systems such as the Rockall score (RS), Glasgow-Blatchford score (GBS), and AIMS65 score for risk stratification and prognosis prediction in peptic ulcer bleeding patients. This study aimed to assess scoring systems in predicting clinical outcomes of patients with peptic ulcer bleeding. A total of 682 peptic ulcer bleeding patients who underwent esophagogastroduodenoscopy between January 2013 and December 2017 were found eligible for this study. The area under the receiver-operating characteristic curve (AUROC) of each score was calculated for predicting rebleeding, hospitalization, blood transfusion, and mortality. The median age of patients was 64 (interquartile range, 56-75) years. Of the patients, 74.9% were men, and 373 underwent endoscopic intervention. The median RS, GBS, and AIMS65 scores were significantly higher in patients who underwent endoscopic intervention than in those who did not. The AUROC of RS for predicting rebleeding was significantly higher than that of GBS (P = .022) or AIMS65 (P < .001). GBS best predicted the need for blood transfusion than either pre-RS (P = .013) or AIMS65 (P = .001). AIMS65 score showed the highest AUROC for mortality (0.652 vs. 0.622 vs. 0.691). RS was significantly associated with rebleeding (odds ratio, 1.430; P < .001) and overall survival (hazard ratio, 1.217; P < .001). The RS, GBS, and AIMS65 scoring systems are acceptable tools for predicting clinical outcomes in peptic ulcer bleeding. RS is an independent prognostic factor of rebleeding and overall survival.

Nature and treatment outcomes of bleeding post-bulbar duodenal ulcers.

BACKGROUND: Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS: Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in-hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. CONCLUSION: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location.

A multicenter prospective study of the treatment and outcome of patients with gastroduodenal peptic ulcer bleeding in Japan.

Gastroduodenal peptic ulcers are the main cause of nonvariceal upper gastrointestinal bleeding (UGIB). We believe that recent advances in endoscopic techniques and devices for diagnosing upper gastrointestinal tract tumors have advanced hemostasis for UGIB. However, few prospective multicenter studies have examined how these changes affect the prognosis. This prospective study included 246 patients with gastroduodenal peptic ulcers treated at 14 participating facilities. The primary endpoint was in-hospital mortality within 4 weeks, and the secondary endpoints required intervention and refractory bleeding. Subsequently, risk factors affecting these outcomes were examined using various clinical items. Furthermore, the usefulness of the risk stratification using the Glasgow-Blatchford score, rockall score and AIMS65 based on data from the day of the first urgent endoscopy were examined in 205 cases in which all items were complete there are two periods. Thirteen (5%) patients died within 4 weeks; and only 2 died from bleeding. Significant risk factors for poor outcomes were older age and severe comorbidities. Hemostasis was required in 177 (72%) cases, with 20 cases of refractory bleeding (2 due to unsuccessful endoscopic treatment and 18 due to rebleeding). Soft coagulation was the first choice for endoscopic hemostasis in 57% of the cases and was selected in more than 70% of the cases where combined use was required. Rockall score and AIMS65 predicted mortality equally, and Glasgow-Blatchford score was the most useful in predicting the requirement for intervention. All scores predicted refractory bleeding similarly. Although endoscopic hemostasis for UGIB due to peptic ulcer had a favorable outcome, old age and severe comorbidities were risk factors for poor prognosis. We recommend that patients with UGIB should undergo early risk stratification using a risk scoring system.

ABC score is an effective predictor of outcomes in peptic ulcer bleeding.

BACKGROUND: Risk stratification is recommended for patients with gastrointestinal (GI) bleeding. The ABC score is a new scoring tool with high accuracy for upper and lower GI bleeding. We aimed to evaluate the effectiveness of the ABC score in predicting the outcomes of patients with peptic ulcer bleeding. METHODS: This single-center retrospective study included 809 patients, each with symptoms of upper GI bleeding, and who were diagnosed with ulcerative lesions between October 2011 and March 2021. The association between the ABC score's variables and the patients' outcome was analyzed. The score's performance in predicting the patients' outcome was validated using receiver-operating characteristic curve analysis and compared with that of other scores. RESULTS: The study analyzed 772 patients with peptic ulcer bleeding. The primary outcome measure was all-cause 30-day mortality. Secondary outcome measures included rebleeding within 30 days and the need for radiologic/surgical intervention. Age (P = .013), serum albumin levels (P < .001), serum creatinine levels (P = .004), mental status (P < .001), and American Society of Anesthesiologists score (P < .001) were associated with the primary outcome. The ABC score predicted the 30-day mortality (area under the receiver-operating characteristic curve [AUROC] 0.927; 95% confidence interval [CI] 0.899-0.956) better than other scores. However, it was less accurate in predicting rebleeding (AUROC 0.630; 95% CI 0.563-0.697) and need for radiologic/surgical intervention (AUROC 0.641; 95% CI 0.550-0.732). CONCLUSIONS: The ABC score accurately predicts the 30-day mortality in patients with peptic ulcer bleeding. However, it may not be suitable for predicting rebleeding or the need for radiologic/surgical interventions.

Long-Term Outcomes in Patients with Post-Bulbar Ulcer Bleeding Compared to Bulbar Ulcer Bleeding in the Duodenum.

BACKGROUND: Duodenal ulcers are classified into bulbar and post-bulbar ulcers. The aim of this study is to compare the long-term outcomes of patients with post-bulbar ulcer bleeding and those with bulbar ulcer bleeding. METHODS: A total of 272 patients with hemorrhagic duodenal ulcers requiring hospitalization were included. Their medical records were retrospectively reviewed. RESULTS: All patients were categorized as bulbar or post-bulbar bleeding ulcer groups. The post-bulbar ulcer group had more patients of advanced age, concurrent malignancy, diabetes mellitus, hypertension, cirrhosis, and chronic kidney disease undergoing hemodialysis. We performed long-term follow-up for an average of 2.6 years. The mortality rate during the follow-up period in the post-bulbar ulcer group was significantly higher than that in the bulbar ulcer group (p < 0.001). The PNED score was a better predictor of 30-day mortality compared to the complete Rockall score and the Glasgow-Blatchford Score. Predictors of mortality were evaluated using a Cox proportional hazards regression model. In multivariate analysis, post-bulbar ulcer, concurrent malignancy, cirrhosis, antiplatelet/anticoagulant use, and transfusion were significant predictors of mortality. CONCLUSIONS: Patients with post-bulbar ulcers have a poorer prognosis than those with bulbar ulcers. After the diagnosis of hemorrhagic post-bulbar duodenal ulcer, close follow-up is necessary.

How Would You Manage This Patient With Nonvariceal Upper Gastrointestinal Bleeding? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Nonvariceal upper gastrointestinal bleeding is common, morbid, and potentially fatal. Cornerstones of inpatient management include fluid resuscitation; blood transfusion; endoscopy; and initiation of proton-pump inhibitor therapy, which continues in an individualized manner based on risk factors for recurrent bleeding in the outpatient setting. The International Consensus Group released guidelines on the management of nonvariceal upper gastrointestinal bleeding in 2019. These guidelines provide a helpful, evidence-based roadmap for management of gastrointestinal bleeding but leave certain management details to the discretion of the treating physician. Here, 2 gastroenterologists consider the care of a patient with nonvariceal upper gastrointestinal bleeding from a peptic ulcer, specifically debating approaches to blood transfusion and endoscopy timing in the hospital, as well as the recommended duration of proton-pump inhibitor therapy after discharge.

Management of Non-Variceal Upper GI Bleeding in the Geriatric Population: An Update.

PURPOSE OF REVIEW: Upper gastrointestinal (GI) bleeding is a significant cause of morbidity and mortality in the geriatric (age > 65 years) population and presents a unique management challenge in the context of multiple medical comorbidities, polypharmacy, and increased risk of adverse outcomes and is confounded by an increased prevalence of obscure GI bleeds. A review of relevant guidelines, literature, and personal observations will enhance management strategies in the elderly. RECENT FINDINGS: Non-variceal bleeding represents a significant proportion of upper GI bleeding (UGIB) in geriatric patients. Peptic ulcer disease (PUD) remains the most common cause in geriatric patients hospitalized for UGIB, but its incidence is decreasing. Esophagogastroduodenoscopy (EGD) is the gold standard for treating UGIB in geriatrics with a therapeutic yield of approximately 75%. Scoring systems such as Glasgow-Blatchford (GBS) and AIMS-65 may be useful for risk stratification but are not validated in trials. Obscure bleeds account for up to 30% of hospitalizations and must be considered during triage and management. Video capsule endoscopy (VCE) technology is efficacious for detecting obscure jejunal bleeding after failed EGD and may enhance the yield of balloon-assisted enteroscopy (BAE). The most significant factor for the increased morbidity and mortality in the geriatric population is the presence of multiple medical comorbidities and polypharmacy. An EGD should be done within 24 h of hospital presentation. If non-diagnostic, VCE may be a viable option for diagnosing an obscure small-bowel bleed, representing up to 30% of GI bleeds in this population.

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15-0.85; P = .02; I2 = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10-0.83; P = .02; I2 = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43-1.08; P = .10; I2 = 0%) and length of hospitalization (mean difference, -0.32; 95% CI, -1.88 to 1.24; P = .69; I2 = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09-97.98; I2 = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00-1.28; I2 = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.

Critical peptic ulcer bleeding requiring massive blood transfusion: outcomes of 270 cases.

BACKGROUND: Critical peptic ulcer bleeding requiring massive transfusion is a gastroenterological emergency. Few data exist on management and outcomes. The Australian and New Zealand Massive Transfusion Registry collects comprehensive data on adult patients receiving massive transfusion across all bleeding contexts. AIM: To evaluate clinical factors, management (procedural interventions, transfusions) and outcomes after massive transfusion for critical peptic ulcer bleeding. METHOD: Demographics, diagnosis, procedures and mortality data were available for 5482 massive transfusion cases from 23 hospitals. International Classification of Diseases 10th Edition, Australian Modification codes were used to determine peptic ulcer bleeding and the Australian Classification of Health Intervention for interventions (i.e. endoscopic, radiological, surgical). RESULTS: Peptic ulcer bleeding accounted for 270 (4.9%) of all in-hospital massive transfusion cases; 70% were male. Median number of red blood cell (RBC) units transfused was 7 (interquartile range, 6-10). Thirty-day mortality was 19.6%. Age (75 vs 67 years; P = 0.009) and Charlson Comorbidity Index (3 vs 1; P < 0.001) were higher in those who died. Highest 24-h international normalised ratio (1.5 vs 1.4; P < 0.001) and creatinine (118 µmol/L vs 96 µmol/L; P = 0.03) and nadir platelet count (86 × 109 /L vs 118 × 109 /L; P = 0.01) were also associated with 30-day mortality. There were no differences in mortality according to number of RBC, platelets or plasma units transfused, gastroscopy (with or without intervention), interventional radiology or surgery. CONCLUSION: One in five patients with critical peptic ulcer bleeding requiring massive transfusion died by 30 days. Mortality was associated with patient characteristics rather than clinical interventions (e.g. procedures, blood product transfusion).

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.