Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding.

BACKGROUND AND AIMS: Despite advances in pharmacological and endoscopic management of non-variceal upper gastrointestinal bleeding (NVUGIB), mortality is still relevant. TC-325 (Hemospray-Cook Medical) is a mineral powder with adsorptive properties, designed for endoscopic hemostasis. There are still no comparative trials studying this new hemostatic modality. The objective of this research was to compare the use of TC-325 (associated with epinephrine injection) with the combined technique of endoscopic clipping and epinephrine injection for the treatment of patients with NVUGIB. METHODS: We conducted a pilot randomized controlled trial with patients that presented NVUGIB with an actively bleeding lesion at the endoscopic evaluation. Patients were randomized either to the Hemospray or Hemoclip group. The randomization list was generated by a computer program and remained unknown throughout the entire trial. All patients underwent second-look endoscopy. RESULTS: Thirty-nine patients were enrolled. Peptic ulcer was the most frequent etiology. Primary hemostasis was achieved in all Hemospray cases and in 90% of Hemoclip group (p = 0.487). Five patients in Hemospray group underwent an additional hemostatic procedure during second-look endoscopy, while no patient in the Hemoclip group needed it (p = 0.04). Rebleeding, emergency surgery and mortality rates were similar in both groups. No toxicity, allergy events, or gastrointestinal obstruction signs were observed in Hemospray group. CONCLUSIONS: TC-325 presents similar hemostatic results when compared with conventional dual therapy for patients with NVUGIB. Hemospray's excellent primary hemostasis rate certifies it as a valuable tool in arduous situations of severe bleeding or difficult location site.

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 for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The incidence of obscure gastrointestinal bleeding, which originates from the small bowel and is mainly associated with the use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), is rising. We assessed the efficacy and safety of misoprostol for the treatment of small bowel ulcers and erosions in patients taking low-dose aspirin or NSAIDs with obscure gastrointestinal bleeding. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients (aged ≥18 years) with small bowel ulcers who were taking low-dose aspirin, NSAIDs, or both for a minimum of 4 weeks, at University Hospital Crosshouse (Kilmarnock, UK). Eligible patients had evidence of obscure gastrointestinal bleeding (iron deficiency anaemia, a decrease in haemoglobin concentration of ≥20 × 103 mg/L, or positive faecal occult blood test) and normal upper endoscopy and colonoscopy. Patients were randomly assigned (1:1) using an interactive voice response system to receive 200 µg oral misoprostol or placebo four times daily for 8 weeks. Patients, investigators, and assessors were masked to treatment allocation. The primary endpoint was the complete healing of small bowel ulcers and erosions, assessed by video capsule endoscopy after 8 weeks of treatment. Primary analysis was by modified intention to treat, which included all randomised patients who received at least one dose of study treatment. Safety was assessed in the same population. The trial is registered with ClinicalTrials.gov, number NCT02202967. FINDINGS: Between Jan 7, 2016, and Oct 11, 2017, we randomly allocated 104 eligible patients: 52 to receive misoprostol and 52 to receive placebo. Two patients allocated to misoprostol were later found to meet one of the exclusion criteria, thus 50 randomly assigned patients in the misoprostol group and 52 patients in the placebo group received at least one dose of study treatment. Complete healing of small bowel ulcers and erosions was noted at week 8 in 27 (54%) of 50 patients in the misoprostol group and nine (17%) of 52 patients in the placebo group (percentage difference 36·7%, 95% CI 19·5-53·9; p=0·0002). Adverse events occurred in 23 (46%) of 50 patients in the misoprostol group and 22 (42%) of 52 patients in the placebo group. The most common adverse events were abdominal pain (ten [20%] in the misoprostol group vs 13 [25%] in the placebo group), nausea or vomiting (nine [18%] vs seven [13%]), and diarrhoea (11 [22%] vs six [12%]). Four (8%) of 50 patients in the misoprostol group had severe adverse events, compared with none in the placebo group. No serious adverse events were reported. INTERPRETATION: Misoprostol is effective for the treatment of small bowel ulcers and erosions in patients using low-dose aspirin and NSAIDs. Misoprostol might represent a pharmacological treatment option for lesions causing obscure gastrointestinal bleeding that is associated with aspirin and NSAIDs, but its use should be balanced against the risk of side-effects. FUNDING: National Health Service (NHS) Greater Glasgow and Clyde and NHS Ayrshire and Arran.

[Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years].

OBJECTIVE: To investigate the clinical epidemiology change trend of upper gastrointestinal bleeding (UGIB) over the past 15 years. METHODS: Consecutive patients who was diagnosed as continuous UGIB in the endoscopy center of The First Affiliated Hospital of Sun-Yat University during the period from 1 January 1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013 were enrolled in this study. Their gender, age, etiology, ulcer classification, endoscopic treatment and hospitalization mortality were compared between two periods. RESULTS: In periods from 1997 to 1998 and 2012 to 2013, the detection rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(χ2=360.089, P=0.000); the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092) (χ2=0.179, P=0.672), and the onset age was (47.3±16.4) years and (51.4±18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first etiology of UGIB was peptic ulcer bleeding, accounting for 65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB, but the ratio obviously decreased to 52.7%(575/1092)(χ2=32.467, P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of duodenal ulcer bleeding was the main reason (χ2=53.724, P=0.000). Esophageal and gastric varices bleeding became the second cause (15.1%,165/1 092, χ2=38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092, χ2=3.352, P=0.067). The largest increasing amplitude of the onset age was peptic ulcer bleeding [(46.2±16.7) years vs. (51.9±18.9) years, t=-5.548, P=0.000), and the greatest contribution to the amplitude was duodenal ulcer bleeding [(43.4±15.9) years vs. (48.4±19.4) years, t=-3.935, P=0.000], while the onset age of esophageal and gastric varices bleeding [(49.8±14.1) years vs. (48.8±13.9) years, t=0.458, P=0.648] and cancer [(58.4±13.4) years vs. (58.9±16.7) years, t=-0.196, P=0.845] did not change significantly. Compared with the period from 1997 to 1998, the detection rate of high risk peptic ulcer rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (χ2=39.958, P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6% (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the achievement ratio of hemostasis was 96.9%(253/261), which was significantly higher (χ2=23.287, P=0.000). Compared to the period from 1997 to 1998, more patients with variceal bleeding or non-variceal bleeding received endoscopic treatment in time (39.0% vs. 70.3%, χ2=51.930, P=0.000; 3.6% vs. 15.6%, χ2=62.292, P=0.000, respectively), and higher ratio of patients staging Forrest stage I(a to II(b also received endoscopic treatment in the period from 2012 to 2013 [27.4%(26/95) vs. 68.5%(111/162), χ2=40.739, P=0.000]. More qualified endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs. 15.2%, χ2=79.518, P=0.000), hemostatic clip (0 vs. 55.9%, χ2=20.879, P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%, χ2=5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%, χ2=10.420, P=0.001), and single spraying for hemostasis was completely abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs. 6.0%(65/1092), χ2=7.970, P=0.005], while no significant difference was found in mortality during hospitalization between two periods. CONCLUSION: Compared with the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the cure rate of endoscopic treatment for UGIB increased, more reasonable and immediate hemostatic methods were used, but overall mortality did not change obviously in the period from 2012 to 2013.

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.

BACKGROUND: Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy. METHODS: Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials. RESULTS: Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone. CONCLUSIONS: Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

SURGICAL TREATMENT OF DUODENAL ULCER, COMPLICATED BY HEMORRHAGE.

Detailed statistic alanalysis of the treatment results in patients, who have had suffered gastroduodenal ulcer hemorrhage, in The Gastro­Intestinal Hemorrhage Centre, was performed. Application of exteriorization procedure, using original method of double sticking and out sticking of the needle bilaterally from ulcerative defect, for duodenal ulcer, complicated by hemorrhage, have had guaranteed mechanical squeezing of the periulcer zone vessels and effective removal of the ulcer out side the gut lumen. This have had promoted improvement of the patients' treatment results.

[TREATMENT MODALITIES OF THE FOREGUT HEMORRHAGES WHILE PERFORMING ENDOSCOPIC MONITORING].

Complex clinical examination was done in 107 patients, in whom gastrointestinal hemorrhage (GIH) of various etiology, have had occurred. Special attention was drawn toward early conduction of esophagogastroduodenofibroscopy, as a leading instrumental method, permitting to reveal a GIH source, its character and degree of hemostasis in accordance to J. Forrest scale. The patients state severity while hemorrhage from the foregut presence was estimated in accordance to routine principles, depending on the circulating blood volume deficiency. The structure algorithm for the patients' management, in accordance to which treatment tactic must be selected individually, permitting to improve the quality of the medical help delivery for the patients, was elaborated.

[Gastroduodenal mucosa sensitivity to estrogen in ulcers complicated by hemorrhage].

Expression of alpha-receptors of estrogen (RE) in accordance to immunohistochemical (IHC) labeling in gastroduodenal mucosa cells was studied up in patients, suffering the ulcer disease and without it. In 4 patients (group I) a gastroduodenal mucosa affection was revealed, they were operated on for hemorrhage from gastroduodenal ulcers; in 3 patients (group II) gastroduodenal mucosa affection was not observed; in 4 patients (group III, control), a mammary gland cancer was diagnosed, a positive reaction on alpha-RE was noted. In groups I and II the biopsies were studied, obtained from pylorus and gastric fundus, as well as from duodenal ampula, and in a group III--obtained from the tumor. In a control group a positive labeling of nuclei was revealed in biopsies. In patients of groups I and II the alpha-RE expression by cellular nuclei was not revealed, but, the lots of positive IHC labeling of cytoplasm in glandular and stromal mucosal cells of the investigated gut were noted. Positive IHC labeling of cytoplasm for alpha-RE witnesses about sensitivity to them in norma and pathological processes. But, a trustworthy difference of alpha-RE expression by cellular nuclei was not noted. For confirmation or denial of this hypothesis further clinical and IHC investigations are needed.

[HORMONAL-GENETIC SCREENING IN PATIENTS, SUFFERING GASTRODUODENAL ULCER HEMORRHAGE].

Genetic-hormonal regulation plays a key pathophysiologic role in a blood loss on background of complicated gastroduodenal ulcer disease, but a clinical significance of some genes of compensatory steroidogenesis remains unrevealed. Examination of 63 patients, using a chain reaction with polymerase (CRP); analysis of length of restriction fragments (CRP-RFLP) and immunohistochemical investigation of gastroduodenal mucosa were performed on the base of a Sumsky Rural Clinical Hospital. Trustworthy difference of distribution of polymorphic genes ESR1 and VKORC1 in patients of both gender in presence of the ulcer hemorrhage was not revealed, excluding genotype A/A VKORC1, what trustworthy more frequently was revealed in women (p < 0.05). There was established, that intact zone of gastric fundus owes immunoreactivity towards alpha-receptors of estrogen in nuclei of epitheliocytes and stromocytes. Diagnosis of polymorphic gene VKORC1 and expression of the estrogen receptors may serve the base for pathogenetic therapy in patients with hemorrhage occurrence.

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.

[Mucosal changes in the periulcer zone and endocrine system in patients with gastroduodenal ulcer, complicated by hemorrhage].

Examination of patients, suffering gastroduodenal ulcer, complicated by hemorrhage, was conducted, using clinical, microbiological, immunohistochemical methods and chromatomassspectrography. Enhanced activity of inducible NO-synthase, contamination of periulcer zone with microorganisms Klebsiella pneumoniae, Streptococcus beta-haemoliticus, enhancement of contents of catecholamines and serotonin in the blood serum were revealed. These changes are most expressed in severe blood loss, unstable local endoscopic hemostasis, high risk of a recurrent hemorrhage occurrence. The data obtained permit to prognosticate severity of a pathologic process course and to improve the treatment programe.

Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on repair mechanisms in acute peptic ulcer bleeding.

BACKGROUND: Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown. AIMS: We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB. METHODS: There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls. RESULTS: Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment. CONCLUSIONS: Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer.

Outcome of holiday and nonholiday admission patients with acute peptic ulcer bleeding: a real-world report from southern Taiwan.

BACKGROUND: Recent findings suggest that patients admitted on the weekend with peptic ulcer bleeding might be at increased risk of adverse outcomes. However, other reports found that there was no "holiday effect." The purpose of this study was to determine if these findings hold true for a real-life Taiwanese medical gastroenterology practice. MATERIALS AND METHODS: We reviewed the medical files of hospital admissions for patients with peptic ulcer bleeding who received initial endoscopic hemostasis between January 2009 and March 2011. A total of 744 patients were enrolled (nonholiday group, n = 615; holiday group, n = 129) after applying strict exclusion criteria. Holidays were defined as weekends and national holidays in Taiwan. RESULTS: Our results showed that there was no significant difference in baseline characteristics between the two groups. We also observed that, compared to the nonholiday group, patients in the holiday group received earlier endoscopy treatment (12.20 hours versus 16.68 hours, P = 0.005), needed less transfused blood (4.8 units versus 6.6 units, P = 0.02), shifted from intravenous to oral proton-pump inhibitors (PPIs) more quickly (5.3 days versus 6.9 days, P = 0.05), and had shorter hospital stays (13.05 days versus 17.36 days, P = 0.005). In the holiday and nonholiday groups, the rebleeding rates were 17.8% and 23.41% (P = 0.167), the mortality rates were 11.63% versus 13.66% (P = 0.537), and surgery was required in 2.11% versus 4.66% (P = 0.093), respectively. CONCLUSIONS: Patients who presented with peptic ulcer bleeding on holidays did not experience delayed endoscopy or increased adverse outcomes. In fact, patients who received endoscopic hemostasis on the holiday had shorter waiting times, needed less transfused blood, switched to oral PPIs quicker, and experienced shorter hospital stays.

[Prognostication of gastroduodenal ulcer course complicated by hemorrhage].

Dynamics of the blood serum level of serotonin in the patients, suffering gastroduodenal ulcer, Complicated by hemorrhage, was analyzed. The highest level of serotonin was observed in gastric ulcer, complicated by hemorrhage. These changes correlate with the blood loss severity enhancement, the achievement of a nonstable state of endoscopic hemostasis, high activity of inducible NO-synthase (iNOS) of periulcerative mucosa. The obtained data analysis permits to prognosticate the pathological process course and to improve the program of treatment.

Methods of emergency surgery in high-risk stigmata peptic ulcer hemorrhage.

AIM: The choice of emergency operative methods in management of peptic ulcer hemorrhage (PUH) is controversial. The aim of this study was to analyze the patient characteristics, surgical methods and treatment outcome of patients with PUH during 10 years. METHODS: Of the 953 admitted PUH patients all 67 (7.0%) operated cases had high-risk stigmata PUH (Forrest classification). These patients were grouped and their data were compared under two 5-year periods: period I - 32 patients (2003-2007) and period II - 35 patients (2008-2012). RESULTS: The majority of the patients had giant ulcer (diameter ≥ 2 cm) hemorrhage at 75.0% (24/32) and 94.3% (33/35) during study periods I and II, respectively (P=0.04). Giant duodenal and gastric ulcers for PUH were operated in 16 and 8 vs 27 and 6 during periods I and II, respectively. Ulcer exclusion or ulcerectomy combined with definitive acid reducing surgery was applied in 68.7% (22/32) and 71.4% (25/35) of the patients, respectively, without early recurrent hemorrhage. Postoperative in hospital mortality in the 10-year study period was 6.0% (4/67); 2.1% (1/48) of the patients died after definitive operations and 15.8% (3/19) (P=0.04) died after non-definitive operations. CONCLUSION: The surgical treatment of high-risk stigmata PUH was mainly associated with giant, particularly giant duodenal ulcer. As a rule, ulcer exclusion or ulcerectomy as hemorrhage control, combined with definitive surgery, was applied in the majority of the cases with an in hospital mortality of 2.1%.

Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection and without exposure to non-steroidal anti-inflammatory drugs.

BACKGROUND/AIM: A high risk of bleeding in Helicobacter pylori (H. pylori)-negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. METHODS: A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs and proton pump inhibitors (PPI) within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF) and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI). RESULTS: Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509) and exposure to stress (p = 0.944). Aspirin was used by 16/48 (33.3%) patients with bleeding ulcer, as opposed to 7/47 (14.9%) patients who did not bleed (p = 0.036). Abnormal platelet function had 12/48 (25.0%) patients who bled, as opposed to 2/47 (4.3%) patients who did not bleed (p = 0.004). Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023). There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.20%) patients with bleeding ulcer and in only 5/47 (10.6%) patients who had ulcer without bleeding (p = 0.024). CONCLUSION: Abnormal platelet function, aspirin use and antrum atrophy were the risk factors for ulcer bleeding in non-H. pylori, non- NSAIDs ulcer disease.

Protective effects of acetaminophen on ibuprofen-induced gastric mucosal damage in rats with associated suppression of matrix metalloproteinase.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofen-induced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1ß (IL-1ß), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.

Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers.

BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.

[Recurrent duodenal ulcer bleeding as the first manifestation of a solid pseudopapillary neoplasm of the pancreas with hepatic metastases]. / Rezidivierte duodenale Ulkusblutung als Erstmanifestation einer hepatisch metastasierten solid-pseudopapillären Neoplasie des Pankreas.

HISTORY AND ADMISSION FINDINGS: In a 17-year-old girl recurrent duodenal ulcer bleeding had led to severe anemia. INVESTIGATIONS: Sonography and computed tomography revealed a partially cystic tumour of the pancreatic head and suspicious hepatic lesions. TREATMENT AND PATHOLOGICAL DIAGNOSIS: A partial duodenopancreatectomy was performed and two liver metastases were resected. Histological examination of the resected pancreatic specimen revealed a solid pseudopapillary neoplasm of the pancreas (SPN) with hepatic metastases. CLINICAL COURSE AND PROGNOSIS: The seven remaining liver metastases were removed in a second procedure (right hepatectomy). One year later two new liver metastases were treated by radiofrequency ablation. Two years after the initial operation, the patient is well and tumor-free. CONCLUSION: SPN is a rare cystic tumor that is mainly found in young women. Direct tumor infiltration of stomach or duodenum can cause gastrointestinal bleedings in rare cases. Resection of the primary tumor and surgical or interventional removal of metastases are the treatment of choice.