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

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

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.

[Lethal cases of bleeding to the upper gastrointestinal tract]. / Letální prípady krvácení do horní cásti gastrointestinálního traktu.

We report three lethal cases of bleeding to the upper gastrointestinal tract as immediate cause of death. The first two cases are in connection with homelessness. First is a male who was found dead in a railway station, seated on a bench with dried blood beneath him. The second is a male who was found lifeless in a wooden shelter, where upon the good will of the landowners, he lived. At autopsy, gastroduodenal ulcer disease with a damaged blood vessel at the ulcer base was found in both. The cause of death was stated as hypovolemic shock, arising from loss of blood from bleeding gastroduodenal ulcer disease. The third case shows a man with liver cirrhosis, who was transported to hospital when his health deteriorated, where he died with blood vomiting. The case was closed as hypovolemic shock from loss of blood and was ascribed to haemorrhagic diathesis and chronic liver insufficiency, and excluded haemoptysis as the cause of the bleeding. The paper draws attention to the risk of mortality in patients with gastroduodenal ulcer disease, with irregular food intake, including alcohol abuse. The cases demonstrate the importance of medical care for patients who are prone to gastric ulcers, or to patients who have been diagnosed and/or treated for gastroduodenal ulcer disease, as the severe risk of ulcer bleeding, leading eventually to ulcer perforation. Our case reports may inform ambulance crews responding to at-risk individuals, such as homeless people, to the immediate threat of possible gastroduodenal ulcer disease with ulcer bleeding, or ulcer perforation.Key words: bleeding - death - gastric ulcer - gastroduodenal ulcer disease - nutrition - preventive medicine.

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.

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.

[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.

[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.

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.

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.

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%.

[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.

[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.

[The ways of prophylaxis of the gastro-intestinal hemorrhage recurrence].

Through three-years period 57 patients, suffering gastro-intestinal hemorrhage (GIH) of the ulcer genesis, were treated in the clinic. Among them were 37 (64.9%) men and 20 (35.1%) women. The patients have had (56.3 +/- 4.7) yrs old at average. The treatment programm for the patients have included a local arrest of GIH, medicinal therapy, directed on restoration of the circulating blood volume, gastric secretion inhibition, rising of the blood coagulation property. In cases of a middle and severe blood loss the blood preparations were transfused--the erythrocytic mass and freshly frozen plasm. Three patients were operated in the high period of GIH. The GIH recurrence was absent. In 7 - 8 days, if a persistent hemostasis was achieved, the patients were transferred to therapeutic department for the conservative therapy prolongation.

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.

[Principal characteristics of the endoscopic programmed hemostasis in ulcerative gastroduodenal bleedings in patients with high operational-anesthesiological risk].

Application of the endoscopic programmed hemostasis for patients with ulcer gastroduodenal bleedings and with high operational-anesthetic risk provided metabolic rehabilitation (5% solutions of glucose and ascorbic acid) for the purpose of prevention of recurrence of the bleedings which have arisen after a hemostasis at 5.5% of patients.

[Experimental investigation of efficacy and safety of different methods of endoscopic hemostasis].

Treatment of ulcerative gastroduodenal bleedings remains one of the most pressing problems in urgent surgery. Available methods of endoscopic hemostasis are not fully eligible to safety requirements, effectiveness and reliability. In this connection persist high levels of general and postoperative mortality in our country and around the world. The aim of this study is to identify the advantages and disadvantages of endoscopic radiofrequency effects in comparison with standard techniques of hemostasis, used in the treatment of ulcer bleeding in the world practice.

Characteristics of serious complicated gastroduodenal ulcers in Japan.

BACKGROUND/AIMS: Even in Japan where the incidence of H. pylori infection is high, patients with gastroduodenal ulcers caused by NSAIDs are on the increase. A prospective study was conducted to elucidate the characteristics of gastroduodenal ulcers complicated with ulcerous hemorrhage and perforation among Japanese. METHODOLOGY: The subjects were 305 consecutive cases with hemorrhaging ulcers and 76 consecutive cases with perforated ulcers basis at Kagawa Prefectural Central Hospital between January 2000 and December 2008. These subjects were divided into 3 groups (lowdose aspirin, non-aspirin NSAIDs and non-NSAIDs) and were further stratified by the presence of an H. pylori infection. RESULTS: The 76 perforating ulcers were composed of 54 non-NSAIDs ulcers and 22 NSAIDs-related ulcers. The 305 hemorrhaging ulcers were composed of 156 non-NSAIDs ulcers, 94 non-aspirin NSAIDs ulcers and 55 on low-dose aspirin. The mortality for the non-aspirin NSAIDs group (12.8%, 12/94) and for the low-dose aspirin group (10.9%, 6/55) was significantly higher (p<0.01 and p<0.05, respectively) than the corresponding figure (2.6%, 4/156) for the non-NSAIDs group. The causes of death were exacerbation of or complications from the background diseases (Charlson Co-morbidity Index 3≤) (Odds ratios (OR) 6.01, 95% CI (1.98-18.89)). CONCLUSIONS: Approximately 50% of the gastroduodenal ulcers with complications found in Japanese are NSAIDs-related and may take a fatal turn. It is necessary to take measures to prevent the complicated ulcers corresponding to risk factors such as the severity of background diseases.