Ulcer-healing drugs are required after eradication of Helicobacter pylori in patients with gastric ulcer but not duodenal ulcer haemorrhage

AIM: To study the efficacy of a 2-week anti-Helicobacter therapy in the healing of H. pylori-associated bleeding peptic ulcers. METHODS: Omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to 180 patients with H. pylori-associated bleeding peptic ulcers. Endoscopy was repeated 4 weeks after the eradication therapy to assess healing of the peptic ulcers. RESULTS: Repeat endoscopies were performed in 168 patients (42 gastric ulcer and 126 duodenal ulcer) who followed the protocol. Thirty-eight patients with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs. duodenal ulcer: 98%; P=0. 035). No patients who were compliant to the study medications suffered from re-bleeding. Stepwise discriminant analysis demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best predicted healing of the peptic ulcers. CONCLUSIONS: Ulcer-healing drugs should be continued after a 2-week course of omeprazole-containing anti-Helicobacter therapy for gastric ulcers and large peptic ulcers that have bled, but can be omitted in most patients with a bleeding duodenal ulcer.     

The outcome of peptic ulcer haemorrhage in relation to consumption of nonsteroidal anti-inflammatory drugs or aspirin

Aim: To compare the outcome of 76 patients who presented with severe peptic ulcer haemorrhage whilst taking nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with that of 112 patients who were not taking these drugs and who developed peptic ulcer haemorrhage over the same time period. Methods: The two groups of patients were managed identically and endoscopic therapy was attempted in all cases. Results: The group taking NSAIDs or aspirin tended to be older and had a higher prevalence of cardio-respiratory disease. The severity of bleeding (as assessed by the presence of shock, anaemia and endoscopic stigmata) was similar in the two groups. Outcome in terms of uncontrolled haemorrhage, rebleeding and blood transfusion requirements did not differ significantly in the two groups. The NSAID group had a significantly longer duration of admission, almost certainly attributable to a higher prevalence of co-morbid diseases. Conclusions: Despite the deleterious effects of NSAIDs and aspirin upon renal and platelet function, the prognosis of peptic ulcer bleeding is not adversely affected by NSAID or aspirin therapy.     

Perforated duodenal ulcer: A rare complication of deferasirox in children

Duodenal ulcer perforation in pediatric age group is an uncommon entity; hence, it is not usually considered in the differential diagnosis of acute abdomen in these patients. It is important for the emergency physician to consider perforated peptic ulcer in the differential diagnosis of children presenting with acute abdominal pain, gastrointestinal bleeding, or shock. We report a 6½-year-old male child with thalassemia major who presented to emergency room with an acute abdomen and shock, who was subsequently found to have a perforated duodenal ulcer, probably related to use of oral chelating agent, deferasirox. Although, gastrointestinal symptoms like nausea, vomiting, and abdominal pain has been mentioned as infrequent adverse event in the scientific product information of deferasirox, in our current knowledge this is the first case report of perforated duodenal ulcer after oral deferasirox. The severity of this event justifies the reporting of this case. This patient had an atypical presentation in that there were no signs or symptoms of peptic ulcer disease before perforation and shock he was successfully managed with open surgery after initial resuscitation and stabilization of his general condition.KEY WORDS: Chelating agent, deferasirox, duodenal perforation     

Nonsteroidal antiinflammatory drug-induced mucosal lesions of the upper gastrointestinal tract and their relationship to Helicobacter pylori

The aim of the present study was to determine the prevalence of Helicobacter pylori infection in a group of patients hospitalized at the clinic of rheumatology who presented peptic ulcers and erosions associated with nonsteroidal antiinflammatory drugs (NSAIDs). Of a group of 4,256 hospitalized patients receiving therapy with NSAIDs, 221 patients with persistent dyspepsia underwent endoscopic examination of the upper segment of the gastrointestinal tract. Among them, mucosal abnormalities in the stomach and duodenum were confirmed in 69 patients. H. pylori was found in 42% (29/69) of the examined patients. Peptic ulcers were confirmed in 19 patients. Localization was gastric in 12 patients and duodenal in seven. H. pylori was found in only 17% of the patients (2/12) with gastric ulcers, but in as many as 86% (6/7) of those with duodenal ulcers. Patients with H. pylori taking NSAIDs were at higher risk of developing duodenal mucosal abnormalities, both ulcers (OR: 10.17; 95% CI: 1.08-23.88, p = 0.013) and erosions (OR: 2.67; 95 CI: 1.94-3.66, p = 0.001). Concomitant administration of corticoids and NSAIDs did not increase the risk of gastrotoxicity in patients with positive finding of H. pylori (OR: 0.32; 95% CI: 0.1-0.96). In conclusion, a close association was found between H. pylori infection and duodenal ulcers and erosions, but not between gastric ulcers and gastric erosions in a group of patients hospitalized for rheumatic diseases and undergoing NSAID therapy.     

Should NSAID/low‐dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing

Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can each result in gastric or duodenal ulcer(s) and ulcer complications. Together, H. pylori infection and NSAIDs account for approximately 90% of peptic ulcer disease. In 2003, the results of studies suggest, and guidelines recommend, the careful selection of anti-inflammatory drugs - NSAIDs or selective COX-2 inhibitors (coxibs) based upon patients gastrointestinal history and use of aspirin therapy. Testing for, and cure of, H. pylori infection is recommended in patients prior to the initiation of NSAID therapy and in those who are currently receiving NSAIDs and have a history of dyspepsia, peptic ulcer or ulcer complications. For patients who present with peptic ulcer bleeding but require NSAIDs long-term, H. pylori eradication therapy should be considered, followed by continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless of which kind of NSAID (nonselective NSAID /coxib) is being prescribed. Routine testing for, and eradication of, H. pylori infection has not been recommended for current takers of NSAIDs with no or low risk of complications. The management of patients taking low-dose aspirin is complex, but eradication of H. pylori infection alone in those with a past history of bleeding does not guarantee complete protection and therefore a proton pump inhibitor should also be given. The success of eradication therapy should always be confirmed, because of the risk of ulcer recurrence and bleeding in H. pylori-infected patients who require anti-inflammatory treatments.     

Bleeding peptic ulcer – time trends in incidence, treatment and mortality in Sweden

Background  The incidence of peptic ulcer disease was expected to decrease following the introduction of acid inhibitors and Helicobacter pylori eradication.
Aim  To analyse possible changes in the incidence of bleeding peptic ulcer, treatment and mortality over time.
Methods  Residents of Malmö hospitalized for bleeding gastric or duodenal ulcer disease during 1987–2004 were identified in hospital databases ( n  = 1610). The material was divided into 6-year periods to identify changes over time. All patients who had been submitted to emergency surgery ( n  = 137) were reviewed.
Results  The incidence rate for bleeding gastric or duodenal ulcers decreased by one half in males and by one-third in females and emergency operations decreased significantly (9.2%, 7.5% and 5.7% during the three time periods, respectively ( P  < 0.05). The post-operative mortality tended to decrease (9.7, 2.4 and 3.7%, respectively) and the 30-day mortality rates in the whole material were 1.2%, 3.6% and 3.4% during the different time periods.
Conclusion  The incidence of bleeding gastric and duodenal ulcer disease has decreased markedly. Operative treatment has been replaced by endoscopic treatment. The bleeding ulcer-related mortality was less than 4% and has not changed over time.     

High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease

BACKGROUND: In average-risk patients, the new anti-platelet agent, clopidogrel, causes less upper gastrointestinal adverse events than aspirin. However, there are no safety data on the use of clopidogrel in high-risk patients. AIM: To evaluate the safety of clopidogrel in patients with peptic ulcer disease in a retrospective cohort longitudinal study. METHODS: During the period from January 2000 to May 2002, 70 patients who were prescribed clopidogrel (75 mg/day) for a previous history of non-aspirin-related peptic ulcer disease or a history of aspirin-related gastrointestinal complications (dyspepsia or peptic ulcer) were recruited. The occurrence of ulcer complications (bleeding/perforation/obstruction) was the primary end-point. RESULTS: After a median follow-up of 1 year, nine patients (12%) developed gastrointestinal bleeding and one had a perforated peptic ulcer. Clopidogrel-associated gastrointestinal bleeding was significantly more common in patients with a history of gastrointestinal bleeding than in those without (22% vs. 0%; P = 0.007; odds ratio, 1.3; 95% confidence interval, 1.1-1.5). CONCLUSIONS: Clopidogrel is associated with a high incidence of upper gastrointestinal bleeding in high-risk patients. A previous history of gastrointestinal bleeding appears to be a predictor of adverse gastrointestinal events.     

Controlled study of the effects of intravenous famotidine on intragastric pH in bleeding peptic ulcers

As blood coagulation and platelet aggregation are abolished at pH less than 5.4 the failure of antisecretory drugs to promote haemostasis in bleeding peptic ulcers may reflect inadequate pH control. This study examined the ability of famotidine, a potent, long-acting H2 blocker to maintain intragastric pH above 5.4 in patients presenting with bleeding peptic ulcers. Twenty patients with acute upper gastrointestinal haemorrhage confirmed endoscopically to be related to peptic ulceration (17 duodenal, 3 gastric ulcers), were entered into the study within 24 h of presentation. Each patient was randomly allocated to receive either intravenous famotidine (n = 10) administered as a 10 mg bolus followed by a constant infusion of 3.2 mg/h or similarly administered placebo (n = 10). All patients remained fasted over the 22-h study period. Their median intragastric pH values ranged from 6.8 to 7.9 (median 7.1) in the famotidine group and from 1.1 to 6.9 (median 1.6) in the placebo group (P less than 0.001). Over this same period intragastric pH was greater than 6 for 64%-100% (median 98%) of the recording time in the famotidine group compared with 0%-93% (median 13%) in the placebo group (P less than 0.001). We conclude that intravenous famotidine can maintain intragastric pH greater than 6 in fasting patients with acute upper gastro-intestinal bleeding from peptic ulceration. This provides a rational basis for further studies assessing its clinical efficacy in such patients.     

Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users

BACKGROUND: The effect of Helicobacter pylori infection on NSAID-induced gastroduodenal damage is unclear. AIM: To determine the role of H. pylori and NSAID use in complicated peptic ulcers. METHODS: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection. RESULTS: H. pylori (odds ratio [OR]=5. 98; 2.9-12.3) and NSAID use (OR=5.74; 3.4-9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5-27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04-0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low-dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers. CONCLUSION: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.     

Fibrin sealant: a review of its use in surgery and endoscopy

Fibrin sealant (fibrin adhesive; fibrin glue; Beriplast P1) is a haemostatic and wound support product consisting of the blood coagulation factors fibrinogen, factor XIII and thrombin, the antifibrinolytic agent aprotinin and calcium chloride. Fibrin sealant has been used to good effect in a wide variety of surgical and endoscopic procedures. Suture support was provided in series of patients with oesophageal, gastric, colonic or rectal anastomoses, and fibrin sealant was as effective in haemostasis as microcrystalline collagen powder in hepatic surgery. It did not reduce postoperative peritoneal drainage after elective cholecystectomy, however. A 41% reduction (p<0.02) in incidence of air leakage was achieved when fibrin sealant was added to sutures in patients undergoing pulmonary resection in a randomised single-blind study. A high rate of complete remission of malignant pleural effusion has been reported after intrapleural instillation of fibrin sealant, and successful sealing of CSF leaks after trauma or surgery has also been achieved. Attenuation of prolonged or excessive haemorrhage after dental extraction has been achieved in patients on anticoagulant therapy or with haemorrhagic disorders who received fibrin sealant with packing and suturing. Repeated endoscopic injection of fibrin sealant was superior to single injection sclerotherapy with polidocanol 1% in a randomised study in 805 patients with bleeding peptic ulcers. Other data suggest that endoscopic injection of fibrin sealant is associated with lower recurrence of bleeding and need for emergency surgery than thrombin with adrenaline (epinephrine) or hypertonic saline with adrenaline. Similar haemostatic efficacy to laser photocoagulation or sclerotherapy was reported in a retrospective comparison. A statistically significant reduction relative to suturing in the incidence of wound dehiscence was reported after the use of fibrin sealant in cataract surgery, and benefit of the sealant has also been noted in patients receiving skin grafts and in those undergoing transurethral resection of the prostate gland. CONCLUSIONS: Although comparative studies would assist in the clarification of the place of the product discussed with respect to other haemostatic or wound support techniques and to other fibrin sealants, the formulation reviewed here has been shown overall to be effective and well tolerated in a variety of haemostatic and wound healing support roles in numerous types of surgery. Fibrin sealant has also been shown to be useful when administered endoscopically, with superiority over sclerotherapy being shown after repeated application in patients with peptic ulceration. Fibrin sealant can therefore be considered useful in a number of surgical and endoscopic settings.     

非甾体抗炎药的胃肠损害及其预防

非甾体抗炎药（NSAIDs）在临床上广泛用于风湿性疾病及心血管疾病的治疗。NSAIDs的常见不良反应为胃肠道不适、恶心，严重不良反应有消化性溃疡、胃肠道出血或穿孔。胃肠损伤发生的原因是由于NSAIDs抑制了环氧酶（COX）系统而阻断了前列腺素的合成，因此干扰了正常黏膜保护机制导致局部受损。NSAIDs致胃肠道损伤的危险因素为高龄、有消化性溃疡或出血史。预防NSAIDs所致胃肠损伤的措施有：应用预防溃疡的药物，选择新一代高选择性COX-2抑制剂，根据患者情况应用抗幽门螺杆菌疗法，依据患者相关的危险因素采用不同的治疗方案。     

非甾体抗炎药致老年人消化性溃疡的临床特点分析

目的:分析非甾体抗炎药(NSAIDs)所致的老年人消化性溃疡的临床特点。方法:回顾性调查上海市金山区亭林医院1999年1月至2006年12月间因消化性溃疡和(或)合并出血入院治疗的491例老年病人的临床资料,根据入院前1周内有无服用NSAIDs史将病人分为两组,对两组病人的临床资料进行分析比较。结果:服药组105例,未服药组386例。与未服药组比较,服药组病人的贫血更明显(P<0.05);复合溃疡和多发溃疡在服药组更多见(P<0.05)。服药组幽门螺杆菌的感染率为67.6%(71/105),未服药组为58.3%(225/386),两组间差别无统计学意义(P>0.05)。结论:应加强对老年人使用NSAIDs所致消化性溃疡的临床特点的认识,减少NSAIDs的不良反应。     

Effect of drug therapy on the relapse of peptic ulcers. 1st communication: the effect of acute therapy.

The following study was conducted in order to investigate the effect of drug therapy on the relapse of peptic ulcers. Acute therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (100 mg/d) or cimetidine (CAS 51481-61-9) (800 mg/d) was given to 402 patients with peptic ulcers using the envelope method. Subsequently, 1-year maintenance therapy with pirenzepine (75 mg/d) or placebo was carried out in a double-blind study in 251 patients who had been cured within 3 months. During the study period, an endoscopic examination was repeated regularly to study the relapse of ulcers. When the results were stratified and analyzed by Cutler-Ederer's life table method to see changes in relapse over time, it was noted that the acute therapy for active ulcers did have an influence on the course of relapse after the ulcer lesions had been cured. Pirenzepine, a M1 antagonist, was superior to cimetidine, a H2 antagonist, in the prevention of relapse of ulcers after they had been cured. The results suggest that the prevention of relapse of peptic ulcers should be started at the stage of acute therapy for active ulcers and that care should be taken in selecting drugs. The results also suggest that the natural history of peptic ulcers with respect to their relapse can be modified to a certain extent by drug therapy although the period for such cannot be specified.     

Under-utilization of gastroprotective drugs in patients with NSAID-related ulcers

OBJECTIVE: To determine the proportion of patients with a risk of NSAID gastropathy receiving adequate gastroprotection. METHODS: This observational study was performed between November 2001 and December 2003. We selected patients who were hospitalized with perforated and bleeding gastroduodenal ulcers attributable to NSAID use and controls without ulcers. Data were collected on their sociodemographic characteristics, actual and recent medication, comorbidity and medical history. For each patient and control the number of different risk factors associated with NSAID gastropathy was calculated. A composite risk factor (CRF) was obtained from the sum of all separate risk factors. RESULTS: During the observational period a total of 388 patients using NSAID were included in the study, 104 patient cases and 284 matched community-based controls. The mean CRF was significantly higher in patient cases than in controls (cases mean CRF 3.31 (SD 1.67) and controls mean CRF 2.76 (SD 1.45), p = 0.002). A total of 148 (38%) patients used an adequate preventive strategy. Significant variables for using a preventive strategy were concomitant use of steroids (corrected odds ratio 4.22, 95% CI 2.11 8.47, p < 0.001), a history of gastroduodenal ulcers (corrected odds ratio 2.90, 95% CI 1.51 - 5.56, p = 0.001) and concomitant use of low-dose aspirin (corrected odds ratio 1.96,95% CI 1.18 3.25, p= 0.01). Among patients with 4 or more risk factors associated with NSAID gastropathy, 47% still did not use adequate gastroprotection. CONCLUSION: Gastroprotective drugs are greatly under-utilized in patients with a risk of NSAID gastropathy.     

围手术期抗血小板治疗策略

目前由于心脑血管疾病的增多,越来越多的患者应用抗血小板药物作为一级、二级预防,尤其是接受心脏手术后的病人更需要长期接受抗血小板药物治疗。但是,当这些病人需要手术治疗时,术前充分地评估患者心脑血管血栓事件的风险和术后抗血小板药物引起的出血风险至关重要。     

Treatment of peptic ulcer disease in the arthritic patient

Dyspepsia associated with arthritis and non-steroidal anti-inflammatory drugs (NSAIDs) is a common clinical problem. Up to 80% of deaths attributable to peptic ulceration may be associated with NSAID usage. The problem is foremost in the elderly population, in which there has been an increase both in the incidence of peptic ulcers and in the use of NSAIDs. Although the development of duodenal ulceration is not clearly associated with NSAIDs, it is accepted that these drugs increase the risk of gastric ulceration and the occurrence of peptic ulcer complications. Asymptomatic peptic ulceration is common, and patients taking NSAIDs are often asymptomatic prior to presentation with life-threatening complications. The key principle in management of this problem is prevention through careful selection of patients for NSAID use, adequate treatment of peptic ulceration and maintenance of remission. A variety of effective drugs are available for the treatment of peptic ulcers, including H2-receptor antagonists, pirenzepine, sucralfate and colloidal bismuth subcitrate. However, it is recognised that peptic ulceration is a chronic disease with a relapsing-remitting course, often with asymptomatic ulcer episodes. The knowledge that current ulcer-healing strategies do not significantly alter this natural history has lead to increasing efforts to prevent relapse with effective 'maintenance' therapy.     

Cost-effectiveness in Canada of intravenous proton pump inhibitors for all patients presenting with acute upper gastrointestinal bleeding

BACKGROUND: The administration of proton pump inhibitors intravenously after endoscopic treatment of peptic ulcers significantly reduces the recurrence of bleeding. AIM: To evaluate the incremental cost-effectiveness in Canada of intravenous proton pump inhibitor before endoscopic therapy to patients presenting with acute upper gastrointestinal bleeding, compared with endoscopic treatment alone. METHODS: From a third-party payer perspective, we modelled the costs and effectiveness over 60 days of the two approaches using decision analysis. The probabilities of various outcomes, such as re-bleeding and the need for surgery, were taken from the published literature. We included the costs of intravenous proton pump inhibitor, therapeutic endoscopy, surgical procedures and hospitalizations, all expressed in 2001 Canadian dollars. RESULTS: In a hypothetical cohort of 1000 patients, the intravenous proton pump inhibitor approach resulted in mean savings of 20,700 Canadian dollars with 37 re-bleeding episodes averted. The investigation of uncertainty resulted in a likelihood of intravenous proton pump inhibitor being cost-effective of at least 0.73. CONCLUSION: It is common in Canada to administer intravenous proton pump inhibitors to patients with upper gastrointestinal bleeding even before endoscopic confirmation of bleeding peptic ulcers. Our results suggest that this approach has a high likelihood of being cost-effective.