Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis

BACKGROUND: Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications. METHODS: Cases were consecutive NSAID users admitted with an ulcer complication (n = 118), and controls were a random sample of all NSAID users without ulcer complication identified by a pharmacoepidemiologic database (n = 540). RESULTS: Ninety-four of 118 cases were interviewed, and 324 of 540 controls answered the questionnaire. Analysis showed no difference between included and non-included subjects. Risk factors for patients at start of NSAID therapy were high age: 60-75 years (odds ratio (OR), 3.5 (95% confidence interval (Cl), 1.8-7.1); > 75 years (OR, 8.9 (4.3-18.3)); male sex (OR 1.7 (1.0-3.0)); ulcer history (OR 2.5 (1.2-5.1)); steroid treatment (OR 2.0 (0.8-4.6)); smoking (OR 1.6 (0.9-2.7)); and alcohol use (OR 1.8 (0.9-3.6)). Risk factors for patients receiving NSAID therapy were high age, male sex, ulcer history, smoking and, furthermore, dyspepsia (OR 2.0 (1.0-4.2)), especially NSAID-related dyspepsia (OR 8.7 (4.0-18.9)). Risk was lower for patients treated more than 3 months. CONCLUSION: Risk measured from this design can be shown to correlate strongly with the rate difference, a measure that is more clinically relevant than conventional relative risk estimates. Strong risk factors for NSAID-related ulcer complication are high age, male sex, ulcer history, and dyspepsia related to the NSAID therapy. Avoiding NSAID therapy in these high-risk patients, whenever possible, might prevent many adverse events.     

Non-verbal communication: evaluation of a computer-assisted learning package

To assess the effect of 4 weeks' therapy with ranitidine 150 mg twice daily on the healing of symptomatic NSAID-associated gastric and duodenal ulcers, 149 arthritic patients were randomly allocated to one of three treatment groups: ranitidine with NSAID continued, ranitidine with NSAID discontinued, and placebo with NSAID discontinued. The healing frequency in patients with gastric ulceration was 67, 68 and 47%, and in those with duodenal ulceration 61, 81 and 42%, respectively. Only the difference between the duodenal ulcer healing rates for ranitidine with NSAID discontinued and placebo was statistically significant (P = 0.02). Healing rates were uninfluenced by gender, age, smoking habits, alcohol consumption, ulcer frequency or size, arthritic disease, or participating country.     

Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly

OBJECTIVE: To report 3 cases of gastrointestinal (GI) complications associated with the use of intramuscular ketorolac tromethamine therapy in elderly patients. CASE SUMMARIES: In case 1, an 88-year-old woman was taken to surgery for the management of an acute abdomen and repair of a 2+ cm perforated prepyloric gastric ulcer. The patient had received a total 16 doses of ketorolac 30 mg im. The patient died after surgery from complications associated with bacterial and candidal sepsis, as well as acute renal failure. In case 2, an 80-year-old woman with no known history of GI problems developed a prepyloric gastric ulcer, which perforated and penetrated into the pancreas after the patient received 13 doses of ketorolac 30 mg im. The patient died from complications associated with candidal sepsis, peritonitis, and cardiopulmonary collapse. In case 3, an 85-year-old man with a history of a gastric ulcer developed GI bleeding after receiving a total of 9 doses of ketorolac 30 mg im. The bleeding was stabilized and the patient was discharged 12 days later in stable condition. DISCUSSION: Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug with potent analgesic properties. We report 3 cases of GI complications associated with intramuscular ketorolac therapy in the elderly. A temporal relationship was established with the development of gastric ulceration in 2 patients and the recurrence of a gastric ulcer in the third patient. CONCLUSIONS: We recommend that the manufacturer's guidelines be followed when ketorolac is used in elderly patients, and the drug should not be used in patients with a history of gastric ulcer disease. The use of misoprostol may be warranted as prophylactic therapy in high-risk patients who are receiving ketorolac.     

The epidemiology of the gastroduodenal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs

A substantial body of studies (controlled, cohort and case-control studies) now confirm the long established impression that there is an increased prevalence of gastric and duodenal ulcer and of associated complications in subjects treated with aspirin (ASA) or with non-steroidal anti-inflammatory drugs (NSAIDs). The overall percentage of ulcers/erosions in patients treated with ASA ranges from 10 to 50% with a relative risk of bleeding ranging from 1.8 to 15%. The overall relative risk of ulcers/erosions in NSAIDs-treated subjects is around 3%, with complications detectable in 2.4% of cases. The risk of lesions and complications associated with ASA/NSAIDs is more marked in patients aged over 65, in those with a previous history of ulcer (both symptomatic and silent), in those treated with substantial doses or with combinations of NSAIDs and in those concomitantly using anticoagulants and/or steroids. The epidemiological data highlight the importance of implementing ASA/NSAIDs therapy only when strictly necessary as well as the advisability of adopting as broad a range of measures as possible to reduce the tissue-damaging effects of these pharmacological agents.     

The combined treatment of peptic ulcer with the differentiated use of nontraditional physiotherapeutic methods

Efficiency was studied of multimodality treatment of 586 patients with ulcer disease. Of these, 110 had gastric ulcer, 460 patients had duodenal ulcer, sixteen were suffering from both gastric and duodenal ulcer. 275 patients (46.8%) had various concurrent chronic disorders involving cardiovascular system and alimentary canal. Three groups of patients were identified: those receiving magnetoresonance therapy apart from conventional antiulcer therapy (n = 89), those undergoing laser therapy (n = 170), those exposed to hyperbaric oxygenation (HBO), variable magnetic field (VMF) and acupuncture (AP) according to generally accepted techniques. In the control group, drug therapy promoted ulcer healing in 73.3% of patients, whereas multimodality treatment involving MRT induced healing in 80.6% that of incorporating computer-aided laser therapy led to healing in 85.7 to 89.4%. HBO, VMF and AP group demonstrated healing in 92.4 to 93.7%.     

Cost effectiveness of misoprostol therapy in prevention of NSAID-induced stomach ulcers

The efficacy of 400 micrograms misoprostol daily in the prevention of NSAID (non-steroidal anti-inflammatory drug)-induced gastric ulcer has been proven. We calculated the cost-effectiveness of a 3-month course of treatment of 200 micrograms twice daily for patients of the sick fund "Wiener Gebietskrankenkasse", based on charges of the year 1993. Since efficacy in preventing NSAID-induced gastric ulcers has not yet been proven for any other drug, we compared misoprostol-treated patients with untreated controls. The model was based on the following assumptions: 70% compliance with respect to misoprostol treatment, 5.6% incidence of gastric ulcer in patients protected with misoprostol, 21.7% incidence among unprotected NSAID users, 20% hospitalisation among patients with gastric ulcer. When using "Kassenpreis" (drug price paid by the sick funds) misoprostol treatment is cost-effective at costs of AS 64,100,--for inpatient care, upwards and at costs of AS 43,361,-upwards when using "Apothekeneinstandspreis" (drug price paid by pharmacies to wholesalers). In Austria costing system of inpatient care is based on a per diem fee. In 1993 the above costs corresponded to an average of 13 and 9 days, respectively, of inpatient care in Vienna. But costs of care increase by almost 25% per year and, hence, this conclusion is only temporarily valid and already in 1994 cost-effectiveness will be reached in less days of inpatient care. Sensitivity analysis shows that cost-effectiveness mainly varies according to the incidence of gastric ulcer among unprotected adults, and the hospitalisation rate of gastric ulcer patients. Efficacy (gastric ulcer rate among misoprostol treated patients) and compliance have a relatively low impact.(ABSTRACT TRUNCATED AT 250 WORDS)     

Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. A randomized, placebo-controlled pilot study

BACKGROUND: Chemotherapy (CT) may induce acute mucosal injury to the stomach and duodenum, but its prevention has been scarcely investigated. METHODS: One hundred and eighty-two cancer patients with normal stomach and duodenum or having fewer than 3 erosions, selected to be treated with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (77 breast carcinoma patients) or 5-fluorouracil (5-FU) (105 colon carcinoma patients), were randomly assigned to prophylactic treatment with misoprostol, 400 micrograms twice a day; omeprazole, 20 mg once a day; or placebo, 1 tablet twice a day. Seven days after the end of the second source of CT, all patients underwent control esophagogastroduodenoscopy. Endoscopic findings were quantified on the basis of an arbitrary score: 0 = normal; 1 = less than 3 erosions; 2 = 3-15 erosions; 3 = more than 15 erosions or ulcer; 4 = giant ulcer (greatest dimension of more than 2 cm) or multiple ulcers with cumulative greatest dimension exceeding 2 cm. RESULTS: Mean score increased significantly in the placebo and misoprostol groups, either after CMF (P < 0.001 and P < 0.05, respectively) or after 5-FU (P < 0.001 for both), whereas it did not in the omeprazole group. Gastric and duodenal ulcers were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.05 after both CMF and 5-FU). No significant difference was observed between placebo and misoprostol. Omeprazole was significantly more effective than placebo and misoprostol in reducing the frequency and degree of the endoscopic worsening, either after CMF or after 5-FU (P < 0.05 for both CT regimens). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.01) or misoprostol (P < 0.001). CONCLUSIONS: The strong and prolonged inhibition of gastric acid production induced by omeprazole seems to be effective in preventing chemotherapy-induced gastroduodenal mucosal injury. Further trials are necessary to verify whether such a prevention of endoscopically observed injury can translate into prevention of clinically significant injury.     

Serum lipids in patients with liver disease (author''s transl)

A long-term controlled therapeutic trial of gefarnate (600 mg daily) in the treatment of chronic gastric ulcer was carried out in 32 patients. Assessment was based on the clinical course and on repeated radiological and endoscopic examinations, which were performed after 3-months' treatment, at the end of the 1-year trial period, and towards the end of a follow-up period of approximately 2 1/2 to 3 1/2 years. In men with gastric ulcer, gefarnate proved to be highly effective, with 10 out of the 11 patients who received this treatment showing persistent healing of the ulcer compared with only 4 out of the 11 who were on dummy treatment. In the very small group of women it was not possible to show any difference between treatments. No adverse reactions to gefarnate occurred. These results suggest that gefarnate is a safe and effective treatment for chronic gastric ulcer.     

The course of the reparative process in patients with gastric and duodenal peptic ulcers (a clinico-statistical study)

Clinico-statistical evaluation of reparative process in 332 gastric ulcer and 294 duodenal ulcer patients revealed factors of objective value to its course. In order of significance the factors rank as follows: area of ulcer, localization, combination with certain mucosal erosions, total fasting acidity, free fasting hydrochloric acid, basal gastric secretion, cardial function, duodenogastric reflux, sex, age, number of cigarettes smoked daily. When studying treatment effects on regeneration in ulcer patients in is necessary to take into consideration basal clinico-endoscopic parameters.     

Renal side-effects of non-steroidal antirheumatic drugs

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are increasingly used for analgesia, as antirheumatics and to inhibit platelet aggregation. Renal side effects occur mainly in patients at risk, e.g. those with pre-existing renal insufficiency, or when used together with diuretics or a second NSAID. PATIENTS: In these patients, reversible impairment of renal function, disturbance of electrolyte homeostasis, edema and hypertension are quite common. Nephrotic syndrome with or without interstitial nephritis and renal failure is a rare complication of long-term NSAID therapy. Analgesic nephropathy may result from chronic NSAID use. These three renal complications are exemplified by case reports. CONCLUSIONS: Since side effects of NSAIDs are initially reversible, careful observation of patients can prevent chronic illness. Only rarely dialysis or treatment with glucocorticoids is indicated in patients with interstitial nephritis. Given the large number of patients taking NSAIDs, however, renal side effects are rare, and usually have no long-term consequences. Nevertheless, early detection of side effects is of importance for the prevention of long-term medical complications.     

Therapeutic indications in hemorrhaging duodenal and gastric ulcers

Ulcer complications including bleeding and perforation were increasingly observed during the last decade due to the greater life expectancy and the increased NSAID consumption. The unchanging mortality rate, which has been around 6-10% for several decades, could be explained by the fact that age and the prevalence of concurrent illness are important predictors of death. Rebleeding which is also an independent prognostic factor can be predicted by the presence of hypovolemic shock and of endoscopic stigmata such as active bleeding or a visible vessel. Endoscopic hemostatic therapy, specially injection therapy which is the most widely used method, has become the treatment of choice. It has been proven to significantly reduce rates of further bleeding, surgery and mortality. Surgical intervention is indicated in cases of immediate or secondary failure of endoscopic therapy (20%) and should not be delayed in high-risk patients. Once hemostasis has been achieved therapeutic goals are to heal the ulcer and to prevent the occurrence of further complications including bleeding and also perforation.     

Endoscopic injection treatment of gastrointestinal bleeding in hemophiliacs

The aims of this prospective study were to determine the patterns of gastrointestinal (GI) bleeding in hemophiliacs and to assess the hemostatic effect of injection therapy with alcohol. During a 5-year period (1990-1994) 89 hemophiliacs were admitted to our department with acute GI bleeding. Among these patients duodenal ulcer was found endoscopically to be the most common (42.7%) cause of hemorrhage; gastric ulcer was the source of the bleeding in only three patients (3.4%). A group of 46 patients met the criteria of active or recent bleeding and underwent injection therapy with alcohol. The injected bleeding lesions were duodenal ulcer in 32 patients, duodenal erosion in 2, gastric ulcer in 3, and other gastric lesions (Mallory-Weiss tear, Dieulafoy lesion, stomal ulcer, erosions) in 9 patients. Initial hemostasis was achieved in 100% and permanent hemostasis in 82.6%. Rebleeding was observed in eight patients (17.4%), with five of them successfully treated by reinjections. Three patients (6.5%) required emergency surgery. The mortality rate in the group of injected patients was 2.2%. One patient died of stroke on day 10 after partial gastrectomy. All injected patients were given replacement therapy with factor VIII or IX for 2 days (29 patients) or 7 to 14 days (17 patients). Analysis of the hemostatic effect achieved in these two subgroups indicate that short-term replacement therapy (2 days) may be sufficient to ensure adequate hemostasis in hemophiliacs. The results of the present study indicate that injection therapy with alcohol is an effective, safe, proved method to control GI bleeding in hemophiliacs.     

A multicenter, randomized, double-blind comparison of roxatidine with ranitidine in the treatment of patients with uncomplicated benign gastric ulcer disease. The Multicenter Roxatidine Cooperative Study Group

Roxatidine (150 mg, 312 patients) was compared with ranitidine (300 mg, 308 patients) in a randomized, double-blind, parallel-group, 6-week therapeutic study for the treatment of patients with uncomplicated, benign gastric ulcer disease. The study end points (verified by using endoscopy results) were fully healed ulcers at 4 or 6 weeks. The results of roxatidine therapy were comparable to those of ranitidine therapy: healing rates of 52% and 54% at week 4 and 77% and 76% at week 6 were recorded for roxatidine and ranitidine, respectively. The drugs produced comparable reductions in ulcer diameters and decreases in abdominal pain. Adverse events associated with both roxatidine (27%) and ranitidine (28%) were headache, diarrhea, and dizziness; rash was associated in 6 of 8 cases and in only 1 case with roxatidine. In this trial, roxatidine 150 mg once daily was as efficacious and safe as ranitidine 300 mg once daily for treatment of patients with uncomplicated, benign gastric ulcer disease.     

Multiple recurring gastric erosions/aphthous ulcers)

Five patients are described who had repeated endoscopy because of continuing dyspeptic symptoms associated with a negative barium meal. They were found to have multiple recurring gastric erosions (aphthous ulcers). No common aetiological factor could be found, although four of these patients did have a mild or moderatley active superficial chronic gastritis. Conventional peptic ulcer therapy failed to control either symptoms or ulceration. Two patients finally came to gastric surgery (highly selective vagotomy), which resulted in the relief of symptoms and healing of the gastric aphthous ulceration.     

Postoperative recurrent ulcer after gastric resection--results of surgical treatment]

Within a 10-year period, 50 patients with postoperative ulcer recurrence after gastric resection were treated; 31 of these had one, 8 two, 5 three and 6 four previous gastric operations. Ulcer recurrence was attributed to surgery-related causes in 78% of the cases; excessively large gastric remnant 56%, anastomotic stenosis 18%, loop problems 4%. Some 22% of the patients had causes independent of previous surgery: abuse of non-steroidal antirheumatics (NSAR) 10%, hyperacidity of normal gastric remnant 6%, Zollinger-Ellison-Syndrome 6%. The most important co-factor of ulcer genesis was chronic abuse of NSAR (38% of the total series). The interval between onset of complaints of ulcer disease and the last ulcer-dependent operation amounted on average to 13.8 (0.5-36) years. The definitive treatment of recurrent ulceration was surgery in 34 cases-indicated by ulcer complications (73.5%) or failure of medical therapy (26.5%)-and conservative treatment in 16 cases. Surgery comprised 21 re-resections, 7 thoracic truncal vagotomies 4 total gastrectomies 1 Whipple procedure and 1 enucleation of gastrinoma (hospital mortality 0%). During the follow-up period (median 7.1 years, follow-up rate 96%), the cumulative ulcer re-recurrence rate was 57% for the conservatively treated group and 17.6% for the patients treated by surgery (p < 0.05). In none of the eight patients who died during long-term follow-up was the cause of death ulcer-related.     

Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

BACKGROUND: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.     

Efficacy of famotidine in the healing of active benign gastric ulceration: comparison of nonsteroidal anti-inflammatory- or aspirin-induced gastric ulcer and idiopathic gastric ulceration. Long Island Jewish Medical Center Acid-Peptic Study Group

Seventy-one of 85 consecutive patients with endoscopically confirmed active benign gastric ulcers completed an 8-week study to evaluate the effects on healing of famotidine 40 mg given as a single dose at night. The healing rate in the 48 patients in whom the ulcers were associated with nonsteroidal anti-inflammatory drug (NSAID) or aspirin (ASA) use was compared with that in the 23 patients with idiopathic ulcers. Endoscopy, symptom assessments, antacid use, hematology, and serum chemistry were performed at weeks 4 and 8 of treatment. Famotidine 40 mg at bedtime healed 63 (89%) of the 71 ulcers at 8 weeks; the healing rate for NSAID/ASA-associated ulcers was 46 (96%) of 48, which was significantly greater than that for idiopathic ulcers (17 of 23; 74%) (P = 0.0119). Of the 54 patients who returned a questionnaire 1 to 2 years after completing the study, 20% were still taking an NSAID/ASA (mainly for cardiovascular prophylaxis). About half of the patients surveyed were taking anti-ulcer medication. None of these patients had experienced any serious ulcer complication. The results of this study suggest that differentiating NSAID/ASA-induced ulcers from idiopathic ulcers may be important with regard to healing rates and duration of therapy.     

The role of endogenous acid in the development of acute gastric ulcer induced by ischemia-reperfusion in the rat

We investigated the role of endogenous gastric acid in the development of gastric ulcer from erosion induced by ischemia-reperfusion of the celiac artery in the rat. A half-hour clamping of the celiac artery (ischemia) caused acute gastric erosions 1 hour after reperfusion and such acute injuries progressed to ulcers 48-72 hours after reperfusion without any necrotizing agents. Gastric acid secretion decreased immediately after ischemia and didn't recover until 12 hours after reperfusion. Intraperitoneal administrations of cimetidine (100 mg/kg, every 12 hours) or omeprazole (30 mg/kg, every 24 hours) were started at 1, 6, or 12 hours after reperfusion. When administrations were started 1 hour after reperfusion, both drugs significantly decreased the total damaged area and prevented the progression of gastric erosions to ulcers. However, administrations started 6 or 12 hours after reperfusion failed to inhibit the total damaged area and to prevent ulcer formation. These results suggest that endogenous gastric acid may play an important role in the progression of gastric erosions to ulcers although ischemia itself reduces acid secretion. Furthermore, treatment with anti-acid-secretory drugs in the early stage of mucosal damage may be important for the prevention of ulcer.     

The medical care of patients with gastrointestinal bleeding after endoscopy

After endoscopic hemostasis, eradication therapy should be given to those who are infected by H. pylori to prevent ulcer relapse and recurrent bleeding. Maintenance acid suppression is not required after successful eradication of H. pylori. Proton pump inhibitor is preferred for the healing of NSAID-induced ulcers. Use of the lowest possible dose, or discontinuation of NSAIDs, is recommended for those with history of ulcer disease. High risk patients who require long-term NSAID therapy should be put on maintenance misoprostal.     

Goal attainment and life satisfaction: variables under study

AIM: The study of clinical running of gastric or duodenal ulcer in associated coronary heart disease (CHD). MATERIALS AND METHODS: 209 CHD patients with gastric ulcer (GU) or duodenal ulcer (DU) were examined clinically plus histological examination of gastric or duodenal mucosa biopsies was made. RESULTS: In CHD patients GU occurred more frequently (56%) than DU. The lesions involved more frequently lesser curvature of the stomach and pyloric part of the stomach. Males developed ulcers 3.5 times more frequently than females. Ulcers tended to a painless course without season exacerbations. The disease manifested first with gastric bleeding in 52% of the patients. GU and DU ran with frequent recurrences and long-term exacerbations (76% of patients) which coincided in time with CHD exacerbations. 68% of patients developed exacerbations within 10 days after myocardial infarction or aortocoronary bypass operation. Helicobacter pylori was present as a resolving factor in arising ulcer in 26% of patients. Microcirculatory disorders, reduced blood flow speed in gastric or duodenal mucosa, hypocoagulation syndrome, dyslipidemia provoked exacerbations in 62% of patients. Examinations of biopsies from gastric and duodenal mucosa showed marked dystrophic changes in the mucosa, its connective tissue basis in the vessels in the presence of mild inflammation at ulcer site. CONCLUSION: The onset of ulcers and erosions in the mucosa of the gastrointestinal tract in CHD may be due to circulatory disorders in gastric mucosa. The main factors of aggression are hypoxia, hypoxia-induced trophic defects in gastric and duodenal mucosa, circulatory disorders.