Duodenal Ulcer Recurrence Research Articles

1034 Measures of Obesity and Risk of Gastric and Duodenal Ulcers

G A A b st ra ct s the recurrence of LDA-related peptic ulcers has not been reported. We conducted a randomized, double-blind, double-dummy, active-controlled trial to assess the efficacy, doseresponse relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients in long-term LDA therapy. Methods: Patients were eligible for the trial if they had an endoscopically confirmed gastric or duodenal ulcer scars and were receiving long-term LDA (81 mg/day or 100 mg/day) therapy for cardiovascular and cerebrovascular protection. Patients on long-term LDA therapy were also eligible if they had a previous history of endoscopically confirmed active peptic ulcers, but did not present them at baseline endoscopy. Patients were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily or teprenone (mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of gastric and duodenal ulcers over 24 weeks. Secondary endpoints included an occurrence of bleeding ulcers with stigmata of recent hemorrhage or drop in hemoglobin level of more than 2 g/dl, changes from baseline in the modified Lanza score (endoscopic scoring system for gastroduodenal damage) or upper gastrointestinal symptom score, and newly-developed erosive esophagitis. Results: Among 472 randomized patients, 452 patients (rabeprazole 10 mg, n=151; rabeprazole 5 mg, n= 150; teprenone 150 mg, n=151) constituted the full analysis set. The cumulative recurrence rates of gastric and duodenal ulcers over 24 weeks in the 5and 10-mg rabeprazole groups were 2.8% and 1.4%, respectively, and both were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 6.1%, while bleeding ulcers were not observed in the 5or 10-mg rabeprazole groups. The rates of worsening in the modified Lanza and upper gastrointestinal symptom scores in the 5and 10-mg rabeprazole groups were significantly lower than those in the teprenone group. Significantly fewer patients developed erosive esophagitis in the 5 mg rabeprazole group (2%) and 10 mg rabeprazole group (0%), compared with the teprenone group (8.6%). Rabeprazole was well-tolerated at both doses. Conclusions: Rabeprazole prevents the recurrence of gastroduodenal ulcers with no evidence of a major dose response effect in patients taking LDA, and is well-tolerated.

1032 Prevention of Recurrence of Gastric and Duodenal Ulcers by Rabeprazole in Patients Taking Low-Dose Aspirin -A Phase 2/3, Randomized, Parallel-Group, Double-Blind, Double-Dummy, Active-Controlled, Multicenter Study

1032 Prevention of Recurrence of Gastric and Duodenal Ulcers by Rabeprazole in Patients Taking Low-Dose Aspirin -A Phase 2/3, Randomized, Parallel-Group, Double-Blind, Double-Dummy, Active-Controlled, Multicenter Study

1033 Underestimation of Small Bowel Bleeding in Users of Nonselective Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Low-Dose Aspirin (ASA): A Prospective Study

G A A b st ra ct s the recurrence of LDA-related peptic ulcers has not been reported. We conducted a randomized, double-blind, double-dummy, active-controlled trial to assess the efficacy, doseresponse relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients in long-term LDA therapy. Methods: Patients were eligible for the trial if they had an endoscopically confirmed gastric or duodenal ulcer scars and were receiving long-term LDA (81 mg/day or 100 mg/day) therapy for cardiovascular and cerebrovascular protection. Patients on long-term LDA therapy were also eligible if they had a previous history of endoscopically confirmed active peptic ulcers, but did not present them at baseline endoscopy. Patients were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily or teprenone (mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of gastric and duodenal ulcers over 24 weeks. Secondary endpoints included an occurrence of bleeding ulcers with stigmata of recent hemorrhage or drop in hemoglobin level of more than 2 g/dl, changes from baseline in the modified Lanza score (endoscopic scoring system for gastroduodenal damage) or upper gastrointestinal symptom score, and newly-developed erosive esophagitis. Results: Among 472 randomized patients, 452 patients (rabeprazole 10 mg, n=151; rabeprazole 5 mg, n= 150; teprenone 150 mg, n=151) constituted the full analysis set. The cumulative recurrence rates of gastric and duodenal ulcers over 24 weeks in the 5and 10-mg rabeprazole groups were 2.8% and 1.4%, respectively, and both were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 6.1%, while bleeding ulcers were not observed in the 5or 10-mg rabeprazole groups. The rates of worsening in the modified Lanza and upper gastrointestinal symptom scores in the 5and 10-mg rabeprazole groups were significantly lower than those in the teprenone group. Significantly fewer patients developed erosive esophagitis in the 5 mg rabeprazole group (2%) and 10 mg rabeprazole group (0%), compared with the teprenone group (8.6%). Rabeprazole was well-tolerated at both doses. Conclusions: Rabeprazole prevents the recurrence of gastroduodenal ulcers with no evidence of a major dose response effect in patients taking LDA, and is well-tolerated.

Pancreatic Polypeptide-Rich Islets in the Posterior Portion of the Pancreatic Head—A Tumor Mimic in Somatostatin Receptor Scintigraphy

A 74-year-old man with recurrent duodenal ulcers underwent somatostatin receptor scintigraphy (SRS) in suspicion of gastrinoma. A 2-cm area of focal uptake was visualized within the pancreatic head. Serum chromogranin A levels were elevated, but serum gastrin levels and the secretin test were normal. Computed tomography and endoscopic ultrasonography were not conclusive. After partial duodenopancreatectomy, pathological examination failed to reveal any neuroendocrine tumor. Instead, the dorsal portion of the pancreatic head was found to be densely populated by pancreatic polypeptide cell-rich islets. This area correlated with the site of tracer uptake seen on SRS. Thus, pancreatic polypeptide cell-rich islets in elderly patients should be kept in mind when interpreting SRS results to avoid unnecessary major pancreatic resections.

Patient care services: What pharmacists do

Patient care services: What pharmacists do

APhA honors outstanding achievements at Annual Meeting

Each year, APhA recognizes exceptional contributors to the profession at the Annual Meeting. The following award winners will be honored at APhA2014 in Orlando.

Letter: lansoprazole consumption is more common in Japanese patients with collagenous colitis – authors’ reply

pean patients with CC. CC has been increasingly reported in Japan during the past decade. It is especially the case for lansoprazole-associated CC, and the consumption rate of lansoprazole in Japanese patients ranges from 53% to 83%. At our institution, lansoprazole was administered in 39 of 45 (87%) patients at the time of diagnosis. Such an obvious difference in the rate of lansoprazole use between European and Japanese patients with CC seems to be a consequence of differences in environmental and genetic factors. We experienced an intriguing case of lansoprazole-associated CC. A 77-year-old Japanese female complained of intractable watery diarrhoea, and she had been continuously taking lansoprazole for her recurrent duodenal ulcers. Because histological findings on colonic biopsy were compatible with CC, lansoprazole was changed to rabeprazole, resulting in a resolution of her symptoms. In consideration of the difference in the metabolic pathway between lansoprazole and rabeprazole, we investigated possible genetic polymorphism in CYP2C19 of the patient. She was determined to be a poor metaboliser of CYP2C19 (*3/*3) by direct sequencing analysis (Figure 1). Lansoprazole is primarily metabolised in the liver by CYP2C19. The prevalence of poor metabolisers of CYP2C19 substrates is much higher in Asians (15–30%) than in Caucasians (3–6%). It is thus possible that differences in genetically determined drug-metabolising enzyme activities contribute to the ethnic difference in the occurrence of CC. This needs to be investigated further.

Rezidivierte duodenale Ulkusblutung als Erstmanifestation einer hepatisch metastasierten solid-pseudopapillären Neoplasie des Pankreas

In a 17-year-old girl recurrent duodenal ulcer bleeding had led to severe anemia. 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. 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.

Helicobacter pylorieradication and reflux disease onset: Did gastric acid get "crazy"?

Gastroesophageal reflux disease (GORD) is highly prevalent in the general population. In the last decade, a potential relationship between Helicobacter pylori (H. pylori) eradication and GORD onset has been claimed. The main putative mechanism is the gastric acid hypersecretion that develops after bacterial cure in those patients with corpus-predominant gastritis. We performed a critical reappraisal of the intricate pathogenesis and clinical data available in this field. Oesophagitis onset after H. pylori eradication in duodenal ulcer patients has been ascribed to a gastric acid hypersecretion, which could develop following body gastritis healing. However, the absence of an acid hypersecretive status in these patients is documented by both pathophysiology and clinical studies. Indeed, duodenal ulcer recurrence is virtually abolished following H. pylori eradication. In addition, intra-oesophageal pH recording studies failed to demonstrated increased acid reflux following bacterial eradication. Moreover, oesophageal manometric studies suggest that H. pylori eradication would reduce--rather than favor--acid reflux into the oesophagus. Finally, data of clinical studies would suggest that H. pylori eradication is not significantly associated with either reflux symptoms or erosive oesophagitis onset, some data suggesting also an advantage in curing the infection when oesophagitis is already present. Therefore, the legend of "crazy acid" remains--as all the others--a fascinating, but imaginary tale.

Choledochoduodenal Fistula Associated With Recurrent Peptic Ulcer

A male 33 years of age who had a history of recurrent duodenal ulcer was admitted to our hospital because of frequent vomiting and weight loss. The blood tests showed hypokalemia and acute renal dysfunction due to dehydration. Abdominal CT revealed dilatation of the stomach with pneumobilia of the intrahepatic bile duce, and endoscopy showed duodenal ulcer with stricture of the duodenal bulb. The diagnosis of choledochoduodenal fistula due to duodenal ulcer was made, so he underwent surgical operation because the obstruction was severe. Both choledochobiliary fistula and duodenal stricture are relatively rare complications of duodenal ulcer. Here we report on a case accompanied by the both complications, requiring surgical operation. J Med Cases. 2012;3(4):243-246 doi: https://doi.org/10.4021/jmc595w

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial

BackgroundLow-dose lansoprazole has not been intensively evaluated for its efficacy in the prevention of recurrent gastric or duodenal ulcers in patients receiving long-term non-steroidal anti-inflammatory drug (NSAID) therapy for pain relief in such diseases as rheumatoid arthritis, osteoarthritis, and low back pain.MethodsThis multi-center, prospective, double-blind, randomized, active-controlled study involving 99 sites in Japan was designed to compare the efficacy of lansoprazole (15 mg daily) with gefarnate (50 mg twice daily). Patients with a history of gastric or duodenal ulcers who required long-term NSAID therapy were randomized to receive lansoprazole 15 mg daily (n = 185) or gefarnate 50 mg twice daily (n = 181) and followed up for 12 months or longer prospectively.ResultsThe cumulative incidence of gastric or duodenal ulcer at days 91, 181, and 361 from the start of the study was calculated by the Kaplan–Meier method as 3.3, 5.9, and 12.7%, respectively, in the lansoprazole group versus 18.7, 28.5, and 36.9%, respectively, in the gefarnate group. The risk for ulcer development was significantly (log-rank test, P < 0.0001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.2510 (95% CI 0.1400–0.4499). A long-term follow-up study showed an acceptable safety profile for low-dose lansoprazole therapy, with diarrhea as the most frequent adverse event.ConclusionLansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term NSAID therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-012-0541-z) contains supplementary material, which is available to authorized users.

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial

BackgroundThe efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers.MethodsPatients were randomized to receive lansoprazole 15 mg daily (n = 226) or gefarnate 50 mg twice daily (n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease.ResultsThe primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan–Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P < 0.001) lower in the lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042–0.230).ConclusionLansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-011-0397-7) contains supplementary material, which is available to authorized users.

Dietary Phytosterols Protective Against Peptic Ulceration.

BackgroundIn developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols.MethodsSterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS).ResultsThe protective phytosterol fraction was shown to consist of stigmasterol, β-sitosterol and a third as yet unidentified sterol, isomeric with β-sitosterol.ConclusionsDietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs.

Peripancreatic lymph node gastrinoma

ABSTRACTGastrinoma is one of the most symptomatic pancreatic endocrine tumors and is associated with recurrent gastric or duodenal ulcer and an induction of chronic gastric acid hypersecretion. This tumor is commonly involved within the gastrinoma triangle. Herein we report a peripancreatic lymph node gastrinoma in a 56‐year‐old man who was suffered from a recurrent duodenal or jejunal ulcer perforation. Octreotide scan detected a peripancreatic or periduodenal mass and the serum gastrin level was set in upper normal range (107.73 pg/mL). Whipple's procedure was performed. The resected specimen showed multiple duodenal ulcers, hypertrophic gastric body mucosa and an enlarged peripancreatic node, measured 1.5 × 1.0 cm in cross diameter. Microscopic examination revealed a single enlarged lymph node replaced by tumor cell nests with pale eosinophilic cytoplasm and ‘salt‐and‐pepper’ chromatin pattern. On immunohistochemical staining, the tumor cells were diffusely positive for chromogranin, synaptophysin, gastrin and focally positive for CD56. He was finally diagnosed as a primary lymph node gastrinoma. After operation, the patient revisited our hospital due to severe esophageal stricture and he underwent endoscopic esophagoplasty.

Recurrent Duodenal Ulcer Due to Nonsteroidal Anti-Inflammatories Following the Suspension of Antiulcer Medication

The patient was a 62-year-old woman with a personal history of chronic alcoholism and a medical history of duodenal ulcer, congestive heart failure, atrial fibrillation, dilated cardiomyopathy, and recurring urinary tract infections. She had osteoporosis, cirrhosis of the liver and portal hypertension. She had undergone surgery for multiple arm fractures after an accidental fall in the previous year and had received NSAIDs without concomitant gastric protection. On the fourth day of hospitalization she had an episode of haematemesis. The patient continued to take NSAIDs as required, as well as habitual medication of propranolol 40 mg/day, spironolactone 25 mg/day, furosemide 40 mg/day, pantoprazole 40 mg/day and strontium 2 g/day. Upper digestive endoscopy (UDE) revealed level I/II (Baveno) oesophageal varicose veins with no signs of haemorrhage and portal hypertensive gastropathy. The duodenal bulbous was deformed by an extensive ulcer with blood clots and one vessel was visible along the antero-superior portion (Forrest IIa classification). Numerous superficial ulcers with haemosiderin pigment at D2 were observed. Endoscopic haemostasis was achieved with epinephrine and bipolar probe. Food was suspended and the patient received continuous intravenous treatment with pantoprazole 8 mg/h. UDE repeated after 48 hours showed no signs of haemorrhaging from the ulcer. After 72 hours, the pantoprazole dose was changed to 40 mg every 12 hours and food was allowed. After 12 days with no recurrence of the haemorrhagic incident, the patient was prescribed oral pantoprazole 40 mg once daily and released from hospital.

Assessing the risks and benefits of treating Helicobacter pylori infection

Since the discovery of Helicobacter pylori by Warren and Marshall [Marshall and Warren, 1984] in 1982, much has been learned about this Gram-negative microaerophilic bacterium and its associated pathology. In 1994, the National Institutes of Health recognized that most recurrent duodenal and gastric ulcers were caused by H. pylori and antibiotic treatment was recommended. In the same year, the International Agency for Research on Cancer (IARC) declared H. pylori to be a group I human carcinogen for gastric adenocarcinoma [IARC, 1994]. Since then, physicians have been working diligently in diagnosing and treating H. pylori. Despite the fact that evidence has shown clearly H. pylori to be the culprit for gastritis, peptic ulcers and gastric malignancies including mucosa associated lymphoid tissue (MALT) lymphoma and gastric adenocarcinoma, the effect of H. pylori treatment in patients with gastroesophageal reflux disease remains controversial. In this review, we will discuss the risks and benefits of the treatment of H. pylori in different disease entities. This is summarized in Table 1. Table 1. Summary of benefits and risks of H. pylori eradication. Evidence of the clinical benefits of H. pylori eradication Gastric and duodenal ulcer The strong association between H. pylori infection and peptic ulcer disease is unarguable. Meta-analysis studies have showed superior ulcer remission rate for both gastric and duodenal ulcer in patients successfully eradicated of H. pylori infection [Singh and Ghoshal, 2006; Leodolter et al. 2001]. H. pylori eradication therapy was also more superior and cost-effective than maintenance acid suppressive therapy in preventing duodenal ulcer [Ford et al. 2004]. A study by Sharma et al. [2001] also found that H. pylori eradication was more successful in decreasing recurrent gastroduodenal ulcer bleeding compared with ulcer healing treatment alone (17% versus 4% respectively). Maintenance acid suppression therapy was also not necessary after successful H. pylori eradication and ulcer healing [Liu et al. 2003].

Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: A Case Report

An ectopic opening of the common bile duct into the duodenal bulb is a very rare congenital malformation of the bile duct, which may cause a recurrent duodenal ulcer or biliary diseases including choledocholithiasis or cholangitis. ERCP plays major role in the diagnosis of this biliary malformation. We report a case of an ectopic opening of the common bile duct into the duodenal bulb, which was detected on the upper gastrointestinal series.

Duodenal ulcers dominate acute upper gastrointestinal tract bleeding in childhood: A 10‐year experience from Hong Kong

Systematic reports on acute upper gastrointestinal bleeding in children/adolescents are scanty. The aim of this study is to analyze its presentation, pathology and outcome in Hong Kong. A retrospective review of the hospital database for admissions up to the age of 18 years with signs of acute upper gastrointestinal bleeding between 1 June 1996 and 31 May 2006. During the 10-year period 76 patients (55 boys) were admitted with signs of upper gastrointestinal bleeding. The median age was 13.5 (range 0.25-18) years. Melena and hematemesis were by far the most frequent presentations. Medication was implicated in 16 cases (21%) as the possible cause for the bleeding. Endoscopic findings were a duodenal ulcer in 57 (75%) patients (50 boys) and a gastric ulcer in eight (10.5%). Helicobacter pylori infection was identified in 42 (55%) patients, of which 38 were found in duodenal ulcer patients. Eleven patients (14.5%) had interventions to achieve hemostasis: six epinephrine spray only, three thermal probe and two vessel ligation. After a median follow-up time of 3.5 years six patients had a recurrent duodenal ulcer. Three patients died of unrelated illnesses. Acute upper gastrointestinal tract bleeding in children and adolescents in Hong Kong is dominated by a duodenal ulcer in 75% of the patients. Acute bleeding is more frequent in boys (boy to girl ratio 2.6:1). Medication is a predisposing factor in 20% of the bleedings. Six patients (8%) have recurrent duodenal ulcers.

The course of gastric type epithelium in duodenal ulcer and duodenitis; role on the eradication of Helicobacter pylori

The course of gastric type epithelium during the healing process and beyond the scarring stage of duodenal ulcer was studied in patients with and without Helicobacter pylori (H. pylori) eradication. Materials were consist of 110 patients with active H. pylori ulcers, 27 patients with H. pylori positive ulcer scars and 6 patients with active H. pylori positive duodenitis. The results obtained were as follows. 1) In the non-eradication group, the degree of gastric type epithelium increased as the ulcers healed, but gastric type epithelium remained immature compared with the eradication group. 2) In the non-eradication group, the degree of gastric type epithelium decreased subsequently with or without recurrence of the duodenal ulcer. Under H. pylori positive condition, the degree of gastric type epithelium appeared to be reduced because of invasion by H. pylori. When this condition continued, ulcers probably recurred because of diminished defences against acid in damaged areas of gastric type epithelium. 3) In the successful eradication group, gastric type epithelium became well developed and mature state (grade 4), and remained in this condition for long period because it was not invaded by H. pylori. The appearance of mature state of gastric type epithelium appears to play a role in the prevention of ulcer recurrences by maintaining an adequate defence mechanisms against acid. 4) In the unsuccessful eradication group, the degree of gastric type epithelium remained lower mature state than that of successful eradication group. 5) In cases of H. pylori positive ulcer scar, the degree of gastric type epithelium reached also well developed and mature state when H. pylori was successfully eradicated, and maintained in this condition for a prolonged period. Ulcer recurrence was not observed. 6) In case of H. pylori positive duodenitis, the degree of gastric type epithelium reached mature state after successful eradication, and endoscopic findings of inflammation was improved.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding

To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. Electronic databases and major conference proceedings were searched up to February 2006. Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.