Pekka Miettinen

Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group.

BACKGROUND AND AIM The efficacy of antireflux surgery (ARS) and omeprazole treatment in the control of gastrooesophageal reflux disease (GORD) are well established. We have compared these two therapeutic options in a randomized, clinical trial. PATIENTS AND METHODS Three hundred and ten patients with erosive oesophagitis were enrolled into the trial. After a run-in period when all patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and relieve symptoms, 155 patients were randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. One hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups, respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and endoscopy were used to document the outcome. Quality of life was evaluated by the psychological general well-being (PGWB) index and the gastrointestinal symptom rating scale (GSRS). RESULTS Analysis of time to treatment failure (defined as moderate to severe GORD symptoms for > or = 3 days during the last 7 days, oesophagitis or changed therapy) revealed a significant difference in favour of antireflux surgery (P = 0.0016). Seventeen patients originally submitted to antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at endoscopy and another six had omeprazole for different reasons, leaving 97 patients in clinical remission after 3 years. The corresponding figures in the omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving 77 patients in remission. Allowing a dose adjustment in the case of relapse in those on omeprazole therapy to either 40 or 60 mg, the curves describing the failure rates were not significantly different from each other. Quality of life assessment showed a comparable outcome in the two study groups. CONCLUSION In this randomized multicentre trial we found antireflux surgery to be very efficacious in controlling GORD, a level of control which could also be achieved by omeprazole provided that advantage was taken of the opportunity of adjusting the dose.

Comparison of Outcomes Twelve Years After Antireflux Surgery or Omeprazole Maintenance Therapy for Reflux Esophagitis

BACKGROUND & AIMS It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease (GERD). In a 12-year study, we compared the effects of therapy with omeprazole with those of antireflux surgery. METHODS This open, parallel group study included 310 patients with esophagitis enrolled from outpatient clinics in Nordic countries. Of the 155 patients randomly assigned to each arm of the study, 154 received omeprazole (1 withdrew before therapy began), and 144 received surgery (11 withdrew before surgery). In patients who remained in remission after treatment, post-fundoplication complaints, other symptoms, and safety variables were assessed. RESULTS Of the patients enrolled in the study, 71 who were given omeprazole (46%) and 53 treated with surgery (37%) were followed for a 12-year follow-up period. At this time point, 53% of patients who underwent surgery remained in continuous remission, compared with 45% of patients given omeprazole with a dose adjustment (P = .022) and 40% without dose adjustment (P = .002). In addition, 38% of surgical patients required a change in therapeutic strategy (eg, to medical therapy or another operation), compared with 15% of those on omeprazole. Heartburn and regurgitation were significantly more common in patients given omeprazole, whereas dysphagia, rectal flatulence, and the inability to belch or vomit were significantly more common in surgical patients. The therapies were otherwise well-tolerated. CONCLUSIONS As long-term therapeutic strategies for chronic GERD, surgery and omeprazole are effective and well-tolerated. Antireflux surgery is superior to omeprazole in controlling overall disease manifestations, but post-fundoplication complaints continue after surgery.

Regular-dose versus High-dose Omeprazole in Peptic Ulcer Bleeding A Prospective Randomized Double-blind Study

Background: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. Methods: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. Results: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled ( P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. Conclusion: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.BACKGROUND It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.

Expression of the Splicing Factor Gene SFRS10 is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis

Alternative mRNA splicing provides transcript diversity and may contribute to human disease. We demonstrate that expression of several genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. We evaluated a representative splicing factor, SFRS10, downregulated in both obese human liver and muscle and in high-fat-fed mice, and determined metabolic impact of reduced expression. SFRS10-specific siRNA induces lipogenesis and lipid accumulation in hepatocytes. Moreover, Sfrs10 heterozygous mice have increased hepatic lipogenic gene expression, VLDL secretion, and plasma triglycerides. We demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10; reduced SFRS10 favors the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished lipogenic effects of decreased SFRS10 expression. Together, our results indicate that reduced expression of SFRS10, as observed in tissues from obese humans, alters LPIN1 splicing, induces lipogenesis, and therefore contributes to metabolic phenotypes associated with obesity.

Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized study with special reference to obesity.

BackgroundMinilaparotomy cholecystectomy (MC) has recently challenged the role of the laparoscopic approach (LC) for cholecystectomies. However, the situation is far from clear when operating times and recovery are evaluated.MethodsAltogether 157 patients with uncomplicated symptomatic gallstones were randomized into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of age, body mass index, American Society of Anesthesiology (ASA) physical fitness classification, and operating surgeon.ResultsThe mean operating time was 55 ± 19.5 min in the MC group and 79 ± 27.0 min in the LC group (p < 0.0001). The postoperative hospital stay and length of sick leave did not differ between the two groups. There were no significant differences in postoperative pain, analgesic consumption, or postoperative pulmonary function between the groups. The body mass index did not influence operating time or patient recovery in either group. No major complications occurred in either groups.ConclusionThe MC procedure seems to be a faster technique than the LC approach for noncomplicated gallstone disease, with no difference in recovery times. The MC procedure also seems to be suitable for the obese patient.

Analysis of the risk factors and their combinations in acute gastroduodenal ulcer bleeding: A case-control study

Objective. Traditional non-steroidal anti-inflammatory drugs (NSAIDs) including ASA for thrombosis prophylaxis (ASA-TP), for pain medication (ASA-P) or non-ASA NSAIDs (NANSAIDs), Helicobacter pylori infection, CagA strains of H. pylori and smoking are reported risk factors for peptic ulcer bleeding (PUB), but the combined and the dose effects of these factors are controversial. The aim of this study was to estimate the significance of these risk factors and their combinations in PUB. Material and methods. PUB patients (n=94) were compared with an age- (±5 years) and gender-matched control group of non-ulcer patients (n=94) attending elective endoscopy. A questionnaire on the possible risk factors (previous gastric and duodenal ulcer, use of ASA-TP, ASA-P, NANSAIDs, warfarin, alcohol and smoking) was completed. H. pylori infection was determined as positive if histology and/or urease tests were positive. CagA antibodies of IgG class were determined using an immunoblot method. Results. H. pylori infection (odds ratio (OR) 8.8), the use of ASA-P (OR 3.5), ASA-TP (OR 4.07), NANSAIDs with ≥1 defined daily dose (OR 6.56), smoking ≥20 cigarettes daily (OR 6.43) and previous duodenal ulcer (DU) (OR 8.96) were independent risk factors for PUB. At least two risk factors were present in 65% of PUB patients. CagA strains were detected in 97% of the H. pylori-positive cases and in 96% of the respective controls. ASA, ibuprofen, ketoprofen and smoking were dose-dependent risk factors for PUB. Conclusions. Previous DU, H. pylori, the use of any ASA and smoking explained the majority of the PUB episodes. CagA strains of H. pylori were not associated with PUB. Two-thirds of the PUB patients had at least two risk factors, but their combination did not potentiate the risk.

Structure and function of medial temporal and posteromedial cortices in early Alzheimer’s disease

Medial temporal lobe (MTL) atrophy and posteromedial cortical hypometabolism are consistent imaging findings in Alzheimer’s disease (AD). As the MTL memory structures are affected early in the course of AD by neurofibrillary tangle pathology, the posteromedial metabolic abnormalities have been postulated to represent remote effects of MTL alterations. In this study, we investigated with functional MRI (fMRI) the structure–function relationship between the MTL and posteromedial regions, including the retrosplenial, posterior cingulate and precuneal cortices, in 21 older controls (OCs), 18 subjects with amnestic mild cognitive impairment (MCI) and 16 AD patients during a word list learning task. In the voxel‐based morphometric and volumetric analyses, the MCI subjects showed smaller entorhinal volume than OCs (P = 0.0001), whereas there was no difference in the hippocampal or posteromedial volume. AD patients, as compared with MCI patients, showed pronounced loss of volume in the entorhinal (P = 0.0001), hippocampal (P = 0.01) and posteromedial (P = 0.001) regions. The normal pattern of posteromedial fMRI task‐induced deactivation during active encoding of words was observed bilaterally in the OCs, but only in restricted unilateral left posteromedial areas in the MCI and AD patients. Across all subjects, more extensive impairment of the retrosplenial and posterior cingulate function was significantly related to smaller entorhinal (P = 0.001) and hippocampal (P = 0.0002) volume. These findings demonstrate that entorhinal atrophy and posteromedial cortical dysfunction are early characteristics of prodromal AD, and precede and/or overwhelm atrophy of the hippocampus and posteromedial cortices. Disturbances in posteromedial cortical function are associated with morphological changes in the MTL across the continuum from normal aging to clinical AD.

Seasonal variations of acute appendicitis and nonspecific abdominal pain in Finland

AIM To investigate whether seasonal changes had an effect on the incidence of acute appendicitis (AA) or nonspecific abdominal pain (NSAP). METHODS We carried out a national register study of all patients with a hospital discharge diagnosis of AA and acute NSAP in Finland. Data were analyzed for the whole country and correlated to seasonal and weather parameters (temperature, humidity). Moreover, additional sub-analyses were performed for five geographically different area of Finland. RESULTS The observation period spanned 21 years, with 186558 appendectomies, of which 137528 (74%) cases were reported as AA. The incidence of AA declined for 32% over the study period. The average incidence of the NSAP was 34/10000 per year. The mean annual temperature, but not relative humidity, showed clear geographical variations. The incidence of AA decreased significantly during the cold months of the year. No correlation was detected between temperature and incidence of NSAP. Humidity had a statistically significant impact on NSAP. CONCLUSION The incidence of acute appendicitis is declining in Finland. We detected a clear seasonality in the incidence of AA and NSAP.

Effect of Short-term Treatment with Regular or High Doses of Omeprazole on the Detection of Helicobacter pylori in Bleeding Peptic Ulcer Patients

Background: It is unknown whether short-term regular or high-dose omeprazole has any influence on the colonization of Helicobacter pylori in the stomach. We therefore studied the effect of 3-day treatment of 2 different doses of omeprazole. Methods: H. pylori -positive patients with peptic ulcer bleeding ( n r = r 101) were randomized to receive either a regular dose (20 r mg/day for 3 days) ( n r = r 51) or a high dose of omeprazole (80 r mg bolus r + r 8 r mg/h infusion/day for 3 days) ( n r = r 50). H. pylori status was assessed by histology and urease testing of gastric biopsies pre-entry and after 3-day therapy. Results: With the high dose of omeprazole, tests for the diagnosis of H. pylori became negative significantly more often than with the regular dose (60% versus 27.5%, P r = r 0.001 (any test), 67.6% versus 31.7%, P r = r 0.003 (histology) and 82.2% versus 43.6%, P r = r 0.001 (urease test)). Conclusion: Conversion of the H. pylori tests negative after 3-day treatment of omeprazole is dose-dependent. The diagnosis of H. pylori infection depends on the timing of biopsies in relation to the beginning of proton-pump inhibitor treatment. If samples to find H. pylori are not taken before the treatment, the presence of the bacteria may be overlooked.Background: It is unknown whether short-term regular or high-dose omeprazole has any influence on the colonization of Helicobacter pylori in the stomach. We therefore studied the effect of 3-day treatment of 2 different doses of omeprazole. Methods: H. pylori -positive patients with peptic ulcer bleeding ( n r = r 101) were randomized to receive either a regular dose (20 r mg/day for 3 days) ( n r = r 51) or a high dose of omeprazole (80 r mg bolus r + r 8 r mg/h infusion/day for 3 days) ( n r = r 50). H. pylori status was assessed by histology and urease testing of gastric biopsies pre-entry and after 3-day therapy. Results: With the high dose of omeprazole, tests for the diagnosis of H. pylori became negative significantly more often than with the regular dose (60% versus 27.5%, P r = r 0.001 (any test), 67.6% versus 31.7%, P r = r 0.003 (histology) and 82.2% versus 43.6%, P r = r 0.001 (urease test)). Conclusion: Conversion of the H. p...

The effect of regular and high doses of omeprazole on the intragastric acidity in patients with bleeding peptic ulcer treated endoscopically: a clinical trial with continuous intragastric pH monitoring.

Objective In peptic ulcer bleeding (PUB), pH level >4 is considered necessary to prevent dissolving of a formed fibrin clot. The effect of regular or high doses of omeprazole on the intragastric pH in patients with acute PUB was studied. Methods In our earlier study, after endoscopic therapy, PUB patients were randomized to receive a regular dose of intravenous omeprazole (20 mg; i.e. 60 mg/3 days) or a high dose of omeprazole (80 mg bolus+8 mg/h; i.e. 652 mg/3 days). Of these 142 analysed and reported patients, 13 PUB patients also had intragastric pH monitoring for these 3 days; seven of these patients had a regular dose and six received a high dose of omeprazole. Results The mean 24-h intragastric pH (regular versus high dose) on day 1 was 4.9±1.6 versus 6.3±0.5 (P=0.035), on day 2 was 4.9±1.8 versus 6.7±0.3 (P=0.001), and on day 3 was 5.7±1.1 versus 6.7±0.5 (P=NS). The medians of the intragastric pH were 6 versus 6.5 (P=0.082) on day 1, 5.8 versus 6.8 (P=0.001) on day 2, and 6.2 versus 6.8 (P=0.17) on day 3. The proportion of time when pH <4 on day 1 was 29.2±34.1 versus 5.4±5.7% (P=NS). Conclusions A regular dose of omeprazole raises the mean and median 24-h intragastric pH >4 in patients with PUB. This reduction in the acidity together with endoscopic therapy is probably sufficient to maintain haemostasis. A high dose of omeprazole keeps the pH almost constantly >6.