Prevention of duodenal ulcer recurrence with 15 mg lansoprazole: a double-blind placebo-controlled study. The Lansoprazole Study Group

Although eradication of Helicobacter pylori cures duodenal ulcer, some patients are not infected and others are treatment failures. This randomized, double-blind, placebo-controlled study assessed the value of treatment with low-dose lansoprazole in preventing duodenal ulcer recurrence. One hundred eighty-six patients with endoscopic documentation of healed duodenal ulcer received 15 mg/day lansoprazole or placebo for 12 months or until ulcer recurred. Endoscopy results, symptom assessment, and fasting serum gastrin levels were obtained at multiple time points. Densities of E, EC, and G cells were assessed by biopsy when the ulcer recurred or at the final visit. Time to ulcer recurrence was significantly longer (P < 0.001) in the lansoprazole group (median >12 months) compared to placebo (median <3 months), and patients taking lansoprazole were asymptomatic longer (P < 0.05). Maintenance therapy with lansoprazole 15 mg/day suppresses acid and controls recurrence of duodenal ulcer disease.     

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.     

Seasonal behaviour of healed duodenal ulcer

Incidence of peptic ulcer is more in people living at higher altitude and similarly relapse of healed duodenal ulcer is more in winter season. Seasonal behaviour of healed duodenal ulcer with or without maintenance therapy with H2 blockers was studied among subjects residing around Shimla (approximate altitude 7000 feet above mean sea level). Sixty-four subjects of endoscopically healed duodenal ulcer were alternatively advised placebo (32 subjects) and ranitidine 150 mg (32 subjects) at bed time as maintenance therapy for period of one year. Subjects were reviewed endoscopically and evaluated for H pylori by rapid urease test, every months or earlier if symptomatic. Relapse rate was analysed among 60 subjects at the end of one year. Cumulative relapse rate was found 60% in ranitidine group and 100% in placebo group. In ranitidine group percentage of relapse to number of endoscopic examinations was 21.4% throughout the year, but in placebo group during winter and spring season relapse was 87.5% of endoscopic examination whereas 57.2% during summer and fall season. Incidence of duodenal ulcer relapse without maintenance therapy was more in winter and spring season (October to March) as compared to summer and fall (April to September), whereas intermittent seasonal treatment is efficacious in prevention of duodenal ulcer relapse and also improves cost benefit ratio of ulcer treatment.     

Histamine and peptic ulcer: a prospective study of mucosal histamine concentration in duodenal ulcer patients and in control subjects suffering from various gastrointestinal diseases

In a prospective study the histamine content of the mucosa of the body of the stomach was measured in 100 patients consisting of control subjects, patients with duodenal ulcer and patients suffering from various gastrointestinal diseases. The histamine content was found to be 43 mug/g in male control subjects (median) while in duodenal ulcer patients levels attained were significantly lower by about 30 per cent. In all the other groups of patients histamine concentrations in gastric mucosa were found to be "normal". Since in most species it is extremely diffcult to alter the mucosal histamine concentration by any form of treatment, the diminished histamine content of the gastric mucosa in patients with duodenal ulcer seems remarkable. Among several possible explanations offered for this finding we think the most likely is that histamine release is increased in duodenal ulcer disease.     

Problems with parsimony in sequences of biased base composition

In almost all eradication regimens, which contain antibiotics and bismuth derivatives, the administration of acid suppressing drugs for 4-6 weeks is recommended for healing of duodenal ulcer. The aim of this multicenter double blind study is to elucidate the effect of two classic antibiotics tetracycline (CAS 60-54-8) and metronidazole (CAS 443-48-1) alone or combined with ranitidine (CAS 66357-35-5) on the healing of duodenal ulcer and eradication of Helicobacter Pylori. Patients with duodenal ulcer were randomized to two treatment groups: group A received either ranitidine 4 x 150 mg or tetracycline 4 x 500 mg or metronidazole 3 x 250 mg for 2 weeks. Group B received 4 x placebo + tetracycline and metronidazole as in group A for 2 weeks. A final endoscopy was performed after 8 weeks. Four biopsy specimens were obtained from the antrum (two) and corpus (two) for both urease test and hematoxylin stain for detection of H. pylori. Out of 201 patients entering the study 156 completed the study (78 in A and 78 in B). The healing rate of duodenal ulcer was 98.7% in group A and 97.5 in group B. The eradication rate was only 33.3% in group B but 64% in group A (p < 0.001), when additionally ranitidine was given. The present study shows that treatment with the two antibiotics tetracycline and metronidazole alone results in a very low H. pylori eradication, but almost complete healing of duodenal ulcer after 8 weeks. Prolonged administration of antisecretory drugs in eradication regimens containing two antibiotics is not necessary for duodenal ulcer healing. However, the addition of H2-receptor antagonists or proton pump inhibitors to antibiotics increases the eradication rate.     

Effect of chronic duodenal ulceration and its treatment with lanzoprazole or sucralfate on gastroduodenal mucosal protein turnover and TGF-alpha, bFGF, and EGF receptor expression in humans

In order to investigate whether chronic duodenal ulcer disease is a consequence of disturbed mucosal turnover and growth factor expression, we studied 16 patients with duodenal ulcers before, during, and after endoscopic healing with lansoprazole or sucralfate. Before treatment, gastric fundal and antral mucosal protein turnover rates were higher in patients than controls, without parallel increases in growth factors. Both forms of therapy produced similar changes, with overall increases in duodenal mucosal turnover and transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGF-r) levels. Measurements after healing showed persistent elevations of mucosal turnover in the antrum and duodenum and depressions of basic fibroblast growth factor (bFGF) in gastric fundal and duodenal mucosa. We conclude that mucosal turnover is abnormally high in patients with chronic duodenal ulcer disease and is not easily explained by growth factor changes. The failure of lansoprazole and sucralfate to normalize rates, despite endoscopic healing, may explain the high ulcer relapse rates in non-HP-eradicated patients.     

Triple therapy in duodenal ulcer healing--a follow up study

Thirty-nine Helicobacter pylori (HP) positive chronic duodenal ulcer patients completed the 4 weeks treatment of triple therapy (Denol, Metronidazole and Amoxil). Of these 29 showed healed duodenal ulcer and negative CLO test at 8 weeks (eradication). They were followed at 3,6 and 12 months and at each follow-up, endoscopy and CLO testing were repeated. At 12 weeks, 54% showed a healed ulcer and negative CLO and these figures reached to 69 and 66% at 6 and 12 months respectively. Thirty percent relapsed within 1 year. The present study indicates a prolonged remission of duodenal ulcer following HP eradication.     

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%.     

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (+/- SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6 +/- 2.8 and 6.8 +/- 2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P < 0.05) lower than those from dyspeptic patients (13.6 +/- 6.9 and 10.9 +/- 3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2 +/- 125.6 pg/mg tissue) was significantly (P < 0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1 +/- 188.2 pg/mg tissue) and from dyspeptic patients (276.8 +/- 138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.     

The effect of H. pylori in perforation of duodenal ulcer

BACKGROUND/AIMS: H. pylori has been described as an opportunistic pathogen attracted by changes in the gastric mucosa caused by inflammation and ulceration. However, the role of H. pylori infection in the perforation of duodenal ulcers has not yet been clearly determined. The aim of this study was to assess the prevalence of H. pylori infection in patients undergoing laparotomy for repair of a perforated duodenal ulcer. METHODOLOGY: Patients who underwent surgery for a perforated duodenal ulcer in our Surgical Unit between January 1994 and July 1996 were included in this study. The study population consisted of eighteen patients with a mean age of 32.7 (21-48) years. All of the patients were male. Patients with chronic duodenal ulcer perforation and with no contraindications for definitive surgery, such as peritonitis, shock (blood pressure <90 mm Hg), age >60 years, or more than a 12-hour elapse from the time of perforation, were treated by bilateral truncal vagotomy and Weinberg pyloroplasty. The ulcer was excised with the pyloric ring. The cut was then extented by about 2 cm on both the gastric and duodenal sides. Two biopsies were taken from the antral mucosa by endoscopic biopsy forceps. The defect was closed transversely. The ulcer specimen and the antral biopsies were fixed separately in 10% formalin solution and sent to the department of Histopathology. The specimens were stained with Hematoxylin-Eosin and examined for H. pylori . Sections of the ulcer specimen were especially investigated for the presence of H. pylori through all layers of the ulcer. RESULTS: H. pylori was found in the antral biopsies of 16 patients (88.8%). In seven of the ulcer specimens (38.8%), H. pylori was present in the mucosa and also extended through the wall of the ulcer. H. pylori was positive in the antral biopsies of all patients with H. pylori present in the ulcer wall. CONCLUSIONS: In our study, H. pylori was present at a high ratio in the antral biopsies of patients with duodenal ulcer perforation. The presence of H. pylori throughout the ulcer wall to a considerable extent emphasizes the fact that eradication of H. pylori is important in the treatment of perforated duodenal ulcer.     

Aspects of excision of the perforative duodenal ulcer complicated by penetration and stenosis

The results of treatment of 259 patients with perforative duodenal ulcer, complicated by penetration and stenosis, were analysed. The original methods of ulcer excision are proposed. Excellent and good late follow-up result was noted in 159 (84.6%) patients, fair--in 15 (8.2%), bad (ulcer recurrence)--in 8 (4.4%).     

Drug therapy of patients treated in hospitals for duodenal ulcers

Drug therapy in hospitalized patients treated for duodenal ulcer disease was reviewed retrospectively. The information was obtained by the means of a medical audit of patient records indexed by the discharge diagnosis of duodenal ulcers. A total of 485 cases were abstracted. Antacids were found to be the cornerstone of duodenal ulcer drug therapy. Anticholinergic drugs occupied a central role throughout the medical treatment of duodenal ulcers. The investigators identified a need for the dissemination of information concerning the use of anticholinergics in duodenal ulcer patients experiencing the complications of hemorrhage and obstruction.     

Characterisation of macrophage inflammatory protein-5/human CC cytokine-2, a member of the macrophage-inflammatory-protein family of chemokines

The aim of this study was to determine the level of endogenous prostaglandin E2 (PGE2), prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) in the gastric and duodenal mucosa of patients with duodenal ulcer and duodenitis. Besides, the investigation aimed at determining the effect of smoking and infection by Helicobater pylori on prostaglandin synthesis. The investigation comprised 62 patients with duodenal ulcer, 46 patients with duodenitis and 44 controls. The results of our investigation indicate that the decreased prostaglandin synthesis in gastric and duodenal mucosa determined in patients with duodenal ulcer may have a considerable role in development of duodenal ulcer. Furthermore, the harmful effects of smoking on the gastric and duodenal mucosa may be mediated by the decreased prostaglandin synthesis in the gastric and duodenal mucosa. However, Helicobacter pylori seems to affect the development of duodenal ulcer through other mechanisms.     

Bifid ribs observed in the third and the fourth ribs

The laparoscopic repair of a perforated duodenal ulcer was effectively done in two patients both of whom were poor risks for surgery. One was a 39-year-old woman with a history of bronchial asthma since she was 20 years of age, while the other was a 76-year-old man with hepatocellular carcinoma, lung cancer, and diabetes mellitus. The postoperative course of these patients was uneventful. Based on these findings, the laparoscopic repair of a perforated duodenal ulcer should thus be considered as a first choice of treatment for a perforated duodenal ulcer, even in poor-risk patients.     

Does smoking influence the eradication of Helicobacter pylori and duodenal ulcer healing with different regimens?

To determine the effect of smoking on Helicobacter pylori eradication and ulcer healing, we investigated 232 patients with H. pylori-positive duodenal ulcer. Patients were given one of seven different treatment protocols and divided into three groups according to smoking habits. Group 1 (n = 128) consisted of non-smokers, group 2 (n = 65) of mild smokers (5-20 cigarettes/day) and group 3 (n = 39) of heavy smokers (> 20/day). The eradication of H. pylori and ulcer healing rate was controlled eight weeks later after ceasing the therapy. The overall eradication rate was 66% in all patients and 68%, 66%, 59% in each group, respectively. The eradication rates showed no statistical difference between groups. Complete ulcer healing was achieved in 84% of all patients and ulcer healing rate between groups did not show any significance (85%, 83% and 82% respectively). These results suggest that smoking status does not influence the eradication of H. pylori and duodenal ulcer healing rates at eight weeks in patients on different treatment schedules.     

Duodenal bicarbonate secretion: eradication of Helicobacter pylori and duodenal structure and function in humans

BACKGROUND & AIMS: Eradication of Helicobacter pylori expedites duodenal ulcer healing and prevents recurrences. Most patients with duodenal ulcers have impaired proximal duodenal mucosal bicarbonate secretion (DMBS). In patients with inactive, healed duodenal ulcers and normal subjects, the effect of H. pylori infection on DMBS and proximal duodenal secretory function and structure were examined. METHODS: DMBS was quantitated before and after eradication of H. pylori. Mucosal structure (duodenal bulb histopathology) and function (DMBS at rest and stimulated, effect of active vs. healed ulcer and of age) were determined in patients with duodenal ulcers and normal subjects. RESULTS: In patients with duodenal ulcers, H. pylori eradication normalized proximal DMBS. Histological examination of duodenal biopsy samples was comparable in patients with duodenal ulcers and normal subjects without apparent relationship between inflammation and DMBS. Significantly impaired DMBS occurred in response to all agonists tested (luminal acid, prostaglandin E2, and cephalic-vagal stimulation) in patients with duodenal ulcers, suggesting a generalized secretory defect. Neither the presence of active (vs.inactive) ulcer nor age significantly affected bicarbonate secretion. CONCLUSIONS: In patients with duodenal ulcers, eradication of H. pylori normalized proximal DMBS and may thereby reduce ulcer recurrences. Altered DMBS in patients with duodenal ulcers was unrelated to histopathologic abnormalities. Impaired bicarbonate secretion in patients with duodenal ulcers could be caused by a cellular and/or physiological regulatory transport defect possibly related to H. pylori.     

Parietal cells in the duodenal bulb and their relation to Helicobacter pylori infection

AIM: To investigate the prevalence, and relation to Helicobacter pylori, of parietal cells in the duodenal bulb using a monoclonal antibody directed against H+,K(+)-ATPase (HK12.18). METHODS: Twenty six patients with duodenal ulcer disease and 16 healthy controls were studied. H pylori status was determined by gastric histology and culture and by the 13C-urea breath test. Four biopsy specimens were taken from the duodenal bulb and stained with HK12.18. The presence/absence and number of parietal cells in the duodenal bulb were assessed blindly by a histopathologist. RESULTS: The overall prevalence of parietal cells in the duodenal bulb was 31% (13/42) and was similar in patients with duodenal ulcer and in controls, and in H pylori positive and negative subjects. The median (range) number of parietal cells in the duodenal bulb was 7.5 (4-20) parietal cells/subject, and was similar in all four groups. CONCLUSIONS: The prevalence of parietal cells in the duodenal bulb (31%) is notably higher than previously reported in endoscopic studies, and is in keeping with reports from studies on necropsy/operative specimens. There was no difference in the prevalence or number of parietal cells in the duodenal bulb between patients with duodenal ulcer and controls, regardless of H pylori status. These findings suggest that parietal cells in the duodenal bulb do not contribute to the pathogenesis of duodenal ulcer.     

Differential north to south gastric cancer-duodenal ulcer gradient in China. China Ulcer Study Group

There are suggestions that duodenal ulcer protects individuals from gastric cancer and that rice is ulcerogenic while wheat is gastro-protective. We aimed to examine the relationship of gastric cancer, duodenal and gastric ulcers in different geographical regions in China and identified dietary risk factors for duodenal ulcer and gastric cancer. The prevalence of peptic ulcer and gastric cancer among symptomatic patients in eight major cities, four each from the north and the south representing all the six defined regions of China were studied. Endoscopy and case records over a 10 year period were reviewed and cases of confirmed duodenal and gastric ulcer and gastric cancer, together with the total number of endoscopies performed per year, were recorded. Rates were expressed as cases/1000 endoscopies. Results were compared to another epidemiological study on diet and mortality in the same regions in China conducted at the same time. Duodenal ulcer rates were 2.4-fold higher in southern China than northern China, whereas gastric cancer rates were 1.6-fold higher in the north than in the south. Correlation studies showed for the first time an inverse linear relationship between the gastric cancer rates and the duodenal ulcer rates (r=-0.8076, P=0.015), as well as the duodenal ulcer: gastric ulcer ratios (r=-0.9133, P=0.002). Gastric ulcer rates were higher in southern China but did not correlate with the gastric cancer rates (r=0.1455, P=0.731). Duodenal ulcer rates were found to be related to daily rice intake (r=0.8554, P=0.029) and inversely related to daily wheat flour intake (r=-0.8472, P=0.033). Gastric cancer rates were not related to any dietary risk factors tested. We concluded there was an inverse relationship between gastric cancer rates and duodenal ulcer rates. Although duodenal ulceration and gastric cancer are both linked to Helicobacter pylori infection, the findings of this study indicate independent additional aetiological factors for the pathogenesis of these conditions. Dietary factors such as rice or wheat intake may play a role.     

Helicobacter pylori infection and duodenal ulcer in children and adolescents

To investigate the relationship between H. pylori infection and duodenal ulcer in children and adolescents, the markers of H. pylori infection were studied in 22 children and adolescents who had duodenal ulcers and were followed prospectively (Group A). Another 36 patients with gastrointestinal symptoms, but without ulcer, were also studied for comparison (Group B). Antral and duodenal tissues were biopsied and analyzed for the presence of H. pylori using three standard methods: urease test, culture and histology. The specific IgG antibody against H. pylori positivity using the ELISA method were also analysed. By these three methods, H. pylori positivity in the antral tissues, chronic active antral gastritis, and seroprevalence rate were found to be much higher in Group A than Group B. However, a similar trend was not found in the duodenal tissues. H. pylori was found in four of five patients during postoperative follow-up for duodenal ulcer. Among the four patients, no duodenal ulcer but chronic active gastritis was detected endoscopically in three who received vagotomy. Only the one who received simple closure of the perforated duodenal ulcer had a recurrent duodenal ulcer. It was concluded that a close relationship among duodenal ulcer, chronic active gastritis and H. pylori is present in children and adolescents.     

The etiological and pathogenetic characteristics of duodenal peptic ulcer in adolescents

Studied by endoscopy were 100 adolescents with diagnosed duodenal ulcer, as were 100 essentially healthy subjects and 90 ones of the same age presenting with primary chronic gastroduodenitis together with 60 adults who had duodenal ulcer. The following items were etiologic risk factors for duodenal ulcer, if combined, in the above adolescent series: Frequent episodes nervous of tension, hereditary predisposition and helicobacteriosis. In juveniles with duodenal ulcer, secretion and motility of the stomach appeared to be subjected to changes to a higher degree than it was in adult subjects with duodenal ulcer, while functions of the psychovegetative and immune systems were found to be less changeable in the former. In adolescents presenting with duodenal ulcer and primary chronic gastroduodenitis, the etiologic risk factors and pathogenetic changes were found out to be identical.