bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of proton pump inhibitors for cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes
Authors: AMANO Y. , CHINUKI D. , YUKI T. , TAKAHASHI Y. , ISHIMURA N. , KAZUMORI H. , KUSHIYAMA Y. , KARIM RUMI M. A. , ISHIHARA S. , KINOSHITA Y.
Published: July 2010

Background

Controversy exists concerning the efficacy of acid suppressants in the regression of Barrett's oesophagus.

Aim

To evaluate the effect of proton pump inhibitors on cyclooxygenase‐2 expression, cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes.

Methods

Four hundred and sixty‐six biopsy samples of Barrett's oesophagus from 358 non‐treatment patients and 81 from 61 chronic proton pump inhibitor users were immunohistochemically examined using anti‐cyclooxygenase‐2 protein, anti‐proliferating cell nuclear antigen and anti‐single stranded DNA antigens in both mucin phenotypes of Barrett's oesophagus.

Results

Prevalence of the cyclooxygenase‐2 expression pattern did not significantly differ between the non‐treatment and proton pump inhibitor users. In those using proton pump inhibitors, significant suppression of the proliferating cell nuclear antigen index was found in Barrett's oesophagus with the gastric‐predominant mucin phenotype, but not with the intestinal‐predominant mucin phenotype. Apoptosis indices in chronic proton pump inhibitor users did not significantly differ between the two mucin phenotypes.

Conclusions

Proton pump inhibitors suppress cellular proliferation in Barrett's oesophagus with the gastric‐predominant mucin phenotype but not in that with the intestinal‐predominant mucin phenotype. This finding may at least partly explain the ongoing controversy surrounding the notion that all cases of Barrett's oesophagus respond to acid‐suppressive therapy.
Intravenous ghrelin administration enhances gastric acid secretion – evaluation using wireless pH capsule
Authors: MORI M. , SUZUKI H. , MASAOKA T. , IMAEDA H. , NOMOTO Y. , HOSODA H. , NISHIZAWA T. , KANGAWA K. , HIBI T.
Published: July 2010

Background

Ghrelin, a recently discovered peptide hormone, has been shown to be produced mainly by the A‐like cells of the gastric mucosa. Ghrelin not only stimulates growth hormone (GH) release but also promotes gastric motility. While the effect of ghrelin on the gastric acid secretion in rats has been reported, no such reports appeared to date from studies in humans.

Aim

To investigate the effect of ghrelin administration on the gastric pH in humans, using a novel wireless pH capsule (Bravo, Medtronic, Shoreview, MN, USA).

Methods

Four healthy volunteers (male; average age, 35.0 years; Helicobacter pylori‐negative) were enrolled. The pH capsule was attached endoscopically to the gastric mucosa and the data were transmitted to a portable receiver. Thirty minutes after a stabilization period, synthetic ghrelin (5 μg/kg body weight) was injected intravenously into the subjects and the data were monitored for more than 120 min while the subjects lay supine.

Results

The average minimum gastric pH in four cases (1.2 ± 0.10) was significantly decreased after injection of ghrelin, as compared with the basal pH value (1.8 ± 0.06). The serum gastrin level, however, showed no change after the ghrelin injection.

Conclusion

These results suggest that exogenous ghrelin could enhance gastric acid secretion in humans.
Increased levels of plasma ghrelin in peptic ulcer disease
Authors: SUZUKI H. , MASAOKA T. , NOMOTO Y. , HOSODA H. , MORI M. , NISHIZAWA T. , MINEGISHI Y. , KANGAWA K. , HIBI T.
Published: July 2010

Background

Ghrelin is a novel appetite‐promoting peptide secreted primarily from the A‐like cells in the gastric fundic mucosa. As gastric inflammation caused by Helicobacter pylori infection extends, the number of ghrelin‐producing A‐like cells is diminished and gastric ghrelin content decreases significantly. We previously reported that plasma levels of ghrelin, which correlated well with the serum levels of pepsinogen (PG) I and PG I/II ratio, decreased as gastric mucosal atrophy increased in non‐ulcerogenic conditions and that plasma ghrelin level increased in rats with cysteamine‐induced duodenal ulcer.

Aim

To investigate the plasma levels of ghrelin in patients with peptic ulcer disease.

Patients and Methods

Two hundred and eighty‐six patients with epigastric symptoms, who underwent upper gastrointestinal endoscopy, were enrolled. Blood samples were collected after a 12‐h fast before endoscopy. Patients were divided into four groups, namely chronic gastritis with high PG (n = 197), chronic gastritis with low PG (n = 58), duodenal ulcer (n = 14) and gastric ulcer (n = 17) and plasma concentrations of total and active ghrelin as well as serum concentrations of PG I and PG II were measured by radioimmunoassay. Six patients with duodenal ulcer and seven with gastric ulcer were also examined after ulcer healing.

Results

Plasma ghrelin levels were significantly higher in patients with duodenal ulcer or gastric ulcer than in those without ulcers. Elevated plasma total ghrelin levels did not significantly change after the healing of ulcers.

Conclusions

Plasma ghrelin levels were significantly higher in patients with peptic ulcer than in those with gastritis without ulcer. This finding suggests a possible relationship between mucosal injury susceptibility and elevated fasting plasma ghrelin.
Relationship between ghrelin and Helicobacter pylori infection in Polish adult shepherds and their children
Authors: PLONKA M. , KONTUREK P. C. , BIELANSKI W. , PAWLIK T. , BRZOZOWSKI T. , KONTUREK S. J.
Published: July 2010

Background

Ghrelin stimulates food intake and body weight gain. The stomach is the major source of circulating ghrelin, but controversy exists over the relationship between ghrelin release and Helicobacter pylori infection.

Aim

To assess the relationship between H. pylori infection and ghrelin, leptin and gastrin release in adult shepherds and their children, and to measure the effect of H. pylori eradication on gastric ghrelin content.

Methods

H. pylori prevalence was compared in 42 shepherds with full contact with sheep, 148 farmers without sheep contact and in 61 age‐matched urban adult controls as well as in 58 shepherd children with sheep contact, 88 mountain children without contact and 141 urban children controls. Serum levels of ghrelin, leptin and gastrin in adult shepherds and their children with and without H. pylori infection were measured.

Results

The major source of circulating ghrelin was gastric corpus mucosa, as ghrelin content was severalfold higher than that in antral mucosa and was significantly higher in the H. pylori‐eradicated than that in H. pylori‐infected mucosa. Serum levels of ghrelin were greatly increased, while gastrin levels were significantly decreased in H. pylori‐negative as compared with H. pylori‐positive subjects. In mountain children, serum levels of ghrelin and leptin were about twofold higher in H. pylori‐negative than in H. pylori‐positive children, whereas gastrin levels were significantly reduced in H. pylori‐negative children.

Conclusions

The high incidence of H. pylori infection in shepherds and their children seems to contribute to the decreased serum levels of ghrelin and increased levels of gastrin in H. pylori‐infected mountain children and to their decreased appetite and dyspeptic symptoms.
Helicobacter pylori eradication prevents the development of gastric cancer – results of a long‐term retrospective study in Japan
Authors: KATO M. , ASAKA M. , NAKAMURA T. , AZUMA T. , TOMITA E. , KAMOSHIDA T. , SATO K. , INABA T. , SHIRASAKA D. , OKAMOTO S. , TAKAHASHI S. , TERAO S. , SUWAKI K. , ISOMOTO H. , YAMAGATA H. , NOMURA H. , YAGI K. , SONE Y. , URABE T. , AKAMATSU T. , OHARA S. , TAKAGI A. , MIWA J. , INATSUCHI S.
Published: July 2010

Aim

This large‐scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan.

Methods

This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow‐up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection.

Results

Three‐thousand twenty‐one patients were enrolled. The median follow‐up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62).

Conclusion

This large‐scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.
Host serological response to Helicobacter pylori after successful eradication: long‐term follow‐up in patients with cured and persistent infection
Authors: TANAKA J. , OHKUSA T. , YOKOYAMA T. , MATSUHISA T. , KAWAI T. , HASHIMOTO H. , TOMITA T. , HORI K. , NAKAJIMA K. , MATSUMOTO T. , MIWA H.
Published: July 2010

Aim

To systematically determine the usefulness of Helicobacter pylori IgG antibody titer decline as a predictor of treatment success after H. pylori eradication in large patient samples.

Patients and Methods

Serum samples from 258 H. pylori positive patients (52.8 yrs, 65% males) were retrospectively collected from five medical centers, and H. pylori titers were quantitatively determined by ELISA. Serial serum samples were collected at baseline and for up to 4.9 years after treatment. 169 patients underwent successful eradication while 89 remained infected. The median total observation period was 635 days (range, 51 to 1,800 days). Chronological changes in H. pylori titers were analyzed and compared between cured and infection persistent subjects.

Results

The proportion of infection persistent patients who developed negative H. pylori IgG antibody titers was below 5%. A receiver operating characteristic (ROC) curve for the confirmation of successful eradication according to the percent decline over baseline at each time‐point showed that a 60% decline at 1 year or more after eradication treatment strongly correlated with successful eradication (sensitivity = 90% and specificity = 87%).

Conclusion

A 60% decline in H. pylori IgG titers (HEL‐p kit) from baseline to one year or greater is a reliable predictor of successful H. pylori eradication.
Review article: anti‐tryptase therapy in inflammatory bowel disease
Authors: YOSHIDA N. , ISOZAKI Y. , TAKAGI T. , TAKENAKA S. , UCHIKAWA R. , ARIZONO N. , YOSHIKAWA T. , OKANOUE T.
Published: July 2010

A number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases.

Tryptase is one of the serine proteases that stored almost exclusively in the secretory granules of mast cells. It acts to induce microvascular leakage, the chemotaxis of inflammatory cells, and stimulates the release of inflammatory cytokines through the mitogen‐activated protein kinase /activator protein‐1 pathway and protease‐activated receptor (PAR) nuclear factor‐κB pathway.

Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis.

The effect of anti‐tryptase therapy on human inflammatory bowel disease and experimental colitis has been demonstrated. The result of a pilot study has revealed that systemic administration of a specific tryptase inhibitor is safe and there is evidence of activity in the treatment of ulcerative colitis. Recently, we found that nafamostat mesilate, which selectively inhibits tryptase activity at low concentration, could reduce intestinal inflammation in rats. In addition, nafamostat mesilate enema improved clinical and endoscopic findings in ulcerative colitis patients, resistant to conventional therapy such as corticosteroids and sulfasalazine/5‐aminosalicylic acid.

These studies suggest that anti‐tryptase therapy may represent a new therapeutic strategy for human inflammatory bowel disease.
Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer
Authors: KOBAYASHI T. , SAKAGAMI T. , KOIZUKA H. , YAMAMOTO N. , SASAKI T. , MAEDA Y. , OMURO Y. , OKAMOTO R. , MIKOSHIBA M. , SASAKI E. , MATSUMOTO T. , MIWA H.
Published: July 2010

Background

No adequate second‐line chemotherapy regimen for advanced gastric cancer is available.

Aims

To determine the safety and optimal dose of paclitaxel/irinotecan as a second‐line chemotherapy for patients with advanced and recurrent gastric cancer.

Patients and methods

Sixteen patients with refractory and advanced measurable gastric cancer who were resistant to 5‐FU plus cis‐diamminedichloroplatinum (CDDP) therapy (FP) were enrolled. Paclitaxel/irinotecan was given intravenously on days 1, 8, and 15 in repeated 4‐week cycles. Paclitaxel/irinotecan doses were escalated in a stepwise fashion as follows: 50/40 mg/m2, 50/50 mg/m2, 50/60 mg/m2, 60/60 mg/m2, 60/70 mg/m2 in levels I, II, III, IV and V, respectively.

Results

Because of one patient with Grade 3 febrile neutropenia at level I, three more patients were enrolled in level I. Doses were consequently escalated, and in level IV, Grade 3 febrile neutropenia occurred in one patient. Since an additional patient in level IV had grade 4 neutropenia, Level IV was judged as the maximum tolerated dose (MTD). The recommended dose and schedule for phase II study is paclitaxel 50 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every 4 weeks. Partial response was observed in 4 of 16 patients.

Conclusion

Paclitaxel/irinotecan combination regimen at the level III dosage was safe and well tolerated.
Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells
Authors: FUJII Y. , SHIMADA T. , KOIKE T. , HOSAKA K. , TABEI K. , NAMATAME T. , TAJIMA A. , YONEDA M. , TERANO A. , HIRAISHI H.
Published: July 2010

Trefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.

Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach.

TFF1 was originally discovered as an oestrogen‐inducible gene in MCF‐7 breast cancer cells, and its expression is dependent on oestrogen in MCF‐7 and other hormone‐dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis‐regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL‐6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.

Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue‐specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.
Discrimination between gastric ectopic pancreas and mesenchymal tumours, including GIST – from 12 years‘ surgical experience in one institute
Authors: OTANI Y. , YOSHIDA M. , SAIKAWA Y. , WADA N. , KUBOTA T. , KUMAI K. , SUGINO Y. , MUKAI M. , KAMEYAMA K. , KITAJIMA M.
Published: July 2010

Background

Although recent immunochemical analysis enabled the discrimination of gastrointestinal stromal tumour (GIST) to other mesenchymal tumours, preoperative diagnosis of these tumours is not always easy.

Aim

To discriminate between ectopic pancreas (EP) and mesenchymal tumours, including GIST, 12 years surgical experience at Keio University Hospital was reviewed.

Methods

Clinicopathological findings were analysed for 131 patients with gastric submucosal tumours (SMT), including GIST (67 cases), myogenic tumour (21 cases), Schwannoma (11 cases), EP (12 cases) and others (20 cases) surgically treated at Keio University Hospital since 1993.

Results

Analysis of clinicopathological findings of these tumours showed that GIST, myogenic tumour and Schwannoma mimic each other from the standpoint of size and location of the tumour. In contrast, comparison of mesenchymal tumours showed that, compared with gastrointestinal mesenchymal tumour, EP tends to exist at middle or lower third of the stomach (P = 0.004), and the tumour size was smaller than 3 cm (P = 0.0006). All EPs were laparoscopically resected and no malignant features were evident.

Conclusion

To avoid unnecessary surgery for EP, SMT smaller than 3 cm occurring in the middle or lower third of the stomach should be carefully selected as a candidate of surgical resection.
Review article: the role of bile and pepsin in the pathophysiology and treatment of gastro‐oesophageal reflux disease
Authors: TACK J.
Published: July 2010

Gastro‐oesophageal reflux disease is a multifaceted and multifactorial disorder which results from the reflux of gastric contents into the oesophagus. Animal studies suggest that synergism between acid and pepsin and conjugated bile acids have the greatest damaging potential for oesophageal mucosa, although unconjugated bile acids may be caustic at more neutral pH.

Human studies are compatible with a synergistic action between acid and duodenogastric reflux in inducing lesions. During prolonged monitoring studies, typical gastro‐oesophageal reflux symptoms are more related to acid reflux events than to non‐acid reflux events.

However, symptoms that persist during acid suppressive therapy are often related to non‐acid reflux events. The therapeutic options for the non‐acid component of the refluxate, including acid suppression, prokinetics, baclofen, surgery and mucosal protective agents like alginates, are discussed.
Comparison of gastric pH with omeprazole magnesium 20.6 mg (Prilosec OTC) o.m. famotidine 10 mg (Pepcid AC) b.d. and famotidine 20 mg b.d. over 14 days of treatment
Authors: MINER P. B. , ALLGOOD L. D. , GRENDER J. M.
Published: July 2010

Background

The onset of acid inhibition for proton pump inhibitors is slower than with H2RAs and generally considered to be at a steady‐state after 5 days. Thus, little direct comparison data exists between H2RAs and proton pump inhibitors for gastric acid suppression on day 1 of therapy. Furthermore, the durability of their acid suppression has not been systematically compared.

Aim

To compare the effects of 20.6 mg omeprazole magnesium o.m. (Ome‐Mg 20), famotidine 10 mg b.d. (Fam 10) and famotidine 20 mg b.d. (Fam 20) on intragastric pH on day 1 and throughout 14 days of dosing.

Methods

The study was a randomized, double‐blind, three‐dosing regimens, three‐period crossover. Healthy adults with frequent heartburn (≥2 days/week) underwent 24‐h gastric pH monitoring on days 0 (baseline), 1, 3, 7 and 14.

Results

Thirty‐one subjects were included in the per‐protocol analyses. On day 1, the mean percentage time pH > 4 (pH4%) was higher for Ome‐Mg 20, 44.6%, than for Fam 10, 36.7% (P = 0.032), and not different from Fam 20, 46.9% (P = 0.541). The pH4% was higher for Ome‐Mg 20 than either famotidine regimen on all subsequent monitoring days (P < 0.001). The 24‐h area under the mean intragastric pH curve showed a similar pattern. Furthermore, after day 1, Ome‐Mg 20 demonstrated an increasing and sustained effect in contrast to a decreasing effect for famotidine, consistent with H2RA tolerance.

Conclusion

Gastric acid suppression on Ome‐Mg 20 mg o.m. over 14 days was comparable with Fam 10 mg b.d. or Fam 20 mg b.d. on day 1, and superior thereafter.
Review article: medical management of the liver transplant recipient – a primer for non‐transplant doctors
Authors: SETHI A. , STRAVITZ R. T.
Published: July 2010

Background

Survival 10 years after orthotopic liver transplantation now approaches 65%. Consequently, community doctors must manage the metabolic and neoplastic complications of orthotopic liver transplantation in an ageing population.

Aims

To review common sources of morbidity and mortality in long‐term orthotopic liver transplantation recipients, and to make evidence‐based recommendations regarding their management.

Methods

Pertinent studies and reviews were identified by literature search through PubMed. Where evidence‐based recommendations could not be gleaned from the literature, expert opinion was obtained from syllabi of national meetings.

Results

The two most common causes of morbidity and mortality in orthotopic liver transplantation recipients are atherosclerotic vascular disease andde novomalignancy. The pathogenesis of many complications begins before orthotopic liver transplantation, and many are potentially modifiable. Most complications, however, can be directly ascribed to immunosuppressive agents. Despite improvements in our understanding of the pathogenesis and epidemiology of the metabolic and neoplastic complications of orthotopic liver transplantation, remarkably few randomized‐controlled studies exist to define their optimal management.

Conclusions

Orthotopic liver transplantation recipients experience and succumb to the same afflictions of old age as non‐transplant patients, but with greater frequency and at an earlier age. Most recommendations regarding surveillance for, and treatment of, medical complications of orthotopic liver transplantation remain based upon expert opinion rather than evidence‐based medicine.
Perioperative acute upper gastrointestinal haemorrhage in older patients with hip fracture: incidence, risk factors and prevention
Authors: FISHER L. , FISHER A. , PAVLI P. , DAVIS M.
Published: July 2010

Background

No specific preventive strategy exists for acute gastrointestinal haemorrhage in hip fracture patients.

Aims

To determine the effectiveness of prophylactic use of proton pump inhibitors in patients with risk factors for acute gastrointestinal haemorrhage.

Methods

Prospective two‐stage study of 822 consecutive older (≥60 years) hip fracture patients.

Results

Acute gastrointestinal haemorrhage occurred in 16 (3.9%) of 407 patients and was associated with increased length of hospital stay (28.7 vs. 15.9; P = 0.0027) and mortality (18.8% vs. 4.3%; P = 0.043). Multiple analysis identified five independent risk factors for acute gastrointestinal haemorrhage: pre‐existing peptic ulcer (OR 4.3; P = 0.043), current smoking (OR 3.1; P = 0.023), post‐operative use of an antiplatelet agent (OR 6.5; P = 0.046), post‐operative use of non‐steroidal anti‐inflammatory drug/cyclo‐oxygenase‐2 inhibitor (OR 4.9; P = 0.06) and blood group O (OR 1.7; P = 0.046). These risk factors were highly sensitive and had a negative predictive value of 99.8%. Prophylactic use of proton pump inhibitors in patients with risk factor for acute gastrointestinal haemorrhage significantly reduced the incidence of this complication (0.72% in treated patients vs. 13.4% in untreated; P < 0.001); the number needed to treat was 7.9.

Conclusions

In older hip fracture patients perioperative acute gastrointestinal haemorrhage occurs in 3.9% and is associated with poor outcome. Preventive proton pump inhibitor therapy in patients at risk of acute gastrointestinal haemorrhage is effective and safe.
GI Epidemiology: databases for epidemiological studies
Authors: DAVILA J. A. , EL‐SERAG H. B.
Published: July 2010

Background

Large databases are being increasingly used for examining the epidemiology and outcomes of digestive and liver disorders. The complexity and rigor of the methods used to conduct these studies are often underestimated.

Aims

For the most commonly used databases, we provide a brief description of the contents, highlight strengths and weakness, and provide links for more detailed information. We also present a systematic approach to utilizing large databases for addressing research questions, highlighting commonly encountered study design issues, as well as strategies for resolving these issues.

Conclusions

1. Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions.

2. The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered.

3. Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential.

Key points

•Large databases can be a powerful source of information to examine the clinical epidemiology and outcomes of digestive and liver disorders.

• Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions.

• The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered.

• Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential.

• Examples of commonly used large databases are presented with a synopsis of information contained in the database, as well as strengths and limitations of using the database for research.
Combined type‐1 plasminogen activator inhibitor and NOD2/CARD15 genotyping predicts complicated Crohn's disease behaviour
Authors: ALVAREZ‐LOBOS M. , AROSTEGUI J. I. , SANS M. , TASSIES D. , PIU J. , REVERTER J. C. , PIQUE J. M. , YAGÜE J. , PANÉS J.
Published: July 2010

Background

NOD2/CARD15 gene variants have not been universally associated with stricturing behaviour in Crohn's disease. Other behaviour modifying genes could explain these results.

Aim

To study the combined influence of NOD2/CARD15 variants and 4G/4G genotype of type‐1 plasminogen activator inhibitor (PAI‐1) gene on Crohn's disease behaviour.

Methods

One hundred and seventy Crohn's disease patients were studied prospectively, with a mean follow‐up of 7± 6 years. Disease behaviour was registered by using two criteria: the Vienna classification and a non‐hierarchical classification based on the behavioural Vienna categories.

Results

In the multivariate analysis for stricturing behaviour according to the Vienna categories, only absence of colonic disease (OR, 4.0; 95% CI: 1.49–11.1; P = 0.006) was an independent predictive factor. However, in the multivariate analysis for stricturing disease applying a non‐hierarchical criteria, ileal disease (OR, 4.19; 95% CI: 1.30–13.5; P = 0.01), and carrying both NOD2/CARD15 variants and the 4G/4G PAI‐1 genotype (OR, 5.02; 95% CI: 1.44–17.48; P = 0.01) were independent predictive factors. In the multivariate analysis for penetrating behaviour, the 4G/4G PAI‐1 (OR, 3.10; 95% CI: 1.54–6.23; P = 0.001) and male sex (OR, 2.44; 95% CI: 1.30–4.60; P = 0.005) were independent predictive factors irrespective of criteria applied.

Conclusions

Combined PAI‐1 and NOD2/CARD15 genotyping predict complicated Crohn's disease. Patients with these variants could benefit from early interventions.
Efficacy of esomeprazole for resolution of symptoms of heartburn and acid regurgitation in continuous users of non‐steroidal anti‐inflammatory drugs
Authors: HAWKEY C. J. , JONES R. H. , YEOMANS N. D. , SCHEIMAN J. M. , TALLEY N. J. , GOLDSTEIN J. L. , AHLBOM H. , NÆSDAL J.
Published: July 2010

Background

The use of non‐steroidal anti‐inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation.

Aim

To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs.

Methods

A post hoc analysis of five clinical trials was performed. Two identically designed, placebo‐controlled, 4‐week studies (NASA1, SPACE1) enrolled non‐ulcer, NSAIDs‐treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo‐controlled, 6‐month studies that enrolled patients at risk of NSAIDs‐induced ulcers. Study 285 was an 8‐week comparative study with ranitidine (300 mg/day) in patients with NSAIDs‐induced gastric ulcers. Resolution of investigator‐assessed heartburn and acid regurgitation was defined as symptom severity of ‘none’ in the last 7 days.

Results

In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P ≤ 0.001), and than with ranitidine in study 285 (P < 0.05 for esomeprazole 20 mg).

Conclusion

Heartburn and regurgitation are common in patients taking NSAIDs and esomeprazole is efficacious for resolution of these symptoms.
The safety of endoscopic sphincterotomy in patients receiving antiplatelet agents – a case–control study
Authors: HUSSAIN N. , ALSULAIMAN R. , BURTIN P. , TOUBOUTI Y. , RAHME E. , BOIVIN J. ‐F. , BARKUN A. N.
Published: July 2010

Objective  To determine whether antiplatelet agents are associated with endoscopic sphincterotomy‐related haemorrhage as few well‐controlled data exist on this controversial issue.

Methods  A case–control study in a tertiary care setting included cases with bleeding following endoscopic sphincterotomy, matched with 2–3 controls selected according to age ± 15 years, sex, and procedural date± 2 years. Cases and controls were compared for possible risk factors of postendoscopic sphincterotomy bleeding (presence of a coagulopathy and cholangitis). The main outcome measurement was the association between the use of antiplatelet medications and postendoscopic sphincterotomy bleeding after adjustment for possible confounding.

Results  The 40 cases [mean age 68 ± 17 (s.d.) years, 50% female] and 86 controls [68 ± 16 years, 50% female] were comparable except for differences noted in International Normalized Ratio (INR) (>2 in four cases vs. two controls), and pre‐endoscopic sphincterotomy cholangitis (45% vs. 20%). Amongst cases, 13% were on aspirin and 3% on clopidogrel; 17% of controls took aspirin, and 4% a non‐steroidal anti‐inflammatory drug. 53% of cases bled immediately; the remainder haemorrhaged at 2 ± 3 days. After adjustment for an elevated INR and cholangitis, exposure to antiplatelet agents was not significantly associated with procedure‐related bleeding (odds ratio = 0.41, 95% CI [ 0.13; 1.31]).

Conclusion  This case–control study provides controlled data suggesting that antiplatelet agents do not significantly increase the risk of clinically‐important bleeding related to endoscopic sphincterotomy. The low prevalences of non‐steroidal anti‐inflammatory drugs and clopidogrel use limit any definite conclusion on their elective use before endoscopic sphincterotomy.
Predictors of reduced health‐related quality of life in adults with coeliac disease
Authors: HÄUSER W. , STALLMACH A. , CASPARY W. F. , STEIN J.
Published: July 2010

Background  Data available on predictors of reduced health‐related quality of life in coeliac disease are not consistent.

Aim  To test predictors of reduced health‐related quality of life, described in the literature, by a multivariate approach.

Methods  1000 adult coeliacs of the German Coeliac Society completed a medical and a sociodemographic questionnaire, the Short‐Form Health Survey (SF‐36), the Coeliac Disease Questionnaire and the Hospital Anxiety and Depression Scale within a postal survey. Predictors of reduced health‐related quality of life were tested for by logistic regression analysis.

Results  Physical comorbidities (β = −0.41; OR = 0.66, P < 0.001) and mental disorder (β = 0.88; OR = 2.4, P = 0.03) were associated with a reduced physical summary score of the SF‐36. Mental disorder (β = 2.5; OR = 11.9, P < 0.001), physical comorbidities (β = −0.26; OR = 0.77, P = 0.004) and younger age at diagnosis (β = −0.10; OR = 0.91, P = 0.05) predicted a reduced mental summary score of the SF‐36. Mental disorder (β = 0.90; OR = 2.5, P = 0.03), non‐compliance with gluten‐free diet (β = 0.44; OR = 1.6, P = 0.009), active medical comorbidities (β = −0.28; OR = 0.76, P = 0.007) and dissatisfaction with doctor–patient communication (β = 0.55; OR = 1.7, P = 0.03) were associated with reduced Coeliac Disease Questionnaire scores.

Conclusions  Reduced health‐related quality of life in coeliac disease is associated not only with physical and mental comorbidities, but also with non‐compliance with gluten‐free diet and dissatisfaction with doctor–patient communication.
An open‐label study of chronic polyethylene glycol laxative use in chronic constipation
Authors: DI PALMA J. A. , CLEVELAND M. VB. , MCGOWAN J. , HERRERA J. L.
Published: July 2010

Background

Polyethylene glycol 3350 (MiraLAX, Braintree Laboratories Inc., Braintree, MA, USA) is approved for the short‐term treatment of occasional constipation.

Aim

To extend the safety data of polyethylene glycol used for chronic treatment of chronic constipation.

Methods

Study subjects who met defined criteria for chronic constipation were enrolled in this open‐labelled, single‐treatment multi‐centre study to receive polyethylene glycol laxative as a single daily dose of 17 g for 12 months. Subjects returned to their study centres after 2, 4, 6, 9 and 12 months of treatment where blood and urine samples were collected and adverse events were reviewed. At each visit, subjects were queried for ROME constipation criteria and they rated their overall improvement using a global efficacy scale.

Results

311 patients including 117, age 65 and older, were enrolled and received treatment at one of 50 centres. One hundred and eighty‐four completed all 12 months of treatment. With respect to the ‘Global Efficacy Assessment’, depending on the month of observation, 80–88% of enrolled patients, and 84–94% of the elderly, were treated successfully. Similar results were obtained from secondary efficacy measures that assessed individual ROME constipation criteria at each visit. The response to treatment was durable over time. Over the 1‐year course of study representing 218 patient‐years at the labelled dose, medication‐associated adverse effects were gastrointestinal complaints of diarrhoea, loose stool, flatulence and nausea. These effects were generally mild or moderate in severity. There were no clinically significant changes in haematology or blood chemistry, particularly electrolytes, for the study population as a whole or the elderly group.

Conclusions

Polyethylene glycol laxative is safe and effective for treating constipation in adult and elderly patients for periods up to 12 months, with no evidence of tachyphylaxis.
The changing incidence of oesophageal and gastric adenocarcinoma by anatomic sub‐site
Authors: CRANE S. J. , RICHARD LOCKE G. , HARMSEN W. S. , DIEHL N. N. , ZINSMEISTER A. R. , JOSEPH MELTON L. , ROMERO Y. , TALLEY N. J.
Published: July 2010

Background

The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub‐sites.

Aim

To use a population‐based approach to describe the trends in the site‐specific incidence of oesophageal and gastric adenocarcinoma.

Methods

Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified (n = 186). Complete in‐patient and out‐patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports.

Results

Between the decades of 1971–1980 and 1991–2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person‐years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person‐years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person‐years) was as common as gastric adenocarcinoma (3.4 per 100 000 person‐years) in 1991–2000.

Conclusions

The incidence rates of adenocarcinoma involving proximal gastric sub‐sites do not appear to be increasing in a manner similar to those involving oesophageal sub‐sites.
The Short‐Form Leeds Dyspepsia Questionnaire validation study
Authors: FRASER A. , DELANEY B. C. , FORD A. C. , QUME M. , MOAYYEDI P.
Published: July 2010

Background

Assessment of symptoms should be the primary outcome measure in dyspepsia clinical trials. This requires a reliable, valid and responsive questionnaire that measures the frequency and severity of dyspepsia. The Leeds Dyspepsia Questionnaire fulfils these characteristics, but is long and was not designed for self‐completion, so a shorter questionnaire was developed (the Short‐Form Leeds Dyspepsia Questionnaire).

Aim

To assess the acceptability, interpretability, internal consistency, reliability, validity and responsiveness of the Short‐Form Leeds Dyspepsia Questionnaire in primary and secondary care.

Methods

Unselected primary and secondary care patients completed the Short‐Form Leeds Dyspepsia Questionnaire. Test–retest reliability was assessed after 2 days. Validity was measured by comparison with general practitioners’ diagnosis. Sensitivity analysis and logistic regression were employed to determine the most valid scoring system. Responsiveness was determined before and after treatment for endoscopically proven disease.

Results

The Short‐Form Leeds Dyspepsia Questionnaire was administered to 388 primary care and 204 secondary care patients. The Pearson coefficient for test–retest reliability was 0.93. The Short‐Form Leeds Dyspepsia Questionnaire had a sensitivity of 77% and a specificity of 75%. A highly significant response to change was observed (P < 0.005).

Conclusions

The Short‐Form Leeds Dyspepsia Questionnaire is a reliable, valid and responsive self‐completed outcome measure for quantifying the frequency and severity of dyspepsia symptoms, which is shorter and more convenient than the Leeds Dyspepsia Questionnaire.
Meta‐analysis: cancer risk of low‐grade dysplasia in chronic ulcerative colitis
Authors: THOMAS T. , ABRAMS K. A. , ROBINSON R. J. , MAYBERRY J. F.
Published: July 2010

Background

The cancer risk of low‐grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious.

Aim

To determine the risk of cancer or any advanced lesion once LGD is diagnosed.

Methods

A MEDLINE, EMBASE and Pub Med search was conducted using the key words ‘surveillance’, ‘colorectal cancer’, ‘low‐grade dysplasia’ and ‘ulcerative colitis’. A random effects model of meta‐analysis was used.

Results

Twenty surveillance studies had 508 flat LGD or LGD with dysplasia‐associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post‐LGD diagnosis (range: 3–7.6). An average of 18 biopsies taken per colonoscopy (range: 9–24) detected 73 advanced lesions (cancer or high‐grade dysplasia) pre‐operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0–34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12–76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0–20.5) and 12‐fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2–27).

Conclusions

The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision‐making when LGD is encountered on surveillance.
Variability of the area under the receiver operating characteristic curves in the diagnostic evaluation of liver fibrosis markers: impact of biopsy length and fragmentation
Authors: POYNARD T. , HALFON P. , CASTERA L. , CHARLOTTE F. , BAIL B. LE , MUNTEANU M. , MESSOUS D. , RATZIU V. , BENHAMOU Y. , BOURLIÈRE M. , LEDINGHEN V. DE ,   THE FIBROPACA GROUP
Published: July 2010

Background

The area under the receiver operating characteristic (ROC) curve is widely used as an estimate of the diagnostic value for fibrosis markers. Biopsy length and fragmentation are known as risk factors of false positive or false negative of biopsy but their quantitative impact on area under the receiver operating characteristic curve variability has not been assessed.

Aim

To assess these relationships to better compare the fibrosis markers.

Methods

The area under the ROC curves of FibroTest for the diagnosis of fibrosis was estimated in patients with chronic hepatitis C using an integrated database including 1312 patients with FibroTest and biopsy. To take into account the biopsy length, we used two adjustment factors: one in which an observed area under the ROC curve could be adjusted according to the relative area under the receiver operating characteristic curve of a biopsy of a given length vs. the entire liver and one taking into account the prevalence of each fibrosis stage defining advanced and non‐advanced fibrosis.

Results

The mean biopsy length was smaller for cirrhosis (F4, 16 mm) vs. F3, (18 mm, P = 0.01) and F0 (19 mm, P = 0.01). The mean number of fragments was higher for cirrhosis (F4 = 4.1 fragments) vs. all the other stages (F0 = 1.9, F1 = 1.9, F2 = 1.9, F3 = 2.3; P < 0.001 vs. F4). The FibroTest area under the ROC curves for the diagnosis of advanced fibrosis, adjusted for stages’ prevalence, ranged from 0.80 to 0.98 depending on biopsy length and fragmentation, respectively.

Conclusion

The comparison of the area under the ROC curves of fibrosis markers should take into account the biopsy length and fragmentation.
Hyperhomocysteinaemia is associated with osteoporosis in patients with Crohn’s disease
Authors: ROBLIN X. , PHELIP J. M. , GENEVOIS M. , DUCROS V. , BONAZ B.
Published: July 2010

Background

A high prevalence of osteoporosis is observed in Crohn’s disease. Recent data have shown that homocysteinaemia is an important risk factor in low‐bone mineralization and fracture.

Aim

To look for an association between homocysteinaemia and low‐bone mineralization in Crohn’s disease patients.

Patients and methods

Ninety‐two consecutive patients (sex ratio M/F 0.87; mean age: 36.6 ± 13.2 years) were recruited between 2003 and 2005. Bone densitometry was performed on inclusion. The following parameters were analysed: age, sex, Crohn’s Disease Activity Index, duration and extent of Crohn’s disease, smoking status, corticosteroid treatment, immunosuppressive drugs, plasma homocysteine, folate and vitamin B12 concentration.

Results

The prevalence of a high homocysteine level (>15 µmol/L) was 60%. Osteoporosis and low‐bone mineralization observed in 26 (28%), and 60 (65%) patients, respectively. On a multivariate analysis, associated factors for osteoporosis and low‐bone mineralization were respectively: hyperhomocysteinaemia (OR: 61.4; CI: 95: 23–250; P < 0.001), and ileal Crohn’s disease [OR: 13.8; CI: 95: 2.5–150; P =  0.036] for osteoporosis and hyperhomocysteinaemia [OR: 63.7; CI: 95: 8.5–250; P < 0.001] and disease duration of at least 5 years [OR: 11.4; CI: 95: 1.31–99; P =  0.039] for low‐bone mineralization. Results were similar whichever site osteoporosis was detected.

Conclusion

Hyperhomocysteinaemia was observed in 60% of our Crohn’s disease patients and was strongly associated with low‐bone mineralization and osteoporosis (OR: 61.4).
Is there a benefit from intensified medical and psychological interventions in patients with functional dyspepsia not responding to conventional therapy?
Authors: HAAG S. , SENF W. , TAGAY S. , LANGKAFEL M. , BRAUN‐LANG U. , PIETSCH A. , HEUFT G. , TALLEY N. J. , HOLTMANN G.
Published: July 2010

Aim In a prospective randomized, controlled trial, to compare the long‐term outcome of intensive medical therapy (with or without cognitive‐behavioural or muscle relaxation therapy) vs. standard medical therapy in patients with refractory functional dyspepsia (FD), referred to a tertiary referral medical center.

Methods A total of 100 consecutive FD patients were allocated to a standardized symptom‐oriented 4 month therapy (SMT, n = 24), intensive medical therapy (IMT, medical therapy with testing‐for and targeting‐of abnormalities of motor‐and‐sensory function, n = 28) or IMT plus psychological interventions (either progressive‐muscle relaxation (IMT‐MR, n = 20) or cognitive‐behavioural therapy (IMT‐CBT, n = 28). The symptom intensity (SI) and health‐related quality‐of‐life (HRQoL) after 12 months were prespecified primary outcome parameters.

Results After 12 months, significantly greater improvement of SI occurred in patients with IMT‐all (with or without psychological interventions) compared with SMT (P < 0.025 vs. IMT‐all). IMT, IMT‐MR and IMT‐CBT alone also resulted in significantly better improvement of the primary outcome parameters (P all < 0.025 vs. SMT). HRQoL significantly improved in all groups with intensive medical therapy but not standard medical therapy. Differences between intensive medical therapy‐all and standard medical therapy were not significant. Concomitant anxiety and depression was improved significantly by IMT‐CBT (vs. SMT) but not other treatments.

Conclusions In FD patients with refractory symptoms, intensified medical management involving function testing and psychological intervention yields superior long‐term‐outcomes. Additional CBT may be effective for the control of concomitant anxiety and depression.
Air swallowing, belching, acid and non‐acid reflux in patients with functional dyspepsia
Authors: CONCHILLO J. M. , SELIMAH M. , BREDENOORD A. J. , SAMSOM M. , SMOUT A. J. P. M.
Published: July 2010

Background Frequent belching is a common symptom in patients with functional dyspepsia with a reported incidence up to 80%. We hypothesized that patients with functional dyspepsia possibly have a higher frequency of belching than healthy subjects secondary to frequent air swallowing.

Aim To assess air swallowing, belching, acid and non‐acid reflux patterns of patients with functional dyspepsia.

Methods Combined 24‐h oesophageal impedance and pH monitoring was performed in 10 functional dyspepsia patients and 10 controls. Analysis of the impedance‐pH signals included incidence of air swallows, belching, acid and non‐acid reflux.

Results The incidence of air swallows in functional dyspepsia patients were significantly higher compared with controls (153 ± 15 vs. 79 ± 10, P < 0.001), while the incidence of liquid‐only swallows were not significantly increased. The proportions of gas‐containing reflux episodes (belches) and non‐acid reflux episodes in functional dyspepsia patients were significantly higher when compared with controls (66.4 vs. 44.4%, P = 0.04 and 70.1 vs. 45.9%, P = 0.009, respectively).

Conclusion Patients with functional dyspepsia swallow air more frequently than controls and this is associated with an increased incidence of non‐acid gaseous gastro‐oesophageal reflux.