Patient adherence to prescribed medication instructions for dyspepsia: the DIAMOND-study.

BACKGROUND: Insight into patient adherence is needed to enable an effect evaluation of medication for dyspepsia. OBJECTIVES: Adherence was explored by investigating two adherence outcome measures (completeness and intake fidelity) using data from the DIAMOND-study. METHODS: The DIAMOND-study is a pragmatic RCT comparing a 'step-up' with a 'step-down' treatment strategy. In step 1 participants (n =653) were instructed to use five pills/day for maximally 30 days: an antacid 4dd plus a placebo 1dd ('step-up') or a proton pump inhibitor 1dd plus a placebo 4dd ('step-down'). If the complaints persisted, step 2 was started (H(2)-receptor antagonist 2dd), and subsequently step 3 (five pills/day, placebo and verum vice versa from step 1). Completeness was assessed by pill counts, intake fidelity by patient questionnaires measuring the degree to which patients adhered to specific instructions concerning timing, frequency, dose and way of intake. RESULTS: In step 1, patients used on average 3.9 pills/day (78% of the prescribed doses), in step 2, 1.7 pills/day (85%) and in step 3, 3.6 pills/day (72%). For the four times daily pills, half of the patients used less than 80% of the prescribed pills per day. This was one third of the patients for the twice daily pills and one quarter for the once daily pills. There were no completeness differences between active or placebo medication and no differences between the study arms. As regards intake fidelity, 70% of the patients made one or more errors in the medication intake. CONCLUSION: There is room for improvement in adherence rates for dyspepsia medication.

Effect of proximal gastric volume on hiatal hernia.

BACKGROUND: Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro-esophageal reflux. This can be studied with high-resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. METHODS: Twenty gastro-esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High-resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three-dimensional ultrasonography before and every 15 min after meal ingestion. KEY RESULTS: During fasting, the hernia profile [2 separate high-pressure zones (HPZs) at manometry] was present for 31.9 +/- 4.9 min h(-1) (53.2%) in GERD patients, and 8.7 +/- 3.3 min h(-1) (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 +/- 4.2 min h(-1), 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 +/- 1.1 per hour in GERD patients and 2.5 +/- 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 +/- 1.1 per hour and 18.4 +/- 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 +/- 0.6 per hour; P < 0.05 and 3.8 +/- 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = -0.45; P < 0.05) in GERD patients, but not in controls. CONCLUSIONS & INFERENCES: (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra-thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.

In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epithelium.

Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6-12% and SAP > or = 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P-value < 1(E)- 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell-cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function.

High prevalence of esophageal involvement in lichen planus: a study using magnification chromoendoscopy.

BACKGROUND AND STUDY AIMS: The first cases of squamous cell carcinoma in esophageal lichen planus were recently described. We performed a study to establish the prevalence of endoscopic and histopathologic abnormalities consistent with lichen planus and (pre-) malignancy in a cohort of patients with lichen planus. PATIENTS AND METHODS: A total of 24 patients with lichen planus were prospectively studied using high-magnification chromoendoscopy. Focal esophageal abnormalities were mapped, classified, and biopsied. Biopsies were also taken from normal-appearing esophageal mucosa at three levels (proximal, middle, and distal). The presence of a lymphohistiocytic interface inflammatory infiltrate and Civatte bodies (i. e. apoptotic basal keratinocytes) at histopathologic examination was considered diagnostic for esophageal lichen planus. Symptoms were assessed using validated questionnaires. RESULTS: A total of 38 focal abnormalities were biopsied. These consisted of: layers of mucosa peeling off, hyperemic lesions, papular lesions, submucosal plaques/papules, a flat polypoid lesion, and segments of cylindrical epithelium. No endoscopic signs of dysplasia were present. Esophagitis consistent with gastroesophageal reflux disease was noted in 12 / 24 patients. Histopathology showed chronic inflammation of the esophageal mucosa in the majority (18 / 24) of patients. In 50 % (12 / 24), the diagnosis of esophageal lichen planus was made. Dysplasia was not present. There were no differences in symptoms between patients with and without esophageal lichen planus. CONCLUSIONS: At screening endoscopy a high prevalence (50 %) of esophageal lichen planus was found in patients with orocutaneous lichen planus. No dysplasia was found.

Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum.

Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring (pH+), defined as pH<4 > or = 6% of time. A symptom index (SI) > or = 50% was considered positive, as well as a symptom association probability (SAP) > or = 95%. We included 84 GORD patients with physiological acid exposure (pH-) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND-36 quality of life scale. pH- patients were younger (45 vs 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH- patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH- patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH- patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH- patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.

Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3).

OBJECTIVES: Visceral hypersensitivity is involved in the etiology of reflux symptoms. Familial clustering and twin studies demonstrated a genetic predisposition to gastroesophageal reflux disease (GERD). G-protein-coupled receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral factors modulating esophageal sensory function. Thus, polymorphisms in G-proteins are putative genetic factors contributing to GERD manifestation. A functional polymorphism in the G-protein beta3 subunit gene (GNB3) is associated with functional dyspepsia (FD), in which visceral hypersensitivity is implicated in symptom generation. We evaluated the association of the GNB3 C825T polymorphism with GERD and GERD subgroups classified according to esophageal acid exposure time, symptom-reflux correlation, or coexistence of FD and/or irritable bowel syndrome (IBS) symptoms. METHODS: In total, 363 GERD patients, defined as having esophageal pH < 4 > or = 6% of time and/or symptom index (SI) > or = 50% or symptom association probability (SAP) > or = 95%, participated. In addition, 373 healthy controls free of gastrointestinal symptoms were studied. Genotyping was performed by molecular beacon assay. RESULTS: The CT genotype was more prevalent in GERD patients relative to healthy controls (adjusted odds ratio (OR)=1.43, 95% CI 1.04-1.98). GERD patients sensitive to physiological amounts of reflux displayed a higher OR (1.59), as did GERD patients with a positive symptom association score (1.50). The strongest association was detected in patients without concomitant FD and/or IBS symptoms (OR=1.66). CONCLUSIONS: GERD is associated with GNB3 C825T. The results for GERD subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele, underlies this association.

Psychopathology is associated with dyspeptic symptom severity in primary care patients with a new episode of dyspepsia.

BACKGROUND: Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia. AIM: To study the association between dyspeptic symptom severity and psychopathology, major life events and coping ability in patients with a new episode of dyspepsia. METHODS; Dyspeptic symptom severity was measured using the validated eight symptom Veldhuyzen van Zanten questionnaire. Psychopathology was measured using the Symptom Check List-90 (SCL 90). Major life events were measured with a modified version of the Social Readjustment Rating Scale (SRRS). Coping styles were measured by a short version of the Utrecht Coping Questionnaire, distinguishing six coping styles. Linear regression was used to assess the relationship between dyspepsia symptom severity and psychological factors. RESULTS: In all, 664 patients with a new episode of uninvestigated dyspepsia, aged >18 years were included. Dyspeptic symptom severity was positively correlated with the presence of depression (P < 0.01), somatization symptoms (P < 0.01), use of an active coping style (P < 0.01) and negatively correlated with age (P < 0.01). CONCLUSIONS: Primary care patients consulting with dyspepsia have higher levels of depression and somatization especially at younger age. An active coping style is associated with dyspepsia symptom severity.

Validation of a disease-specific quality-of-life questionnaire in a large sample of Dutch achalasia patients.

SUMMARY: The aim of this study was to validate a translated version of an achalasia-specific quality-of-life questionnaire (achalasia-DSQoL) by examining its psychometric properties in a Dutch cohort of achalasia patients. The achalasia-DSQoL was administered to 171 treated achalasia patients together with a clinical symptom score and the RAND-36. Validation methods included factor analysis, known-group techniques, Cronbach's alpha and Spearman rank correlation with other questionnaires and feasibility. About 72.5% of the achalasia patients completed the questionnaires. The achalasia-DSQoL showed evidence of an underlying construct and seems reliable with a Cronbach's alpha of 0.77. The question concerning heartburn did not correlate with the other items on the questionnaire. Known-group techniques demonstrated that the achalasia-DSQoL discriminates between achalasia patients in clinical remission and patients who are not. There was a moderate correlation between the achalasia-DSQoL and the RAND-36 subscales. The questionnaire was easy in use. The translated version of the achalasia-DSQoL is a valid and reliable instrument to compare groups of achalasia patients although the question concerning heartburn should be excluded.

High frequency of early colorectal cancer in inflammatory bowel disease.

BACKGROUND AND AIMS: To detect precancerous dysplasia or asymptomatic cancer, patients suffering from inflammatory bowel disease often undergo colonoscopic surveillance based on American or British guidelines. It is recommended that surveillance is initiated after 8-10 years of extensive colitis, or after 15-20 years for left-sided disease. These starting points, however, are not based on solid scientific evidence. Our aim was to assess the time interval between onset of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and subsequently evaluate how many patients developed cancer before their surveillance was recommended to commence. METHODS: A nationwide automated pathology database (PALGA) was consulted to identify patients with IBD-associated colorectal carcinoma in seven university medical centres in The Netherlands between January 1990 and June 2006. Data were collected retrospectively from patient charts. Time intervals between onset of disease and cancer diagnosis were calculated in months. RESULTS: 149 patients were identified with confirmed diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn's disease n = 59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22% of patients developed cancer before the 8 or 15 year starting points of surveillance, and 28% if surveillance was commenced 10 or 20 years after diagnosis for extensive or left-sided disease, respectively. Using onset of symptoms to calculate the time interval, 17-22% of patients would present with cancer prior to the surveillance starting points. CONCLUSIONS: These results show that the diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17-28%) when conducting surveillance strictly according to formal guidelines.

Candidate genotypes associated with functional dyspepsia.

There is accumulating evidence of a genetic predisposition for developing a functional gastrointestinal (GI) disorder. Identification of the genetic factors may improve understanding of underlying pathophysiological mechanisms. We aimed to test the association of functional polymorphisms in genes involved in serotonergic signalling and G-protein-mediated signal transduction, both affecting gastroduodenal sensory and motor function, with functional dyspepsia (FD). FD patients, send to our tertiary referral centre, were studied (n = 112). Healthy controls (n = 336) free of GI symptoms were matched 1 : 3 for age and gender. Polymorphisms in genes encoding the serotonin receptor type three A subunit (HTR3A), the serotonin transporter (SERT) and the G-protein beta3 subunit (GNB3) were analysed. The FD patients displayed a higher prevalence of the T allele of the GNB3 C825T polymorphism compared to healthy controls (OR = 1.60, 95% CI: 1.03-2.49, P = 0.038). No association between FD and the genotype of the insertion/deletion polymorphism in the promoter of SERT (SERT-P) or HTR3A C178T polymorphism was observed. Tertiary referral FD is associated with the 825T allele of the GNB3 gene. The increased signal transduction associated with this allele may contribute to the abnormalities in gastroduodenal sensory and motor function observed in FD.

Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients.

Colorectal and small intestinal visceral hypersensitivity has been demonstrated in irritable bowel syndrome (IBS). Serine protease signalling via protease-activated receptor (PAR)-2 promotes hyperalgesia to mechanical distension. Furthermore, serotonergic pathways are involved in gastrointestinal visceral sensitivity. Abnormalities of serine protease and serotonergic signalling components have been identified in IBS colorectal mucosal biopsies. We determined the role of altered mucosal serine protease and serotonergic signalling in small intestine of IBS patients. Duodenal mucosal biopsies of 34 IBS patients (10 constipation-,11 diarrhoea-predominant and 13 alternating) and 20 healthy subjects (HS) were collected. Gene transcripts of PAR-2, trypsinogen IV, TPH-1, SERT (serotonin transport protein) and serotonin (5-HT(3)) subunits were quantified using real-time PCR and 5-HT content was measured by ELISA. Irritable bowel syndrome patients showed 1.5-fold higher trypsinogen IV mRNA level compared to HS (P = 0.016). SERT expression was 1.8-fold higher in IBS compared to HS (P = 0.007). Mucosal 5-HT content was 1.7-fold higher in IBS compared to HS (P = 0.015). The increase was 2.1-fold in IBS-C relative to HS (P = 0.018). Transcript levels of PAR-2, TPH-1 and 5-HT(3) receptor subunits did not differ between IBS and HS. In conclusion enhanced trypsinogen IV expression in IBS may cause increased PAR-2 activation. Increased SERT expression and mucosal 5-HT content in IBS suggest higher 5-HT availability. Both may contribute to small intestinal visceral hypersensitivity in IBS patients.

Serotonergic signalling in the stomach and duodenum of patients with gastroparesis.

Serotonin (5-HT) is involved in the regulation of motoric and sensory functions of the upper gastrointestinal tract. The aim of the current study was to determine whether serotonergic signalling is altered in patients with idiopathic gastroparesis. Mucosal biopsy specimens were collected from the duodenum, antrum and fundus of 11 patients with idiopathic gastroparesis and 11 healthy controls. Neuroendocrine cells, specifically 5-HT producing cells, were counted after immunohistochemistry, and non-neuronal mRNA expression levels of tryptophan hydroxylase (TPH)-1, 5-HT transport protein (SERT), 5-HT3 and 5-HT4 receptor were quantified by real time RT-PCR. The number of 5-HT producing cells was comparable between patients and controls. No difference in expression of TPH-1 (rate limiting enzyme in 5-HT biosynthetic pathway) and SERT (responsible for 5-HT uptake) was found between patients and controls (P > 0.05). In the duodenum, the expression of the 5-HT3 receptor subunits and the 5-HT4 receptor was comparable between both groups. However, the 5-HT4(c) splice variant was expressed more abundantly in healthy controls compared to patients (P = 0.015). This study suggests that the delayed gastric emptying and upper abdominal symptoms in idiopathic gastroparesis do not result from altered mucosal 5-HT biosynthetic and uptake capacity.

Persisting symptoms and decreased health-related quality-of-life in a cross-sectional study of treated achalasia patients.

BACKGROUND: Little is known about symptom characteristics of treated achalasia patients and their effect on health-related quality-of-life (HRQoL). AIMS: To examine clinical remission, achalasia-associated symptoms and HRQoL in treated achalasia patients. METHODS: The Eckardt clinical symptom score, RAND-36 and a disease-specific HRQoL questionnaire were sent to 171 treated achalasia patients. RESULTS: 76.6% of the patients returned their questionnaire. 44.9% of them were not in symptomatic remission. Prevalence of frequent dysphagia (at least daily) and chest pain (at least weekly) was 46% and 38%, respectively. Achalasia patients had lower general HRQoL scores than control subjects (all RAND-36 subscales, except health change; P < or = 0.002). Patients with frequent symptoms of chest pain and dysphagia showed lower HRQoL than patients with less frequent symptoms on three RAND-36 subscales (pain, social functioning and general health perceptions; P < 0.003). Patients in clinical remission showed higher HRQoL than patients who were not, however HRQoL in the 'remission group' remained significantly impaired as compared to controls (all RAND-36 subscales except emotional role limitations and mental health; P < 0.001). CONCLUSIONS: Many achalasia patients remain severely symptomatic after treatment and have decreased HRQoL. Frequent symptoms are associated with lower HRQoL. Patients in clinical remission show substantially improved, but not restored HRQoL.

Role of intra-oesophageal impedance monitoring in the evaluation of endoscopic gastroplication for gastro-oesophageal reflux disease.

BACKGROUND: In the evaluation of several endoscopic antireflux procedures, a discrepancy in the degree of improvement between symptoms and objective reflux parameters as measured by pH-metry has been reported. AIM: To assess the additional value of impedance monitoring in the evaluation of endoscopic gastroplication for gastro-oesophageal reflux disease. METHODS: Eighteen patients with gastro-oesophageal reflux disease were treated with three endoscopic gastroplications, and underwent 24 h pH-impedance monitoring before and 3 months after treatment. RESULTS: Total reflux exposure time as assessed by pH-metry and impedance monitoring was significantly decreased after treatment (P = 0.047 and <0.001, respectively). When assessed with impedance monitoring, the mean number of reflux episodes was significantly decreased after the procedure (82 vs. 56, pre vs. post, P < 0.001). Furthermore, the mean numbers of liquid and acid reflux episodes in patients with symptomatic improvement were significantly reduced after treatment (P = 0.04 and 0.02, respectively). After treatment, mean volume clearance time (s) and mean number of proximal reflux episodes were significantly decreased (P < 0.001 and 0.002, respectively). CONCLUSIONS: Impedance monitoring can identify the specific effect of endoscopic gastroplication on the different types of reflux episodes with regard to gas-liquid composition and pH, as well as on volume clearance and the proximal extent of the refluxate.

Regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the human stomach and duodenum.

The aim of this study was to increase the understanding of the role of serotonergic signalling in normal gastroduodenal function at a molecular level. Mucosal biopsy specimens were collected from the fundus, antrum and duodenum of 11 healthy subjects. Serotonin (5-HT)-positive cells were counted and the mRNA levels of tryptophan hydroxylase (TPH), serotonin transporter (SERT), 5-HT(4) receptor and 5-HT(3) receptor subunits were quantified by real-time reverse transcription polymerase chain reaction. The number of 5-HT-positive cells was larger in the duodenum compared with the stomach (P < 0.001). Serotonin transport protein expression was 19-fold higher in the duodenum compared with the antrum and 457-fold higher compared with the fundus (P < 0.001). Tryptophan hydroxylase-1 expression was lower in the duodenum compared with the antrum and fundus (regional differences -2.3 and -3.6, respectively). The 5-HT(4) receptor and the 5-HT(3C) and 5-HT(3E) receptor subunits were more abundantly expressed in duodenum compared with the stomach (P < 0.001). The larger number of 5-HT-positive cells, the higher expression of 5-HT(3) and 5-HT(4) receptors, and in particularly the higher uptake capacity of 5-HT in the duodenum, point out to a more prominent role of serotonergic signalling at the mucosal level in the duodenum compared with the stomach.

Air swallowing, belching, acid and non-acid reflux in patients with functional dyspepsia.

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.

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial.

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. PATIENTS AND INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.

[British and American screening guidelines inadequate for prevention of colorectal carcinoma in patients with inflammatory bowel disease]. / Preventie van colorectaal carcinoom bij inflammatoir darmlijden onvoldoende met de Britse en Amerikaanse opsporingsrichtlijnen.

OBJECTIVE: To determine how many cases of inflammatory bowel disease (IBD)-related colorectal cancer (CRC) occur before recommended colonoscopy screening commences. DESIGN: Descriptive. METHOD: A nationwide automated histological and cytopathological archive (PALGA) was used to identify patients with IBD and CRC in the period January 1990-June 2006 at the University Medical Center Utrecht, The Netherlands. The interval between the diagnosis of IBD or IBD-related symptoms and the diagnosis of CRC was calculated. The observed interval was compared with the recommended starting point for surveillance according to the British Society of Gastroenterology (BSG) and the American Gastroenterological Association (AGA), i.e. after 8-10 years for pancolitis or after 15-20 years for left-sided colitis. RESULTS: 33 colorectal cancers were found in 29 patients with IBD. The median age at the time of diagnosis was 29 years (range: 11-82) for IBD and 47 years (range: 23-82) for CRC. 7 of the 29 patients (24%) developed CRC before the minimum recommended time to initiate screening (8 years for pancolitis, 15 years for left-sided colitis), and 9 patients (31%) developed CRC within the maximum recommended time to initiate screening (10 years for pancolitis, 20 years for left-sided colitis). If the onset of IBD-related symptoms was considered the starting point of the disease (rather than the diagnosis of IBD), 17-24% of patients developed a CRC before surveillance would have commenced. CONCLUSION: These results suggest that, by following the British and American guidelines for screening for IBD-related CRC, a substantial portion of cases (17-31%) would not be diagnosed in a timely manner.

The gastro-oesophageal common cavity revisited.

The manometric common cavity phenomenon has been used as indicator of gastro-oesophageal reflux of liquid or gaseous substances. Using combined pH and impedance recording as reference standard the value of a common cavity as indicator of gastro-oesophageal reflux was tested. Ten healthy male subjects underwent combined stationary pressure, pH and impedance recording for 4.5 h. After 1.15 h of recording, a reflux-eliciting meal was consumed. The chi-squared and Kolmogorov-Smirnov tests were used for the statistical analysis. A common cavity was found in 95 (43%) of the 223 reflux events detected by impedance, while seven common cavities were unrelated to a reflux episode. In 54% of the reflux events detected by impedance without a common cavity, a possible common cavity was obscured by either contractile activity or artefacts of various origin. The types of reflux associated with a common cavity (liquid 60%, mixed 31%, gas 9%) and without a common cavity (liquid 59%, mixed 29%, gas 12%) did not differ, or did the acidity of the reflux episodes (with common cavity: acid 67%; without common cavity: acid 58%). The common cavity is a specific but not a sensitive marker of gastro-oesophageal reflux. Furthermore, common cavities are not specific for a particular type of reflux.

Assessment of oesophageal emptying in achalasia patients by intraluminal impedance monitoring.

Oesophageal emptying can be assessed by radiographic and scintigraphic tests with radiation exposure or by multichannel intraluminal impedance monitoring (MII). The aim of this study was to evaluate the applicability of MII for the assessment of oesophageal emptying in achalasia patients. In 10 achalasia patients, impedance tracings were scored independently by three observers after ingestion of a 100-mL barium bolus. Bolus clearance time (BCT) and height of barium column were scored using fluoroscopic images acquired at 20-s intervals. All patients showed a low baseline impedance level in the distal oesophagus. Air trapping in the proximal oesophagus was detected in nine patients. BCT on MII was similar to that on fluoroscopy in 40-70% of the patients. Correlations between height of barium on fluoroscopy and fluid level on MII were poor to moderate at different time intervals. Concordance (Kendall's coefficient) between the three observers for assessment of fluid level on MII was 0.31 (P = 0.04) at 1 and 5 min, 0.26 (P = 0.08) at 10 and 0.44 (P = 0.01) at 15 min. We conclude that in achalasia patients, low baseline impedance levels and air entrapment in the proximal oesophagus limit the value of intraluminal impedance monitoring as a test of oesophageal emptying.