Ambulatory pH-impedance-pressure monitoring as a diagnostic tool for the reflux-cough syndrome.

Gastroesophageal reflux is considered to be a significant contributing factor to chronic unexplained cough. Patients are often presumed to have reflux-induced cough and are exposed to high-dose and long-term empirical therapy with proton pump inhibitors (PPIs) despite the limited treatment efficacy in this population. We aimed to assess the diagnostic value of 24-hour ambulatory pH-impedance-pressure monitoring for the diagnosis of reflux-induced chronic cough. In this multicenter study, we evaluated 192 patients with chronic cough using 24-hour pH-impedance-pressure monitoring off PPIs. Manometry was used to detect all cough bursts while pH-impedance allowed for the evaluation of all reflux episodes, including weakly acidic reflux. The symptom association probability was used to determine a temporal relationship between reflux and cough. A diagnosis of reflux-induced cough was made in 25.5% of the patients. If only acid reflux episodes were used, 22.4% of those patients would not have been diagnosed. Significantly more patients with reflux-induced cough had typical reflux symptoms (P = 0.031) and a pathological distal acid exposure time (P = 0.025) in comparison to patients without the diagnosis. A diagnosis of cough-induced reflux was made in 24.0% of the patients. Only 59% of all cough bursts were registered by the patients. Overall, only approximately one quarter of patients with chronic unexplained cough have reflux-induced cough, explaining the observation that the vast majority of patients with chronic cough do not benefit from antireflux therapy. pH-impedance-pressure monitoring helps to identify patients who are likely to have reflux as a cause of their chronic cough.

A pregnant patient with excessive belching.

We present a patient that developed severe belching during pregnancy. Esophageal pH-impedance monitoring revealed frequent supragastric belching, but not gastroesophageal reflux disease (GERD). Thus, severe belching during pregnancy can be due to a behavioral disorder in the absence of GERD. Belching complaints during pregnancy should therefore not always be treated as GERD.

Birch pollen sensitization with cross-reactivity to food allergens predominates in adults with eosinophilic esophagitis.

EoE patients show variable sensitization patterns to food and aeroallergens. The value of allergy testing in adult EoE patients is unclear. Component-resolved diagnosis (CRD) may offer additional insights into sensitization patterns. The aim of this study was to characterize sensitization patterns in adult EoE patients using CRD. Serum from 76 patients (17 female), age 38.6 ± 1.5 years, was analyzed for reactivity to 112 different allergen components using an immuno-solid-phase allergen chip (ISAC). We observed any sensitization in 59 patients (78%), of which 54 patients were polysensitized. Aeroallergen sensitization, mostly against components of grass or tree pollen, or house dust mite, was observed in 74% of the patients. Birch pollen (rBet v 1) sensitization with cross-reactivity to food allergen components was observed in 30 patients (39%). In conclusion, food sensitizations in EoE patients are mainly caused by cross-reactivity to food allergens after primary birch pollen sensitization. Pollen and food sensitizations may cause or maintain esophageal inflammation in EoE patients. CRD provides more insight into sensitization patterns, identifies additional food allergen sensitizations and might be useful to direct dietary therapy in EoE.

The effect of endoscopic mucosal resection and transanal endoscopic microsurgery on anorectal function.

AIM: The study assessed the impact on anorectal function of endoscopic mucosal resection (EMR) and transanal endoscopic microsurgery (TEM) of large rectal adenomas. METHOD: Patients with a large (≥ 3 cm) rectal adenoma undergoing EMR or TEM were included. Self-reported faecal incontinence was assessed using the Colorectal Functional Outcome (COREFO) questionnaire and the Wexner Incontinence Grading Scale. Anorectal manometry was performed before and at 6 months after treatment to measure anal resting (ARP) and squeeze pressure (SP), squeeze endurance (SE), the rectoanal inhibitory reflex (RAIR), rectal volumetry of first sensation (FS), first urge (FU), maximum tolerable volume (MTV) and rectal compliance (RC). RESULTS: Twenty-four patients were included in the study, of whom 11 underwent EMR and 13 underwent TEM. The mean adenoma size was 51 ± 19 mm and the median distance from the anal verge was 3 cm (interquartile range 1-10 cm). Follow-up data were available from 20 patients; one patient had died and three had undergone total mesorectal excision. Incontinence for liquid stool and Wexner score decreased significantly after treatment. In contrast, none of the measured parameters of anorectal motility (ARP, SP, SE, RAIR, RC) and perception (FS, FU, MTV) was affected by adenoma resection. No differences were found in baseline and follow-up incontinence and functional parameters between intervention groups, except for postprocedural ARP, which was lower after TEM than after EMR. CONCLUSION: Continence in patients with a large rectal adenoma improved after EMR or TEM, probably due to decreased rectal mucus production. Anal sphincter pressure, rectoanal reflexes, rectal sensation and compliance were not affected by adenoma resection.

Effects of anti-reflux surgery on weakly acidic reflux and belching.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the most frequently performed operation for gastro-oesophageal reflux disease (GORD). However, 12% of the patients have persistent reflux symptoms and 19% develop gas-related symptoms after LNF. Weakly acidic reflux and inability to belch have been alleged to cause these symptoms, respectively. The effect of LNF on weakly acidic reflux and (supra) gastric belching was evaluated. METHODS: In 31 patients upper gastrointestinal endoscopy, stationary oesophageal manometry and 24-h impedance-pH monitoring off acid secretion inhibiting drugs was performed before and 6 months after primary LNF for GORD that was refractory to proton pump inhibitors. Patients filled out validated questionnaires on GERD-HRQoL before and 3, 6 and 12 months after surgery. RESULTS: LNF reduced reflux symptoms (18.6→1.6; p = 0.015). The procedure drastically reduced the incidence (number per 24 h) of acid (76.0→1.6; p < 0.001) and weakly acidic (13.6→5.7; p = 0.001) as well as liquid (53.4→5.4; p<0.001) and mixed reflux episodes (36.3→1.9; p < 0.001). In contrast, gas reflux was reduced to lesser extent (35.6→25.7; p = 0.022). Proximal, mid-oesophageal and distal reflux were reduced to a similar extent. Persistent GORD symptoms were neither preceded by acid nor by weakly acidic reflux. The number of air swallows did not change, but the number of gastric belches (GBs) was greatly reduced (68.5→23.9; p < 0.001). Twenty-three patients had supragastric belches (SGBs), both before and after surgery, whereas eight patients had no SGBs at all. The majority of SGBs were not reflux associated and the frequency was greatly increased after LNF (20.8→46.0; p = 0.036). Reflux-associated SGBs were abolished after surgery (14.0→0.4; p < 0.001). CONCLUSIONS: LNF similarly controls acid and weakly acidic reflux, but gas reflux is reduced to lesser extent. Persistent reflux symptoms are neither caused by acid nor by weakly acidic reflux. LNF alters the belching pattern by reducing GBs (air venting from stomach) and increasing SGBs (no air venting from stomach). This explains the increase in belching experienced by some patients after LNF, despite the reduction in gastric belching. It can be hypothesised that the reduction in GBs after LNF incites patients to increase SGBs in a futile attempt to vent air from the stomach.

Esophageal acid exposure decreases intraluminal baseline impedance levels.

OBJECTIVES: Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in healthy controls. METHODS: Ambulatory 24-h pH-impedance monitoring was performed in (i) 24 GERD patients with and 24 without pathological esophageal acid exposure as well as in 10 healthy controls and in (ii) 20 patients with refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline impedance levels in the most distal and the most proximal impedance channels were assessed. RESULTS: Median (interquartile range) distal baseline impedance in patients with physiological (2,090 (1,537-2,547) Ω) and pathological (781 (612-1,137) Ω) acid exposure was lower than in controls (2,827 (2,127-3,270) Ω, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure time and baseline impedance was observed (r=-0.7, P<0.001). In patients measured off and on PPI, median distal baseline impedance off PPI was significantly lower than on PPI (886 (716-1,354) vs. 1,372 (961-1,955) Ω, P<0.05) and distal baseline impedance in these groups was significantly lower than in healthy controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ significantly between the patients off PPI and on PPI (1,793 (1,384-2,489) vs. 1,893 (1,610-2,561) Ω); however, baseline impedance values in both measurements were significantly lower than in healthy controls (3,648 (2,815-3,932) Ω, both P<0.001). CONCLUSIONS: These findings suggest that baseline impedance is related to esophageal acid exposure and could be a marker of reflux-induced changes to the esophageal mucosa.

Predictors of objectively identified recurrent reflux after primary Nissen fundoplication.

BACKGROUND: Laparoscopic Nissen fundoplication is the most frequently performed operation for gastro-oesophageal reflux disease (GORD). Studies on predictors of subjective outcome of fundoplication have yielded inconsistent results. This study identified predictors of objective reflux control after Nissen fundoplication. METHODS: This was a retrospective analysis of prospectively collected data from patients who underwent Nissen fundoplication for proton pump inhibitor-refractory GORD with pathological acid exposure in a single centre between 1997 and 2005. The predictive value of demographics, endoscopic hiatal hernia size, oesophagitis, lower oesophageal sphincter pressure, distal oesophageal contraction amplitude, percentage of peristaltic contractions and acid exposure was determined. Endpoints were recurrent pathological acid exposure on 24-h pH monitoring at 6 months and surgical reintervention for recurrent GORD up to 6 years. RESULTS: Of 177 patients, 22 had recurrent pathological acid exposure at 6 months for which 11 had surgery within 6 years. Only low percentage of peristaltic contractions (odds ratio (OR) 0·97, 95 per cent confidence interval 0·95 to 0·99; P = 0·004) and high supine acid exposure (OR 1·03, 1·00 to 1·07; P = 0·025) were independent predictors of recurrent pathological acid exposure. The absolute risk of recurrent exposure was 45·5 per cent in patients with both predictors. High supine acid exposure was also an independent predictor of surgical reintervention (OR 1·05, 1·01 to 1·08; P = 0·006). CONCLUSION: Nissen fundoplication should not necessarily be withheld from patients with poor oesophageal peristalsis or excessive supine acid exposure. As about half of patients with both variables experience recurrent pathological acid exposure after primary Nissen fundoplication, surgery should be restricted in this group.

Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study.

OBJECTIVES: Recent studies have raised concerns on the clinical effectiveness of clopidogrel when taken in combination with proton pump inhibitors (PPIs), demonstrating an increase in the occurrence of cardiovascular events. In this study, the association between the co-administration of a PPI and clopidogrel and the occurrence of cardiovascular and gastrointestinal (GI) events in a large cohort in the Netherlands was investigated. METHODS: A retrospective study was conducted using data from 4 million individuals. New clopidogrel users were identified between January 2006 and December 2007 and followed over time. The Kaplan-Meier method and Cox proportional hazard regression [corrected]analysis were used to calculate the risk of cardiovascular and GI outcomes in clopidogrel patients with or without PPI use. RESULTS: A total of 18,139 new clopidogrel users were identified; 5,734 subjects (32%) used PPIs concurrently. Patients on PPIs were significantly older, used more co-medications and suffered from more comorbidities. Use of clopidogrel and PPIs was associated with an increased risk of myocardial infarction (hazard ratio (HR) 1.93, 95% confidence interval (CI) 1.40-2.65), unstable angina pectoris (HR 1.79, 95% CI 1.60-2.03), and the composite endpoint (HR 1.75, 95% CI 1.58-1.94) compared with clopidogrel users without PPIs. PPI users also had an increased risk of GI events compared with non-PPI users (HR 4.76, 95% CI 1.18-19.17). CONCLUSIONS: New clopidogrel users on PPIs are at an increased risk of cardiovascular and GI complications compared with those who are not using a PPI. The inferior cardiovascular profile of clopidogrel users on PPIs and the occurrence of channeling bias may be important factors underlying this observation.

Role of chemical stimulation of the duodenum in dyspeptic symptom generation.

The response to chemical stimuli such as acid, nutrients, and capsaicin at the level of the duodenum is increasingly recognized as important in the etiology of dyspeptic symptoms. Increased duodenal acid exposure has been reported for patients with dyspeptic symptoms. Duodenal hypersensitivity to acid and the enhancing effect of duodenal acid on gastroduodenal mechanosensitivity may also contribute to dyspeptic symptom generation. Serotonergic signaling pathways may be involved in acid-induced dyspeptic symptoms. As for nutrients, lipid has been unequivocally shown to have a function in the pathogenesis of dyspeptic symptoms. Cholecystokinin (CCK) is an important mediator of the effects of duodenal lipid on gastroduodenal sensorimotor activities. It is unclear whether CCK hypersecretion or hypersensitivity to CCK is responsible for symptoms in dyspeptic patients. The presence of capsaicin in the duodenum evokes symptoms and affects gastric sensorimotor function. In patients with dyspepsia, capsaicin-induced symptoms appeared to occur earlier and to be more severe, however the effects of duodenal infusion and putative consequent gastric sensorimotor abnormalities have not been examined. Capsaicin activates transient receptor potential ion channel of the vanilloid type I, which can also be activated and sensitized by acid. The interaction between the different chemical stimuli is complex and has not yet been studied in patients with dyspeptic symptoms. In conclusion, the mechanisms underlying an enhanced response to duodenal chemical stimulation in patients with dyspeptic symptoms are partially understood. At the level of the duodenum, abnormalities may exist in stimulus intensity, mucosal mRNA expression, biosynthesis, release, or inactivation of mucosal mediators, or receptor expression on afferent nerve endings. Elucidation of the abnormalities involved will provide a basis for rational treatment of dyspeptic symptoms.

Systematic review and meta-analysis of laparoscopic Nissen (posterior total) versus Toupet (posterior partial) fundoplication for gastro-oesophageal reflux disease.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is currently considered the surgical approach of choice for gastro-oesophageal reflux disease (GORD). Laparoscopic Toupet fundoplication (LTF) has been said to reduce troublesome dysphagia and gas-related symptoms. A systematic review and meta-analysis of randomized clinical trials (RCTs) was performed to compare LNF and LTF. METHODS: Four electronic databases (MEDLINE, Embase, Cochrane Library and ISI Web of Knowledge CPCI-S) were searched and the methodological quality of included trials was evaluated. Outcomes included recurrent pathological acid exposure, oesophagitis, dysphagia, dilatation for dysphagia and reoperation rate. Results were pooled in meta-analyses as risk ratios (RRs) and weighted mean differences. RESULTS: Seven eligible RCTs comparing LNF (n = 404) with LTF (n = 388) were identified. LNF was associated with a significantly higher prevalence of postoperative dysphagia (RR 1.61 (95 per cent confidence interval 1.06 to 2.44); P = 0.02) and dilatation for dysphagia (RR 2.45 (1.06 to 5.68); P = 0.04). There were more surgical reinterventions after LNF (RR 2.19 (1.09 to 4.40); P = 0.03), but no differences regarding recurrent pathological acid exposure (RR 1.26 (0.82 to 1.95); P = 0.29), oesophagitis (RR 1.20 (0.78 to 1.85); P = 0.40), subjective reflux recurrence, patient satisfaction, operating time or in-hospital complications. Inability to belch (RR 2.04 (1.19 to 3.49); P = 0.009) and gas bloating (RR 1.58 (1.21 to 2.05); P < 0.001) were more prevalent after LNF. CONCLUSION: LTF reduces postoperative dysphagia and dilatation for dysphagia compared with LNF. Reoperation rate and prevalence of gas-related symptoms were lower after LTF, with similar reflux control. These results provide level 1a support for the use of LTF as the posterior fundoplication of choice for GORD.

Laparoscopic Nissen fundoplication after failed EsophyX fundoplication.

BACKGROUND: Reflux control may be ineffective in a substantial number of patients after endoluminal EsophyX fundoplication for gastro-oesophageal reflux disease. Subsequent laparoscopic Nissen fundoplication (LNF) might be required to relieve symptoms. The aim of this study was to evaluate the outcome of LNF after previous EsophyX fundoplication. METHODS: EsophyX failure was defined as recurrence or persistence of typical symptoms, with or without anatomical failure of the wrap or persisting pathological oesophageal acid exposure. Consecutive patients who underwent LNF after failed EsophyX fundoplication were identified. Symptomatic outcome was obtained by standardized questionnaire, and objective outcome by endoscopy, oesophageal manometry and pH monitoring. RESULTS: Eleven patients were included. During LNF, intraoperative gastric perforation occurred in two patients and one developed a subphrenic abscess after operation. Daily heartburn was present in one patient after LNF and three had troublesome daily dysphagia. General quality of life after LNF was not significantly better than that before EsophyX fundoplication. Oesophageal acid exposure was normalized in all patients after surgery. Oesophagitis was absent after LNF in all except one patient who had persisting grade A oesophagitis. CONCLUSION: Symptomatic and objective reflux control are satisfactory after LNF for a failed EsophyX procedure. Previous EsophyX fundoplication, however, is associated with a risk of gastric injury during LNF and a relatively high rate of postfundoplication dysphagia.

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.

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.

Weight loss after laparoscopic adjustable gastric banding is not caused by altered gastric emptying.

BACKGROUND: In order to know the role of gastric emptying in the mechanism of weight loss and early satiety after a restrictive surgical procedure for treatment of morbid obesity, a consecutive series of patients were scintigraphically investigated before and after laparoscopic adjustable gastric banding. METHODS: Sixteen patients undergoing laparoscopic adjustable gastric banding underwent preoperatively, and at 6 months postoperatively, a gastric emptying study (solid meal and single isotope). Esophageal retention time, lag phase, peak activity time, gastric emptying rate, fundus emptying rate, and weight loss were recorded. Upper GI symptom assessment was carried out by using a standardized questionnaire. Gastric emptying parameters were correlated with the upper GI symptoms. RESULTS: Gastric band placement showed no significant influence on postoperative gastric emptying rate [median % (interquartile range): 42 (23.3-59) preoperatively vs 38 (31-71) postoperatively and fundus emptying rate: 59(37-91) preoperatively vs 70 (53-89) postoperatively]; however, an increase in early satiety was found. Neither gastric emptying rate nor fundus emptying rate showed a relation with early satiety or weight loss. Furthermore, no correlation was found between early satiety and lag phase, esophageal retention time, start of activity, and peak activity time in proximal stomach. CONCLUSION: Laparoscopic adjustable gastric banding seems not to affect gastric emptying. Neither a relation between postoperative gastric emptying rate and weight loss nor between early satiety and weight loss was found. Therefore, it is unlikely that gastric emptying plays a role in the mechanism of weight loss following laparoscopic adjustable gastric banding.

Mechanisms of acid, weakly acidic and gas reflux after anti-reflux surgery.

BACKGROUND: Whereas it is well documented that fundoplication reduces acid reflux, the effects of the procedure on non-acid and gas reflux and the mechanisms through which this is achieved have not been fully elucidated. METHODS: In 14 patients, reflux was measured with impedance-pH monitoring during a postprandial 90 min stationary recording period before and 3 months after fundoplication. Concomitantly, the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) and morphology of the oesophagogastric junction were studied with high-resolution manometry. This was followed by 24 h ambulatory impedance-pH monitoring. RESULTS: Before fundoplication, two separate high-pressure zones (hernia profile) were detected during 24.9% of total time, during which there was a large increase in reflux rate. After fundoplication, the hernia profile did not occur. Fundoplication decreased the number of TLOSRs (from 10.5 (SEM 1.2) to 4.5 (0.7), p<0.01) and also the percentage of TLOSRs associated with acidic or weakly acidic reflux (from 72.7% to 4.1%, p<0.01). Nadir pressure during TLOSRs increased after surgery (from 0 (0-0) to 1.0 (1-2) kPa, p<0.05). In the ambulatory study, there was a large decrease in prevalence of both acid (-96%, from 47.0 (5.9) to 1.8 (0.5), p<0.01) and weakly acidic reflux (-92%, from 25.0 (9.7) to 2.3 (0.9), p<0.01). The decrease in gas reflux was less pronounced (-53%, from 24.2 (4.9) to 11.3 (3.0), p<0.01). CONCLUSIONS: Fundoplication greatly reduces both acid and weakly acidic liquid reflux; gas reflux is reduced to a lesser extent. Three mechanisms play a role: (1) abolition of the double high-pressure zone profile (hiatal hernia); (2) reduced incidence of TLOSRs; and (3) decreased percentage of TLOSRs associated with reflux.

Predictors of symptomatic and objective outcomes after surgical reintervention for failed antireflux surgery.

BACKGROUND: Recurrent gastro-oesophageal reflux disease (GORD) and troublesome dysphagia after primary antireflux surgery are treated successfully by reoperation in 70 per cent of patients. Identifying predictors of outcome could allow selection of patients likely to benefit from further surgery. The aim was to identify such predictors in patients reoperated on for recurrent GORD or troublesome dysphagia. METHODS: Between 1994 and 2005, 83 patients (mean(s.d.) age 47.2(14.4) years; 47 men) with recurrent GORD and 47 (aged 50.7(13.4) years; 18 men) with troublesome dysphagia had further surgery. The predictive values of demographic, anatomical and manometric variables, and 24-h pH monitoring were analysed with respect to symptomatic and objective outcomes in each group. RESULTS: None of the factors included in a multivariable analysis predicted outcome after surgery for recurrent GORD. Independent predictors of symptomatic outcome after reoperation for dysphagia were amplitude of distal oesophageal contractions (odds ratio (OR) 1.613 (95 per cent confidence interval (c.i.) 1.087 to 2.393); P = 0.017), intrathoracic wrap migration (OR 0.077 (0.003 to 1.755); P = 0.108) and an abdominal approach (OR 0.012 (0.001 to 0.337); P = 0.009). CONCLUSION: Low-amplitude distal oesophageal contractions, intrathoracic wrap migration and an abdominal approach were significant predictors of an unsuccessful symptomatic outcome after reoperation for troublesome dysphagia.

High-resolution manometry.

Recently, high-resolution oesophageal manometry was added to the armamentarium of researchers and gastroenterologists. Current studies suggest that the yield of high-resolution oesophageal manometry is higher than that of conventional pull-through manometry and is at least comparable to that of sleeve sensor manometry. Probably the most important advantage of solid-state high-resolution manometry is that it makes oesophageal manometry faster and easier to perform. Topographic plotting of high-resolution manometry signals facilitates their interpretation. It is concluded that high-resolution manometry is a promising technique for the evaluation of oesophageal motor function. Further studies will have to determine whether high-resolution manometry is superior to conventional manometry in the diagnostic work-up of patients with oesophageal symptoms.

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.

[Therapy resistance of gastro-oesophageal reflux symptoms: acid reflux, non-acid reflux or no reflux]. / Therapieresistentie van gastro-oesofageale refluxklachten: zure reflux, niet-zure reflux of geen reflux.

The introduction of proton pump inhibitors (PPIs) was a huge step forward in the treatment of gastric acid-related disorders such as reflux disease and gastric ulcers. Despite the strong effectiveness of PPIs, in a small number of patients reflux symptoms are not adequately relieved by these drugs. The amount of acid inhibition that can be achieved using a PPI depends on a number of different factors, such as Helicobacter pylori infection, genetic variation in metabolizing enzymes, and lack of compliance. Nocturnal gastric acid breakthrough does not appear to be important in the pathogenesis of therapy-resistant reflux symptoms. Not all reflux from the stomach into the oesophagus appears to be acidic. Episodes of non-acid reflux may also elicit typical reflux symptoms. This can be established by impedance measurements of the oesophagus. However, most patients whose symptoms do not respond satisfactorily to PPI therapy appear not to have reflux disease but instead be suffering from other conditions such as functional dyspepsia, aerophagy or rumination. Careful history-taking is pivotal in patients with reflux symptoms and should always precede additional investigations such as upper endoscopy and if necessary 24-hour reflux monitoring.

[Therapy-resistant gastro-oesophageal reflux disease: endoluminal treatment not yet sufficiently compared with the gold standard, the laparoscopic Nissen fundoplication]. / Therapieresistente gastro-oesofageale refluxziekte: endoluminale behandeling nog onvoldoende vergeleken met de gouden standaard, laparoscopische fundoplicatie volgens Nissen.

Gastro-oesophageal reflux disease (GORD) is treated primarily with proton pump inhibitors. More invasive treatment is only indicated for patients with persistent symptoms or when complications occur. Anti-reflux surgery is successful in 85-90% of patients in terms of symptom control, healing of oesophagitis and normalization of oesophageal stomach-acid exposure. Laparoscopic Nissen fundoplication is the standard surgical procedure and favourable results persist for at least 5 years. Endoluminal treatment for GORD is a new development for which no long-term results are known and which can probably only be implemented in some of the patients with disease refractory to therapy. The effect of the new endoluminal treatments will have to be evaluated in randomised trials and to be compared with the medical gold standard of treatment, proton pump inhibitors, and with the surgical gold standard, laparoscopic Nissen fundoplication.