[Familial intestinal degenerative neuropathy with chronic pseudo-obstruction linked to duplication in chromosome 9]. / Helsingborgssjukan kopplad till duplikation i kromosom 9.

The so-called Helsingborg Disease is an intestinal degenerative neuropathy discovered in a kindred in South Sweden. Affected subjects develop severe intestinal symptoms, the most common being chronic diarrhea, but abdominal pain, constipation and severe vomiting are common. Chronic intestinal pseudo-obstruction is the end-stage with high mortality from intestinal failure. Two families with affected members were shown by histopathology and genealogy to be one large kindred with the same underlying disease. Genetic analysis shows that this disease, having an autosomal dominant transmission, is strongly linked to a region in the short arm of chromosome 9 and a 1.2 Mb duplication in this region. The duplication includes 22 protein-coding genes, most of them are interferon genes. Family members not carrying the duplication have no increased prevalence of gut diseases. Genetic analysis including gene-dose array should be important for etiologic diagnosis and for genetic guidance in this kindred.

Familial intestinal degenerative neuropathy with chronic intestinal pseudo-obstruction linked to a gene locus with duplication in chromosome 9.

Background: Intestinal degenerative neuropathy without extra-intestinal involvement occurs as familial forms (FIDN) but the genetics behind is unknown. We studied a Swedish family with autosomal dominant disease and several cases of chronic intestinal pseudo-obstruction (CIP).Methods: We included 33 members of a family sharing a male ancestor. Chronic intestinal symptoms including diarrhoea occurred in 11, four had severe CIP. DNA was analysed with SNP-microarray (Affymetrix), linkage (Allegro Software) and gene dosage (CNAG 3.0).Results: Genetic linkage was found to the short arm of Ch9 to a 9.7 Mb region with 45 protein-coding genes, 22 of which were duplicated (1.2 Mb duplication) (dup(9)(p21.3) with breaking point in the FOCAD-gene. Lod score for the region was 3.4. Fourteen subjects were duplication carriers including all 11 subjects having severe chronic symptoms/CIP. Nineteen subjects had no duplication. The occurrence of gastrointestinal symptoms in the family was strongly linked to duplication carrier-ship (p = .0005). The two branches of the family had separate maternal ancestors (A and B). Including the previous generation, severe disease (overt CIP and/or death from intestinal failure) was assessed to occur in 100% (5/5) of duplication carriers in branch A and in 21% (3/14) in branch B (p = .005). In branch B the onset of symptoms was later (median 38 vs. 24 yrs) and three duplication carriers were symptom-free.Conclusions: In this family with autosomal dominant hereditary intestinal neuropathy, the disorder is linked to a 9.7 Mb region in Ch9 including a 1.2 Mb duplication. There is a significant difference in disease expressivity between family branches, seemingly related to separate maternal ancestors.

Efficacy of Gastric Electrical Stimulation for Gastroparesis: US/European Comparison.

BACKGROUND: Gastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location. METHODS: We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female. RESULTS: European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023). CONCLUSIONS: Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.

Are the definitions for chronic diarrhoea adequate? Evaluation of two different definitions in patients with chronic diarrhoea.

BACKGROUND: The classical definition of chronic diarrhoea is ≥3 defecations/day, with a stool weight of more than 200 g and duration of ≥4 weeks. However, with this definition many patients with substantial symptoms and pathology will be excluded from further investigations. As a consequence other definitions have been proposed, mainly based on evaluation of the stool form. OBJECTIVE: To evaluate the accuracy of the classic criteria for diarrhoea in comparison with a definition based on stool consistency, using the Bristol Stool Form Scale. METHODS: All patients were investigated with laboratory tests, upper and lower gastrointestinal endoscopy with biopsies, and SeHCAT test. They were asked to complete a diary recording stool frequency and consistency during a week, as well as other gastrointestinal symptoms (pain, bloating and gas). RESULTS: One hundred and thirty-nine subjects were eligible for analysis. Ninety-one had an organic cause of diarrhoea. Fifty-three patients had ≥3 loose stools/day, whereas 86 reported <3 stools/day. Ninety had a median stool consistency that was mushy or loose and 49 had harder stools. A higher proportion of subjects with an organic cause of their diarrhoea compared with subjects with a functional bowel disorder had ≥3 loose stools/day, 43/91 (47%) vs. 10/48 (21%) (p < 0.01). Similarly, more subjects with an organic cause of their diarrhoea versus patients with a functional bowel disorder had a median stool consistency that was mushy or watery, 73/91 (80%) vs. 17/48 (35%), p < 0.0001. When diarrhoea was defined according to stool form, more patients were classified correctly as having a functional disorder or organic disorder, compared with the classical definition (p < 0.05). CONCLUSION: Loose stools defined according to the Bristol Stool Form scale seem to be the best predictor of having an organic cause of the diarrhoea.

Gastrointestinal motility and neurogastroenterology.

Nordic research on gastrointestinal motility has since 1965 made substantial contributions to our current understanding of gastrointestinal function. During the last decade, the term neurogastroenterology has widened the concept of motility research into the study of gastrointestinal sensory-motor function, including the complex central nervous system interaction. The discovery of a non-adrenergic non-cholinergic (NANC) innervation of the gut in the sixties was made by considerable contributions from the Nordic countries with the Martinson group in Sweden as central innovators. Important discoveries regarding the intramural nerve ganglia as mediators of the autonomic nervous input has also been produced from this research. In clinical motility research, the study of the migrating motor complex in the small bowel has revealed its ability to act as a retroperistaltic pump in the proximal duodenum (Sweden) and its important role for gut microbial homeostasis (Norway). Also in the development of methodology to study gut sensory-motor function, the Nordic countries has contributed. Examples are the physical characteristics of the esophageal manometry catheter (Denmark), the use of ultrasound for assessment of gastric function (Norway), a temporary electrical stimulation method in patients with severe nausea and vomiting (Sweden), a rectal barostat method for clinical evaluation of recto-anal function and a colonic transit time method utilizing radio-opaque markers (Sweden). In later years, the research collaborations have increasingly become worldwide in a manner making it less easy to define pure Nordic contributions.

Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects.

AIM: To assess the long-term effects of physical activity on irritable bowel syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety. METHODS: Seventy-six patients from a previous randomized controlled interventional study on increased physical activity in IBS were asked to participate in this long-term follow-up study. The included patients attended one visit in which they filled out questionnaires and they underwent a submaximal cycle ergometer test. The primary end point was the change in the IBS Severity Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow-up. The secondary endpoints were changes in quality of life, fatigue, depression and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years] patients were included in this follow-up. Median follow-up time was 5.2 (range: 3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS: 276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of the dimensions of psychological symptoms such as disease specific quality of life, fatigue, depression and anxiety. The reported time of physical activity during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported were walking, aerobics and cycling. There was no significant difference in the oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6) mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical activity has positive long-term effects on IBS symptoms and psychological symptoms.

Effects on gastrointestinal transit and antroduodenojejunal manometry after gut-directed hypnotherapy in irritable bowel syndrome (IBS).

BACKGROUND: Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. METHODS: We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. RESULTS: No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. CONCLUSIONS: In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.

Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome.

OBJECTIVE: Gut-directed hypnotherapy is considered to be an effective treatment in irritable bowel syndrome (IBS) but few studies report the long-term effects. This retrospective study aims to evaluate the long-term perceived efficacy of gut-directed hypnotherapy given outside highly specialized hypnotherapy centers. METHODS: 208 patients, who all had received gut-directed hypnotherapy, were retrospectively evaluated. The Subjective Assessment Questionnaire (SAQ) was used to measure changes in IBS symptoms, and patients were classified as responders and non-responders. Patients were also asked to report changes in health-care seeking, use of drugs for IBS symptoms, use of alternative non-pharmacological treatments, and if they still actively used hypnotherapy. RESULTS: Immediately after hypnotherapy, 103 of 208 patients (49%) were responders and 75 of these (73%) had improved further at the follow-up 2-7 years after hypnotherapy (mean 4 years). A majority of the responders still used hypnotherapy on a regular basis at follow-up (73%), and the responders reported a greater reduction in health-care seeking than non-responders. A total of 87% of all patients reported that they considered gut-directed hypnotherapy to be worthwhile, and this differed between responders and non-responders (100% vs. 74%; p < 0.0001). CONCLUSION: This long-term follow-up study indicates that gut-directed hypnotherapy in refractory IBS is an effective treatment option with long-lasting effects, also when given outside highly specialized hypnotherapy centers. Apart from the clinical benefits, the reduction in health-care utilization has the potential to reduce the health-care costs.

Colonic transit time and IBS symptoms: what's the link?

OBJECTIVES: The relevance of colonic transit alterations for the overall symptom pattern in irritable bowel syndrome (IBS) is incompletely understood. The aim of this study was to assess the total and segmental colonic transit time (CTT) and their relationship to symptoms and subgroups in a large sample of IBS patients. METHODS: Total and segmental CTT was assessed using radiopaque markers in 359 patients with IBS (279 females). These results were compared with existing normal values for healthy men and women without gastrointestinal (GI) symptoms. Stool frequency and consistency (Bristol Stool Form (BSF) scale), and the perceived severity of three GI symptoms (bloating, flatulence, and abdominal pain) were noted in a daily diary during the measurement week. Patients could be classified by the BSF scale characteristics into Rome III subtypes (n=338), or by use of the Rome II modular questionnaire into Rome II subtypes (n=143). RESULTS: CTT was normal in 287 patients (80%), whereas 53 (15%) had accelerated and 19 (5%) had delayed CTT. Transit abnormalities in relation to gender-specific reference values were more common in males (30.0%) than in females (17.2%; P < 0.05). IBS subgrouping according to Rome III (P < 0.0001) and Rome II criteria (P < 0.001) was associated with the presence of abnormal CTT. Stool form (r=-0.40; P < 0.0001) and stool frequency (r=-0.30; P<0.0001) were moderately and negatively correlated to total CTT. No correlations of clinical significance were found between transit data and the three GI symptoms. CONCLUSIONS: Total and segmental colonic transit alterations are of importance for the abnormal bowel habit seen in men and women with IBS, but of no or minor importance for other IBS symptoms.

Effects of gut-directed hypnotherapy on IBS in different clinical settings-results from two randomized, controlled trials.

OBJECTIVES: Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. METHODS: The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. RESULTS: We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year. CONCLUSIONS: Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers.

Temporary percutaneous and permanent gastric electrical stimulation in children younger than 3 years with chronic vomiting.

BACKGROUND: The aim was to investigate whether young children with drug-refractory nausea and vomiting can be treated with gastric electrical stimulation (GES) in a similar way as adults and to evaluate whether temporary percutaneous gastric electrical stimulation (TPGES) can be used in the pediatric population to select the patients who are responders to GES treatment. We report the clinical results in 3 children between 2 and 3 years of age. To the best of our knowledge, these are the youngest patients treated with GES. METHODS: Three patients younger than 3 years with intractable vomiting underwent TPGES. Custom-made leads were percutaneously implanted in the gastric wall under gastroscopic guidance. Symptoms were recorded daily during the TPGES stimulation time (12-40 days). Responders were offered permanent GES treatment. RESULTS: There were no technical problems. All 3 patients were responders to TPGES. They are now treated with surgically implanted permanent GES and reported greater than 50% vomiting reduction at last visit. CONCLUSION: Children younger than 3 years can be treated with GES in a similar way as adolescents and adults. Temporary percutaneous GES is a safe, feasible technique even in small children, with the possibility to perform the test over several weeks to select responders to GES treatment.

Bile acids: short and long term effects in the intestine.

Bile acids have secretory, motility and antimicrobial effects in the intestine. In patients with bile acid malabsorption the amount of primary bile acids in the colon is increased compared to healthy controls. Deoxycholic acid is affecting the intestinal smooth muscle activity. Chenodeoxycholic acid has the highest potency to affect intestinal secretion. Litocholic acid has little effect in the lumen of intestine compared to both deoxycholic acid and chenodeoxycholic acid. There is no firm evidence that clinically relevant concentrations of bile acids induce colon cancer. Alterations in bile acid metabolism may be involved in the pathophysiology of constipation.

A slow caloric satiety drinking test in patients with temporary and permanent gastric electrical stimulation.

OBJECTIVES: Improvement of gastric accommodation has been proposed as a potential explanation for the positive effect of gastric electrical stimulation (GES) on nausea/vomiting. A drinking test has been suggested as a noninvasive measure of gastric accommodation capacity. METHODS: Eight patients with therapy refractory nausea and vomiting and nonapproved diagnosis for GES (chronic intestinal pseudo-obstruction (CIP, n=1), functional dyspepsia (FD, n=3), postsurgical gastroparesis (PSGP, n=4) underwent temporary percutaneous GES for 10-14 days, randomized to stimulation ON or OFF, respectively. 19 patients [CIP (n=1), diabetic gastroparesis (n=5), FD (n=5), idiopathic gastroparesis (n=4), PSGP (n=4)] received permanent GES (Enterra, Medtronic) (follow-up at baseline, 6 and 12 months). At the end of each stimulation period a slow caloric satiety drinking test was performed (Nutridrink 1.5 kcal/ml, 15 ml/min). RESULTS: Healthy volunteers had higher drinking capacity compared to patients at baseline (1630 + or - 496 kcal vs. 887 + or - 412; P<0.001) and less composite symptom score (128 + or - 51 vs. 235 + or - 83; P<0.001). With temporary percutaneous GES, there was no significant change in drinking capacity during stimulation ON versus OFF (746 + or - 383 vs. 734 + or - 427 kcal) and symptom severity at the drinking test was unchanged. For patients having permanent GES there was no significant difference at 6 months (876 + or - 277 kcal) versus baseline, and no difference between symptomatic responders and nonresponders in change in drinking capacity (P=0.7). CONCLUSION: GES had no effect on proximal gastric function as evaluated by the slow caloric satiety drinking test. This seems to be the case for patients with approved as well as nonapproved indications for GES, and irrespective of the symptomatic response.

Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG).

Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.

Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation.

OBJECTIVE: Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. MATERIAL AND METHODS: Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference < or =4.3 days) and stool frequency were measured. C4 (7-alpha-hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. RESULTS: When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p <0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p <0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. CONCLUSIONS: Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.

Altered rectal perception in irritable bowel syndrome is associated with symptom severity.

BACKGROUND & AIMS: Diverging results exist regarding the connection between altered visceral perception and gastrointestinal (GI) symptoms, as well as the effects of psychological status on visceral sensitivity. We sought to investigate different aspects of rectal perception in irritable bowel syndrome (IBS) and the association with GI and psychological symptoms. METHODS: We included 109 patients with IBS meeting Rome II criteria (77 women; age range, 20-71 years) and 29 healthy controls (21 women; age range, 20-68 years). They underwent rectal balloon distentions determining sensory thresholds for discomfort and pain, the perceived intensity of unpleasantness, and the viscerosomatic referral area. The fifth percentile (thresholds) and 95th percentile (unpleasantness and referral area) in controls were used to define altered perception. Questionnaires were used to assess severity of IBS-related GI symptoms and psychological symptoms. RESULTS: When combining the 3 aspects of perception, 67 patients (61%) had altered rectal perception. These patients, compared with normosensitive patients, more frequently reported moderate or severe pain (73% vs 44%; P < .01), bloating (73% vs 36%; P < .0001), diarrhea (47% vs 21%; P < .01), satiety (39% vs 13%; P < .01), and clinically significant anxiety (31% vs 12%; P < .05). In a multivariate analysis, only pain and bloating remained associated with altered rectal perception. CONCLUSIONS: Altered rectal perception is common in IBS and seems to be one important pathophysiologic factor associated with GI symptom severity in general and pain and bloating in particular. It is not just a reflection of the psychological state of the patient.

Why do subjects with irritable bowel syndrome seek health care for their symptoms?

OBJECTIVE: Irritable bowel syndrome (IBS) is common in the population, but not all subjects seek professional health care for their symptoms. The aim of this study was to compare consulters in secondary/tertiary care with those in primary care and non-consulters by using questionnaires to investigate factors of importance for health-care seeking in IBS. MATERIAL AND METHODS: The study included 218 subjects with IBS: 70 non-consulters, 53 patients from primary care and 95 from secondary/tertiary care. The subjects completed questionnaires on gastrointestinal (GI) and psychological symptoms, coping resources, health-related quality of life (HRQOL) and reasons for not seeking health care. RESULTS: Consulters (primary and secondary/tertiary care combined) had poorer HRQOL, more severe psychological symptoms, higher levels of GI-specific anxiety and poor coping resources compared with non-consulters, but the GI symptom severity was similar. Mental health and poor social, emotional and physical functioning were independently predictive of being a health-care seeker (r (2)=0.41). Independent predictors for being a consulter in secondary/tertiary care were a high degree of anxiety, low scores on physical functioning, physical role and food (IBSQOL) (r (2)=0.65). Several non-consulters reported mild symptoms and ability to control symptoms as reasons for not seeking health care. Having a close relative with similar symptoms reduced the need to seek health care. Thirty-six non-consulters had sought alternative care or advice from friends and/or relatives about their GI symptoms. CONCLUSIONS: GI symptom severity alone cannot explain the illness behavior in IBS. HRQOL and psychological symptoms are important for experience of GI symptoms and the health-care seeking pattern in IBS.

Severe gastroparesis: new treatment alternatives.

Dopamine antagonists, such as metoclopramide and domperidone, and the motilin receptor agonist erythromycin have been the cornerstones in drug treatment of severe gastroparesis for more than a decade. No new drugs have been approved for treatment of this disorder in this period. Instead, the 5-HT4 agonist cisapride has been withdrawn due to side-effects. The effectiveness of intrapyloric botulinum toxin for gastroparesis remains to be shown. In the last decade, gastric electrical stimulation (GES) with a fully implantable device has evolved as a promising treatment, with significant effects on nausea and vomiting in most patients with severe, drug-refractory diabetic gastroparesis and postsurgical gastroparesis. A proportion of patients with severe idiopathic gastroparesis and patients with idiopathic nausea and vomiting also respond. More research is needed to achieve precise selection of responders/non-responders to GES, and to study the potential benefit of GES in other patient groups suffering from severe nausea or vomiting.