Severe Functional Dyspepsia Research Articles

Outcomes of pediatric endoscopic ultrasound-guided celiac plexus block: A single center pilot study.

Celiac plexus blocks (CPB) using endoscopic ultrasound (EUS) guidance provide significant pain relief in adults with chronic pancreatitis. We present on EUS-guided CPB for pediatric patients with abdominal pain from chronic pancreatitis or severe functional dyspepsia necessitating clinically assisted nutrition and hydration. Patients who underwent EUS-CPB were included and followed prospectively at 2-, 4-, and 8-weeks postprocedure about pain, enteral tolerance, and school/activity attendance. Thirteen patients underwent EUS-guided CPB with a total of 21 procedures. In the pancreatitis cohort, mean pain relief was 11.7 weeks for those who responded. In the functional dyspepsia cohort, mean improvement (in either pain or enteral tolerance) was 4.8 weeks. Symptom improvement varied between the two cohorts. Acute recurrent/chronic pancreatitis patients demonstrated more sustained relief than the functional dyspepsia cohort. This study adds to the limited data investigating the utility of EUS-CPB as part of a multimodal treatment plan in pediatrics.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ=0.64) and fairly correlated with the other four scores (ρ=0.32-0.55) (all P<0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P<0.10). FDSD≥20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P<0.001) and HAMD≥13 (OR 2.9, 95% CI: 1.8-4.6, P<0.001) were independently associated with patient-reported severe FD. This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD≥20 and HAMD≥13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

A Case of the Therapeutic Effect of Nangan-jeon on Refractory Functional Dyspepsia Caused by “Liver-Kidney Deficiency Cold”

Objective: This study explored the clinical usefulness of Nangan-jeon decoction to treat refractory functional dyspepsia.Methods: A 61-year-old female had been suffering from severe functional dyspepsia for about 40 years, but the dyspeptic symptoms rapidly improved after taking Nangan-jeon decoction. The clinical outcome was assessed by the numerical rating scale (NRS) and the self-reporting method.Result: After there was no improvement from various herbal treatments in a department of a Korean college hospital, the patient moved to the author’s clinic. She had been diagnosed with the pattern identification of “liver-kidney deficiency cold” and prescribed with Nangan-jeon decoction. This herbal drug rapidly improved her dyspeptic symptoms, from NRS 10 to NRS 2 (after 3 weeks) and NRS 1 (after 7 weeks).Conclusion: This case report is the first to present the potential of Nangan-jeon decoction to improve refractory functional dyspepsia.

A Novel, Duodenal-Release Formulation of a Combination of Caraway Oil and L-Menthol for the Treatment of Functional Dyspepsia: A Randomized Controlled Trial.

OBJECTIVES:We conducted a randomized, placebo-controlled trial, which evaluated a novel formulation of caraway oil and L-menthol using microsphere-based site-specific targeting (COLM-SST) vs placebo in patients with functional dyspepsia (FD).METHODS:Adult men and women with FD defined by Rome III criteria were recruited. Patients were randomized to COLM-SST (25 mg of caraway oil and 20.75 mg of L-menthol per capsule, at 2 capsules per dose, twice per day) or placebo. Efficacy was measured at 24 hours, 2 weeks, and 4 weeks. Patients were allowed to take concomitant medications for their FD throughout the trial, and rescue medicines were allowed, 48 hours after start of dosing.RESULTS:Ninety-five patients were enrolled (mean age = 43.4 years; 75.8% women). At 24 hours, the active arm reported a statistically significant reduction in postprandial distress syndrome symptoms (P = 0.039), and a nonsignificant trend toward benefit of epigastric pain syndrome symptoms (P = 0.074). In patients with more severe symptoms, approximately 3 quarters of patients showed substantial global improvement (i.e., clinical global impressions), after 4 weeks of treatment, vs half in the control arm. These differences were statistically significant for patients with epigastric pain syndrome (P = 0.046), and trending toward significance for patients with postprandial distress syndrome (P = 0.091). There was no statistically significant difference between groups for Global Overall Symptom scores for the overall population at 2 and 4 weeks. Treatment emergent adverse events were mild to moderate, and no serious adverse events were reported.DISCUSSION:In patients taking their usual medications for FD, COLM-SST provided rapid relief (within 24 hours) and relief of severe FD symptoms. It was safe and well tolerated.

Overlap of Irritable Bowel Syndrome and Functional Dyspepsia in the Clinical Setting: Prevalence and Risk Factors.

According to Rome IV criteria, functional dyspepsia (FD) and irritable bowel syndrome (IBS) are distinct functional gastrointestinal disorders (FGID); however, overlap of these conditions is common in population-based studies, but clinical data are lacking. To determine the overlap of FD and IBS in the clinical setting and define risk factors for the overlap of FD/IBS. A total of 1127 consecutive gastroenterology outpatients of a tertiary center were recruited and symptoms assessed with a standardized validated questionnaire. Patients without evidence for structural or biochemical abnormalities as a cause of symptoms were then categorized based upon the symptom pattern as having FD, IBS or FD/IBS overlap. Additionally, this categorization was compared with the clinical diagnosis documented in the integrated electronic medical records system. A total of 120 patients had a clinical diagnosis of a FGID. Based upon standardized assessment with a questionnaire, 64% of patients had FD/IBS overlap as compared to 23% based upon the routine clinical documentation. In patients with severe IBS or FD symptoms (defined as symptoms affecting quality of life), the likelihood of FD/IBS overlap was substantially increased (OR = 3.1; 95%CI 1.9-5.0) and (OR = 9.0; 95%CI 3.5-22.7), respectively. Thus, symptom severity for IBS- or FD symptoms were significantly higher for patients with FD/IBS overlap as compared to patients with FD or IBS alone (p all < 0.01). Age, gender and IBS-subtype were not associated with overlap. In the clinical setting, overlap of FD and IBS is the norm rather than the exception. FD/IBS overlap is associated with a more severe manifestation of a FGID.

Altered intrinsic regional activity and corresponding brain pathways reflect the symptom severity of functional dyspepsia

Increasing evidence shows central abnormalities in functional dyspepsia (FD) patients, but whether the symptom severity is directly reflected in altered brain patterns remains unclear. The purpose of this study was to explore how FD affected the resting functional brain patterns for different degrees of symptom severity. Functional magnetic resonance imaging was carried out in 40 FD patients and 20 healthy controls. The resting-state brain changes in regional homogeneity (ReHo) and seed correlation analysis were investigated in patients relative to controls. To what degree the brain changes reflected the severity of the disease was assessed by a pattern classification technique. Altered ReHo values (p<0.05, FDR corrected) were discovered in multiple brain areas in FD patients, and only the anterior cingulate cortex (ACC) and thalamus exhibited significant correlation with the severity of dyspepsia symptoms. Compared with controls, the neural signal changes of the thalamus were not found in the less severe FD patient group but in the relatively more severe group, while the ACC showed aberrations in both groups. Seed-based correlation analysis revealed ACC- and thalamus-related functional connectivity differences between FD patients and controls at a voxel-wise level, and the altered thalamic circuits provided the best performance in distinguishing FD patients with different levels of symptom severity. Our results indicated that the functional abnormalities of the ACC and thalamus may occur at different clinical courses in FD. This may help us better understand the progression of FD.

Trastornos funcionales y motores digestivos

This article discusses the most interesting studies on functional and motility gastrointestinal disorders presented in Digestive Diseases Week (DDW) in 2013. New data were reported on the clinical importance of functional gastrointestinal disorders (FGID) and on how they can produce numerous disturbances such as inflammatory bowel disease. These disturbances are associated with somatic functional disease and particularly with fatigue. In addition, new data have emerged on the physiopathology of these disorders, with some studies reporting that environmental factors and events in early infancy can favor their development. Data were also presented on how bile acids can increase susceptibility to diarrhea in patients with irritable bowel syndrome (IBS) and on how the type of food intake can favor the development of symptoms. More data are available on the presence of underlying celiac disease in patients with IBS, which should prompt us to investigate this disease in our patients. Likewise, indiscriminate application of a gluten-free diet in patients with IBS has been shown not to produce a clear improvement. Regarding the physiopathology of functional dyspepsia (FD), results have been presented on how psychological factors can modify gastric accommodation and how this is in turn related to visceral hypersensitivity and gastric emptying. Regarding therapy, mirtazapine can improve symptoms and lead to weight gain in patients with severe FD and substantial weight loss. Results were presented on new drugs for IBS such as ibodutant and on old drugs with new applications such as mesalazine and ebastine. The antinociceptive effect of linaclotide is now better understood and a meta-analysis has shown its effectiveness in IBS with constipation as the main symptom. In patients with constipation, pelvic floor dysynergy can be diagnosed by a simple clinical interview and rectal touch. More data are available on the efficacy of prucalopride (which has been shown to accelerate colon transit time) and data were provided on plecanatide, a potential new drug that could be useful in constipation. Finally, results were presented on the use of botulinum toxin injection in patients with spastic motility disorders of the esophagus. Also worthy of mention is a study confirming a higher frequency of esophageal cancer patients with achalasia who receive treatment.

Abnormal Resting Brain Activity in Patients With Functional Dyspepsia Is Related to Symptom Severity

Abnormal processing of visceral sensation at the level of the central nervous system is believed to be involved in functional dyspepsia. However, compared with studies of stimulation-related changes in brain activity, few studies have focused on resting brain activity, which also is important in pathogenesis. We mapped changes in resting brain glucometabolism of patients with functional dyspepsia, compared with healthy subjects, and attempted to correlate abnormal brain activity with symptom severity. We performed fluorodeoxyglucose positron emission tomography-computed tomography on 40 patients with functional dyspepsia and 20 healthy subjects who were in resting states. The symptom index of dyspepsia and the Nepean dyspepsia index were used to determine symptom severity. The positron emission tomography-computed tomography data were analyzed using statistical parametric mapping software. Compared with healthy subjects, patients with functional dyspepsia had higher levels of glycometabolism in the bilateral insula, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), cerebellum, thalamus, prefrontal cortex, precentral gyrus, postcentral gyrus, middle temporal gyrus, superior temporal gyrus, putamen, right parahippocampal gyrus, claustrum, and left precuneus (P < .001). The signal increase in the ACC, insula, thalamus, MCC, and cerebellum was correlated with symptom index of dyspepsia scores and Nepean dyspepsia index scores (P < .01). The glycometabolism in ACC, insula, thalamus, MCC, and cerebellum of patients with more severe functional dyspepsia was significantly higher than that of patients with less severe functional dyspepsia (P < .005). In patients with functional dyspepsia, resting cerebral glycometabolism differs significantly from that of healthy subjects. The ACC, insula, thalamus, MCC, and cerebellum might be the key regions that determine the severity of symptoms.

Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings

Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in factors associated with pathophysiological mechanisms. The aims of this study were: (i) to assess the prevalence of dyspeptic symptoms with and without overlapping reflux symptoms in the general population and their impact on daily life and on healthcare utilization; and (ii) to compare symptom groupings in the general population to FD patients. A total of 2025 subjects, representative of the Belgian general population, were used in this study. The subjects were submitted to a questionnaire with validated questions on their dyspeptic and reflux symptoms and with evaluators of impact on daily life and use of healthcare resources. Significant dyspeptic symptoms were found in 417 (20.6%). Overlapping reflux symptoms were present in 141 (33.8%). In this group, symptoms were more frequent and more severe. Dyspeptic symptoms induced weight loss (12.7%) and absenteeism (12.4%), affected daily life (61.2%) and generated use of healthcare resources, such as medical consultations (61.4%) and medication (70.9%). Factor analysis revealed a three-component structure with factor 1 including fullness, bloating and early satiety, factor 2 including nausea and vomiting and factor 3 including discomfort, pain, belching and reflux. If forced in a four-factor model, the analysis separates belching as independent factor. Dyspeptic symptoms are frequent in the general population, with overlapping reflux symptoms and increased symptom burden in about a third.

Health-related quality of life in functional dyspepsia.

We performed a systematic review of the literature to compare the health-related quality of life (HRQOL) of patients with functional dyspepsia with either healthy controls or those with other diseases. Full-length published manuscripts during 1980-2002 were included if (a) patients had functional dyspepsia, but not uninvestigated dyspepsia; and (b) HRQOL was measured using a validated generic or dyspepsia-specific instruments, but not global assessment alone. Twelve studies were reviewed; six fulfilled the selection criteria. None examined HRQOL among samples of the general population. None used dyspepsia-specific HRQOL instruments. Three studies contained four comparisons of HRQOL between functional dyspepsia patients and controls; two studies examined HRQOL changes in response to therapy. Two studies demonstrated a significant reduction at least in some domains of HRQOL among patients with functional dyspepsia compared to controls, while one study was negative. In general, studies that reported a decline in HRQOL Short Form-36 (SF-36) showed that changes in the physical domain were similar to those on mental domain of the SF-36. There is some evidence for a decrease in HRQOL in patients with moderate to severe functional dyspepsia who seek care for their symptoms; however, more studies are needed. A therapeutic response in functional dyspepsia-related pain or discomfort might result in a corresponding improvement in HRQOL.

Heterogeneity of symptom pattern, psychosocial factors, and pathophysiological mechanisms in severe functional dyspepsia

Background & Aims: Categorization of functional dyspepsia into subgroups is based on expert opinion according to (dominant) symptoms or on underlying pathophysiological mechanisms. We used an evidence-based approach to the determination of subtypes of functional dyspepsia. Methods: Consecutive functional dyspepsia patients were recruited from a tertiary referral center. The following were performed: (1) exploratory (EFA) and confirmatory factor analysis (CFA) of symptom patterns in a large group of patients with functional dyspepsia; (2) external validation of these factors by the determination of their association pattern with physio- and psychopathological mechanisms, and with health-related quality of life and sickness behavior; and (3) cluster analysis of their distribution in this population. Results: Both EFA and CFA do not support the existence of functional dyspepsia as a homogeneous (unidimensional) condition. A 4-factor model is found to be valid, with differential distribution within the patient population according to cluster analysis. Factor 1 is characterized by nausea, vomiting, early satiety, and weight loss and factor 2 by postprandial fullness and bloating. Both factor 1 and 2 are associated with delayed emptying, but only factor 1 is associated with younger age, female sex, and sickness behavior. Factor 3 is characterized by pain symptoms and associated with gastric hypersensitivity and several psychosocial dimensions including medically unexplained symptoms and health-related quality of life dimensions. Factor 4, characterized by belching, is also associated with hypersensitivity, but is unrelated to psychosocial dimensions. Conclusions: In a tertiary care population, functional dyspepsia is a heterogeneous condition characterized by 4 major dimensions differentially associated with psychopathological and physiopathological mechanisms.

Electrogastrography Before and After a High-Caloric, Liquid Test Meal in Healthy Volunteers and Patients with Severe Functional Dyspepsia

Background: The cutaneous recording of gastric electric rhythm, so-called electrogastrography (EGG), has been purported as a non-invasive method for studying patients with functional dyspepsia and unexplained nausea and vomiting. The aims of this study were to determine normal values for EGG characteristics before and after a liquid, high-caloric test meal and to investigate whether EGG could discriminate between patients with functional dyspepsia and normal controls. Methods: In studying 20 healthy volunteers and 10 patients with functional dyspepsia, we recorded gastric electrical activity during the 30 min before and after a liquid 1.0-1.5 kcal/ml test meal. Satiety before and after the meal was estimated on a 10-point scale. EGG was analysed regarding dominant frequency, instability of the dominant frequency, power ratio and percentage activity in the normal frequency range. Results: The mean ( ± s ) caloric intake in patients with functional dyspepsia (286 ± 160 kcal) was significantly lower ( P < 0.001) than in healthy volunteers (610 ± 211 kcal). The patients reported a more pronounced feeling of satiety before the test meal (5.6 ± 3.2) compared to healthy volunteers (3.6 ± 1.2, P < 0.05), but at the end of the test meal there was no difference in satiety (7.9 ± 2.5 versus 7.7 ± 1.0). However, none of the EGG parameters showed any difference between patients and healthy volunteers. Conclusions: EGG before and after a high-caloric test meal showed large variation in healthy subjects and seemed to be of little value for differentiating between healthy individuals and patients with functional dyspepsia.

Efficacy of sumatriptan in patients with severe functional dyspepsia

Efficacy of sumatriptan in patients with severe functional dyspepsia

Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric sensorial responses

Objective: Therapeutic trials in functional dyspepsia consistently show a substantial placebo response, but there is no clear explanation for such an effect. Our aim was to evaluate symptomatic, gastrointestinal motor, and gastric sensorial responses to placebo treatment in patients with chronic and severe functional dyspepsia who were part of a therapeutic trial. Methods: Thirty patients were treated during 8 wk with placebo (white-colored 8-mm tablets containing cellulose) by mouth, 20 min before breakfast, lunch, and dinner. We quantified the symptomatic response to placebo as a change in global health status, and also as a change in the individual and combined (global symptom index) of a five-symptom complex: upper abdominal pain, nausea, vomiting, bloating/fullness, and early satiety. Gastroduodenal motility, during fasting and postprandially, was evaluated by manometry in all patients pretreatment and in 17 patients posttreatment. Gastric sensitivity to distension was evaluated in 18 patients pretreatment and in five patients posttreatment (all of them clinical responders). Results: Placebo treatment produced a striking symptomatic improvement; by 8 wk 80% of the patients reported an improved global health status and their global symptom index markedly decreased (23.9 ± 1.3 pretreatment vs 9.1 ± 1.2; p < 0.05). Placebo increased the number of gastric phases III starting in the antrum during the fasting period (1.1 ± 0.1 vs 1.6 ± 0.2; p < 0.05). As a group, no significant changes in postprandial gastroduodenal motility were observed after placebo treatment. However, after placebo a significant improvement in the antral motility index (MI) was observed in the subset of patients with antral hypomotility (MI pretreatment: 7.9 ± 1.0; MI posttreatment: 11.7 ± 0.4; p < 0.05). Before placebo treatment, patients with functional dyspepsia showed increased sensitivity to stepwise distension of the stomach relative to healthy individuals. After 8 wk of placebo treatment sensitivity to distension remained unchanged, even though patients’ clinical status was markedly improved. Conclusion: In patients with functional dyspepsia, the symptomatic response to placebo is substantial. Some significant changes were also observed in gastric motility: increase in the gastric phase III number as well as in the postprandial antral motility index in those with hypomotility pretreatment. Remarkably, however, clinical improvement seems to occur independently of detectable changes in gastroduodenal motor activity or gastric hypersensitivity to distension.

Placebo in functional dyspepsia: symptomatic, gastrointestinal motor, and gastric sensorial responses.

Therapeutic trials in functional dyspepsia consistently show a substantial placebo response, but there is no clear explanation for such an effect. Our aim was to evaluate symptomatic, gastrointestinal motor, and gastric sensorial responses to placebo treatment in patients with chronic and severe functional dyspepsia who were part of a therapeutic trial. Thirty patients were treated during 8 wk with placebo (white-colored 8-mm tablets containing cellulose) by mouth, 20 min before breakfast, lunch, and dinner. We quantified the symptomatic response to placebo as a change in global health status, and also as a change in the individual and combined (global symptom index) of a five-symptom complex: upper abdominal pain, nausea, vomiting, bloating/fullness, and early satiety. Gastroduodenal motility, during fasting and postprandially, was evaluated by manometry in all patients pretreatment and in 17 patients posttreatment. Gastric sensitivity to distension was evaluated in 18 patients pretreatment and in five patients posttreatment (all of them clinical responders). Placebo treatment produced a striking symptomatic improvement; by 8 wk 80% of the patients reported an improved global health status and their global symptom index markedly decreased (23.9+/-1.3 pretreatment vs 9.1+/-1.2; p < 0.05). Placebo increased the number of gastric phases III starting in the antrum during the fasting period (1.1+/-0.1 vs 1.6+/-0.2; p < 0.05). As a group, no significant changes in postprandial gastroduodenal motility were observed after placebo treatment. However, after placebo a significant improvement in the antral motility index (MI) was observed in the subset of patients with antral hypomotility (MI pretreatment: 7.9+/-1.0; MI posttreatment: 11.7+/-0.4; p < 0.05). Before placebo treatment, patients with functional dyspepsia showed increased sensitivity to stepwise distension of the stomach relative to healthy individuals. After 8 wk of placebo treatment sensitivity to distension remained unchanged, even though patients' clinical status was markedly improved. In patients with functional dyspepsia, the symptomatic response to placebo is substantial. Some significant changes were also observed in gastric motility: increase in the gastric phase III number as well as in the postprandial antral motility index in those with hypomotility pretreatment. Remarkably, however, clinical improvement seems to occur independently of detectable changes in gastroduodenal motor activity or gastric hypersensitivity to distension.

Evaluation of gastric antral motor performance in patients with dysmotility-like dyspepsia using real-time high-resolution ultrasound.

Although manometric antral hypomotility and delayed gastric emptying have been reported separately in patients with dyspepsia, relationships between symptoms, antral contractility and emptying rate have not been sought. The present study therefore aimed to evaluate, simultaneously, gastric antral excursion characteristics and emptying in a sub-group of patients with severe functional dyspepsia using high-resolution real-time ultrasound. The circumference of the relaxed and contracted antrum was measured at 15-min intervals after ingestion of a 360 mL mixed nutrient meal in 36 chronic dyspepsia patients with symptoms of post-prandial bloating and epigastric distension, and in 25 healthy volunteers. Antral emptying (measured as the rate of decrease in circumference of the relaxed antrum) was slower in patients than normals (P = 0.02). In both groups, the average values for antral excursion were similar but the range of excursion in patients was significantly wider than in controls (F < 0.001), with 11 patients showing values above, and 8 showing values below the normal range. There was no relationship between antral emptying and antral excursion in either patients or volunteers. In conclusion, patients with severe functional dyspepsia show a wide range of antral performance characteristics, suggesting not only that the mechanisms responsible for the control of antral motor function are disturbed but also that the cause of the symptoms and the disturbed antral motor function are probably not directly related.