The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of ...gastroparesis.
Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models.
Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls.
A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly “organic” gastric neuromuscular disorders.
NCT00398801, NCT01696747
Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum ...plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.
Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological ...factors and general tendency to report symptoms.
We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression.
In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η
: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05).
A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased ...interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world’s first country to list “functional dyspepsia” as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor–patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation).
H. pylori
eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.
Dyspepsia refers to group of upper gastrointestinal symptoms that occur commonly in adults. Dyspepsia is known to result from organic causes, but the majority of patients suffer from non-ulcer or ...functional dyspepsia. Epidemiological data from population-based studies of various geographical locations have been reviewed, as they provide more realistic information. Population-based studies on true functional dyspepsia (FD) are few, due to the logistic difficulties of excluding structural disease in large numbers of people. Globally, the prevalence of uninvestigated dyspepsia (UD) varies between 7%-45%, depending on definition used and geographical location, whilst the prevalence of FD has been noted to vary between 11%-29.2%. Risk factors for FD have been shown to include females and underlying psychological disturbances, whilst environmental/ lifestyle habits such as poor socio-economic status, smoking, increased caffeine intake and ingestion of non-steroidal anti-inflammatory drugs appear to be more relevant to UD. It is clear that dyspepsia and FD in particular are common conditions globally, affecting most populations, regardless of location.
Functional dyspepsia Ford, Alexander C; Mahadeva, Sanjiv; Carbone, M Florencia ...
The Lancet,
11/2020, Letnik:
396, Številka:
10263
Journal Article
Recenzirano
Odprti dostop
Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately ...80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.
Background and Aim
Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group ...remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS‐FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS‐FD.
Methods
Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5‐HTTLPR and ADRA2A 1291 G alleles and CCK‐1R intron 779T>C were assessed using a multivariate logistic regression model.
Results
A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS‐FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non‐overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS‐FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS‐FD overlap among FD patients. 5‐HTTLPR L/L was a risk factor for the co‐occurrence of IBS‐C among FD patients (OR: 12.47; 95% CI: 2.00–77.75; P = 0.007).
Conclusions
Bloating was a risk factor for IBS‐FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation‐dominant IBS.
Background & Aims Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial ...fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. Methods We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. Results An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) ( P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1−9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2−0.8). Both antidepressants improved overall quality of life. Conclusions Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.
Background
Functional dyspepsia (FD) is a very common condition affecting more than 10% of the population. While there is no cure, a few drugs have been found to be effective for the relief of ...symptoms, although most are only effective in a subgroup of patients. We assess and compare the efficacy of a fixed peppermint/caraway‐oil‐combination (Menthacarin) on symptoms and quality of life (QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS).
Methods
In a prospective, double‐blind, multicenter trial, 114 outpatients with chronic or recurrent FD were randomized and treated for 4 weeks with the proprietary peppermint‐ and caraway‐oil‐preparation Menthacarin or placebo (2×1 capsule/day). Improvement of abdominal pain and discomfort were used as co‐primary efficacy measures (scores measured with the validated Nepean Dyspepsia Index).
Key Results
After 2 and 4 weeks, active treatment was superior to placebo in alleviating symptoms consistent with PDS and EPS (P all <.001). After 4 weeks of treatment, pain and discomfort scores improved by 7.6±4.8 and 3.6±2.5 points (full analysis set; mean±SD) for Menthacarin and by 3.4±4.3 and 1.3±2.1 points for placebo, respectively. All secondary efficacy measures showed advantages for Menthacarin.
Conclusions & Inferences
Menthacarin is an effective therapy for the relief of pain and discomfort and improvement of disease‐specific QoL in patients with FD and significantly improves symptoms consistent with EPS and PDS.
We assessed and compared the efficacy of a fixed peppermint/caraway‐oil‐combination (Menthacarin) on symptoms and quality of life (QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). We conducted a prospective, double‐blind, multicenter trial, 114 outpatients with chronic or recurrent FD were randomized and treated for 4 weeks with the proprietary peppermint‐ and caraway‐oil‐preparation Menthacarin or placebo (2×1 capsule/day). Menthacarin is an effective therapy for the relief of pain (graph 1) and discomfort and improvement of disease‐specific QoL in patients with FD and significantly improves symptoms consistent with EPS and PDS.
View the podcast on this paper at the following sites:iTunes: https://itunes.apple.com/gb/podcast/neurogastroenterology-motility-november-2017-1-episode/id1294295308?mt=2 Youtube: https://youtu.be/WERNZnAdif8
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