Epigastric Pain Syndrome Patients Research Articles

The Efficacy of Paraprobiotic, Probiotic, and Mineral Supplementation on the Eradication Rate of Helicobacter pylori in Patients with Dyspepsia: A Randomized Clinical Trial

Background. Helicobacter pylori (H. pylori) eradication regimens have been a concern, all along. Our study is aimed at assessing the effect of para- and probiotics plus minerals (Pyloshot) on H. pylori eradication rate. Methods. In this open-label randomized trial, 69 eligible adult patients with naïve H. pylori infection-related dyspepsia were randomly assigned into the group A, who received esomeprazole 40 mg BID, amoxicillin 1000 mg BID, and clarithromycin 500 mg BID, and group B with the same regimen plus one Pyloshot capsule BID for 10 days. Demographics and dyspepsia symptom severity scores (SSS), number needed to treat (NNT), dyspepsia SSS, and drug adverse effects were recorded at baseline and the end of treatment. H. pylori eradication was confirmed via 14C UBT eight weeks later. Results. Sixty-six patients completed the study. The intention-to-treat (ITT) and per-protocol (PP) eradication rates were slightly better in group B (85.2% vs. 80%, p=0.562, and 87.8% vs. 84.8%, p=0.720, respectively). Adverse effects were significantly lower in group B (20.6% vs. 54.3%; p=0.004). No significant differences in dyspepsia symptom improvement rates (p=0.255) and mean difference of SSS (p=0.231) were found between treatment groups. NNT for overall dyspepsia and epigastric pain syndrome (EPS) was 11 and 5 at the end of treatment, respectively. Conclusion. Adding Pyloshot to the H. pylori regimen could slightly improve the eradication rate and SSS of dyspepsia. NNT was considerably better among EPS patients. Adverse effects were significantly decreased by this regimen. Further trials with larger sample sizes should be thought out. This trial is registered with IRCT20141201020178N10.

The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia.

An unidentified cause of functional dyspepsia (FD) is closely associated with medication resistance. Acid suppression is a traditional and preferential method for the treatment of FD, but the efficacy of this treatment varies between epigastric pain syndrome (EPS) and postprandial syndrome (PDS): it is efficient in the former but not much in the latter. Transepithelial electrical resistance (TEER), a surrogate of mucosal barrier function, was measured under pH 3 and pH 5 acidic conditions using duodenal biopsy specimens obtained from the patients with EPS and PDS and asymptomatic healthy controls. The infiltration of inflammatory cells to the duodenal mucosa was accessed by immunohistochemical analysis. The duodenal mucosal TEER in EPS patients was decreased by exposure to the acidic solution compared to that of the controls and the PDS patients. The decrease in TEER of the EPS patients was observed even under pH 5 weak acidic condition and was correlated to degree of the epigastric pain. Moreover, the duodenal mucosa of EPS patients presented an increase in mast cells and plasma cells that expressed Ig-E. Duodenal mucosal vulnerability to acid is likely to develop EPS.

Effects of Low-Dose Amitriptyline on Epigastric Pain Syndrome in Functional Dyspepsia Patients

AimTo observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia.MethodsSixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively.ResultsAll items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI–symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p < 0.05). However, no differences were found in the frequency of NDI checklist, psychological status (HAMD/HAMA scores) of EPS, or sleep quality (PSQI score) between the two groups after treatment. In addition, the time to fall asleep was shorter in the AMT group compared with the RT group after 4 weeks of treatment (p < 0.05).ConclusionLow-dose AMT effectively improved the dyspepsia symptoms and the time to fall asleep in the EPS patients, compared with pantoprazole, although it did not reduce the psychological distress. Therefore, AMT could be considered as a good candidate for EPS treatment in the clinic.

Similarity and diversity of spontaneous brain activity in functional dyspepsia subtypes.

Functional dyspepsia (FD) subtypes may differ in terms of pathophysiology, but the underlying mechanisms remain poorly understood. To explore spontaneous brain activity in two main FD subtypes, namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), using the amplitude of low-frequency fluctuation (ALFF). Thirty-one FD patients (18 EPS and 13 PDS) and 22 matched healthy controls (HC) underwent resting-state functional MRI scanning. Spontaneous brain activity was evaluated by measuring the ALFF and then compared among the EPS, PDS, and HC groups with ANOVA test. Pearson correlation analysis was performed between the ALFF values and clinical indices. Compared to healthy controls, both EPS and PDS patients had increased ALFF in the bilateral precentral/postcentral gyri, insula, and thalami. Furthermore, only the EPS patients displayed increased ALFF in the right middle and inferior frontal gyri, and only the PDS patients showed increased ALFF in the left posterior cingulate cortex (PCC). The ALFF values in the left thalamus were positively correlated with the sleep disturbance in EPS patients, and the ALFF values in the right precentral/postcentral gyri showed a positive correlation with the symptom score in PDS patients. EPS and PDS had similarities of higher spontaneous brain activity in the primary motor/sensory areas and homeostatic-afferent network regions, and differences in the prefrontal region and PCC, providing evidence to suggest the similarity and diversity of pathophysiology in FD subtypes.

CYP2C19 Genotype, CagA Genotype and Antibiotic Resistant Strain of Helicobacter pylori Infection

Background: H. pylori is a class I carcinogen and major cause of gastric cancer. Few previous studies reported relationship between H. pylori infection, CYP2C19 genotype and functional dyspepsia (FD) subtype. The aim of this study was to determine relationship between CYP2C19 genotype and FD subtype patients(host factor) with antibiotic resistant strains of H. pylori infection and CagA genotype(bacterial factor). Methods:FD patients who were investigated with gastroscopy at Thammasat University Hospital, Thailand during March 2017-November 2017 were enrolled. Two antral gastric biopsies were obtained for rapid urease test, E-test and cultures. CagA genotypes (CagA1a and CagA2a) were determined by PCR and CYP2C19 genotype was determined by PCR-RFLP. FD patients were categorized as epigastric pain syndrome(EPS) and postprandial distress syndrome (PDS). Results:93 FD patients with H. pylori infection were enrolled (37 male, 56 female, mean age 54.5 years). There were 33 patients with EPS and 60 patients with PDS. CYP2C19 genotype revealed 55.9% rapid metabolizer (RM), 40.9% intermediate metabolizer (IM) and 3.2% poor metabolizer (PM) genotypes. Antibiotics susceptibility tests demonstrated 62.8% resistant to metronidazole, 12.9% resistant to clarithromycin and 27.1% resistant to fluoroquinolone. CagA 1a and CagA 2a were demonstrated in 6 patients(11.5%) and 46 patients(88.5%). CagA2a genotype was more prevalent in PDS than EPS patients (94.3%vs.76.5%; P =0.08) without significance. In intermediate metabolizer (IM), CagA2a genotype was significant higher in PDS than EPS(100% vs.25%; P=0.004). Conclusions:PDS, CYP2C19 RM genotype and CagA 2a gene of H. pylori infection were the predominant type of FD in Thailand. Metronidazole remain the most common antibiotic resistant strain of H. pylori infection in FD patients. PDS (host factor) was significantly related to CagA2a genotype (bacterial factors) only in patients with intermediate metabolizer. Appropriate dose of proton pump inhibitor (PPI) and correct regimens for H. pylori eradication in FD patients should be consider to improve clinical outcomes.

Changes of gastric mucosal mast cells in patients with functional dyspepsia after Hylicobacter pylori infection

Objective To investigate the changes of gastric mucosal mast cells in patients with functional dyspepsia (FD) after Helicobacter pylori (H.pylori) infection, and to explore the correlation between the changes and dyspeptic symptoms. Methods From November 2012 to March 2014, 32 patients with FD and 16 asymptomatic patients (control group) from Beijing Jishuitan Hospital were enrolled. H. pylori infection situation was examined. The mucosal biopsies from gastric antrum and gastric body were taken for histological examination. The mast cells of gastric mucosa were detected by immunohistochemical stain. T test was performed for statistical analysis. Results Among 32 FD patients, 17 had H. pylori infection (one with gastric body involved, two with gastric antrum involved, 14 with both gastric antrum and gastric body involved), and 15 had no H. pylori infection. Among 16 asymptomatic patients, 12 had H. pylori infection and four had no H. pylori infection. Among FD patients, the percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (61.45±24.86)%, which was higher than that without H. pylori infection group ((48.34±21.63)%), and the difference was statistically significant (t=-2.145, P=0.036). The percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (29.73±12.99)%, which was higher than that without H. pylori infection group ((20.77±10.86)%), and the difference was statistically significant (t=-2.856, P=0.006). In H. pylori infection group, the percentage of degranulated mast cells in gastric body mucosa of FD patients was (66.99±18.85)%, which was higher than that of asymptomatic patients in control group ((46.77±8.43)%), and the difference was statistically significant (t=3.642, P=0.002). The ratio of degranulated mast cells in gastric body mucosa and the density of mast cells in gastric antrum mucosa of prandial distress syndrome (PDS) patients, the density of mast cells in gastric body mucosa of epigastric pain syndrome (EPS) patients and the ratio of degranulated mast cells in gastric body mucosa and the degree of degranulation of mast cells of PDS and EPS patients were all higher than those of asymptomatic patients in control group, and the differences were statistically significant (t=2.750, 3.601, 2.799, 9.522 and 5.755, all P<0.05). Conclusions The dyspeptic symptoms of FD patients with H. pylori infection is correlated with the changes of mast cells. With the infection of H. pylori, dyspeptic symptoms of different subtypes of FD may be correlated with the changes of mast cells in different gastric region. H. pylori infection may cause the dyspeptic symptoms of FD patients by increase the number and activation of mast cells. Key words: Helicobacter pylori; Mast cells; Functional dyspepsia; Dyspeptic symptom

Seroreactivity to Microbial Antigens and Gut‐Homing Immune Responses in Functional Dyspepsia Patients with Postprandial Distress Syndrome

Functional dyspepsia (FD) is characterised by recurrent upper gastrointestinal symptoms with no explainable structural changes seen at endoscopy. FD can be classed by two symptom‐based subtypes: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Although FD is associated with an altered microbiome, the nature and consequence of the host‐microbiota interactions and how they relate to FD symptom subtypes is not well understood. We have previously identified an increase in the abundance of Streptococcus spp. in the duodenal microbiota of FD patients compared to controls (Zhong et al. 2017 Gut). We hypothesised that the microbiota of FD patients influenced immune homeostasis and aimed to investigate whether specific species provoked immune responses in patients with FD.New isolates of Streptococcus and Corynebacterium spp. found to be abundant in the duodenal microbiota of FD patients were selected for further analysis. Whole cell lysates from cultures of these bacteria were separated by polyacrylamide gel electrophoresis and transferred to a PVDF membrane for immunoblotting. Immunoblots were probed with plasma from FD patients or non‐FD controls. Density gradient separation was used to isolate peripheral blood mononuclear cells from blood. Cells were then stained with fluorophore conjugated markers for CD3, CD4, integrins α4 &amp; β7 before analysis by flow cytometry to examine changes in proportions of gut‐homing associated lymphocytes (α4+β7+).For lysate isolated from a Streptococcus spp. strain, seroreactive IgG antibody bands were observed at approximately 70kDa in 9 out of 10 FD patients. This band was absent in all but 2 of the control cohort (total n=8). A further band was observed around 30kDa in 9 FD patients (total n=10) that was only present in 3 controls (total n=8). 8 of the 10 patients reported PDS symptoms, of which all demonstrated seroreactivity at 70kDa, and 7 of the total 8 demonstrated a further band at approximately 30kDa. Cross‐reactivity was also observed with a different strain of the same Streptococcus spp. An increase in the proportion of peripheral α4+β7+ T cells (p&lt;0.05) was seen in PDS patients (n=4) but not in EPS (n=3) or EPS/PDS overlap (n=3) patients.Our data suggest an adaptive immune response against duodenal Streptococcus spp. in PDS but not EPS patients. In addition, PDS patients had significantly higher proportions of circulating gut‐homing T cells. These data suggest that PDS is the result of altered microbiota‐immune interactions. With further work, this finding may become a diagnostic indicator of PDS, and provide further insight into the mechanisms that drive FD.Support or Funding InformationNational Health and Medical Research Council Project Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Rome III functional dyspepsia symptoms classification: Severity vs frequency.

The Rome III criteria subdivide functional dyspepsia (FD) in the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS) based on the frequency of the symptoms to optimize the diagnostic and therapeutic approach. However, it is unclear to which extent the frequency of the symptoms is related to their severity. Our aim was to explore the frequency and severity of dyspeptic symptoms and their relationship in FD patients. Functional dyspepsia patients fulfilling the Rome III diagnostic completed a questionnaire that evaluated the frequency and severity of FD symptoms. The concordance between the severity and frequency categories was analyzed by means of spearman correlation and the concordance correlation coefficient (ρc ). In the entire patient cohort (n=421), the classification of symptoms severity and frequency showed good concordance for all symptoms. In the EPS subgroup (n=….), the symptom severity and frequency score of epigastric pain showed a poor correlation (r=.28; ρc =0.07). The PDS subgroup (n=…) showed a good correlation for most of the symptoms. Due to its limited occurrence in this group, the correlation of the severity and frequency scores for epigastric pain is of little relevance (r=.79; ρc =0.58). The overlap EPS-PDS group showed good correlation for most of the symptoms, except for epigastric pain (pain r=.24; ρc =0.09). We conclude that the information given by the assessment of frequency and severity of PDS symptoms is comparable and hence one of the scores sufficiently identifies symptom pattern in PDS patients. In EPS patients, both the symptom frequency and severity should be taken into account as two separate entities.

Epigastric pain syndrome accompanying pancreatic enzyme abnormalities was overlapped with early chronic pancreatitis using endosonography.

There was not available data about the overlap between functional dyspepsia (FD) and pancreatic diseases. We aimed to determine whether epigastric pain syndrome (EPS) accompanying with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by Japan Pancreas Society (JPS) using endosonography. We enrolled 99 consecutive patients presenting with typical symptoms of FD, including patients with postprandial distress syndrome (PDS) (n = 59), EPS with pancreatic enzyme abnormalities (n = 41) and EPS without pancreatic enzyme abnormalities (n = 42) based on Rome III criteria. Gastric motility was evaluated using the 13C-acetate breath test. Early chronic pancreatitis was detected by endosonography and graded from 0 to 7. The ratio of female patients among EPS patients (34/41) with pancreatic enzyme abnormalities was significantly (p = 0.0018) higher than the ratio of female EPS patients (20/42) without it. Postprandial abdominal distention and physical component summary (PCS) scores in EPS patients with pancreatic enzyme abnormalities were significantly disturbed compared to those in EPS patients without it. Interestingly, AUC5 and AUC15 values (24.85 ± 1.31 and 56.11 ± 2.51, respectively) in EPS patients with pancreatic enzyme abnormalities were also significantly (p = 0.002 and p = 0.001, respectively) increased compared to those (19.75 ± 1.01 and 47.02 ± 1.99, respectively) in EPS patients without it. Overall, 64% of EPS patients with pancreatic enzyme abnormalities were diagnosed by endosonography as having concomitant early chronic pancreatitis proposed by JPS. Further studies are warranted to clarify how EPS patients with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by JPS.

Rome III functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap.

The Rome III consensus proposed to subdivide functional dyspepsia (FD) into two groups: meal-related dyspepsia or postprandial distress syndrome (PDS), and meal-unrelated dyspepsia or epigastric pain syndrome (EPS). However, in clinical practice, overlap between both has been reported to be as high as 50%, thereby hampering clinical applicability. Although EPS is referred to as meal-unrelated dyspepsia, relationship of symptoms to meal ingestion in this category is not formally addressed in the Rome III criteria. The aim of our study was to investigate whether taking into account the relationship of epigastric pain and nausea to meal ingestion may help to improve separation between EPS and PDS. Consecutive ambulatory tertiary-care patients with epigastric symptoms filled out Rome III gastro-duodenal questionnaires with supplementary questions. Those fulfilling Rome III FD criteria and a negative endoscopy were identified and subdivided into 'pure' PDS patients (i.e., meeting criteria for PDS without EPS symptoms), 'pure' EPS (i.e., meeting criteria for EPS without PDS symptoms), and overlapping PDS-EPS (i.e., symptoms of both PDS and EPS). Out of 1029 patients coming to endoscopy, 199 patients (73% females, 45.9 ± 1.0 years, BMI: 23.7 ± 0.35) fulfilled Rome III FD diagnostic criteria, and could be subdivided into pure PDS (69% females, 49 ± 2 years, BMI: 24.2 ± 0.61), pure EPS (59% females, 47.4 ± 2 years, BMI: 23.2 ± 0.97) and overlapping PDS-EPS (64% females, age 43 ± 5 years, BMI: 26 ± 0.46). Compared with pure EPS patients, the overlap PDS-EPS patients were characterized by a higher occurrence of postprandial epigastric pain (70% vs 31%, p < 0.0001), while the occurrence of epigastric pain in between meals was borderline (48% vs 38%, p = 0.05). In addition, the overlap PDS-EPS patients reported a higher occurrence of postprandial nausea (23% vs 0%, p < 0.0001), and bloating (79% vs 28%, p = 0.0001). When postprandial epigastric pain and postprandial nausea were considered as PDS symptoms, the 'adapted' subdivision identified 48% pure PDS, 16% pure EPS, and 36% overlapping PDS-EPS patients. EPS and PDS symptoms frequently coexist in FD patients, with postprandial symptoms substantially contributing to the overlap. A more rigorous linking of postprandially occurring symptoms to PDS, regardless of their qualitative nature, may improve the separation between PDS and EPS.

Which Subtype of Functional Dyspepsia Patients Responses Better to Acupuncture? A Retrospective Analysis of a Randomized Controlled Trial

Background: Whether subgroups of functional dyspepsia (FD) should be treated with different approaches is controversially discussed in research. As our previous study has demonstrated the effect of acupuncture in FD treatment, we now further analyze the therapeutic effect of acupuncture in the treatment of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Methods: A retrospective analysis was conducted in 465 eligible PDS patients and 241 EPS patients. 4 acupuncture groups (group A: specific acupoints along the stomach meridian; group B: non-specific acupoints along the stomach meridian; group C: alarm and transport acupoints; group D: specific acupoints along the gallbladder meridian) were compared with a non-acupoint sham acupuncture group and an itopride group. The patients were treated in 5 consecutive sessions per week for 4 weeks and were followed-up for 12 weeks afterwards. Primary outcome of the study was defined as response rate and symptom improvement as measured by the Symptom Index of Dyspepsia, while secondary outcome was designated as improvement in quality of life (QoL) as determined by the Nepean Dyspepsia Index. Results: Symptoms of dyspepsia and QoL were improved from baseline in all groups. In EPS patients, no statistically significant differences could be observed in response rate (p = 0.239) and symptoms improvement (p = 0.344 for epigastric pain; p = 0.465 for epigastric burning). In contrast, PDS patients of the acupuncture group A showed higher response rate (53.2% vs. 19.7%, p<0.001; 53.2% vs. 35.1%, p = 0.025) and score change in postprandial fullness (1.01 vs. 0.27, p<0.001; 1.01 vs. 0.57, p<0.001), early satiation (0.81 vs. 0.21, p<0.001; 0.81 vs. 0.39, p=0.001), and QoL (14.5 vs. 4.33, p<0.001; 14.5 vs. 8.5, p<0.001) compared to the sham acupuncture and itopride group. Conclusions: FD patients with PDS responded better to the acupuncture therapies, especially at the specific acupoints along the stomach meridian. The positive therapeutic effect of acupuncture on PDS was correlated with the improvement in postprandial fullness. Trial Registration: ClinicalTrial.gov NCT00599677.

Helicobacter pylori infection impacts on functional dyspepsia in Thailand.

Helicobacter pylori (H. pylori) is a well known major cause of gastric cancer and even when asymptomatic infected patients are at elevated risk. Functional dyspepsia (FD) is also one of the most common gastrointestinal diseases, which greatly impacts the quality of life. H. pylori infection and psychosocial stress are frequently associated with FD but limited studies have confirmed the relationships, especially in Southeast Asian countries. Here we aimed to investigate the prevalence and impact of H. pylori infection, anxiety and depression on Thai FD patients. This cross-sectional study was conducted in a tertiary care center in Thailand, during February 2013-January 2014. All FD patients were diagnosed and categorized by Rome III criteria into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) groups. The Hospital Anxiety and Depression Scale was used to evaluate psychological status. The presence of H. pylori was defined as positive with H. pylori culture, positive rapid urease test or positive histology. Three hundred FD patients were included, 174 (58%) female. Overall mean age was 54.8+15.1 years. There were 192 (64%) patients with PDS and 108 (36%) with EPS. H. pylori infection was demonstrated in 70 (23.3%) patients. Anxiety and depression were documented in 69 (23%) and 22 (7.3%), respectively. H. pylori infection, anxiety and depression were significantly higher in PDS than EPS patients (27.1% vs 16.7%; p=0.04; OR=1.86; 95%CI=1.01-3.53 and 29.7% vs 11.1%; p=0.0002; OR=3.4; 95%CI=1.7-7.1 and 10.4% vs 1.9%; p=0.006; OR=6.2; 95%CI=1.4-38.9, respectively). H. pylori infection, anxiety and depression were commonly found in Thai FD patients and more prevalent in PDS than EPS. H. pylori eradication might be the key to success for the treatment of Thai FD patients and prevent the development of gastric cancer.

The association of SLC6A4 5‐HTTLPR and TRPV1 945G&gt;C with functional dyspepsia in Korea

The association of various genetic polymorphisms with functional dyspepsia (FD) has been suggested, but the results were still controversial. The aim of the present study was to assess the association of GNB3 825C>T, SLC6A4 5-HTTLPR, ADRA2A-1291C>G, CCK-1R intron 779T>C, and TRPV1 945G>C polymorphisms with FD based on Rome III criteria in Korea. Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between 2009 and 2012. One hundred and twelve FD patients and 269 controls were enrolled. In SLC6A4 5-HTTLPR polymorphism, the frequency of S/S genotype was significantly lower than that of L/L + L/S genotype in FD compared to controls (P < 0.05). After stratification according to Helicobacter pylori infection, the S/S genotype was significantly associated with H. pylori-positive epigastric pain syndrome (EPS) patients (adjusted odds ratio (OR) 0.46; 95% confidence interval (CI) 0.22-0.99; P = 0.048). In TRPV1 945G>C polymorphism, the frequency of C/C genotype was lower in FD compared to controls (P = 0.057). The C carrier and C/C genotype was significantly associated with postprandial distress syndrome (PDS) and EPS, respectively (adjusted OR 0.47 and 0.43; 95% CI 0.25-0.90 and 0.20-0.93; P = 0.021 and 0.033). After stratification, the significant associations remained in H. pylori-positive PDS and EPS patients (adjusted OR 0.37 and 0.28; 95% CI 0.16-0.88 and 0.09-0.85; P = 0.024 and 0.025). The genetic polymorphism of SLC6A4 5-HTTLPR and TRPV1 945G>C could be one of the pathophysiological factors of FD, especially in the case of H. pylori-positive patients in Korea.

Evaluation of proximal gastric function in functional dyspepsia and its subtypes

Objective To evaluate proximal gastric function in patients with functional dyspepsia (FD) met Rome Ⅲ criteria and its subtypes.Methods Thirty FD patients were enrolled,including 15 patients with postprandial distress syndrome (PDS) and 15 patients with epigastric pain syndrome (EPS).A total of 30 healthy volunteers were recruited as control.All the subjects received barostat examination.Minimal distending pressure (MDP),pressure and volume of thresholds for first sensation and maximal tolerance for gastric sensitivity were recorded.When the pressure level was MDP+2 mmHg (1 mmHg=0.133 kPa),average volume at 30 minutes before meal,averaged volume at 60 minutes after meal and maximum accommodation volume after meal were recorded,and receptive diastolic volume was calculated.The gastric hypersensitivity and impaired accommodation were observed.Student's t test or x2 test was performed for statistical analysis.Results MDP,pressure of first-sensation,maximum sensation pressure,volume of first sensation and maximal sensation volume of FD group were (6.17 ±1.95) mmHg,(8.44±2.01) mmHg,(14.62±3.72) mmHg,(123.59±53.26) mL and (451.26±140.44) mL,respectively; which were lower than those of healthy control group ((9.27±1.99) mmHg,(12.04±2.66) mmHg,(19.74±4.18) mmHg,(168.41±73.06) mL and (556.89±124.07) mL),and the differences were statistically significant (t=-6.080,-5.900,-5.011,-2.723 and-2.995,all P＜0.01).The averaged volume at 30 minutes before meal and 60 minutes after meal was (212.19±120.82) mL and (333.97±121.86) mL while those of healthy control group was (191.69±66.19) mL and (385.58±83.05) mL,and there were no significant differences between the two groups (both P＞0.05).The maximum postprandial accommodation volume and receptive diastolic volume of FD group were (405.10±111.29) mL and (190.16±97.22) mL,which were lower than those of healthy control group ((461.10±87.60) mL and (262.83±78.39) mL),and the differences were statistically significant (t=-2.599 and-3.187,both P＜0.05).The maximum postprandial accommodation volume of FD patients was at 15 to 20 minutes after meal and in healthy control it was at five to ten minutes after meal.Among the 30 FD patients,12 patients (40 ％) had gastric hypersensitivity,including eight PDS patients and four EPS patients,and there was no significant difference in the ratio between two groups (P＞0.05) ;nine patients (30 ％) had impaired accommodation,including five PDS patients and four EPS patients,and there was no significant difference in the ratio between two groups (P＞ 0.05).Conclusions Gastric hypersensitivity and impaired accommodation often appear in FD patients,and there is no significant difference between PDS and EPS subtypes.FD patients with different pathophysiologic mechanisms cannot be efficiently distinguished according to Rome Ⅲ criteria. Key words: Functional dyspepsia; Visceral hypersensitivity; Gastric accommodation

Does Melatonin Homeostasis Play a Role in Continuous Epigastric Pain Syndrome?

Two clinical forms of functional dyspepsia (FD) are listed in the Rome III criteria: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), differing in the recurrence of ailments depending on the diet. Continuous EPS (CEPS) is observed in some EPS patients, also at night, but its cause is still unknown. We showed previously that melatonin (MEL) homeostasis may be associated with FD. In the present work we evaluated selected components of melatonin homeostasis in patients with CEPS. The study included 30 patients with CEPS, 21 women and nine men, aged 21–49 years and 30 control subjects (EPS excluded); organic and mental diseases, as well as Helicobacter pylori infection, were excluded in both groups. The average severity of abdominal pain in the last three months was estimated in a 10-point scale (Visual Analog Scale). The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), the main components of MEL homeostasis, were determined in gastric mucosa with real time PCR. The fasting serum level of MEL (at 09:00 a.m.) and circadian urine excretion of 6-sulfatoxymelatonin (6-HMS) were determined with ELISA. AANAT expression in antral mucosa of control subjects was 1.76 ± 0.41, in the gastric body 1.35 ± 0.38, and in the dyspeptic group 1.42 ± 0.38 (p < 0.05) and 0.92 ± 0.55 (p < 0.05), respectively. HIOMT expression in the control was 2.05 ± 0.70 in the antrum and 1.57 ± 0.69 in the body and in the CEPS group, it was: 1.51 ± 0.57 (p < 0.05) and 0.74 ± 0.31 (p < 0.001), respectively. MEL concentration (pg/mL) was 9.41 ± 3.09 in the control group and 5.62 ± 1.34 (p < 0.01) in the CEPS group. Urinary 6-HMS excretion (μg/24 h) was 11.40 ± 4.46 in the controls and 7.68 ± 2.88 (p < 0.05) in the CEPS. Moreover, a negative correlation was found between the tested parameters and severity of epigastric pain. These results indicate that patients with CEPS may display low level of AANAT and HIOMT expression in gastric mucosa, resulting in decreased MEL synthesis.

Rome III Subgroups of Functional Dyspepsia Exhibit Different Characteristics of Antral Contractions Measured by Strain Rate Imaging – a Pilot Study

Rome III defines two distinct entities of functional dyspepsia (FD), namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). We aimed at studying these subgroups of FD by simultaneously assessing antral strain, gastric accommodation and emptying and visceral hypersensitivity. Strain during antral contractions was assessed by ultrasound strain rate imaging in 15 controls and 19 FD patients (8 EPS patients and 11 PDS patients). Gastric accommodation and emptying were assessed using B-mode ultrasonography. Symptoms were assessed by visual analogue scale (VAS). During fasting, antral strain in EPS patients (mean±SEM) was 61.4 ± 6.4 %, significantly higher than in controls (47.5 ± 3.3 %; p = 0.042) and in PDS patients (28.6 ± 1.7 %; p = 0.001). PDS patients had lower strain than controls (p < 0.001). Postprandially, EPS patients had higher strain than both controls and PDS patients (p < 0.01) but no difference was found between controls and PDS patients. Compared with controls, PDS patients had significantly larger fasting proximal area than controls (14.9 ± 1.6 cm2 vs. 7.8 ± 0.2 cm2; p < 0.001), whereas EPS patients did not differ (12.1 ± 1.9 cm2; p = 0.057). Gastric emptying fraction (1 - proximal area at 40 min postprandially/area at 1 min postprandial × 100) at 40 min postprandially in EPS patients 46.4 ± 6.6 % was lower than in controls (62.9 ± 1.3 %; p = 0.032), but higher than PDS patients (27.4 ± 5.3 %; p = 0.018). Anterior radial strain measured by ultrasound strain rate imaging may discriminate between subgroups of FD and healthy controls. This study supports the Rome III classification of FD into EPS and PDS groups.

The Relationship of Gastric Emptying and Symptoms in Patients with Functional Dyspepsia

Purpose: Functional Dyspepsia (FD), a highly prevalent functional GI disorder, affects quality of life and significantly impacts the health care system. Symptoms of FD include early satiety, postprandial fullness, nausea and epigastric pain or discomfort. It has been proposed that patients with PDS (postprandial distress syndrome) are more likely to have delayed gastric emptying than those with EPS (epigastric pain syndrome). The aim of this study was to characterize gastric emptying abnormalities in FD patients based on subtype and evaluate the relationship between gastric emptying and predominant symptoms. Methods: A retrospective analysis of a prospectively gathered data base was analyzed. Men and women, aged 18 and over, categorized as meeting Rome III criteria for FD were eligible for inclusion. All patients had a normal upper endoscopy. Demographics (age, gender, BMI) were recorded; predominant FD symptoms were identified. Patients were categorized as having EPS, PDS or mixed EPS and PDS according to Rome III criteria. Gastric emptying scans (GES), when performed, were all four hour solid phase scans using a standardized protocol according to internationally recognized guidelines. GES were identified as normal if </= 10% of material remained at the 4-hour mark; rapid if <10% remained at the 2-hour mark; and slow if >10% remained at the 4-hour mark. For those with slow emptying, the extent of delay was further categorized as >20% and >30%. FD patients who did not undergo a gastric emptying scan were not included in this analysis. Results: 76 FD patients were analyzed. The mean age was 43.6 yrs (SD = 14.2); 83% were women. The mean BMI was 26.5 (SD = 6.7). 45% were identified as having EPS, while 46% had PDS and 9% had mixed EPS and PDS. The most common FD symptoms were upper abdominal pain (44.7%), fullness (25%), and early satiety (15.8%). Four-hour gastric emptying scans were normal in 76% of FD patients, rapid in 8% and delayed in 16%. Only two pts (2.6%) had a marked delay in gastric emptying (>30%). Slightly more PDS patients (7; 21%) had delayed gastric emptying than EPS Pts (4; 12%), although this was not statistically significant. Analysis of FD symptoms (pain, discomfort,fullness, nausea, bloating, regurgitation) found that early satiety was the only symptom to be associated with delayed 4 hr emptying (p = .04). Conclusion: The majority of FD patients have normal gastric emptying; very delayed gastric emptying is uncommon. PDS patients do not appear to be more likely to have delayed gastric emptying than EPS patients. Symptoms cannot reliably predict the presence or absence of gastric emptying abnormalities in FD patients. The utility of performing gastric emptying scans in FD patients warrants further scrutiny.

CagA genotype and metronidazole resistant strain of Helicobacter pylori in functional dyspepsia in Thailand

Many previous studies indicated relationship between H. pylori infection and functional dyspepsia (FD) but pathogenesis remains unclear. The aim of this study was to determine relationship between cagA genotype and metronidazole resistant strains of H. pylori in Thai FD patients. Total of 412 Thai FD patients who underwent gastroscopy at Thammasat University Hospital, Thailand between June 2008 and May 2010 were enrolled. Two antral gastric biopsies were obtained for CLO test, cultures and E-test for metronidazole. Cag A genotype was determined by PCR. FD patients were diagnosed by Rome III criteria and categorized as epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). 133 FD patients (31%) were infected with H. pylori (56 male, 77 female). There were 37 patients with EPS and 96 patients with PDS. Cag A genotype was performed in 114 patients and CagA 1a was demonstrated in 24.6%. Cag A 1a was relatively higher prevalence in PDS than EPS without statistical significance (26% vs 22%; P > 0.05). E-test for metronidazole was performed in 100 patients (32 EPS and 68 PDS patients) and metronidazole resistant strains were found in 30%. Metronidazole resistant strains were significantly higher in PDS than EPS patients (38.2% vs 12.5%; P = 0.03). In EPS patients, presence of cagA 2a gene was significantly higher in metronidazole resistant than metronidazole sensitive strains (100% vs 74.1%; OR = 4.8, 95% CI = 1.2-26.8, P = 0.01). PDS was the predominant type of FD in Thailand. Metronidazole resistant strains and cagA 2a gene of H. pylori infection was commonly found in Thai FD patients. In EPS patients, cagA 2a gene might be related to metronidazole resistant strains of H. pylori infection in Thailand.

Secretion of melatonin and 6-sulfatoxymelatonin urinary excretion in functional dyspepsia

To evaluate blood concentration of melatonin and urinary excretion of its metabolite, 6-sulfatoxymelatonin (6-OHMS), in functional dyspepsia (FD). Ninety individuals were enrolled in the study: 30 in each study group: patients with postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and controls. Blood samples were drawn at 02:00 and 09:00 h and 24-h urine collection was performed. Serum melatonin and urinary 6-OHMS concentrations were measured by enzyme-linked immunosorbent assay. Serum melatonin concentration at night and in the morning was significantly (P < 0.001) higher in PDS patients [at 02:00 h-93.3 pg/mL, quartile range (QR): 79.8-116.2; at 09.00 h-14.3 pg/mL, QR: 7.06-19.0] than in EPS (57.2 pg/mL, QR: 42.6-73.1; 8.1 pg/mL, QR: 4.1-9.3) and control patients (57.7 pg/mL, QR: 51.2-62.5; 8.1 pg/mL, QR: 5.4-10.3). A similar relationship was observed for urinary 6-OHMS excretion. Patients with severe PDS symptoms had a higher melatonin concentration than these with moderate syndromes, whereas patients with severe EPS had a lower urinary 6-OHMS excretion than patients with moderate symptoms. Evaluation of melatonin serum concentrations and 24-h urinary 6-OHMS excretion are useful methods for differential diagnosis of various clinical forms of FD.

Comparison of Gastric Emptying and Plasma Ghrelin Levels in Patients with Functional Dyspepsia and Non-Erosive Reflux Disease

Background and Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. Methods: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the T_max value as a marker of gastric emptying using the ¹³C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. Results: The T_max value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and T_max value in PDS patients but not in EPS or NERD patients. Conclusion: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying.