Introduction

STW5-II is a medicinal product composed by 6 herbal extracts that has been shown to relieve clinical symptoms in patients with dyspepsia. The mechanisms of action include selective effects on gastric tone, antro-pyloric activity
and visceral sensitivity. Patients with functional dyspepsia (FD) have a poor tolerance to gastric gas that has been related to a combination of several factors, including delayed gas transit and evacuation, visceral hypersensitivity and altered viscero-visceral reflexes.

Aims & Methods

The aim of the present study was to determine the effect of STW5-II on transit and tolerance of gastric gas in patients with FD. In 27 patients (26 female and 1 male, age range 22-70 years old) with FD and bloating (17 postprandial distress syndrome, 4 epigastric pain syndrome and 6 mixed type dyspepsia), a gas challenge test was performed after two weeks on STW5-II 20 drops t.i.d. or placebo, in a parallel, double blinded, controlled trial. The gas challenge test consisted in infusion of a mixture of gases into stomach through a nasogastric tube at 100 mL/min for 15 minutes (total volume infused 1500 mL) with concomitant gastric nutrient perfusion (Nutridrink 1.5 Kcal/ml, total 315 Kcal), mimicking a normal meal. Rectal gas evacuation, via a rectal tube connected to a barostat, and belching, by an esophageal multilumen impedance catheter, were continuously measured for 90 min from infusion start. Abdominal symptoms, using a 0-6 perception scale, and abdominal distension, using a tape measure, were quantified at 10-min intervals.

Results

Gastric gas infusion was followed by a progressive gas evacuation from the rectum, that was accelerated when patients were on STW5-II, compared to placebo. After 20 min from infusion start (when gas and nutrient perfusion was already finished) only 80±39 mL of gas had been expelled in studies on placebo, whereas 319±81 mL of gas were collected on STW5-II group (p=0.015). Thereafter, both groups continued to expel gas at similar rates, without differences between groups at the end of the study (837±180 mL and 1030±160 mL, saline and STW5-II, respectively; p=0.432). Gastric belches were exceptional in both groups (0.8±1.0 and 1.1±1.6 gastric belches in 90 min, saline and STW5, respectively; p=0.318).
Gastric gas infusion gas associated to a rapid rise in perception of abdominal symptoms, that was significantly lower in patients treated with STW5-II than those treated with placebo (score increment 3.0±0.4 vs 1.9±0.6, placebo and STW5-II, respectively; p=0.036). Following continuous rectal gas evacuation, perception decreased in both groups, however perception remained significantly greater at the end of the 90-min study period in patients on saline (score increment 1.4±0.6; p=0.018 vs infusion start), whereas it had returned to basal levels in patients treated with STW5-II (score increment -0.2±0.4; p=0.324 vs infusion start). There were no significant differences in abdominal girth increment between groups (max increment 16±2 mm and 13±2 mm placebo and STW5-II, respectively; p=0.224).

Conclusion

STW5-II is a medicinal product that improves tolerance to gastric gas in patients with functional dyspepsia, by acceleration of transit and rectal evacuation of gas, and reduction of the intensity of symptoms elicited by gas. Hence, this medicinal product could be beneficial for management of gas-related abdominal symptoms like bloating in patients with functional dyspepsia.
EudraCT: 2019-003976-38

Introduction

Irritable bowel syndrome (IBS) is a highly prevalent disorder. According to Rome IV, the diagnosis relies on the presence of abdominal pain in association with a change in stool consistency or frequency. Guidelines recommend minimal testing to exclude other diseases, while advising on therapeutic options. However, the actual application of these guidelines into practice needs confirmation.

Aims & Methods

This study aims to assess the management of IBS by general practitioners (GP) and gastro-enterologists (GE) in their daily practice. Methods: Belgian GP and GE completed an online vignette-based survey between January and July 2022. Apart from data about years of experience, participants indicated their preferred diagnostic modality or therapeutic option for eight cases of diarrhoea-predominant IBS. Cases varied in age (25, 48 and 65 years), cardinal symptom (pain, discomfort, or diarrhoea) and availability of test results (none, limited to biochemistry and ultrasound, or extensive including endoscopy), while stressing out the prolonged duration of the symptoms and the absence of red flags. Frequencies were compared by Chi-square. The main determinants to the diagnosis of IBS were assessed by logistic regression.

Results

Sixty-four gastroenterologists and 31 general practitioners completed the survey. When considering pain and discomfort as cardinal symptoms in a young patient, 87.4% and 84.1% of participants diagnosed IBS, which decreased to 58.3% with diarrhoea. The diagnosis of IBS dropped to 26.8% for a patient of 65 years. In those cases, GP less frequently diagnosed IBS (all p<0.05), except with diarrhoea as cardinal symptom (p=0.78). According to logistic regression, diagnosing IBS was related to patient age, cardinal symptom, availability of prior test results and specialty, and only borderline related to the experience of the practitioner (p<.001, R²=.293). Even when diagnosing IBS, 89.5% ordered one or more additional tests (77.9% biochemistry, 59.3% stool culture and parasites, 60.5% faecal occult blood testing, 17.4% breath testing, 12.8% imaging, 9.3% endoscopy). Upon normal results, 57% would not order further investigations. Both GP and GE opted for spasmolytics (62.3%) and dietary interventions (28.3%) as the preferred first-line treatment for IBS. Second-line treatment consisted of referral to a specialist or colleague (19.4%), dietary intervention (22.6%), neuromodulators (19.4%) and spasmolytics (14.5%). In second-line, GP favoured referral (61.1%) and dietary intervention (22.2%), while GE preferred neuromodulators (27.3%) and spasmolytics (18.2%). No GP initiated modulators. Similar figures were obtained in third-line.

Conclusion

In Belgium, abdominal pain or discomfort are equivalent cardinal symptoms when diagnosing IBS. Diarrhoea as cardinal symptom, older age and absence of prior testing lowered the preference for IBS, especially in GPs. Even when diagnosing IBS, healthcare providers order a large variety of tests. Spasmolytics and dietary interventions are favoured in first-line. Upon failure, only GE prescribe neuromodulators, while GP opt for referral. Future education of GP and GE should focus on harmonising the diagnostic approach and medical treatment of IBS with existing guidelines.

Disclosure

Consultancy for Truvion Healthcare

Introduction

Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by severe gastrointestinal (GI) dysmotility that mimics a GI obstruction in the absence of any detectable mechanical cause [1]. CIPO can be classified as primary (e.g. linked to a genetic disorder), secondary (to a wide array of conditions) or idiopathic. We recently demonstrated that jejunal longitudinal muscle layer abnormalities associated to vascular changes can contribute to GI dysfunction in a genetically driven form of CIPO [2].

Aims & Methods

The aim of this study was to investigate the presence of jejunal longitudinal muscle layer atrophy and vascular alterations in idiopathic forms of CIPO. Full thickness jejunal biopsies were collected from n=27 well characterized patients and n=10 controls. Formalin fixed-paraffin embedded (FFPE) tissue sections were stained with Sirius Red/Fast Green-collagen-assay to measure longitudinal muscle layer thickness and to spectrophotometrically determine fibrosis. FFPE full thickness jejunal sections were also stained with orcein to quantify and measure blood vessel size. The blood vessels were subdivided in >300µm (large), 300-101µm (medium), 100-51µm (small) and <50µm (very small). Frozen full-thickness tissue was used to assess by western blot the expression of HIF-1α as marker of hypoxia and of thymidine phosphorylase (TP), as this enzyme is involved in the pathophysiology of angiogenesis and is found absent in previously documented CIPO secondary to a genetic disorder [3]. Finally, jejunal muscle thickness was correlated with patients’ clinical data.

Results

Idiopathic CIPO patients showed 1.87 times (431.9±192.2 vs. 837.2±446.4 µm; P=0.0026) decreased thickness of the jejunal longitudinal muscle layer and a higher fibrosis index compared to controls. Idiopathic CIPO patients displayed a lower vascular area with more submucosal vessels/mm²vs. controls; vessels <50 µm increased at the expense of medium and large vessels. Moreover, the jejunum of idiopathic CIPO patients presented an increased HIF-1α expression indicative of hypoxia and a lower TP enzyme expression suggesting alterations in local angiogenesis. Finally, from a clinical standpoint, the jejunal muscle thickness was inversely correlated to the number of sub-obstructive episodes, abdominal distension and pain.

Conclusion

In addition to genetic CIPO, also idiopathic forms of this syndrome exhibit significant changes, i.e. muscular atrophy and fibrosis associated with major vascular remodeling likely dependent to hypoxia and a lower local TP protein expression. These data are clinically relevant as reduced muscular thickness correlates with worse clinical phenotypes of idiopathic CIPO.

References

[1] Downes, T.J.; Cheruvu, M.S.; Karunaratne, T.B.; De Giorgio, R.; Farmer, A.D. Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction. J Clin Gastroenterol 2018, 52, 477-489, doi:10.1097/MCG.0000000000001047.
[2] Boschetti, E.; D'Angelo, R.; Tardio, M.L.; Costa, R.; Giordano, C.; Accarino, A.; Malagelada, C.; Clavenzani, P.; Tugnoli, V.; Caio, G.; et al. Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy. Am J Physiol Gastrointest Liver Physiol 2021, 320, G768-G779, doi:10.1152/ajpgi.00047.2021.
[3] Hirano, M.; Carelli, V.; De Giorgio, R.; Pironi, L.; Accarino, A.; Cenacchi, G.; D'Alessandro, R.; Filosto, M.; Martí, R.; Nonino, F.; et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network. J Inherit Metab Dis 2021, 44, 376-387, doi:10.1002/jimd.12300.

Introduction

Chronic constipation (CC) is one of the most frequent non-motor features of Parkinson’s Disease (PD). Previous studies highlighted the association of CC with PD duration and severity [1]. Furthermore, gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in PD and these alterations are related with clinical manifestations [2,3]. For this reason, probiotics, balancing the gut microbiota, are emerging as a potential therapeutic approach in PD patients.

Aims & Methods

Objective: To evaluate the patients’ satisfaction rates as well as gastroenterological and neurological effects of the administration of a synbiotic in PD patients with CC.
Methods: This study enrolled patients with stable PD who fulfilled Rome IV Criteria for CC or irritable bowel syndrome with constipation (IBS-C). Patients received a synbiotic treatment (Enterolactis ® duo, 4 sachets/day, containing probiotic Lactobacillus casei and prebiotic inulin) for 12 weeks. Two primary endpoints were chosen to monitor the satisfaction with therapy (SWT). SWT was defined when patients were satisfied (satisfaction score >4 on a 7-point Likert scale) or improved after therapy (increase in the global rating of change scale of at least two points on a -7 to +7 visual analogue scale). In addition, a gastrointestinal (GI) evaluation with the Patient Assessment of Constipation-symptoms questionnaire (PAC-SYM), number of complete bowel movements per week, Bristol stool Scale (BSS) were calculated before and after the treatment. The neuropsychological evaluation was performed by the Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Sponsored Revision of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), SCales for Outcomes in Parkinson’s disease - Autonomic Dysfunction (SCOPA-AUT), Toronto Alexithymia Scale (TAS-20), Reading the Mind in the Eyes Test (RMET), Parkinson Anxiety Scale (PAS), State-Trait Anxiety Inventory (STAI-Y), Beck Depression Inventory (BDI II), Hamilton depression rating scale (HAM-D) pre- and post-intervention.

Results

30 patients (10 F) were consecutively enrolled. Satisfaction >4 (endpoint 1) significantly changed from 17% to 60% patients after treatment, p = 0.002. The calculated satisfaction score significantly increased from 4(1) to 5(2) (median (IQR), p = 0.003. Improvement after treatment (endpoint 2) was achieved by 83% of patients. The Global Rating of Change Score changed significantly from 0(3) to 4(2)(median (IQR), p < 0.001. Moreover, a beneficial effect of treatment was shown on GI symptoms. Specifically, PAC-SYM Questionnaire score changed from 1.42(0.94) to 0.91(0.77), p < 0.001, number of complete bowel movements per week from 3(3.5) to 5.5(4.1) p < 0.001 and Bristol stool Scale (BSS) from 2(2) to 3(2) p < 0.001. After treatment PD patients performed better in motor and non-motor features. Specifically, the scores (median (IQR) of TAS-20 significantly changed from 55.0 (22) to 49.5 (21), p=0.03, SCOPA-AUT from 17.0 (7) to 13.5 (10), p = 0.002, MDS-UPDRS part 1 from 13.5 (13) to 9.0 (6), p = 0.001, HAM-D score from 12.5(10) to 9.0 (12), p = 0.045. PAS-A showed a trend towards significance from 7.0(6) to 5.0(7), p = 0.06.

Conclusion

Our results showed that a considerable number of PD patients with CC or IBS-C were satisfied with their defecation after treatment. GI symptoms as well as motor and non-motor features in PD patients improved. Our data suggest that the addition of a synbiotic Enterolactis ® duo may be a useful therapeutic approach in PD possibly acting on the gut-brain-gut axis.

References

References
[1] Krogh K, Ostergaard K, Sabroe S, Laurberg S. Clinical aspects of bowel symptoms in Parkinson’s disease. Acta Neurol Scand. 2008;117(1):60-64.
[2] Shen T, Yue Y, He T, Huang C, Qu B, Lv W, Lai HY. The Association Between the Gut Microbiota and Parkinson’s Disease, a Meta-Analysis. Front Aging Neurosci. 2021 Feb 12;13:636545.
[3] Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord. 2015;30(3):350-358.

Introduction

The pathogenesis of irritable bowel syndrome with constipation (IBS-C) remains unclear. Several studies reported that gut dysbiosis had been observed in IBS patients. The treatment of IBS mostly focuses on symptomatic therapy. Acupuncture is one of the alternative therapies for IBS symptoms. However, the effects of acupuncture on symptoms and gut microbiota profiles of IBS-C patients are still unclear. The present study aimed to determine the alterations of the gut microbiota profiles between IBS-C patients and healthy subjects as well as to investigate the effect of electroacupuncture (EA) on the alterations of the profiles of gut microbiota and IBS symptoms in IBS-C patients.

Aims & Methods

We aim to determine the alterations of the gut-brain-microbiota axis between IBS-C patients and healthy subjects and to investigate the effect of electroacupuncture on the alterations of the gut-brain-microbiota axis in IBS-C patients. Thirty-two participants were enrolled in the study, including 16 healthy participants, as the control group and 16 IBS-C patients. Clinical data, blood, and fecal samples were collected from all participants. Then, 16 IBS-C patients were treated with EA nine times for 1 month. Clinical data, blood, and feces were collected in those IBS-C patients at 2-time points: after the end of EA and 1-month follow-up.

Results

Irritable bowel syndrome symptoms severity scale scores (IBS-SSS) and Irritable bowel syndrome quality of life (IBS-QoL) of IBS patients were significantly greater than the control group. There was no significant difference in cognition and depression scores in Hospital Anxiety and Depression Scale (HADs) between the control and the IBS-C groups. A significant increase in serum cortisol level in the IBS-C group was observed when compared to controls. Clinical outcomes of IBS symptoms were significantly improved after EA. These significances were also found in the 1-month follow-up. There was no significant change in serum cortisol levels following EA therapy. Regarding gut microbiota profiles, alpha diversity was not different between the four groups: control, IBS-C, after EA treatment, and 1-month follow-up. However, the beta diversity was significantly different among groups. The beta diversity used of PERMANOVA analysis showed a significant difference between the controls and IBS-C patients (PERMANOVA q-value < 0.05 in Bray-Curtis, Jaccard, and unweighted UniFrac distances). Immediately after EA therapy in IBS-C patients, the beta diversity showed no difference between pre- and post-treatment. Interestingly, the cluster of gut microbiota profiles shifted away from the IBS group and was similar to the control group after a 1-month follow-up.​

Conclusion

Our findings demonstrated the differences in profiles of gut microbiota profiles between IBS-C patients and healthy, and EA treatment showed the benefit of improving clinical outcomes and profiles of gut microbiota.

References

Chang L, Sundaresh S, Elliott J, Anton P, Baldi P, Licudine A, et al. Dysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis in irritable bowel syndrome. Neurogastroenterology & Motility. 2009.
Chen Y, Zhao Y, Luo D-n, et al. Electroacupuncture regulates disorders of gut-brain interaction by decreasing corticotropin-releasing factor in a rat model of IBS. Gastroenterology research and practice. 2019.
Tan L-h, Li K-g, Wu Y-y, et al. Effect of electroacupuncture at different acupoints on the expression of NMDA receptors in ACC and colon in IBS rats. Evidence-Based Complementary and Alternative Medicine. 2019.
Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017.
Labus JS, Osadchiy V, Hsiao EY, et al. Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome. 2019.
Song Y-F, Pei L-X, Chen L, et al. Electroacupuncture relieves irritable bowel syndrome by regulating IL-18 and gut microbial dysbiosis in a trinitrobenzene sulfonic acid-induced post-inflammatory animal model. The American journal of Chinese medicine. 2020.
etc.

Disclosure

The authors declared that they have no conflicts of interest.

Introduction

Genetic predisposition to accumulate fat by carrying risk alleles of PNPLA3, TM6SF2 and HSD17B13, has been shown to influence the probability of developing cirrhosis and hepatocellular carcinoma (HCC) in several liver diseases characterized by hepatic steatosis including non-alcoholic steatohepatitis, chronic hepatitis C and alcoholic liver disease. Whether these variants have any role in the progression of chronic hepatitis B (CHB) disease, without hepatic steatosis, remains unknown.

Aims & Methods

In this cross-sectional case-control study, we determined PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 variants in a cohort of 148 healthy controls, 91 CHB (57 cirrhotic and 34 non-cirrhotic), and 84 CHB-related HCC patients from a tertiary center. Associations between control and case groups with the alleles and genotypes were investigated using logistic regression analyses, and adjustment for age and sex was applied. Survival analyses were performed using Kaplan-Meier Curves with the log-rank test in the CHB-related HCC cohort.

Results

The genotype and allelic distribution of PNPLA3, TM6SF2 and HSD17B13 were not different between healthy controls, CHB, cirrhosis and HCC groups. No genotype or allele, including the haplotype analysis, was found to be associated with susceptibility to CHB and increased risk for cirrhosis or HCC. Survival analysis revealed that none of the three variants has any influence on overall survival in patients with CHB-related HCC.

Conclusion

Our findings demonstrated that PNPLA3, TM6SF2, and HSD17B13 genetic variants, known for modulating liver fat and disease progression in hepatic steatosis, have no association with disease progression in patients with CHB and survival in CHB-related HCC.

References

1. Abul-Husn NS, Cheng X, Li AH, et al. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med. 2018 Mar 22;378(12):1096-1106.
2. Gellert-Kristensen H, Richardson TG, Davey Smith G, et al. Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population. Hepatology. 2020 Sep;72(3):845-856.
3. Kang Q, Xu J, Luo H, et al. Evaluation of the association of a variant in PNPLA3 and TM6SF2 with fibrosis progression in patients with chronic hepatitis C infection after eradication: A retrospective study. Gene. 2022 Apr 30;820:146235.
4. Stickel F, Buch S, Nischalke HD, et al. Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis. Am J Gastroenterol. 2018 Oct;113(10):1475-1483.

Introduction

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, ranking fourth in terms of mortality and fifth in terms of incidence, according to the 2020 GLOBOCAN report (1). Early detection of preneoplastic conditions such as gastric atrophy and intestinal metaplasia is crucial to reduce GC mortality (2). Moreover, its pathogenesis is a multifactorial process that is influenced by environmental and genetic factors. European guidelines (3) suggest shortening the interval of follow-up in patients with a family history. However, it is a weak recommendation with a low quality of evidence, as evidence regarding familiarity for GC and its related preneoplastic conditions is lacking.

Aims & Methods

To evaluate the risk of GC and preneoplastic conditions and lesions, including gastric atrophy, intestinal metaplasia, and dysplasia, in first-degree relatives for GC patients.
We conducted a systematic review and meta-analysis of case-control studies published on MEDLINE (PubMed and Embase) until November 2022. The primary outcome was the risk of GC in first-degree relatives for GC patients. The secondary findings were the risk of preneoplastic conditions and dysplasia in these patients. Two independent reviewers blindly performed the systematic review and data extraction. The disagreements were resolved through discussion. Homogeneity of effects across studies quantified by I². Odds ratio (OR) and 95% confidence intervals (CIs) were expressed using random effects models.

Results

Of the 1642 studies initially found, 18 studies met the inclusion criteria for GC, and 6 studies were included for preneoplastic conditions. The pooled analysis included a total of 59490 patients for the risk of GC and 4463 patients for the risk of preneoplastic conditions. The results showed a significantly increased risk of GC in first-degree relatives of GC patients (OR = 3.034; 95%CI 2.395 to 3.843; p <.001; I² 85.66%, 95%CI 78.73 to 90.33, p<.001). The risk of gastric atrophy was also significantly increased (OR = 3.812; 95%CI 1.674 to 8.682; p <.001, I² 78,26%, 95%CI 41.41 to 91.93; p = .003). However, the risk of intestinal metaplasia was not significant (OR = 1.207; 95%CI 0.937 to 1.555, p = .15). Furthermore, the risk of gastric dysplasia was found to be significant (OR = 5.480; 95%CI 1.054 to 28.482, p = .043, I² 80.34%, 95%CI 48.18 to 92.55 p = .002).

Conclusion

Our meta-analysis showed that the risk of GC and preneoplastic conditions and lesions, including gastric atrophy and dysplasia, is significantly increased in first-degree relatives for GC patients, even if a significant heterogeneity between studies was found. These findings highlighted the importance of identifying individuals at high risk to facilitate early detection and treatment of preneoplastic conditions, which could potentially reduce the burden of GC.

References

1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
2. Pimentel-Nunes, P., Libânio, D., Marcos-Pinto, R., Areia, M., Leja, M., Esposito, G., ... & Dinis-Ribeiro, M. (2019). Management of epithelial precancerous conditions and lesions in the stomach (maps II): European Society of gastrointestinal endoscopy (ESGE), European Helicobacter and microbiota Study Group (EHMSG), European Society of pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy, 51(04), 365-388.
3. Yaghoobi, M., Bijarchi, R., & Narod, S. A. (2010). Family history and the risk of gastric cancer. British journal of cancer, 102(2), 237-242.