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1.
Gut Microbes ; 16(1): 2350173, 2024.
Article in English | MEDLINE | ID: mdl-38738780

ABSTRACT

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.


Subject(s)
Bacteria , Feces , Gastrointestinal Microbiome , Intestine, Small , Synbiotics , Humans , Synbiotics/administration & dosage , Gastrointestinal Microbiome/physiology , Male , Adult , Intestine, Small/microbiology , Intestine, Small/metabolism , Female , Bacteria/classification , Bacteria/isolation & purification , Bacteria/metabolism , Bacteria/genetics , Feces/microbiology , Young Adult , Probiotics/administration & dosage , Metabolome , Healthy Volunteers , Spatio-Temporal Analysis
2.
Gut ; 73(5): 741-750, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38216328

ABSTRACT

OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Endoscopic Mucosal Resection , Humans , Colonic Polyps/surgery , Colonoscopy , Colorectal Neoplasms/surgery
3.
Ann Surg ; 279(5): 746-754, 2024 May 01.
Article in English | MEDLINE | ID: mdl-37991178

ABSTRACT

OBJECTIVE: Assess the effectiveness of sacral neuromodulation (SNM) versus personalized conservative treatment (PCT) in patients with refractory idiopathic slow-transit constipation (STC). BACKGROUND: Evidence on SNM for idiopathic STC is conflicting and of suboptimal methodological quality. METHODS: The No.2-Trial was a multicenter, open-label, pragmatic, randomized trial performed in 2 Dutch hospitals. Sixty-seven patients with idiopathic STC, a defecation frequency <3 per week and refractory (ie, unresponsive) to maximal conservative (nonoperative) treatment were included. Exclusion criteria included outlet obstruction, rectal prolapse, and previous colon surgery. Patients were randomized (3:2) to SNM (n=41) or PCT (n=26) with randomization minimization between February 21, 2017 and March 12, 2020. In SNM patients, an implantable pulse generator was implanted after a successful 4-week test stimulation. PCT patients received conservative treatment such as laxatives or retrograde colonic irrigation. The primary outcome was treatment success (defined as average defecation frequency ≥3 per week) after 6 months. Secondary outcomes included constipation severity, fatigue, quality of life, and adverse events. Analysis was according to intention-to-treat. RESULTS: After 6 months, 22 (53.7%) patients were successfully treated with SNM versus 1 (3.8%) patient with PCT (odds ratio 36.4, 95% CI 3.4-387.5, P =0.003). At 6 months, SNM patients reported lower constipation severity and fatigue scores ( P <0.001) and improved quality of life compared with PCT ( P <0.001). Eight serious adverse events (6 SNM, 2 PCT) and 78 adverse events (68 SNM, 10 PCT) were reported. CONCLUSIONS: SNM is a promising surgical treatment option in a homogeneous group of adults and adolescents with refractory idiopathic STC. No.2-Trial registered at ClinicalTrials.gov NCT02961582.


Subject(s)
Conservative Treatment , Electric Stimulation Therapy , Adult , Adolescent , Humans , Quality of Life , Constipation/therapy , Electric Stimulation Therapy/adverse effects , Treatment Outcome
4.
Clin Exp Gastroenterol ; 16: 197-211, 2023.
Article in English | MEDLINE | ID: mdl-37954129

ABSTRACT

Dumping syndrome is a common complication after esophageal, gastric and bariatric surgery and has a significant negative impact on the quality of life of patients. This narrative review describes the clinical syndrome, pathophysiology, diagnosis and reports on standard and pragmatic therapeutical treatment options in order to improve the clinical outcome of patients with dumping syndrome. Dumping syndrome consists of early and late dumping symptoms and can be diagnosed using clinical parameters with the help of the Sigstad's score, questionnaires or by provocative testing. The prevalence of dumping syndrome varies depending on the employed definition of dumping syndrome. Overall, dumping syndrome is more frequent nowadays due to increasing numbers of upper gastrointestinal and bariatric surgeries being performed. First treatment step includes dietary adjustment and dietary supplements, which are often sufficient to manage symptoms for the majority of patients. Next step of therapy includes acarbose, which is effective for late dumping symptoms, but the use is limited due to side effects. Somatostatin analogues are indicated after these two steps have failed. Somatostatin analogues are very effective for controlling early and late dumping, also in the long term. Glucagon like peptide-1 receptor agonists, endoscopic and surgical (re)interventions are reported as treatment options for refractory dumping syndrome; however, their use is not recommended in clinical practice due to the limited evidence on and uncertainty of outcomes. These alternatives should be considered only as last resort options in patients with otherwise refractory and invalidating dumping syndrome.

5.
Am J Gastroenterol ; 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37791610

ABSTRACT

INTRODUCTION: Irritable bowel syndrome (IBS) has a major impact on emotional, social, and professional life. This study aimed to evaluate general life satisfaction, a subjective measure of well-being, in IBS patients, and to determine which factors are associated with higher life satisfaction. METHODS: IBS patients (n = 195, mean age 51.4 ± 16.5 years, 73.8% female) recruited from primary and secondary/tertiary care completed questionnaires regarding gastrointestinal symptoms, quality of life, psychological factors, and life satisfaction (Satisfaction With Life Scale, 5 items, range 5-35). A finite mixture model analysis was performed to identify latent classes. Multivariable linear regression was used to identify variables associated with life satisfaction. RESULTS: Overall, 71.3% of the patients were satisfied about their life (Satisfaction With Life Scale-score ≥21). Three latent subgroups could be identified with significantly higher life satisfaction in the subgroup with higher mental quality of life, fewer anxiety and depressive symptoms, lower gastrointestinal specific anxiety, and lower gastrointestinal symptom severity, compared with the other 2 groups. Multivariable linear regression showed that higher physical quality of life (B0.168, P < 0.001) and higher mental quality of life (B0.199, P < 0.001) were associated with higher life satisfaction. Using multivariable regression, no significant association was found between gastrointestinal symptom severity and life satisfaction. DISCUSSION: Higher physical and mental quality of life, but not gastrointestinal symptom severity, were independently associated with higher general life satisfaction in IBS. These findings reinforce the clinical need in IBS treatment to focus on the full extent of the disorder and not merely on gastrointestinal symptom improvement. ClinicalTrials.gov Identifier: NCT00775060.

6.
Ned Tijdschr Geneeskd ; 1672023 10 12.
Article in Dutch | MEDLINE | ID: mdl-37882441

ABSTRACT

Irritable bowel syndrome (IBS) is a prevalent disorder of the gut-brain interaction, of which the multifactorial pathophysiology is still incompletely understood. IBS is a symptom-based diagnosis based on the Rome IV criteria, and additional diagnostics are only indicated when history or physical examination point towards the presence of other (organic) disorders. Diagnosis and treatment should take place in primary care. However, management of IBS can be challenging due to the heterogenous clinical presentation. Furthermore, a variety of treatment options are available, yet only effective in subgroups of patients. Early positive diagnosis, patient education, and shared-decision making are of utmost importance in order to limit individual disease burden and the socioeconomic impact of IBS. In this review we discuss diagnosis, indications for additional investigations or referral to secondary care, and treatment of IBS, based on both the recently updated Dutch guideline and general practice standard on IBS.


Subject(s)
General Practice , Irritable Bowel Syndrome , Humans , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/therapy , Cost of Illness , Referral and Consultation , Secondary Care
7.
Clin Res Hepatol Gastroenterol ; 47(10): 102224, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37813276

ABSTRACT

BACKGROUND: Hyperferritinemia is found in around 12 % of the general population. Analyzing the cause can be difficult. In case of doubt about the presence of major iron overload most guidelines advice to perform a MRI as a reliable non-invasive marker to measure liver iron concentration (LIC). In general, a LIC of ≥ 36 µmol/g dw is considered the be elevated however in hyperferritinemia associated with, for example, obesity or alcohol (over)consumption the LIC can be ≥ 36 µmol/g dw in abscence of major iron overload. So, unfortunately a clear cut-off value to differentiate iron overload from normal iron content is lacking. Previously the liver iron index (LII) (LIC measured in liver biopsy (LIC-b)/age (years)), was introduced to differentiate between patients with major (LII ≥ 2) and minor or no iron overload (LII < 2). Based on the good correlation between the LIC-b and LIC determined with MRI (LIC-MRI), our goal was to investigate whether a LII_MRI ≥ 2 is a good indicator of major iron overload, reflected by a significantly higher amount of iron needed to be mobilized to reach iron depletion. METHODS: We compared the amount of mobilized iron to reach depletion and inflammation-related characteristics in two groups: LII-MRI ≥ 2 versus LII-MRI <2 in 92 hyperferritinemia patients who underwent HFE genotyping and MRI-LIC determination. RESULTS: Significantly more iron needed to be mobilized to reach iron depletion in the LII ≥ 2 group (mean 4741, SD ± 4135 mg) versus the LII-MRI <2 group (mean 1340, SD ± 533 mg), P < 0.001. Furthermore, hyperferritinemia in LII-MRI < 2 patients was more often related to components of the metabolic syndrome while hyperferritinemia in LII-MRI ≥ 2 patients was more often related to HFE mutations. ROC curve analysis showed good performance of LII =2 as cut-off value. However the calculations showed that the optimal cut-off for the LII = 3.4. CONCLUSION: The LII-MRI with a cut-off value of 2 is an effective method to differentiate major from minor iron overload in patients with hyperferritinemia. But the LII-MRI = 3.4 seems a more promising diagnostic test for major iron overload.


Subject(s)
Hyperferritinemia , Iron Overload , Humans , Iron/analysis , Iron/metabolism , Hyperferritinemia/complications , Hyperferritinemia/metabolism , Hyperferritinemia/pathology , Liver/metabolism , Iron Overload/diagnostic imaging , Iron Overload/etiology , Magnetic Resonance Imaging
8.
Microorganisms ; 11(9)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37764197

ABSTRACT

BACKGROUND: The intestinal microbiota plays an important role in the etiology of obesity. Sleeve gastrectomy (SG) is a frequently performed and effective therapy for morbid obesity. OBJECTIVE: To investigate the effect of sleeve gastrectomy on the fecal microbiota of individuals with morbid obesity and to examine whether shifts in microbiota composition are associated with markers of inflammation and intestinal barrier function. METHODS: Fecal and blood samples of healthy individuals (n = 27) and morbidly obese individuals pre-SG (n = 24), and at 2 months (n = 13) and 6 months post-SG (n = 9) were collected. The 16SrRNA gene was sequenced to assess microbiota composition. Fecal calprotectin, plasma inflammatory markers and intestinal permeability markers (multi-sugar test) were determined. RESULTS: Fecal microbiota composition between morbidly obese and lean individuals was significantly different. The fecal microbiota composition changed significantly 2 and 6 months post-SG (p = 0.008) compared to pre-SG but not towards a more lean profile. The post-SG microbiota profile was characterized by an increase in facultative anaerobic bacteria, characteristic for the upper gastrointestinal tract. No correlations were found between inflammatory markers, intestinal permeability and microbial profile changes. CONCLUSIONS: Fecal microbiota composition in morbidly obese individuals changed significantly following SG. This change might be explained by functional changes induced by the SG procedure.

9.
Clin Gastroenterol Hepatol ; 21(10): 2660-2669, 2023 09.
Article in English | MEDLINE | ID: mdl-36731587

ABSTRACT

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with substantial costs to society. Extensive data on direct costs (health care consumption) and indirect costs (health-related productivity loss) are lacking. Hence, we examined the socioeconomic costs of IBS and assessed which patient characteristics are associated with higher costs. METHODS: Cross-sectional data from 3 Rome-defined Dutch IBS patient cohorts (n = 419) were collected. Bootstrapped mean direct and indirect costs were evaluated per patient with IBS using validated questionnaires (ie, medical cost questionnaire and productivity cost questionnaire, respectively). Multivariable regression analyses were performed to identify variables associated with higher costs. RESULTS: Quarterly mean total costs per patient were €2.156 (95% confidence interval (CI), €1793-€2541 [$2444]), consisting of €802 (95% CI, €625-€1010 [$909]) direct costs and €1.354 (95% CI, €1072-€1670 [$1535]) indirect costs. Direct costs consisted primarily of health care professional consultations, with costs related to gastrointestinal clinic visits accounting for 6% and costs related to mental health care visits for 20%. Higher direct costs were significantly associated with older age (P = .007), unemployment (P = .001), IBS subtypes other than constipation (P = .033), lower disease-specific quality of life (P = .027), and more severe depressive symptoms (P = .001). Indirect costs consisted of absenteeism (45%), presenteeism (42%), and productivity loss related to unpaid labor (13%) and were significantly associated with the male sex (P = .014) and more severe depressive symptoms (P = .047). CONCLUSIONS: Productivity loss is the main contributor to the socioeconomic burden of IBS. Direct costs were not predominantly related to gastrointestinal care, but rather to mental health care. Awareness of the nature of costs and contributing patient factors should lead to significant socioeconomic benefits for society.


Subject(s)
Irritable Bowel Syndrome , Male , Humans , Irritable Bowel Syndrome/complications , Quality of Life , Cross-Sectional Studies , Health Care Costs , Delivery of Health Care , Socioeconomic Factors
10.
Dig Liver Dis ; 55(5): 614-621, 2023 05.
Article in English | MEDLINE | ID: mdl-36710170

ABSTRACT

BACKGROUND AND AIM: Intestinal permeability (IP) plays an important role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We assessed site-specific (gastroduodenum, small intestine, colon and whole gut) IP in NAFLD patients and healthy controls (HC) and its association with the degree of hepatic steatosis, hepatic fibrosis and dietary composition in these NAFLD patients. METHODS: In vivo site-specific IP was analysed with a validated multi-sugar test in NAFLD patients and HC. Furthermore, in NAFLD patients, hepatic steatosis (chemical shift MRI), hepatic fibrosis (transient elastography) and dietary composition (food frequency questionnaire) were assessed. RESULTS: Fifty-two NAFLD patients and forty-six HC were included in this study. Small intestinal (P <0.001), colonic (P = 0.004) and whole gut (P <0.001) permeability were increased in NAFLD patients compared to HC. Furthermore, colonic permeability (P = 0.029) was significantly higher in NAFLD patients with clinically significant fibrosis compared to those without. Colonic permeability remained positively associated with the presence of clinically significant fibrosis (P = 0.017) after adjustment for age, sex and BMI. CONCLUSION: Colonic permeability is increased in at least a subset of NAFLD patients compared to HC and is independently associated with clinically significant NAFLD fibrosis.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Liver Cirrhosis/complications , Colon , Intestine, Small , Permeability , Liver/diagnostic imaging , Liver/pathology
11.
Surg Obes Relat Dis ; 19(3): 253-264, 2023 03.
Article in English | MEDLINE | ID: mdl-36274017

ABSTRACT

Management of refractory gastroparesis is challenging after diet, prokinetics, and long-term nutritional support have failed. In this review, the efficacy and safety of surgical interventions (sleeve gastrectomy and Roux-en-Y gastric bypass surgery) are evaluated systematically in patients with refractory gastroparesis. The PubMed, Embase, and Scopus databases were searched to identify relevant studies published up to June 2021. Outcome of interest was symptom improvement and gastric emptying. Nineteen studies with 222 refractory gastroparesis patients (147 Roux-en-Y gastric bypass, 39 sleeve gastrectomy, and 36 subtotal gastrectomy) were included. All studies reported symptom improvement postoperatively, particularly vomiting and nausea. Gastric emptying improved postoperatively in 45% up to 67% for sleeve gastrectomy and 87% for Roux-en-Y gastric bypass. The findings of our systematic review suggest that sleeve gastrectomy and Roux-en-Y gastric bypass surgery improve symptoms and gastric emptying in patients with refractory gastroparesis. Surgery may be effective as treatment for a small group of patients when all other therapies have failed.


Subject(s)
Gastric Bypass , Gastroparesis , Laparoscopy , Obesity, Morbid , Humans , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Gastroparesis/etiology , Gastrectomy/adverse effects , Treatment Outcome , Retrospective Studies
12.
Sci Rep ; 12(1): 16779, 2022 10 06.
Article in English | MEDLINE | ID: mdl-36202957

ABSTRACT

Artificial intelligence (AI) is entering into daily life and has the potential to play a significant role in healthcare. Aim was to investigate the perspectives (knowledge, experience, and opinion) on AI in healthcare among patients with gastrointestinal (GI) disorders, gastroenterologists, and GI-fellows. In this prospective questionnaire study 377 GI-patients, 35 gastroenterologists, and 45 GI-fellows participated. Of GI-patients, 62.5% reported to be familiar with AI and 25.0% of GI-physicians had work-related experience with AI. GI-patients preferred their physicians to use AI (mean 3.9) and GI-physicians were willing to use AI (mean 4.4, on 5-point Likert-scale). More GI-physicians believed in an increase in quality of care (81.3%) than GI-patients (64.9%, χ2(2) = 8.2, p = 0.017). GI-fellows expected AI implementation within 6.0 years, gastroenterologists within 4.2 years (t(76) = - 2.6, p = 0.011), and GI-patients within 6.1 years (t(193) = - 2.0, p = 0.047). GI-patients and GI-physicians agreed on the most important advantages of AI in healthcare: improving quality of care, time saving, and faster diagnostics and shorter waiting times. The most important disadvantage for GI-patients was the potential loss of personal contact, for GI-physicians this was insufficiently developed IT infrastructures. GI-patients and GI-physicians hold positive perspectives towards AI in healthcare. Patients were significantly more reserved compared to GI-fellows and GI-fellows were more reserved compared to gastroenterologists.


Subject(s)
Gastroenterologists , Gastrointestinal Diseases , Physicians , Artificial Intelligence , Delivery of Health Care , Humans , Prospective Studies
13.
Endosc Int Open ; 10(8): E1127-E1135, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36247075

ABSTRACT

Background and study aims Endoscopic mucosal resection of large non-pedunculated colorectal polyps is characterized by a high risk of recurrence. Thermal ablation of the mucosal defect margins may reduce recurrence in these lesions, but a systematic overview of the current evidence is lacking. Methods We searched PubMed, Embase and Cochrane until July 2021, for studies on thermal ablation of mucosal defect margins of large non-pedunculated colorectal polyps. Main goal of this meta-analysis was to identify pooled risk difference of recurrence between thermal ablation vs. no adjuvant treatment. Secondary goal was to identify pooled recurrence rate after snare tip soft coagulation (STSC) and argon plasma coagulation (APC). Results Ten studies on thermal ablation of mucosal defect margins were included, with three studies on argon plasma coagulation, six studies on snare tip soft coagulation and one study comparing both treatment modalities, representing a total of 316 APC cases and 1598 STSC cases. Overall pooled risk difference of recurrence was -0.17 (95 % confidence interval [CI] -0.22 to -0.12) as compared to no adjuvant treatment. Pooled risk difference was -0.16 (95 % CI -0.19 to -0.14) for STSC and -0.26 (95 % CI -0.80 to 0.28) for APC. Pooled recurrence rate was 4 % (95 % CI 2 % to 8 %) for STSC and 9 % (95 % CI 4 % to 19 %) for APC. Conclusions Thermal ablation of mucosal defect margins significantly reduces recurrence rate in large non-pedunculated colorectal lesions compared to no adjuvant treatment. While no evidence for superiority exists, STSC may be preferred over APC, because this method is the most evidence-based, and cost-effective modality.

14.
Clin Transl Gastroenterol ; 13(11): e00518, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35981245

ABSTRACT

INTRODUCTION: Early detection of colorectal cancer (CRC) by screening programs is crucial because survival rates worsen at advanced stages. However, the currently used screening method, the fecal immunochemical test (FIT), suffers from a high number of false-positives and is insensitive for detecting advanced adenomas (AAs), resulting in false-negatives for these premalignant lesions. Therefore, more accurate, noninvasive screening tools are needed. In this study, the utility of analyzing volatile organic compounds (VOCs) in exhaled breath in a FIT-positive population to detect the presence of colorectal neoplasia was studied. METHODS: In this multicenter prospective study, breath samples were collected from 382 FIT-positive patients with subsequent colonoscopy participating in the national Dutch bowel screening program (n = 84 negative controls, n = 130 non-AAs, n = 138 AAs, and n = 30 CRCs). Precolonoscopy exhaled VOCs were analyzed using thermal desorption-gas chromatography-mass spectrometry, and the data were preprocessed and analyzed using machine learning techniques. RESULTS: Using 10 discriminatory VOCs, AAs could be distinguished from negative controls with a sensitivity and specificity of 79% and 70%, respectively. Based on this biomarker profile, CRC and AA combined could be discriminated from controls with a sensitivity and specificity of 77% and 70%, respectively, and CRC alone could be discriminated from controls with a sensitivity and specificity of 80% and 70%, respectively. Moreover, the feasibility to discriminate non-AAs from controls and AAs was shown. DISCUSSION: VOCs in exhaled breath can detect the presence of AAs and CRC in a CRC screening population and may improve CRC screening in the future.


Subject(s)
Adenoma , Colorectal Neoplasms , Volatile Organic Compounds , Humans , Volatile Organic Compounds/analysis , Early Detection of Cancer/methods , Prospective Studies , Adenoma/diagnosis , Adenoma/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology
15.
Neurogastroenterol Motil ; 34(11): e14394, 2022 11.
Article in English | MEDLINE | ID: mdl-35531931

ABSTRACT

BACKGROUND: Gastroparesis (GP) is a gastrointestinal disorder associated with significant morbidity and healthcare costs. GP patients form a heterogeneous population with diverse etiology, and treatment is often challenging due to a poorly understood underlying pathophysiology. The aim of the present study was to assess antroduodenal motility patterns among the different GP etiologies. METHODS: We reviewed antroduodenal manometry (ADM) recordings of patients with confirmed GP between 2009 and 2019. ADM measurements were evaluated for fed period duration, number of phase III contractions and migrating motor complexes (MMCs), motility index (MI), and presence of neuropathic patterns. KEY RESULTS: A total of 167 GP patients (142 women, median age 45 [31-57]) were included. The following etiologies were identified: idiopathic n = 101; post-surgery n = 36; and diabetes n = 30. Fed period duration was significantly longer in idiopathic (p < 0.01) and diabetic GP patients (p < 0.05) compared with post-surgery GP patients. Furthermore, the number and duration of phase III contractions and the number of MMCs were significantly lower in idiopathic and diabetic patients compared with post-surgery GP patients (p < 0.01). Likewise, absence of MMCs during 6-h recording was more often observed in idiopathic and diabetes GP patients compared with post-surgery GP patients (resp. p < 0.01 and p < 0.05). CONCLUSIONS AND INFERENCES: Antroduodenal motility patterns are different among GP etiologies. A dysmotility spectrum was identified with different patterns ranging from post-surgery GP to idiopathic and diabetic GP.


Subject(s)
Diabetic Neuropathies , Gastroparesis , Duodenum/physiology , Female , Gastrointestinal Motility/physiology , Gastroparesis/diagnosis , Gastroparesis/etiology , Humans , Manometry , Middle Aged , Myoelectric Complex, Migrating/physiology
16.
Inflamm Bowel Dis ; 28(9): 1309-1320, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35554535

ABSTRACT

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal cancer (CRC) compared to patients with IBD only. The aim of this study was to perform an extensive screen of known carcinogenic genomic alterations in patients with PSC-IBD, and to investigate whether such changes occur already in nondysplastic mucosa. METHODS: Archival cancer tissue and nondysplastic mucosa from resection specimens of 19 patients with PSC-IBD-CRC were characterized, determining DNA copy-number variations, microsatellite instability (MSI), mutations on 48 cancer genes, and CpG island methylator phenotype (CIMP). Genetic profiles were compared with 2 published cohorts of IBD-associated CRC (IBD-CRC; n = 11) and sporadic CRC (s-CRC; n = 100). RESULTS: Patterns of chromosomal aberrations in PSC-IBD-CRC were similar to those observed in IBD-CRC and s-CRC, MSI occurred only once. Mutation frequencies were comparable between the groups, except for mutations in KRAS, which were less frequent in PSC-IBD-CRC (5%) versus IBD-CRC (38%) and s-CRC (31%; P = .034), and in APC, which were less frequent in PSC-IBD-CRC (5%) and IBD-CRC (0%) versus s-CRC (50%; P < .001). Cases of PSC-IBD-CRC were frequently CIMP positive (44%), at similar levels to cases of s-CRC (34%; P = .574) but less frequent than in cases with IBD-CRC (90%; P = .037). Similar copy number aberrations and mutations were present in matched cancers and adjacent mucosa in 5/15 and 7/11 patients, respectively. CONCLUSIONS: The excess risk of CRC in patients with PSC-IBD was not explained by copy number aberrations, mutations, MSI, nor CIMP status, in cancer tissue, nor in adjacent mucosa. These findings set the stage for further exome-wide and epigenetic studies.


The excessive risk of colorectal carcinoma (CRC) in patients with both primary sclerosing cholangitis and inflammatory bowel disease (IBD) was not explained by an extensive screen of copy number aberrations, mutations, microsatellite instability, and CpG island methylator phenotype status when compared with patients with IBD-CRC and sporadic CRC.


Subject(s)
Cholangitis, Sclerosing , Colorectal Neoplasms , Inflammatory Bowel Diseases , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/genetics , Cholangitis, Sclerosing/surgery , Colorectal Neoplasms/complications , Colorectal Neoplasms/genetics , Genetic Profile , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/genetics , Microsatellite Instability
17.
Clin Transl Gastroenterol ; 13(6): e00499, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35584320

ABSTRACT

OBJECTIVES: To improve colorectal cancer (CRC) survival and lower incidence rates, colonoscopy and/or fecal immunochemical test screening are widely implemented. Although candidate DNA methylation biomarkers have been published to improve or complement the fecal immunochemical test, clinical translation is limited. We describe technical and methodological problems encountered after a systematic literature search and provide recommendations to increase (clinical) value and decrease research waste in biomarker research. In addition, we present current evidence for diagnostic CRC DNA methylation biomarkers. METHODS: A systematic literature search identified 331 diagnostic DNA methylation marker studies published before November 2020 in PubMed, EMBASE, Cochrane Library, and Google Scholar. For 136 bodily fluid studies, extended data extraction was performed. STARD criteria and level of evidence were registered to assess reporting quality and strength for clinical translation. RESULTS: Our systematic literature search revealed multiple issues that hamper the development of DNA methylation biomarkers for CRC diagnosis, including methodological and technical heterogeneity and lack of validation or clinical translation. For example, clinical translation and independent validation were limited, with 100 of 434 markers (23%) studied in bodily fluids, 3 of 434 markers (0.7%) translated into clinical tests, and independent validation for 92 of 411 tissue markers (22%) and 59 of 100 bodily fluids markers (59%). DISCUSSION: This systematic literature search revealed that major requirements to develop clinically relevant diagnostic CRC DNA methylation markers are often lacking. To avoid the resulting research waste, clinical needs, intended biomarker use, and independent validation should be better considered before study design. In addition, improved reporting quality would facilitate meta-analysis, thereby increasing the level of evidence and enabling clinical translation.


Subject(s)
Colorectal Neoplasms , DNA Methylation , Biomarkers, Tumor/genetics , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Humans , Occult Blood
18.
Clin Gastroenterol Hepatol ; 20(11): 2628-2637, 2022 11.
Article in English | MEDLINE | ID: mdl-35181571

ABSTRACT

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder of the gut-brain interaction that significantly affects quality of life. Several treatments, with comparable clinical efficacy, are available. Patient preferences can therefore be an important determinant of an effective management strategy. Treatment preferences of patients regarding decision making remain unclear. We aimed to examine these preferences and estimate trade-offs between different attributes. METHODS: A total of 427 patients from the Maastricht IBS cohort were invited to participate. A labeled discrete choice experiment survey, containing 9 scenarios with each 3 alternatives (medication, diet, psychotherapy), was developed in order to estimate preferences. The treatment scenarios were based on 6 attributes: effectiveness, time to response, time until recurrence, side effects, time required, and frequency of appointments. The preference weights and relative importance were analyzed using a mixed logit model. RESULTS: A total of 185 (43.3%) of 427 potential respondents completed the questionnaire (mean age 49.51 years, 69.2% female). The most preferred treatment was dietary intervention (48.1%), followed by pharmacotherapy (29.2%) and psychotherapy (22.7%). IBS patients preferred a higher effectiveness, shorter time interval to response, longer time interval until recurrence, no severe side effects, and frequent appointments when attending psychotherapy. Younger patients (≤50 years of age) preferred dietary interventions and a long period until recurrence, whereas older patients (>50 years of age) were more inclined to choose pharmacotherapy and the period until recurrence was not important. CONCLUSIONS: Dietary interventions were the most preferred IBS therapy. Identifying patients' treatment preferences during shared decision making will provide more optimal management strategies and could be the best approach to diminish disease burden.


Subject(s)
Irritable Bowel Syndrome , Humans , Female , Middle Aged , Male , Irritable Bowel Syndrome/therapy , Choice Behavior , Quality of Life , Patient Preference , Diet
19.
Dig Endosc ; 34(5): 913-926, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35037327

ABSTRACT

BACKGROUND AND STUDY AIMS: We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation for colonoscopy based on the most recent guidelines. PATIENTS AND METHODS: PubMed and Cochrane were queried for population-based studies examining changes in electrolyte values after bowel preparation, published by July 1, 2021. We report prevalences of serum hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation and changes in mean electrolyte values after vs. before bowel preparation using sodium phosphate (NaP) and polyethylene glycol (PEG). RESULTS: Thirteen studies met the inclusion criteria; 2386 unique patients were included. Overall, hypokalemia was found in 17.2% (95% CI 6.7, 30.9) in the NaP group vs. 4.8% (95% CI 0.27, 13.02) in the PEG group. The magnitude of potassium decrease after NaP bowel preparation was significantly increased compared to PEG (mean difference -0.38; 95% CI -0.49 to -0.27, P < 0.001). No study reported on major complications. CONCLUSIONS: Hypokalemia was found in 17.2% of patients after bowel preparation with NaP and in 4.8% of patients with PEG, a finding that is clinically relevant with respect to choosing the type of bowel preparation. The magnitude of the potassium decrease after NaP was significantly higher compared to PEG. These data provide the evidence that supports the recommendation of the European Society of Gastrointestinal Endoscopy against routine use of NaP for bowel preparation.


Subject(s)
Hypokalemia , Cathartics/adverse effects , Colonoscopy/adverse effects , Colonoscopy/methods , Electrolytes/adverse effects , Humans , Polyethylene Glycols/adverse effects , Potassium
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