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1.
Gastrointest Endosc ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942330

RESUMO

BACKGROUND AND AIMS: Computer-aided diagnosis (CADx) for optical diagnosis of colorectal polyps is thoroughly investigated. However, studies on human-artificial intelligence (AI) interaction are lacking. Aim was to investigate endoscopists' trust in CADx by evaluating whether communicating a calibrated algorithm confidence improved trust. METHODS: Endoscopists optically diagnosed 60 colorectal polyps. Initially, endoscopists diagnosed the polyps without CADx assistance (initial diagnosis). Immediately afterwards, the same polyp was again shown with CADx prediction; either only a prediction (benign or pre-malignant) or a prediction accompanied by a calibrated confidence score (0-100). A confidence score of 0 indicated a benign prediction, 100 a (pre-)malignant prediction. In half of the polyps CADx was mandatory, for the other half CADx was optional. After reviewing the CADx prediction, endoscopists made a final diagnosis. Histopathology was used as gold standard. Endoscopists' trust in CADx was measured as CADx prediction utilization; the willingness to follow CADx predictions when the endoscopists initially disagreed with the CADx prediction. RESULTS: Twenty-three endoscopists participated. Presenting CADx predictions increased the endoscopists' diagnostic accuracy (69.3% initial vs 76.6% final diagnosis, p<0.001). The CADx prediction was utilized in 36.5% (n=183/501) disagreements. Adding a confidence score led to a lower CADx prediction utilization, except when the confidence score surpassed 60. A mandatory CADx decreased CADx prediction utilization compared to an optional CADx. Appropriate trust, utilizing correct or disregarding incorrect CADx predictions was 48.7% (n=244/501). CONCLUSIONS: Appropriate trust was common and CADx prediction utilization was highest for the optional CADx without confidence scores. These results express the importance of a better understanding of human-AI interaction.

2.
Endoscopy ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38657659

RESUMO

BACKGROUND: Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. METHODS: In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps. Real-life recognition of T1 CRC was then evaluated in 25 hospitals. Endoscopic and pathologic reports of T1 CRCs detected during the next year were collected retrospectively, with endoscopists unaware of this evaluation. Sensitivity for T1 CRC recognition, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists. RESULTS: 1 year after e-learning, 528 nonpedunculated T1 CRCs were recorded for endoscopies performed by 251 endoscopists (118 [47 %] trained). Median T1 CRC size was 20 mm. Lesions were mainly located in the distal colorectum (66 %). Trained endoscopists recognized T1 CRCs more frequently than untrained endoscopists (sensitivity 74 % vs. 62 %; mixed model analysis odds ratio [OR] 2.90, 95 %CI 1.54-5.45). R0 resection rate was higher for T1 CRCs detected by trained endoscopists (69 % vs. 56 %; OR 1.73, 95 %CI 1.03-2.91). CONCLUSION: Training in optical recognition of T1 CRCs in community hospitals was associated with increased recognition of T1 CRCs, leading to higher en bloc and R0 resection rates. This may be an important step toward more organ-preserving strategies.

3.
Gut ; 73(5): 741-750, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38216328

RESUMO

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.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia
4.
Ann Surg ; 279(5): 746-754, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37991178

RESUMO

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.


Assuntos
Tratamento Conservador , Terapia por Estimulação Elétrica , Adulto , Adolescente , Humanos , Qualidade de Vida , Constipação Intestinal/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Resultado do Tratamento
5.
Clin Exp Gastroenterol ; 16: 197-211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954129

RESUMO

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.

6.
Clin Res Hepatol Gastroenterol ; 47(10): 102224, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37813276

RESUMO

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.


Assuntos
Hiperferritinemia , Sobrecarga de Ferro , Humanos , Ferro/análise , Ferro/metabolismo , Hiperferritinemia/complicações , Hiperferritinemia/metabolismo , Hiperferritinemia/patologia , Fígado/metabolismo , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética
7.
Br J Cancer ; 129(5): 791-796, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37468570

RESUMO

BACKGROUND: Combining the faecal immunochemical test (FIT) result with risk factors for advanced neoplasia (AN) may increase the yield of colorectal cancer (CRC) screening without increasing the number of colonoscopies. We conducted a randomised controlled trial in the Dutch CRC screening programme to evaluate a previously developed risk model including FIT, age, sex, smoking status, and CRC family history. METHODS: A total of 22,748 individuals aged 56-75 years were pre-randomised to the risk-model group or the FIT-only group. Both groups received the FIT; those allocated to the risk-model group also received a single-page questionnaire. Study participants with a positive result (FIT ≥ 15 µg Hb/g faeces and/or risk ≥0.10) were referred for colonoscopy. The primary outcome measure was the proportion of invitees in whom AN was detected. RESULTS: In the risk-model group, 3113/11,364 invitees (27%) returned the FIT and questionnaire versus 3061/11,384 invitees (27%) in the FIT-only group (p = 0.40). The yield of AN was 3.70/1000 invitees in the risk-model group versus 3.43/1000 in the FIT-only group (absolute difference: 0.27/1000, 95%CI: -1.30 to 1.82, p = 0.82). CONCLUSIONS: Combining FIT with risk factors for CRC did not increase the yield of AN compared to FIT-only in an existing CRC screening programme. There was no difference in participation between groups. CLINICAL TRIAL REGISTRATION: NCT04490551 (ClinicalTrials.gov).


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Fatores de Risco , Sangue Oculto , Fezes/química , Hemoglobinas/análise , Programas de Rastreamento
9.
Endosc Int Open ; 11(5): E513-E518, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206697

RESUMO

Computer-aided diagnosis systems (CADx) can improve colorectal polyp (CRP) optical diagnosis. For integration into clinical practice, better understanding of artificial intelligence (AI) by endoscopists is needed. We aimed to develop an explainable AI CADx capable of automatically generating textual descriptions of CRPs. For training and testing of this CADx, textual descriptions of CRP size and features according to the Blue Light Imaging (BLI) Adenoma Serrated International Classification (BASIC) were used, describing CRP surface, pit pattern, and vessels. CADx was tested using BLI images of 55 CRPs. Reference descriptions with agreement by at least five out of six expert endoscopists were used as gold standard. CADx performance was analyzed by calculating agreement between the CADx generated descriptions and reference descriptions. CADx development for automatic textual description of CRP features succeeded. Gwet's AC1 values comparing the reference and generated descriptions per CRP feature were: size 0.496, surface-mucus 0.930, surface-regularity 0.926, surface-depression 0.940, pits-features 0.921, pits-type 0.957, pits-distribution 0.167, and vessels 0.778. CADx performance differed per CRP feature and was particularly high for surface descriptors while size and pits-distribution description need improvement. Explainable AI can help comprehend reasoning behind CADx diagnoses and therefore facilitate integration into clinical practice and increase trust in AI.

10.
Surg Obes Relat Dis ; 19(3): 253-264, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36274017

RESUMO

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.


Assuntos
Derivação Gástrica , Gastroparesia , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Gastroparesia/etiologia , Gastrectomia/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
11.
Endosc Int Open ; 10(8): E1127-E1135, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36247075

RESUMO

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.

12.
Clin Transl Gastroenterol ; 13(11): e00518, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35981245

RESUMO

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.


Assuntos
Adenoma , Neoplasias Colorretais , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Detecção Precoce de Câncer/métodos , Estudos Prospectivos , Adenoma/diagnóstico , Adenoma/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia
13.
Endosc Int Open ; 10(7): E940-E951, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35845029

RESUMO

Background and study aims Neuroendocrine neoplasms (NEN) account for a small number of colorectal neoplasms. Endoscopic detection is essential for diagnosis, treatment and follow-up. Little is known about incidence of NENs in colonoscopy populations or the relationship between clinical, endoscopic and histopathologic features. We evaluated epidemiology, endoscopic and clinical characteristics of colorectal NENs in a population-based cohort. Patients and methods Medical records of NEN cases were cross-linked with the national pathology database from January 2001 to December 2015, in South Limburg County, the Netherlands, covering four endoscopy units. Senior pathologists reviewed and classified NENs using World Health Organization 5th edition (2019) guidelines. Results The number of colorectal NEN diagnoses was stable over time with 0.6 NEN per 1,000 patients. A total of NENs were detected in 85 patients: 65 neuroendocrine tumors (NETs) and 20 poorly differentiated neuroendocrine carcinomas (NECs). Rectal NETs were usually small sessile/submucosal lesions with yellowish (lipoma-like) color. Colonic NETs were larger sessile/submucosal lesions with darker color compared to background. Colorectal NECs presented as large, dark-colored lesions with ulcerated/necrotizing areas. Conclusions Our population-based data point to a stable and low incidence of 0.6 NEN per 1,000 patients in the Netherlands. Rectal NETs mainly present as small sessile yellowish lesions. Colonic NETs present as larger and darker lesions than background mucosa and NECs as darker lesions than background with ulceration/necrosis. Standardized endoscopic characterization of colorectal NENs is necessary to improve recognition of these lesions and provide a basis for evidence-based treatment and surveillance recommendations.

14.
Clin Transl Gastroenterol ; 13(6): e00499, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35584320

RESUMO

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.


Assuntos
Neoplasias Colorretais , Metilação de DNA , Biomarcadores Tumorais/genética , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Humanos , Sangue Oculto
15.
Inflamm Bowel Dis ; 28(9): 1309-1320, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35554535

RESUMO

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.


Assuntos
Colangite Esclerosante , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Colangite Esclerosante/complicações , Colangite Esclerosante/genética , Colangite Esclerosante/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/genética , Perfil Genético , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Instabilidade de Microssatélites
16.
Neurogastroenterol Motil ; 34(11): e14394, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35531931

RESUMO

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.


Assuntos
Neuropatias Diabéticas , Gastroparesia , Duodeno/fisiologia , Feminino , Motilidade Gastrointestinal/fisiologia , Gastroparesia/diagnóstico , Gastroparesia/etiologia , Humanos , Manometria , Pessoa de Meia-Idade , Complexo Mioelétrico Migratório/fisiologia
17.
Gut Microbes ; 14(1): 2063016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35446234

RESUMO

To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome-metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome-metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome-metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Microbiota , Fezes/química , Microbioma Gastrointestinal/fisiologia , Humanos , Síndrome do Intestino Irritável/metabolismo , Metaboloma , Serotonina/metabolismo
18.
Dig Endosc ; 34(5): 913-926, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35037327

RESUMO

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.


Assuntos
Hipopotassemia , Catárticos/efeitos adversos , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Eletrólitos/efeitos adversos , Humanos , Polietilenoglicóis/efeitos adversos , Potássio
20.
Eur J Gastroenterol Hepatol ; 34(3): 302-307, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775459

RESUMO

OBJECTIVE: The aim of this article was to examine the costs and effectiveness of standardized blood and fecal investigations in patients fulfilling the Rome criteria for irritable bowel syndrome (IBS). METHODS: We conducted a real-life cohort study in patients fulfilling the Rome III criteria for IBS without red flag signs or symptoms, in a center of excellence for IBS patients from 1 January 2015 till 1 January 2019. Standardized blood and fecal investigations [hemoglobin (Hb), thyroid-stimulating hormone (TSH), coeliac serology, and fecal calprotectin (FCP)] were performed during the first consultation. Patients were followed for at least 1 year. Primary outcome was the probability of another diagnosis than IBS with subsequent overall costs. RESULTS: A total of 218 patients were included. In approximately 200 patients blood and fecal investigations were performed and 47 patients underwent a colonoscopy. Two-hundred ten patients were diagnosed with IBS, 5 with inflammatory bowel disease (IBD), 1 with nonspecific acute ileitis, 1 with hyperthyroidism, and 1 with coeliac disease. The number needed to diagnose all included laboratory tests was 34, and for the individual test: TSH 197, coeliac serology 199, and FCP 50. The total costs were approximately €4900 to diagnose one patient with another diagnosis than IBS. CONCLUSION: In our real-life cohort of adult patients under the age of 50 years fulfilling the Rome criteria for IBS without red flag symptoms, standardized blood, and fecal investigations have a very low diagnostic yield accompanied by high additional costs. Colonoscopy is not indicated in patients with Rome III positive IBS and normal FCP.


Assuntos
Síndrome do Intestino Irritável , Adulto , Biomarcadores , Estudos de Coortes , Humanos , Síndrome do Intestino Irritável/diagnóstico , Complexo Antígeno L1 Leucocitário , Pessoa de Meia-Idade , Tireotropina , Adulto Jovem
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