Category Archives: Gastroenterology

A case report of a young adult with progressive bloody diarrhea, protein losing enteropathy and extended polyposis coli.

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A case report of a young adult with progressive bloody diarrhea, protein losing enteropathy and extended polyposis coli.
Gastroenterology. 2018 Sep 08;:
Authors: Borgerink MMH, Weersma RK, Visschedi… Continue reading

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Novel developments in endoscopic mucosal imaging.

Novel developments in endoscopic mucosal imaging.
Gastroenterology. 2018 Feb 17;:
Authors: van der Sommen F, Curvers WL, Nagengast WB
Abstract
Endoscopic techniques such as High-definition and optical… Continue reading

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Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Downregulation of Scavenger Receptor Class B, Type 1.

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Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Downregulation of Scavenger Receptor Class B, Type 1.

Gastroenterology. 2015 Nov…

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Allogeneic Bone Marrow-derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients with Crohn’s Disease.

Allogeneic Bone Marrow-derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients with Crohn’s Disease.
Gastroenterology. 2015 Jun 24;
Authors: Molendijk I, Bonsing BA, Roelofs H, P… Continue reading

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Accuracy of Hereditary Diffuse Gastric Cancer Testing Criteria and Outcomes in Patients with a Germline Mutation in CDH1.

Accuracy of Hereditary Diffuse Gastric Cancer Testing Criteria and Outcomes in Patients with a Germline Mutation in CDH1.

Gastroenterology. 2015 Jun 10;

Authors: van der Post RS, Vogelaar IP, Manders P, van der Kolk LE, Cats A, van Hest LP, Sijmons R, Aalfs CM, Ausems MG, Gómez García EB, Wagner A, Hes FJ, Arts N, Mensenkamp AR, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ

Abstract
BACKGROUND & AIMS: Germline mutations in the cadherin 1, type 1, E-cadherin gene (CDH1) cause a predisposition to gastric cancer. We evaluated the ability of the internationally accepted hereditary diffuse gastric cancer (HDGC) criteria to identify individuals with pathogenic mutations in CDH1, and assessed their outcomes. These criteria are: families with 2 or more cases of diffuse-type gastric cancer (DGC), with at least 1 patient diagnosed before the age of 50; families with 3 or more cases of DGC; families with 1 DGC before the age of 40; and families with a history of DGC and lobular breast cancer, with 1 diagnosis before the age of 50.
METHODS: We collected results of a CDH1 mutation analysis of 578 individuals from 499 families tested in the Netherlands between 1999 and 2014 (118 families met the HDGC criteria for testing and 236 did not; 145 families with incomplete data and/or availability of only first-degree relatives). Data were linked with family histories and findings from clinical and pathology analyses. The Kaplan-Meier method and Cox regression analysis were used to evaluate overall survival of patients with and without CDH1 mutations.
RESULTS: In a cohort study in the Netherlands, the HDGC criteria identify individuals with a germline CDH1 mutation with a positive predictive value of 14% and 89% sensitivity. There were 18 pathogenic CDH1 mutations in 499 families (4%); 16 of these mutations were detected in the 118 families who met the HDGC criteria for testing. One pathogenic CDH1 mutation was detected in the 236 families who did not meet HDGC criteria and 1 in the 145 families with incomplete data and/or availability of only first-degree relatives. No CDH1 mutations were found in the 67 families whose members developed intestinal-type gastric cancer, nor in the 22 families whose families developed lobular breast cancer. Among patients who fulfilled the HDGC criteria and had pathogenic CDH1 mutations, 36% survived for 1 y and 4% survived for 5 y; among patients who fulfilled the HDGC criteria but did not carry pathogenic CDH1 mutations, 48% survived for 1 y and 13% survived for 5 y (P=.014 for comparative survival analysis between patients with and without a CDH1 mutation).
CONCLUSIONS: All individuals with a CDH1 mutation had a personal or family history of diffuse gastric cancer. Patients with gastric cancer and germline CDH1 mutations had shorter survival times than patients who met the HDGC criteria but did not have CDH1 mutations.

PMID: 26072394 [PubMed – as supplied by publisher]

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Maintenance of Clonogenic KIT(+) Human Colon Tumor Cells Requires Secretion of Stem Cell Factor by Differentiated Tumor Cells.

Maintenance of Clonogenic KIT(+) Human Colon Tumor Cells Requires Secretion of Stem Cell Factor by Differentiated Tumor Cells.
Gastroenterology. 2015 May 8;
Authors: Fatrai S, van Schelven SJ, Ubink I, Govaert KM, Ra… Continue reading

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Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett’s esophagus.

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Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett’s esophagus.

Gastroenterology. 2015 Feb;148(2):367-78

Authors: Palles C, Chegwidden L, Li X, Findlay JM, Farnham G, Castro Giner F, Peppelenbosch MP, Kovac M, Adams CL, Prenen H, Briggs S, Harrison R, Sanders S, MacDonald D, Haigh C, Tucker A, Love S, Nanji M, deCaestecker J, Ferry D, Rathbone B, Hapeshi J, Barr H, Moayyedi P, Watson P, Zietek B, Maroo N, Gay L, Underwood T, Boulter L, McMurtry H, Monk D, Patel P, Ragunath K, Al Dulaimi D, Murray I, Koss K, Veitch A, Trudgill N, Nwokolo C, Rembacken B, Atherfold P, Green E, Ang Y, Kuipers EJ, Chow W, Paterson S, Kadri S, Beales I, Grimley C, Mullins P, Beckett C, Farrant M, Dixon A, Kelly S, Johnson M, Wajed S, Dhar A, Sawyer E, Roylance R, Onstad L, Gammon MD, Corley DA, Shaheen NJ, Bird NC, Hardie LJ, Reid BJ, Ye W, Liu G, Romero Y, Bernstein L, Wu AH, Casson AG, Fitzgerald R, Whiteman DC, Risch HA, Levine DM, Vaughan TL, Verhaar AP, van den Brande J, Toxopeus EL, Spaander MC, Wijnhoven BP, van der Laan LJ, Krishnadath K, Wijmenga C, Trynka G, McManus R, Reynolds JV, O’Sullivan J, MacMathuna P, McGarrigle SA, Kelleher D, Vermeire S, Cleynen I, Bisschops R, Tomlinson I, Jankowski J

Abstract
BACKGROUND & AIMS: Barrett’s esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.
METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.
RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).
CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

PMID: 25447851 [PubMed – indexed for MEDLINE]

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Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

Gastroenterology. 2015 Mar 17;

Authors: Walter D, van Boeckel PG, Groenen MJ, Weusten BL, Witteman BJ, Tan G, Brink MA, Nicolai J, Tan AC, Alderliesten J, Venneman NG, Laleman W, Jansen JM, Bodelier A, Wolters FL, van der Waaij LA, Breumelhof R, Peters FT, Scheffer RC, Leenders M, Hirdes MM, Steyerberg EW, Vleggaar FP, Siersema PD

Abstract
BACKGROUND: & Aims: Endoscopic stents are placed for palliation of extra-hepatic bile duct obstruction. Although self-expandable metals stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered [uSEMS], or partially covered [pcSEMS]), is most effective and assessed costs.
METHODS: We performed a multi-center randomized trial in 219 patients at 18 hospitals in the Netherlands from February 2008 through February 2013. Patients were randomly assigned for placement of a plastic stent (n=73), uSEMS (n=75), or pcSEMS (n=71) during endoscopic retrograde cholangiopancreatography. Patients were followed for up to 1 y. Researchers were not blinded to groups. The main study endpoints included functional stent time and costs.
RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P<.005 for uSEMS and pSEMS vs plastic). Initial placement of plastic stents (€1042 or $1106) cost significantly less than of SEMS (€1973 or $2094) (P=.001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P=.61). Furthermore, in patients with short survival times (≤3 months) or metastatic disease, total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS.
CONCLUSION: Although placement of SEMS (uncovered or partially covered) for palliation of extra-hepatic bile duct obstruction is initially more expensive than placement of plastic stents, SEMS have longer functional time. Total costs after 1 y do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

PMID: 25790742 [PubMed – as supplied by publisher]

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A 21-year-old patient with a HER2-positive colorectal cancer.

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A 21-year-old patient with a HER2-positive colorectal cancer.

Gastroenterology. 2015 Jan;148(1):20-1

Authors: Bensch F, van Rooijen JM, Schröder CP, Reyners AK

PMID: 25447849 [PubMed – indexed for MEDLINE]

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Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

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Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

Gastroenterology. 2014 Aug;147(2):443-52.e5

Authors: de Boer YS, van Gerven NM, Zwiers A, Verwer BJ, van Hoek B, van Erpecum KJ, Beuers U, van Buuren HR, Drenth JP, den Ouden JW, Verdonk RC, Koek GH, Brouwer JT, Guichelaar MM, Vrolijk JM, Kraal G, Mulder CJ, van Nieuwkerk CM, Fischer J, Berg T, Stickel F, Sarrazin C, Schramm C, Lohse AW, Weiler-Normann C, Lerch MM, Nauck M, Völzke H, Homuth G, Bloemena E, Verspaget HW, Kumar V, Zhernakova A, Wijmenga C, Franke L, Bouma G, Dutch Autoimmune Hepatitis Study Group, LifeLines Cohort Study, Study of Health in Pomerania

Abstract
BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH.
METHODS: We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region.
RESULTS: We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits.
CONCLUSIONS: In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases.

PMID: 24768677 [PubMed – indexed for MEDLINE]

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Copper Metabolism Domain-containing 1 Represses Genes that Promote Inflammation and Protects Mice From Colitis and Colitis-associated Cancer.

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Copper Metabolism Domain-containing 1 Represses Genes that Promote Inflammation and Protects Mice From Colitis and Colitis-associated Cancer.

Gastroenterology. 2014 Apr 10;

Authors: Li H, Chan L, Bartuzi P, Melton SD, Weber A, Ben-Shlomo S, Varol C, Raetz M, Mao X, Starokadomskyy P, van Sommeren S, Mokadem M, Schneider H, Weisberg R, Westra HJ, Esko T, Metspalu A, Kumar V, Faubion WA, Yarovinsky F, Hofker M, Wijmenga C, Kracht M, Franke L, Aguirre V, Weersma RK, Gluck N, van de Sluis B, Burstein E

Abstract
BACKGROUND: & Aims: Activation of the transcription factor NFκB has been associated with development of inflammatory bowel disease (IBD). COMMD1, a regulator of various transport pathways, has been shown to limit NFκB activation. We investigated the roles of COMMD1 in the pathogenesis of colitis in mice and IBD in humans.
METHODS: We created mice with specific disruption of Commd1 in myeloid cells (Mye-K/O mice); we analyzed immune cell populations and functions and expression of genes regulated by NFκB. Sepsis was induced in Mye-K/O and wild-type mice by cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide (LPS), colitis was induced by administration of dextran sodium sulfate (DSS), and colitis-associated cancer was induced by administration of DSS and azoxymethane. We measured levels of COMMD1 mRNA in colon biopsies from 29 patients with IBD and 16 patients without (controls), and validated findings in an independent cohort (17 patients with IBD and 22 controls). We searched for polymorphisms in or near COMMD1 that were associated with IBD using data from the International IBD Genetics Consortium and performed quantitative trait locus analysis.
RESULTS: In comparing gene expression patterns between myeloid cells from Mye-K/O and wild-type mice, we found that COMMD1 represses expression of genes induced by LPS. Mye-K/O mice had more intense inflammatory responses to LPS and developed more severe sepsis and colitis, with greater mortality. More Mye-K/O mice with colitis developed colon dysplasia and tumors than wild-type mice. We observed reduced expression of COMMD1 in colon biopsies and circulating leukocytes from patients with IBD. We associated single nucleotide variants near COMMD1 with reduced expression of the gene and linked them with increased risk for ulcerative colitis.
CONCLUSIONS: Expression of COMMD1 by myeloid cells has anti-inflammatory effects. Reduced expression or function of COMMD1 could be involved in the pathogenesis of IBD.

PMID: 24727021 [PubMed – as supplied by publisher]

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Prior colorectal neoplasia is associated with increased risk of ileoanal pouch neoplasia in patients with inflammatory bowel disease.

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Prior colorectal neoplasia is associated with increased risk of ileoanal pouch neoplasia in patients with inflammatory bowel disease.
Gastroenterology. 2014 Jan;146(1):119-28.e1
Authors: Derikx LA, Kievit W, D… Continue reading

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Fecal microbiota transfer may increase irritable bowel syndrome and inflammatory bowel diseases-associated bacteria.

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Fecal microbiota transfer may increase irritable bowel syndrome and inflammatory bowel diseases-associated bacteria.
Gastroenterology. 2013 Apr;144(4):e19-20
Authors: Konstantinov SR, Peppelenbosch MP
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Comment on: Glucocorticoids Promote Hepatic Cholestasis in Mice by Inhibiting the Transcriptional Activity of the Farnesoid X Receptor.

Comment on: Glucocorticoids Promote Hepatic Cholestasis in Mice by Inhibiting the Transcriptional Activity of the Farnesoid X Receptor.

Gastroenterology. 2012 Dec 20;

Authors: Out…

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CLMP is required for intestinal development, and loss-of-function mutations cause congenital short-bowel syndrome.

CLMP is required for intestinal development, and loss-of-function mutations cause congenital short-bowel syndrome.

Gastroenterology. 2012 Mar;142(3):453-462.e3

Authors: Van Der…

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