Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells

Hepatic stellate cells (HSC) play a central role in fibrosis development by production of extracellular matrix and also by secretion of matrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs) including TIMP-2 and MMP-2. TIMP-2 has been shown to interact with Gelatinase A in conjunction with MT1-MMP (MMP-14). TIMP-2 has been traditionally considered to be constitutively expressed. There is some evidence that TIMP-2 expression is slightly enhanced in fibrotic disease and activation in tissue culture. Little is known in terms of TIMP-2 expression in the recently described pancreatic stellate cells (PSC). HSC were cultured on plastic having been isolated from rat and human liver resections. After culture on plastic northern analysis was performed for TIMP-2 mRNA expression. TIMP-2 promoter activity was examined in rat pancreatic stellate cells (PSC) and rat hepatic stellate cells. Early work led to subcloning the promoter into a different vector though subsequent promoter studies were unsuccessful. In vivo work in immunohistochemistry studies suggest there is increased TIMP-2 expression in evaluation of rat pancreas and liver in addition to human liver and pancreas specimens. By ribonuclease protection assay TIMP-2 was noted to be upregulated in human fibrotic liver compared to normal human liver tissue. In conclusion there is some evidence that TIMP-2 regulation may be altered in fibrotic liver states as well as in pancreatic inflammatory disease

UK and Ireland Joint Advisory Group (JAG) consensus statements for training and certification in diagnostic endoscopic ultrasound (EUS)

Background and Aims: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK.Methods: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved.Results: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers.Conclusions: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland.</p

UK Joint Advisory Group consensus statements for training and certification in endoscopic retrograde cholangiopancreatography

© 2022 The Authors. Published by Thieme Open. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1629-7540Introduction: Despite the high-risk nature of endoscopic retrograde cholangiopancreatography (ERCP), a robust and standardised credentialing process to ensure competency before independent practice is lacking worldwide. On behalf of the Joint Advisory Group (JAG), we aimed to develop evidence-based recommendations to form the framework of ERCP training and certification in the UK. Methods: Under the oversight of the JAG, a modified Delphi process was conducted with stakeholder representation from the British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on ERCP training and certification were formulated after formal literature review and appraised using the GRADE tool. These were subjected to electronic voting to achieve consensus. Accepted statements were peer-reviewed by JAG and relevant Specialist Advisory Committees before incorporation into the ERCP certification pathway. Results: In total, 27 recommendation statements were generated for the following domains: definition of competence (9 statements), acquisition of competence (8 statements), assessment of competence (6 statements) and post-certification support (4 statements). The consensus process led to the following criteria for ERCP certification: 1) performing ≥300 hands-on procedures; 2) attending a JAG-accredited ERCP skills course; 3) in modified Schutz 1-2 procedures: achieving native papilla cannulation rate ≥80%, complete bile duct clearance ≥70%, successful stenting of distal biliary strictures ≥75%, physically unassisted in ≥80% of cases; 4) 30-day post-ERCP pancreatitis rates ≤5%; 5) satisfactory performance in formative and summative direct observation of procedural skills (DOPS) assessments. Conclusion: JAG certification in ERCP has been developed following evidence-based consensus to quality assure training and to ultimately improve future standards of ERCP practice

Pancreaticoduodenectomy for nonampullary duodenal lesions: indications and results

PD carries a high mortality and morbidity, especially for duodenal lesions. We recommend a careful endoscopic review after the index case with a high-definition optical evaluation of duodenal lesions. This, in addition to an experienced histological assessment of the index biopsy material, forms an essential prerequisite in aiding the multidisciplinary team in the decision-making process with respect to triage of these lesions to conservative management, surveillance, endoscopic resection or finally surgical resection

Expression of transforming growth factor-ß1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis

Pancreatic stellate cells mediate fibrosis in chronic pancreatitis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 are crucial modulators of fibrosis. Transforming growth factor-ß (TGF-ß) is a key regulator of extracellular matrix production and myofibroblast proliferation. We have examined MMP and TIMP synthesis by transformed cultured pancreatic stellate cells and their regulation by TGF-ß1. By Northern analysis they expressed mRNAs for procollagen 1, TIMP-1, TIMP-2, and MMP-2. Expression of membrane type-1 MMP was confirmed by Western blotting. By immunohistochemistry these enzymes localized to fibrotic areas in human chronic pancreatitis. Active TGF-ß1 constitutes 2 to 5% of total TGF-ß1 secreted by pancreatic stellate cells; they express TGF-ß receptors I and II. Exogenous TGF-ß1 (10 ng/ml) significantly increased procollagen-1 mRNA by 69% and collagen protein synthesis by 34%. Similarly TGF-ß1 at 0.1, 1, and 10 ng/ml significantly reduced cellular proliferation rate by 37%, 44%, and 44%, respectively, whereas pan-TGF-ß-neutralizing antibody increased proliferation by 40%. TGF-ß1 (10 ng/ml) down-regulated MMP-9 by 54% and MMP-3 by 34% whereas TGF-ß1-neutralizing antibody increased MMP-9 expression by 39%. Pancreatic stellate cells express both mediators of matrix remodeling and the regulatory cytokine TGF-ß1 that, by autocrine inhibition of MMP-3 and MMP-9, may enhance fibrogenesis by reducing collagen degradation

UK and Ireland Joint Advisory Group (JAG) consensus statements for training and certification in diagnostic endoscopic ultrasound (EUS).

Peer reviewed: TrueBACKGROUND AND AIMS: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK. METHODS: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved. RESULTS: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers. CONCLUSIONS: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland