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ELife Feb 2023Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization...
BACKGROUND
Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases.
METHODS
Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption.
RESULTS
Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation.
CONCLUSIONS
This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases.
FUNDING
The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.
Topics: Humans; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Duodenal Ulcer; Smoking; Alcohol Drinking; Esophageal Neoplasms; Liver Diseases, Alcoholic; Gastritis; Pancreatitis, Chronic; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 36727839
DOI: 10.7554/eLife.84051 -
World Journal of Gastroenterology Jan 2020Esophageo-gastro-duodenoscopy (EGD) is an important procedure used for detection and diagnosis of esophago-gastric lesions. There exists no consensus on the technique of... (Review)
Review
BACKGROUND
Esophageo-gastro-duodenoscopy (EGD) is an important procedure used for detection and diagnosis of esophago-gastric lesions. There exists no consensus on the technique of examination.
AIM
To identify recent advances in diagnostic EGDs to improve diagnostic yield.
METHODS
We queried the PubMed database for relevant articles published between January 2001 and August 2019 as well as hand searched references from recently published endoscopy guidelines. Keywords used included free text and MeSH terms addressing quality indicators and technological innovations in EGDs. Factors affecting diagnostic yield and EGD quality were identified and divided into the follow segments: Pre endoscopy preparation, sedation, examination schema, examination time, routine biopsy, image enhanced endoscopy and future developments.
RESULTS
We identified 120 relevant abstracts of which we utilized 67 of these studies in our review. Adequate pre-endoscopy preparation with simethicone and pronase increases gastric visibility. Proper sedation, especially with propofol, increases patient satisfaction after procedure and may improve detection of superficial gastrointestinal lesions. There is a movement towards mandatory picture documentation during EGD as well as dedicating sufficient time for examination improves diagnostic yield. The use of image enhanced endoscopy and magnifying endoscopy improves detection of squamous cell carcinoma and gastric neoplasm. The magnifying endoscopy simple diagnostic algorithm is useful for diagnosis of early gastric cancer.
CONCLUSION
There is a steady momentum in the past decade towards improving diagnostic yield, quality and reporting in EGDs. Other interesting innovations, such as Raman spectroscopy, endocytoscopy and artificial intelligence may have widespread endoscopic applications in the near future.
Topics: Digestive System Diseases; Early Detection of Cancer; Endoscopy, Digestive System; Gastroenterology; Humans
PubMed: 32063692
DOI: 10.3748/wjg.v26.i4.433 -
United European Gastroenterology Journal Jul 2020The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive...
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
Topics: Adult; Body Weight; Child; Digestive System Diseases; Dose-Response Relationship, Drug; Drug Dosage Calculations; Europe; Evidence-Based Medicine; Gastroenterology; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Severity of Illness Index; Treatment Outcome
PubMed: 32552502
DOI: 10.1177/2050640620934911 -
Expert Review of Gastroenterology &... Apr 2019Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
Topics: Digestive System Diseases; Eye Diseases; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Joint Diseases; Phenotype; Prognosis; Risk Assessment; Risk Factors; Skin Diseases
PubMed: 30791773
DOI: 10.1080/17474124.2019.1574569 -
EMBO Reports Jul 2006The intestinal microflora is a positive health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal... (Review)
Review
The intestinal microflora is a positive health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal immune responses to resident intestinal microflora require precise control and an immunosensory capacity for distinguishing commensal from pathogenic bacteria. In genetically susceptible individuals, some components of the flora can become a liability and contribute to the pathogenesis of various intestinal disorders, including inflammatory bowel diseases. It follows that manipulation of the flora to enhance the beneficial components represents a promising therapeutic strategy. The flora has a collective metabolic activity equal to a virtual organ within an organ, and the mechanisms underlying the conditioning influence of the bacteria on mucosal homeostasis and immune responses are beginning to be unravelled. An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes.
Topics: Animals; Bacteria; Digestive System; Digestive System Diseases; Germ-Free Life; Homeostasis; Humans; Immunity, Mucosal; Intestinal Mucosa; Models, Biological
PubMed: 16819463
DOI: 10.1038/sj.embor.7400731 -
Revista Espanola de Enfermedades... Nov 2015The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and... (Review)
Review
The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.
Topics: Animals; Digestive System Diseases; Humans; Intestinal Mucosa; Intestines; Tight Junctions
PubMed: 26541659
DOI: 10.17235/reed.2015.3846/2015 -
Advanced Science (Weinheim,... Jun 2021Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor...
Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.
Topics: Antigens, Neoplasm; Carbonic Anhydrase IX; Cell Cycle Proteins; Digestive System Diseases; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Fructose-Bisphosphate Aldolase; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Humans; Hyaluronan Receptors; Intracellular Signaling Peptides and Proteins; Janus Kinases; Neoplastic Stem Cells; Organoids; RNA, Long Noncoding; RNA-Seq; STAT Transcription Factors; Single-Cell Analysis; Transcriptome; beta Catenin
PubMed: 34105295
DOI: 10.1002/advs.202003897 -
Gastroenterology Feb 2022Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with...
BACKGROUND & AIMS
Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States.
METHODS
We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH).
RESULTS
Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020.
CONCLUSIONS
Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.
Topics: Ambulatory Care; Biomedical Research; Cost of Illness; Digestive System Neoplasms; Endoscopy, Digestive System; Gastrointestinal Diseases; Health Expenditures; Hospitalization; Humans; Liver Diseases; National Institutes of Health (U.S.); Pancreatic Diseases; Patient Readmission; United States
PubMed: 34678215
DOI: 10.1053/j.gastro.2021.10.017 -
Revista Espanola de Enfermedades... Feb 2021The pandemic caused by SARS-CoV-2 has posed an unprecedented challenge to health systems, leading in many countries to the collapse of health care and a lack of...
The pandemic caused by SARS-CoV-2 has posed an unprecedented challenge to health systems, leading in many countries to the collapse of health care and a lack of preventive measures both for the most vulnerable sections of the population and among healthcare professionals.
Topics: COVID-19; Delivery of Health Care; Digestive System Diseases; Humans
PubMed: 33461301
DOI: 10.17235/reed.2021.7774/2020 -
Gut and Liver May 2017Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of... (Review)
Review
Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.
Topics: Adipokines; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Humans; Insulin Resistance; Obesity; Risk Factors; Weight Loss
PubMed: 27890867
DOI: 10.5009/gnl15557