• Crohn’s disease
• chemoprevention
• colorectal cancer
• inflammatory bowel disease
• ulcerative colitis

• cholangiocarcinoma
• colorectal cancer
• disease management
• dominant stricture
• ursodeoxycholic acid

• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/therapy
• Humans
• Liver Transplantation
• Disease Progression
• Ursodeoxycholic Acid/therapeutic use

• chronic inflammation
• germline mutations
• precancerous lesions
• prevention
• therapy

• Humans
• Neoplasms/prevention & control
• Neoplasms/genetics
• Carcinogenesis/genetics
• Precision Medicine/methods
• Precancerous Conditions/genetics
• Precancerous Conditions/prevention & control
• Inflammation
• Germ-Line Mutation

• 2022ZY1135 Key program of TCM research in Henan Province
• SBGJ202102074 The Medical Science and Technology Project of Henan Province
• National Natural Science Foundation of China
• 82103194 The National Science Foundation of China

• Humans
• Crohn Disease/diagnosis
• Crohn Disease/therapy
• Gastroenterology/standards
• Germany

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Humans
• Gastroenterology/standards
• Practice Guidelines as Topic
• Germany

• cholesterol
• colorectal cancer
• metabolism
• therapeutic approaches
• tumorigenic

• 24-Norursodeoxycholic acid
• Bile acid
• Farnesoid X receptor agonists
• Liver transplant
• Microbiome
• Primary sclerosing cholangitis

• Humans
• Colitis, Ulcerative

• FXR agonist
• PXR agonist
• bile acids
• cholestasis
• fibreates
• fibrosis
• ursodeoxycholic acid

• chemoprevention
• colorectal cancer
• precancerous lesions
• target populations

• IG-23794 Italian Association for Cancer Research
• ID26678 Italian Association for Cancer Research
• ricerca corrente 2021-2023 Italian Ministry of Health
• Ricerca corrente 2022-2024 Italian Ministry of Health
• Ricerca corrente 2023-2025 Italian Ministry of Health

• CAC, CRC
• Colitis-associated cancer
• Diet
• IBD-colorectal cancer

• Adult
• Child
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/therapy
• Humans
• Prognosis

Colorectal cancer (CRC) is one of the most serious potential complications of inflammatory bowel diseases (IBDs). The aging of patients affected by IBDs makes this issue a challenge that will increasingly be faced by clinicians in clinical practice, especially in light of the poorer prognosis for CRC in this group of people when compared with the general population. In this review, we summarize the current epidemiology, risk factors and various prevention strategies proposed for CRC in patients with IBDs.

Colorectal cancer (CRC) is currently the third most frequent form of malignancy and the second in terms of mortality. Inflammatory bowel diseases (IBDs) are recognized risk factors for this type of cancer. Despite a worldwide increase in the incidence of CRC, the risk of CRC-related death in IBD patients has declined over time, probably because of successful surveillance strategies, the use of more effective drugs in the management of remission and improved indications to colectomy. This notwithstanding, CRC 5-year survival in patients with IBD is poorer than in the general population. This review provides a summary of the epidemiological features, risk factors and various prevention strategies proposed for CRC in IBD patients. Moreover, there is a special focus on reporting and highlighting the various prevention strategies proposed by the most important international scientific societies, both in terms of chemoprevention and endoscopic surveillance. Indeed, in conducting the analysis, we have given attention to the current primary, secondary and tertiary prevention guidelines, attempting to emphasize unresolved research and clinical problems related to this topic in order to improve diagnostic strategies and management.

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.

• bile acids
• colorectal cancer
• high-fat diet
• intestinal flora
• tumorigenesis

• chenodeoxycholic
• colitis
• deoxycholic
• lithocholic

• Bile Acids and Salts/metabolism
• Colon/metabolism
• Humans
• Inflammation/metabolism
• Intestinal Mucosa/metabolism
• Permeability

• R01 DK115950 NIDDK NIH HHS
• HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental factors, and a dysbiotic gut microbiota. Although metagenomic approaches have attempted to characterise the dysbiosis occurring in IBD, the precise mechanistic pathways interlinking the gut microbiota and the intestinal mucosa are still yet to be unravelled. To deconvolute these complex interactions, a more reductionist approach involving microbial metabolites has been suggested. Bile acids have emerged as a key class of microbiota-associated metabolites that are perturbed in IBD patients. In recent years, metabolomics studies have revealed a consistent defect in bile acid metabolism with an increase in primary bile acids and a reduction in secondary bile acids in IBD patients. This review explores the evolving evidence that specific bile acid metabolites interact with intestinal epithelial and immune cells to contribute to the inflammatory milieu seen in IBD. Furthermore, we summarise evidence linking bile acids with intracellular pathways that are known to be relevant in IBD including autophagy, apoptosis, and the inflammasome pathway. Finally, we discuss how novel experimental and bioinformatics approaches could further advance our understanding of the role of bile acids and inform novel therapeutic strategies in IBD.

• Crohn’s disease
• bile acids
• gut metabolites
• gut microbiome
• immunology and inflammation
• inflammatory bowel disease
• ulcerative colitis

• Chemoprevention
• Colectomy
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/pathology
• Colorectal Neoplasms/diagnostic imaging
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Crohn Disease/epidemiology
• Crohn Disease/pathology
• Endoscopy, Gastrointestinal
• Population Surveillance
• Primary Prevention
• Risk Factors

• IK2 CX002027 CSRD VA

The detection of dysplasia in patients with inflammatory bowel disease (IBD) continues to be important given the increased risk of colorectal cancer in this population. Therefore, in 2017, we performed a review and update of the recommendations for the management and follow-up of patients with IBD based on the clinical practice guidelines of various scientific societies. The present manuscript focuses on new aspects of the detection, follow-up, and management of dysplasia according to the latest studies and recommendations. While chromoendoscopy with targeted biopsy continues to be the technique of choice for the screening and detection of dysplasia in IBD, the associated difficulties mean that it is now being compared with other techniques (virtual chromoendoscopy), which yield similar results with less technical difficulties. Furthermore, the emergence of new endoscopy techniques that are still being researched but seem promising (e.g., confocal laser endomicroscopy and full-spectrum endoscopy), together with the development of devices that improve endoscopic visualization (e.g., Endocuff Vision), lead us to believe that these approaches can revolutionize the screening and follow-up of dysplasia in patients with IBD. Nevertheless, further studies are warranted to define the optimal follow-up strategy in this patient population.

• Colitis surveillance
• Colitis screening
• Chromoendoscopy
• Colorectal cancer
• Inflammatory bowel disease
• Ulcerative colitis

• Colitis/complications
• Colonoscopy/methods
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/etiology
• Early Detection of Cancer/methods
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/pathology

• 5-Aminosalicylic acid
• Chemoprevention
• Colorectal cancer
• Inflammatory bowel disease
• Ulcerative colitis

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid–gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.

• bile acid-activated receptors
• bile acids
• gut microbiota
• inflammatory bowel disease
• therapy

• Animals
• Bile Acids and Salts/metabolism
• Bile Acids and Salts/physiology
• Gastrointestinal Microbiome/physiology
• Humans
• Inflammatory Bowel Diseases/etiology

• Chromoendoscopy
• Colitis-related cancer
• Colorectal cancer
• Dysplasia
• Inflammatory bowel disease
• Ulcerative colitis

• colorectal dysplasia
• magnetic resonance cholangiogram
• normal liver function
• primary sclerosing cholangitis
• ulcerative colitis

• Crohn’s disease
• Extraintestinal manifestations
• axial spondyloarthritis
• diagnosis and follow-up
• primary sclerosing cholangitis
• ulcerative colitis

• sclerosing cholangitis

• Biliary Tract Neoplasms/diagnosis
• Biliary Tract Neoplasms/etiology
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/etiology
• Diagnosis, Differential
• Diagnostic Techniques, Digestive System
• Humans
• Immunoglobulin G4-Related Disease/diagnosis
• Patient Care Management/methods
• Prognosis
• United Kingdom

• Department of Health

• AMPKα
• ASBT inhibitor
• CYP7A1
• NAFLD
• PPARα

• Cholangiocarcinoma
• Cholangiopathy
• Cholestasis
• Primary sclerosing cholangitis (PSC)

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.

• Bile duct diseases
• Cholangiocarcinoma
• Gallbladder carcinoma
• Hepatocellular carcinoma
• Colorectal cancer
• Chemoprotection
• Inflammatory bowel disease

• Biliary Tract Neoplasms/epidemiology
• Biliary Tract Neoplasms/etiology
• Biliary Tract Neoplasms/prevention & control
• Carcinoma/epidemiology
• Carcinoma/etiology
• Carcinoma/prevention & control
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/prevention & control
• Cholangiocarcinoma/epidemiology
• Cholangiocarcinoma/etiology
• Cholangiocarcinoma/prevention & control
• Cholangitis, Sclerosing/complications
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/prevention & control
• Early Detection of Cancer/methods
• Humans
• Inflammatory Bowel Diseases/complications
• Liver Neoplasms/epidemiology
• Liver Neoplasms/etiology
• Liver Neoplasms/prevention & control
• Population Surveillance
• Risk Factors

• Colorectal cancer
• Crohn’s disease
• Inflammatory bowel disease
• Primary sclerosing cholangitis
• Ulcerative colitis

• Cholangitis, sclerosing
• Colorectal neoplasms
• Diagnosis
• Inflammatory bowel disease
• Liver transplantation

• Ambulatory Care/standards
• Child
• Child Nutritional Physiological Phenomena
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/therapy
• Europe
• Female
• Humans
• Male
• Societies, Medical

• cyclooxygenase-2
• epidermal growth factor receptor
• intestinal barrier
• migration
• ursodeoxycholic acid

• Animals
• Bile Acids and Salts/metabolism
• Bile Acids and Salts/pharmacology
• Cell Movement/physiology
• Cholagogues and Choleretics/metabolism
• Cholagogues and Choleretics/pharmacology
• Cyclooxygenase 2/metabolism
• Disease Models, Animal
• Enterocytes/drug effects
• Enterocytes/physiology
• ErbB Receptors/metabolism
• Intestinal Diseases/complications
• Intestinal Diseases/metabolism
• Mice
• Protective Factors
• Sepsis/etiology
• Sepsis/prevention & control
• Ursodeoxycholic Acid/metabolism
• Ursodeoxycholic Acid/pharmacology

• R01 DK095004 NIDDK NIH HHS

• Antibiotics
• Endoscopy
• Novel therapies
• Primary sclerosing cholangitis
• Surveillance
• Ursodeoxycholic acid

• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/therapy
• Humans

• autoimmune cholangitis
• children
• inflammatory bowel disease
• liver transplantation

Bile acids have been implicated in the development of digestive tract malignancy by epidemiological, clinical and animal studies. The growth and transformation signaling by most of the bile acids is thought to be related to the induced cyclooxygenase-2 (COX-2) expression and increased production of prostaglandin E2 (PGE2). The highly hydrophobic bile acids such as chenodeoxycholic acid (CD) and deoxycholic acid can promote carcinogenesis and stimulate the invasion of colon cancer cells. On the contrary, ursodeoxycholic acid (UDCA), a less hydrophobic stereoisomer of CD, inhibits proliferation and induces apoptosis in colon cancer cells. We examined the effects of bile acid on human gastric cancer cells MKN-74.

Early-passage human gastric cancer MKN-74 cells were used for drug treatment, preparation of whole cell lysates, subcellular extracts and Western blot analysis. The levels of PGE2 released by the cells were measured by enzyme inummoassay to indicate COX-2 enzymatic activity. Cellular invasion assay was performed in Boyden chamber.

Exposure of CD led to activation of protein kinase C (PKC) alpha, increased COX-2 expression and increased PGE2 synthesis. The induced COX-2 protein expression could be detected within 4 h exposure of 200 μM CD, and it was dose- and time-dependent. PGE2 is the product of COX-2, and has been reported to cause tumor invasion and angiogenesis in animal study. Safingol (SAF), a PKC inhibitor, suppressed the COX-2 protein expression and PGE2 production by CD in MKN-74. Furthermore, UDCA suppressed PGE2 production by CD but did not affect COX-2 protein expression induced by CD. Using a Boyden chamber invasion assay, both SAF and UDCA impeded CD induced tumor invasiveness of MKN-74 by 30–50%.

Our results indicate that signaling of hydrophobic bile acid such as CD in gastric cancer cells is through PKC activation and COX-2 induction, which leads to increased cellular invasion. By perturbing the bile acid pool, UDCA attenuates CD-induced PGE2 synthesis and tumor invasiveness.

• Bile acid
• Cancer cell invasion
• Chenodeoxycholic acid
• Cyclooxygenase-2
• Gastric cancer
• Prostaglandin E2
• Ursodeoxycholic acid

To investigate the prevalence and causes of cholestasis in patients with inflammatory bowel diseases in the Swiss Inflammatory Bowel Diseases Cohort.

A retrospective cohort study was performed of all the patients in the Swiss Inflammatory bowel disease Cohort. Total bile acid was measured for all patients and cholestasis was defined as a concentration > 8 μmol/L. The characteristics of patients with or without cholestasis were compared. Bile acid profiles were then determined for 80 patients with high total bile acid and 80 matched patients with low total bile acid. Bile acid profiles were compared for smokers vs nonsmokers, ileal vs colonic disease, and inflammatory vs non inflammatory diseases.

Ninety-six patients had more than 8 μmol/L total bile acid, giving a prevalence of 7.15%. Patients with an obvious cause of cholestasis, such as primary sclerosing cholangitis, were then excluded, leaving 1190 participants with total bile acid < 8 μmol/L and 80 with total bile acid > 8 μmol/L. In multivariate analysis, calcium supplementation was significantly associated with cholestasis (odds ratio, 2.36, 95%CI: 1.00-5.21, P = 0.040) whereas current smoking significantly reduced the risk of cholestasis (odds ratio, 0.42, 95%CI: 0.17-0.91, P = 0.041). Levels of all conjugated bile acids were higher in the cholestasis group than in the control group. When we compared patients with ileal vs colonic disease, the former had higher levels of primary, secondary, and tertiary bile acids whereas patients with colonic disease had higher levels of conjugated bile acids.

Prevalence of cholestasis is high. Smoking appears to reduce cholestasis. Conjugated bile acids are higher in cholestasis and in colonic disease whereas unconjugated in ileal disease.

• Lipid
• Liver
• Crohn’s disease
• Ulcerative colitis
• Cholestasis

• Aging
• Amino acid profile
• Hibernation
• Metabolomics
• Methionine pathway
• Methionine restriction
• Naked mole-rat
• Plasma
• Torpor

• Aging/metabolism
• Animals
• Longevity/physiology
• Male
• Mammals
• Metabolomics/methods
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Mole Rats
• Oxidative Stress/physiology
• Rats
• Species Specificity

• T32 AG021890 NIA NIH HHS
• Glenn Foundation for Medical Research
• National Institute on Aging

• biliary tract diseases
• pharmacotherapy
• primary biliary cholangitis
• primary sclerosing cholangitis
• pruritus

• 5 aminosalicylates
• inflammatory bowel disease
• liver transplantation
• primary sclerosing cholangitis
• ursodeoxycholic acid

• Histologic Inflammation
• Inflammatory Bowel Disease
• Mucosal Healing
• Mucosal Inflammation

• Benign biliary stricture
• Cholestasis
• Guidelines
• Primary sclerosing cholangitis
• Sclerosing cholangitis