• Hepatobiliary disease
• Inflammatory bowel disease
• Microbiota
• Randomised Controlled Trial

• Adult
• Female
• Humans
• Male
• Cholangitis, Sclerosing/therapy
• Clinical Trials, Phase II as Topic
• Fecal Microbiota Transplantation/methods
• Gastrointestinal Microbiome
• Inflammatory Bowel Diseases/therapy
• Inflammatory Bowel Diseases/microbiology
• Multicenter Studies as Topic
• Randomized Controlled Trials as Topic
• Treatment Outcome

• PSC Support
• LifeArc

• Diagnosis
• Mayo endoscopic subscore
• Nancy histological index
• Primary sclerosing cholangitis
• Ulcerative colitis

• Allograft allocation
• Artificial intelligence
• Liver transplantation
• Machine learning models
• Prognostication

• Diagnosis
• Epidemiology
• Presentation
• Primary sclerosing cholangitis

• Humans
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/epidemiology
• Liver Cirrhosis
• Liver Diseases
• Autoimmune Diseases

• Cholangitis, sclerosing
• Colitis, ulcerative
• India
• Inflammatory bowel diseases
• Prevalence

• Gut microbiota
• bile acids
• colitis-associated colorectal cancer
• crohn’s disease
• dysplasia
• inflammatory bowel disease
• ulcerative colitis

• Colorectal cancer
• Crohn’s disease
• Epidemiology of colorectal cancer
• Inflammatory bowel disease
• Risk of colorectal cancer
• Ulcerative colitis

• cancer risk
• inflammatory bowel disease
• molecular biomarkers
• molecular risk factors
• risk factors

• 19771 Cancer Research UK

• Adenomatous Polyposis Coli/genetics
• Adenomatous Polyposis Coli/pathology
• Adolescent
• Adult
• Child
• Child, Preschool
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/pathology
• Female
• Humans
• Male
• Tumor Suppressor Protein p53/genetics
• Young Adult

• Z01 BC010833 Intramural NIH HHS
• Z01 BC010835 Intramural NIH HHS

• Cholangiocellular carcinoma
• HPB-surgery
• Liver resection
• Liver transplantation
• PSC
• Primary sclerosing cholangitis

• Crohn's disease
• IBD
• colorectal cancer
• dysplasia
• surgery
• surveillance
• ulcerative colitis

• Colitis-Associated Cancer
• Colon Cancer
• Genetics
• PSC
• SIRs

Comorbid primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) represent a unique disease phenotype with a different risk profile than PSC or IBD alone. While the pathogenetic mechanisms behind both diseases remain unclear, recent studies have targeted several immune-mediated pathways in an attempt to find a potential therapeutic target. Patients with PSC-associated IBD typically exhibit pancolitis with a right-to-left intestinal inflammatory gradient associated with a greater incidence of backwash ileitis and rectal sparing. Although there is an increased incidence of pancolitis in this population, bowel symptoms tend to be less significant than in IBD alone. Likewise, the degree of inflammation and symptoms of PSC-associated IBD are characteristically less clinically significant. Despite the relatively quiescent clinical presentation of PSC-associated IBD, there is an increased risk for colorectal and hepatobiliary malignancy making vigilance for malignancy essential.

• Crohn’s disease
• Primary sclerosing cholangitis
• inflammatory bowel disease
• ulcerative colitis

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

• Colon Cancer
• Crohn’s Disease
• Primary Sclerosing Cholangitis
• Surveillance
• Ulcerative Colitis

• inflammatory bowel disease
• primary sclerosing cholangitis
• liver tranpslant

• lymphocyte trafficking
• anti-α₄β₇ integrin
• vedolizumab
• primary sclerosing cholangitis
• inflammatory bowel disease

• Ah-receptor
• Flavonoids
• Inflammatory bowel disease

• Aryl Hydrocarbon Receptor Nuclear Translocator/immunology
• Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
• Cell Nucleus/immunology
• Cell Nucleus/metabolism
• Cytokines/immunology
• Cytokines/metabolism
• Flavonoids/immunology
• Flavonoids/therapeutic use
• Humans
• Immune System/drug effects
• Immunosuppressive Agents/immunology
• Immunosuppressive Agents/therapeutic use
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/immunology
• Intestines/drug effects
• Intestines/immunology
• Phytochemicals/immunology
• Phytochemicals/therapeutic use
• Receptors, Aryl Hydrocarbon/immunology
• Receptors, Aryl Hydrocarbon/metabolism
• Up-Regulation

Ulcerative colitis(UC) is important risk factor of colorectal cancer. Many evidences from western countries confirmed this relationship but limited studies were reported in ASEAN. This study was aimed to investigate prevalence, clinical presentations, endoscopic findings, histopathology, disease progression and risk for colorectal cancer(CRC) of UC patients in Thailand.

We conducted a retrospective cohort study using computer data base from Thammasat University Hospital, Pathumthani, Thailand between September 2011 and December 2015, follow-up through May 2016. Diagnosis of UC was confirmed by histopathology and whole clinical course.

We identified 6,082 patients who diagnosed with colitis during the study period. Of whom, only 22 patients(<1%) was confirmed of UC. Male to female ratio was 13:9 (mean age of 47.2 years). Clinical presentations were bloody diarrhea in 86.4%, watery diarrhea in 31.8% and abdominal pain in 59.1%. According to Montreal classification, disease extensions were ulcerative proctitis in 22.7%, distal UC in 50%, and pancolitis in 27.3%. Disease grading was mild in 31.8%, moderate in 9.1%, and severe in 59.1%. The prevalence of precancerous lesions were 2/22 patients(9.1%). There was no definite invasive colorectal cancer patient during study period. However, history of malnutrition was significantly higher in patients with dysplasia than those without dysplastic lesions(50%vs.0%, P-value=0.045). There was no difference in duration and disease extension between 2 groups. Interestingly, subgroup analysis demonstrated that pancolitis was significantly more common in female than male (55.6%vs.7.7%, P-value=0.02, OR=15.0, 95%CI=1.3-169.9). Furthermore, patients’ age> 35 years had significantly more severe colitis than younger group (81.25%vs.0%, P-value=0.0006)

Although UC is rare disease in ASEAN, precancerous lesions for CRC were not uncommon. UC with pancolitis was common in female whereas severe colitis was common in elderly patients. Proper screening program and careful surveillance for precancerous lesions in patients at risk might be appropriate approach for early detection and improvement the treatment outcome.

• Colorectal cancer
• ulcerative colitis
• Thailand

• Colorectal cancer
• Crohn’s disease
• Inflammatory bowel disease
• Ulcerative colitis

• Crohn’s disease
• Surveillance
• carcinoma
• colonoscopy
• colorectal cancer
• ulcerative colitis

• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/etiology
• Crohn Disease/complications
• Crohn Disease/diagnosis
• Humans
• Observational Studies as Topic
• Risk Assessment
• Risk Factors

• Colitis
• Inflammatory bowel disease
• Proctectomy
• Proctocolectomy
• Rectal cancer

Inflammatory bowel disease (IBD) is associated with increased risk of colorectal cancer (CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and inter-observer variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients’ morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes.

• Inflammatory bowel disease
• Dysplasia
• Colorectal cancer
• Endoscopy
• Surveillance
• Colectomy

• Anti-Inflammatory Agents/therapeutic use
• Colectomy/adverse effects
• Colectomy/methods
• Colonoscopy/adverse effects
• Colorectal Neoplasms/diagnostic imaging
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Early Detection of Cancer
• Gastrointestinal Agents/therapeutic use
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/drug therapy
• Neoplasm Staging
• Postoperative Complications/etiology
• Predictive Value of Tests
• Risk Factors
• Treatment Outcome

• Colorectal neoplasms
• Crohn disease
• Inflammatory bowel diseases
• Liver transplantation
• Sclerosing cholangitis
• Ulcerative colitis

• Crohn’s disease
• IBD-associated cancer
• biologics
• colorectal cancer
• inflammatory bowel disease
• lymphoma
• skin cancer
• thiopurines
• ulcerative colitis

Background and aim: Crohn’s colitis (CC) is associated with primary sclerosing cholangitis (PSC). However the risk of colon cancer or dysplasia in CC and PSC is unclear. Our aim was to study the risk of colon neoplasia in CC in patients with and without PSC.

Methods: This is a nested, case-control cohort study of all patients diagnosed with concurrent CC and PSC, seen at the Cleveland Clinic between 1985 and 2012. Forty-three patients with both CC and PSC were compared with a random sample of 159 CC controls without PSC during the same period.

Results: Seven (16.3%) of 43 CC patients with PSC developed colon cancer or dysplasia, compared with 22 (13.8%) of 159 controls (P = 0.98). Of seven colon neoplasia cases in the PSC group, 100% occurred proximal to the splenic flexure, compared with 50% (11/22) cases of colon neoplasia in controls occurring in the proximal colon (P = 0.001). Based on Cox regression analysis, male gender independently increased the risk of neoplasia [hazard ratio (HR) = 2.68; 95% confidence interval (CI) 1.30–5.54; P = 0.008], as did age at CC diagnosis (HR = 1.29; 95% CI 1.14–1.47; P < 0.001), while the use of azathioprine/6-mercaptopurine was protective (HR = 0.30; 95% CI 0.13–0.70; P = 0.005). The presence of PSC did not increase the risk for colon neoplasia (HR = 0.45; 95% CI 0.18–1.13; P = 0.09).

Conclusions: CC patients with PSC appear not to be at increased risk of developing colon neoplasia. Among patients in our cohort with colon neoplasia and concurrent PSC, the neoplasia occurred in the proximal colon in all cases.

• Crohn’s colitis
• colon neoplasia
• primary sclerosing cholangitis

The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.

• Ulcerative colitis-associated colorectal cancer
• Risk factor
• Dysplasia
• Surveillance colonoscopy
• Chemoprevention

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Anticarcinogenic Agents/therapeutic use
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/drug therapy
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/prevention & control
• Early Detection of Cancer/methods
• Humans
• Predictive Value of Tests
• Prognosis
• Risk Assessment
• Risk Factors

• Chemoprevention
• Colonic neoplasms
• Inflammatory bowel diseases
• Surveillance colonoscopy

Background: The comparative outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) in patients with primary sclerosing cholangitis (PSC) are unclear; the aim of our study was to make an objective comparison.

Methods: A total of 273 patients with PSC and inflammatory bowel disease (223 with UC and 50 with CD) were included. Clinical and demographic variables were obtained.

Results: The PSC risk score was similar for both groups. The median follow-up period in patients with PSC-UC was 12 years (range 0–38) and that for PSC-CD was 14 years (range 1–36). The median number of disease flares per year was higher in PSC-UC patients than in the PSC-CD group [1vs.0 (ranges 0–20 and 0–9, respectively); P < 0.001]. More patients with UC developed colon neoplasia than CD (35.9% vs.18%; P = 0.009). On proportional hazards analysis for the risk of colectomy, UC patients had a 12% higher risk for colectomy [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.51–1.51; P = 0.64]. Liver transplantation for PSC was associated with decreased risk (HR = 0.57; 95% CI 0.37–0.89; P = 0.013), while colon neoplasia increased the risk (HR = 3.83; 95% CI 2.63–5.58; P < 0.001) for colectomy. On proportional hazards analysis for the risk of colon neoplasia, UC patients had 56% higher risk of developing colon neoplasia than CD (HR = 0.44; 95% CI 0.16–1.25; P = 0.12).

Conclusions: PSC patients with CD appear to be associated with a lower risk of colon neoplasia and colectomy than PSC patients with UC.

• Crohn’s disease
• colectomy
• colon neoplasia
• liver transplantation
• primary sclerosing cholangitis
• ulcerative colitis

• Crohn's disease
• Inflammatory bowel disease
• dysplasia
• ulcerative colitis

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is activated in cells exposed to various stimuli, including those originating on the cell surface or in the nucleus. Activated NF-κB signaling is thought to enhance cell survival in response to these stimuli, which include chemotherapy and radiation. In the present effort, we determined which anticancer drugs preferentially activate NF-κB in colon cancer cells.

NF-κB reporter cells were established and treated with 5-fluorouracil (5-FU, DNA/RNA damaging), oxaliplatin (DNA damaging), camptothecin (CTP, topoisomerase inhibitor), phleomycin (radiomimetic), or erlotinib (EGFR inhibitor). The activation of NF-κB was assessed by immunofluorescence for p65 translocation, luciferase assays, and downstream targets of NF-κB activation (cIAP2, and Bcl-X_L) were evaluated by immunoblotting, by ELISA (CXCL8 and IL-6 in culture supernatants), or by gene expression analysis.

Colon cancer cells responded variably to different classes of therapeutic agents, and these agents initiated variable responses among different cell types. CPT activated NF-κB in SW480 colon cancer cells in a dose-dependent manner, but not in HCT116 cells that were either wild-type or deficient for p53. In SW480 colon cancer cells, NF-κB activation by CPT was accompanied by secretion of the cytokine CXCL8, but not by up-regulation of the anti-apoptotic genes, cIAP2 or Bcl-X_L. On the contrary, treatment of HCT116 cells with CPT resulted in up-regulation of CXCR2, a receptor for CXCL8, without an increase in cytokine levels. In SW480 cells, NF-κB reporter activity, but not cytokine secretion, was inhibited by SM-7368, an NF-κB inhibitor.

The results show that, in response to cancer therapeutic agents, NF-κB activation varies with the cellular make up and that drug-induced NF-κB activation may be functionally uncoupled from anti-apoptotic outcomes found for other stimuli. Some cancer cells in a heterogeneous tumor tissue may, under therapeutic pressure, release soluble factors that have paracrine activity on neighboring cells that express the cognate receptors.

The online version of this article (doi:10.1186/1471-2407-14-599) contains supplementary material, which is available to authorized users.

• canada
• crohn disease
• delivery of health care
• process assessment
• quality indicators
• ulcerative colitis

• Canada
• Humans
• Inflammatory Bowel Diseases/therapy
• Quality Indicators, Health Care
• Quality of Health Care/standards

• Canadian Institutes of Health Research

• Cholangiocarcinoma
• Cholestasis
• Liver transplantation
• Primary sclerosing cholangitis

• Ulcerative colitis
• colorectal cancer
• mortality
• natural history

• 5-ASA
• 5-aminosalicylic acid
• ACG
• American College of Gastroenterology
• CD
• Crohn's disease
• DALM
• Flat dysplasia;
• HGD
• IBD
• IC
• LGD
• Low grade dysplasia;
• PSC
• Primary sclerosing cholangitis
• UC
• Ulcerative colitis;
• dysplasia associated lesion or mass
• high grade dysplasia
• indeterminate colitis
• inflammatory bowel disease
• low grade dysplasia
• primary sclerosing cholangitis
• ulcerative colitis

• BMI
• CD
• CRC
• Colonoscopy
• Crohn's disease
• Dysplasia
• HGD
• IBD
• Inflammatory bowel disease
• LGD
• Random biopsies
• UC
• Ulcerative colitis
• aOR
• adjusted odds ratio
• body mass index
• colorectal cancer
• high grade dysplasia
• inflammatory bowel disease
• low grade dysplasia
• ulcerative colitis

• Autoimmune hepatitis
• Clinical outcomes
• Immunoglobulin g4
• Overlap syndromes
• Primary biliary cirrhosis
• Primary sclerosing cholangitis

• colorectal carcinoma
• disease duration
• epithelial dysplasia
• inflammation activity
• inflammatory bowel disease
• risk factors

• Algorithms
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Colitis, Ulcerative/classification
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/physiopathology
• Colonic Pouches
• Humans
• Mesalamine/therapeutic use
• Proctocolectomy, Restorative