• analysis
• colorectal cancer
• cost-effectiveness
• screening
• survey

• Crohn's disease
• colorectal cancer
• colorectal polyps
• inflammatory bowel disease
• ulcerative colitis

• Humans
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/genetics
• Female
• Male
• Middle Aged
• Inflammatory Bowel Diseases/pathology
• Inflammatory Bowel Diseases/complications
• Aged
• Colonic Polyps/pathology
• Colonic Polyps/complications
• Retrospective Studies
• Adult

• colorectal cancer
• diet quality
• healthy eating index
• healthy lifestyles
• risk factors

• Animal model
• Colitis-associated cancer
• Colorectal cancer
• Luciferases
• Phosphatidylinositol 3-kinase
• Phosphatidylinositol 3-kinase inhibitor
• Renilla

• Animals
• Mice
• Aminopyridines
• Colitis/chemically induced
• Colitis/complications
• Colitis/drug therapy
• Colitis, Ulcerative/complications
• Colitis-Associated Neoplasms/complications
• Colonic Neoplasms/pathology
• Inflammation/complications
• Luciferases
• Morpholines
• Phosphatidylinositol 3-Kinases/metabolism
• Phosphatidylinositols/adverse effects
• Signal Transduction/genetics

• Saussurea medusa
• anti-inflammatory activity
• iNOS enzyme
• megastigmane
• sesquiterpenoid

• 16S rRNA gene high-throughput sequencing
• Intestinal microbiota
• Radiotherapy
• Rectum
• Therapeutic efficacy

Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.

Background: Inflammatory bowel disease (IBD) is a risk factor in developing colitis-associated colorectal cancer (CA-CRC). CA-CRC causes the death of about 15% IBD patients and the risk is 1.5–2.4 fold higher among IBD sufferers than in the general population. The dysplasia CA-CRC develops in a different mechanism in comparison to sporadic colorectal cancer (CRC). This study aimed at evaluating the surgical treatment and its outcomes as well as 5-year survival rates in the CA-CRC and sporadic CRC patients. Materials and methods: This single-center, retrospective, propensity score-matched case-control study was conducted with 2204 patients operated on due to primary CRC, who were hospitalized from 2003 to 2019. The CA-CRC group consisted of 49 patients with CRC in the course of IBD. The sporadic CRC group was selected with the propensity score matching technique and comprised 98 patients with sporadic CRC who did not have clinical or histopathological features characteristic for IBD. Results: CA-CRC is characterized by a more aggressive clinical course. Surgical treatment of CA-CRC involves more palliative operations and is related with a higher risk of perioperative and postoperative complications. Further studies of CA-CRC risk factor stratification and the development of molecular markers hold promise in reducing CRC in IBD patients in the future were warranted.

• colitis-associated colorectal cancer
• colorectal cancer
• inflammatory bowel diseases

Colorectal cancer (CRC) is a malignancy derived from the glandular epithelial cells in the colon. Patients with inflammatory bowel disease (IBD) are more likely to develop CRC. Cancer proliferation is characterized by the loss of inhibition of apoptosis, which involves caspase-3 activation. This study examined the effects of the pomegranate peel extract on the expression of caspase-3 in mice crypt cells induced by dextran sodium sulfate (DSS) 2%.

The experimental study was done in six groups. All treatments were done in 42 days. The groups were all induced by DSS through water drinking, except for the normal group, which was only given water. The treatments given included the pomegranate extract in two doses (240 mg and 480 mg/kg bw/day), aspirin, and ellagic acid. The specimens were then fixated and stained for the immunohistochemistry scoring for the expression of caspase-3, which was then analyzed statistically.

The H-scores of each treatment group were 213.23 ± 8.32 (DSS group), 243.81 ± 18.69 (normal group), 226.10 ± 12.38 (pomegranate peel extract of 240 mg/kg/d), 238.84 ± 15.81 (pomegranate peel extract of 480 mg/kg/d), 227.47 ± 12.15 (aspirin), and 224.01 ± 18.39 (ellagic acid). Statistical differences were found in one-way analysis of variance (ANOVA) and post hoc analysis among the DSS group, normal group, and dose 2 group (pomegranate peel extract of 480 mg/kg/day).

The ethanol extract of pomegranate was able to induce apoptosis, which was demonstrated by the increase of caspase-3 expression.

• Anxiety
• Cognitive distortion
• Depression
• Inflammatory bowel disease

• Angiogenesis
• Apoptosis
• Autophagy
• Cholangiocarcinoma
• Colon cancer
• Colorectal cancer
• Esophageal cancer
• Gastric cancer
• Gastrointestinal cancers
• Hepatocellular carcinoma
• Inflammation
• Invasion
• Liver cancer
• Melatonin
• Metastasis
• Oral cancer
• Oxidative stress
• Pancreatic cancer
• Proliferation
• Resistance
• Signaling pathway

Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third cause of cancer death in the world, while intestinal microbiota is a community of microbes living in human intestine that can potentially impact human health in many ways. Accumulating evidence suggests that intestinal microbiota, especially that from the intestinal bacteria, play a key role in the CRC development; therefore, identification of bacteria involved in CRC development can provide new targets for the CRC diagnosis, prevention, and treatment. Over the past decade, there have been considerable advances in applying 16S rDNA sequencing data to verify associated intestinal bacteria in CRC patients; however, due to variations of individual and environment factors, these results seem to be inconsistent. In this review, we scrutinized the previous 16S rDNA sequencing data of intestinal bacteria from CRC patients, and identified twelve genera that are specifically enriched in the tumor microenvironment. We have focused on their relationship with the CRC development, and shown that some bacteria could promote CRC development, acting as foes, while others could inhibit CRC development, serving as friends, for human health. Finally, we highlighted their potential applications for the CRC diagnosis, prevention, and treatment.

• 16S rDNA sequencing
• colorectal cancer
• colorectal cancer development
• intestinal microbiota
• tumor microenvironment

• colitis-associated colorectal cancer
• comparative study
• crohn's disease
• inflammatory bowel disease
• ulcerative colitis

• Adult
• Aged
• Canada
• China
• Colitis, Ulcerative/pathology
• Colonoscopy
• Colorectal Neoplasms/pathology
• Crohn Disease/pathology
• Female
• Humans
• Inflammatory Bowel Diseases/pathology
• Male
• Middle Aged

In recent years, there has been a significant increase in the clinical use of organometallic compounds and metal complexes for therapeutic purposes including treatment of inflammatory bowel diseases (IBD). Their action is based on the inhibition of the inflow of pro-inflammatory cytokines, the elimination of free radicals or the modulation of intestinal microbiota. In addition, these compounds are intended for use in the diagnosis and treatment of colorectal cancer (CRC) which is often a consequence of IBD. The aim of this study is to critically discuss recent findings on the use of organometallic compounds and metal complexes in the treatment of IBD and CRC and suggest future trends in drug design.

• colorectal cancer
• free radicals
• inflammatory bowel diseases
• metal complexes
• organometallic compounds

Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.

We analyzed four sets of cancer incidence data from the SEER (USA, 1975–2015), from the Cancer Registry at Mayo Clinic (1970–2015), from Sweden (1970–2015), and from the World Cancer Report in 2012.

We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant.

Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

The online version of this article (10.1186/s12885-019-5902-z) contains supplementary material, which is available to authorized users.

• Cancer incidence
• Human cancers
• Sexual dimorphism

• bioinformatics analysis
• gene
• pathway
• rectal cancer

• Crohn’s disease
• Incidence
• Inflammatory bowel disease
• Prevalence
• Ulcerative colitis

Dysplasia is a precancerous lesion of colorectal cancer in patients with long-standing inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease. Recent guidelines suggest endoscopic resection as a key modality for the treatment of endoscopically resectable dysplasia in patients with colitis. Endoscopic submucosal dissection (ESD) has been suggested as one of the therapeutic options for dysplasia that is potentially resectable but not suitable for the conventional endoscopic mucosal resection technique. Several recent studies supported the feasibility of ESD for the treatment of colitis-associated dysplasia in terms of the en bloc and complete resection rates and the risk of procedure-related complications. However, these studies were performed exclusively in expert centers. Moreover, the local and metachronous recurrence rates were relatively high, and long-term outcome data are still lacking. Endoscopists should be highly skilled in colorectal ESD and have an intensive understanding of not only the lesions but also the conditions of patients with IBDs. Therefore, the decision to perform ESD for colitis-associated dysplasia should be made scrupulously after careful discussion with patients, in collaboration with a multidisciplinary IBD team including physicians, surgeons, and pathologists specialized in IBDs.

• Dysplasia
• Endoscopic submucosal dissection
• Inflammatory bowel disease
• Ulcerative colitis

• NF-kappaB
• colonic neoplasms
• inflammatory bowel disease
• mice
• tauroursodeoxycholic acid

• Colorectal neoplasia
• inflammatory bowel disease
• risk factor

• angiopoietin-2
• chitinase inhibitor
• chitinase-3-like-1 protein
• rectal cancer

Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD.

We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls.

Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn’s disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency.

Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients.

• Deficiency
• Inflammatory bowel diseases
• Selenium
• Vitamin D
• Zinc

• Crohn’s disease
• Epidemiology
• Inflammatory bowel disease
• Ulcerative colitis
• eHealth

Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response.

• Paf15
• cell cycle
• gamma radiation
• prognostic factor
• rectal cancer

A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti–CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09 ± 0.42; P < .001). CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2–positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2–targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.

• Anxiety
• Depression
• Inflammatory bowel diseases

• Colon cancer
• Inflammation
• Microbiota

Patients with inflammatory bowel disease (IBD) are subjected to a large amount of ionizing radiation during the course of their illness. This may increase their risk of malignancy to a greater level than that due to the disease itself. In Caucasian patients with Crohn’s disease, this has been well documented and recommendations are in place to avoid high radiation imaging protocols. However, there are limited data available on radiation exposure in Asian IBD patients. We therefore sought to identify total radiation exposure and any differences between ethnically diverse ulcerative colitis (UC) and Crohn’s disease (CD) patients at our centre along with determining factors that may contribute to any variation.

The cumulative effective dose (CED) was calculated retrospectively from 2000 to 2014 using data from our online radiology database and patients’ medical records. Total CED in the IBD population was measured. High exposure was defined as a radiation dose of greater than 0.2mSv (equivalent to slightly less than ½ a year of background radiation).

A total of 112 cases of IBD (36 CD and 76 UC) were reviewed. Our CD patients were diagnosed at an earlier age than our UC cases (mean age 26.1 vs 45.7). The total CED in our IBD population was 8.53 (95% CI: 4.53-12.52). Patients with CD were exposed to significantly higher radiation compared to those with UC. The mean CED was 18.6 (7.30-29.87) and 3.65 (1.74-5.56, p=0.01) for CD and UC patients respectively. 2 patients were diagnosed as having a malignancy during follow up with respective CED values of 1.76mSv and 10mSv.

CD patients, particularly those with complicated disease, received a higher frequency of diagnostic imaging over a shorter period when compared to UC patients. Usage of low radiation imaging protocols should be encouraged in IBD patients to reduce their risk of consequent malignancy.

• Inflammatory bowel disease
• Crohn’s disease
• computerized tomography
• magnetic resonance imaging

• Carcinoma
• Colorectal neoplasms
• Crohn’s disease
• Mucinous
• Rectal fistula

• Adenocarcinoma, Mucinous/etiology
• Adenocarcinoma, Mucinous/pathology
• Adolescent
• Adult
• Carcinoma, Signet Ring Cell/etiology
• Carcinoma, Signet Ring Cell/pathology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/pathology
• Crohn Disease/complications
• Crohn Disease/pathology
• Female
• Humans
• Male
• Middle Aged
• Neuroendocrine Tumors/etiology
• Neuroendocrine Tumors/pathology
• Republic of Korea
• Young Adult

Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC.

Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003–2013. We performed a retrospective cohort study of 2137 patients with UC.

In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC.

Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.

• COLORECTAL CANCER
• SURVEILLANCE
• ULCERATIVE COLITIS

• COLORECTAL CANCER
• CROHN'S DISEASE
• ULCERATIVE COLITIS

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. In previous epidemiologic studies, the respective correlation between lifestyle factors and comorbidity and CRC has been extensively studied. However, little is known about their joint effects on CRC.

We conducted a retrospective case-control study of 1,144 diagnosed CRC patients and 60,549 community controls. A structured questionnaire was administered to the participants about their socio-demographic factors, anthropometric measures, comorbidity history and lifestyle factors. Logistic regression model was used to calculate the odds ratio (ORs) and 95% confidence intervals (95%CIs) for each factor. According to the results from logistic regression model, we further developed healthy lifestyle index (HLI) and comorbidity history index (CHI) to investigate their independent and joint effects on CRC risk.

Four lifestyle factors (including physical activities, sleep, red meat and vegetable consumption) and four types of comorbidity (including diabetes, hyperlipidemia, history of inflammatory bowel disease and polyps) were found to be independently associated with the risk of CRC in multivariant logistic regression model. Intriguingly, their combined pattern- HLI and CHI demonstrated significant correlation with CRC risk independently (OR_HLI: 3.91, 95%CI: 3.13–4.88; OR_CHI: 2.49, 95%CI: 2.11–2.93) and jointly (OR: 10.33, 95%CI: 6.59–16.18).

There are synergistic effects of lifestyle factors and comorbidity on the risk of colorectal cancer in the Chinese population.

• Adult
• Aged
• Aged, 80 and over
• Anthropometry
• Asian People
• Case-Control Studies
• China/epidemiology
• Colonic Polyps/epidemiology
• Colorectal Neoplasms/epidemiology
• Comorbidity
• Diabetes Mellitus/epidemiology
• Diet
• Female
• Humans
• Hyperlipidemias/epidemiology
• Inflammatory Bowel Diseases/epidemiology
• Life Style
• Male
• Meat
• Middle Aged
• Motor Activity/physiology
• Retrospective Studies
• Risk Factors
• Sleep/physiology
• Socioeconomic Factors
• Surveys and Questionnaires
• Vegetables
• Young Adult

Inflammation is the basis of severe acute and chronic diseases. This study investigated the anti-inflammatory property of a crude methanol extract (MeOH-ex) and the solvent fractions of Ixeris dentata Nakai (IDN) in LPS-stimulated murine macrophage-like cell line RAW264.7. Here, we showed that the ethyl acetate fraction (EtOAc-fr) had the most potent inhibitory activity on LPS-induced nitric oxide (NO) production among the tested samples, i.e., IDN MeOH-ex and the three different solvent fractions (chloroform, n-hexane, and EtOAc). We further found that the EtOAc-fr significantly inhibited LPS-induced prostaglandin PGE2 (PGE₂) generation in RAW264.7 cells. Furthermore, the treatment with EtOAc-fr effectively suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). These results suggest that the EtOAc-fr of IDN MeOH-ex exhibits an anti-inflammatory activity in vitro by inhibiting LPS-induced NO production and PGE₂ generation via suppression of iNOS and COX-2 expression.

• COX-2
• Inflammation
• Ixeris dentate Nakai
• Nitric oxide
• Prostaglandin E2
• iNOS

• Colorectal cancer
• Liver cancer
• Risk factor
• Screening
• Stomach cancer

• Chemoprevention
• Chemotherapeutics
• Clinical trials
• Molecular targeted prevention
• Phytoceuticals

• Asia
• Colorectal Neoplasms/prevention & control
• Esophageal Neoplasms/prevention & control
• Gastrointestinal Neoplasms/prevention & control
• Humans
• Molecular Targeted Therapy/methods
• Phytotherapy/methods
• Stomach Neoplasms/prevention & control

• As4S4
• JQ1
• celecoxib
• cisplatin
• colon cancer
• gastric cancer
• irinotecan

Inflammatory bowel disease (IBD) is defined as a chronic and relapsing inflammatory disorder of the intestine. Intestinal inflammation in IBD has been proposed to be attributable to the interplay between microbial, genetic, environmental, and immunological factors. The incidence and prevalence rates of IBD are rapidly increasing apparently in other parts of the world, with dramatic increases especially in East Asia. Generally, cohort studies are useful for estimating the incidence, prevalence, natural course, prognosis, and risk factors of diseases. In particular, cohort studies performed in Western countries have well described the prevalence, risk factors, and natural course of IBD and investigated its genetic pathophysiology. However, the outcomes of IBD cohort studies performed in Korea are not as persuasive as those of Western studies because of the relatively low prevalence of IBD and short follow-up periods of the cohorts in Korea. Despite this critical limitation, members of the Korean Association for the Study of Intestinal Diseases have demonstrated outstanding results. Some unique features of IBD patients in Korea are well demonstrated, such as thiopurine-induced leukopenia or risks of opportunistic tuberculosis infection in patients receiving tumor necrosis factor-α inhibitors. In this review, the present authors summarized the key points of the results of the cohort studies performed in Korea and explored future perspectives.

• Cohort studies
• Inflammatory bowel diseases
• Korea

• Crohn’s disease
• clinical outcome
• rural environment
• urban environment

• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Copper/blood
• Copper/pharmacokinetics
• Erythrocytes/analysis
• Female
• Hepatolenticular Degeneration/diagnosis
• Humans
• Infant
• Male
• Menkes Kinky Hair Syndrome/diagnosis
• Middle Aged
• Neutropenia/diagnosis
• Osteoporosis/diagnosis
• Reference Values
• Specimen Handling