Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

MicroRNA expression in inflammatory bowel disease-associated colorectal cancer

MicroRNAs(miRNAs)are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders,including inflammatory bowel diseases(IBD).IBD,represented by ulcerative colitis and Crohn’s disease,is characterized by chronic intestinal inflammation associated with an increased risk of colorectal cancer(CRC).CRC is one of the most prevalent tumors in the world,and its main risk factors are obesity,physical inactivity,smoking,alcoholism,advanced age,and some eating habits,in addition to chronic intestinal inflammatory processes and the use of immunosuppressants administered to IBD patients.Recent studies have identified miRNAs associated with an increased risk of developing CRC in this population.The identification of miRNAs involved in this tumorigenic process could be useful to stratify cancer risk development for patients with IBD and to monitor and assess prognosis.Thus,the present review aimed to summarize the role of miRNAs as biomarkers for the diagnosis and prognosis of IBD-associated CRC.In the future,therapies based on miRNA modulation could be used both in clinical practice to achieve remission of the disease and restore the quality of life for patients with IBD,and to identify the patients with IBD at high risk for tumor development.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada

Background:Colorectal cancer(CRC)has become one of the major life-threatening complications in patients with inflammatory bowel disease(IBD),which includes ulcerative colitis(UC)and Crohn's disease(CD).This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associ吐ed CRC(IBD-CRC)between patients in China and Canada.Methods:Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing(China)and Calgary(Canada)over the same past 13 years,including 25(22 UC-associated and three CD-associated)from Beijing group and 53(32 UC-associated and 21 CD-associated)from Calgary group,were compared with regards to their clinical and pathologic characteristics.Results:Several known features of IBD-CRC were seen in both groups,including long duration and large extent of colitis,active inflammation background,multifocal lesions,and advanced tumor-node-metastasis stage.Beijing group showed a significantly higher percentage of UC(88.0%vs.60.4%,P=0.018),younger age at diagnosis of CRC(48.6±12.8 years vs.61.6±14.7 years,P<0.001),lower ratio of mucinous adenocarcinoma(7.1%us.42.4%,P=0.001)compared with Calgary group.None of the Beijing group had concurrent primary sclerosing cholangitis,while 5.7%of Calgary group did.Surveillance colonoscopy favored the detection rate of precancerous lesions(41.4%vs.17.0%,P=0.002).Conclusions:As compared with patients from the Calgary group,the IBD-CRC patients in Beijing group were younger,less CDassociated and had less mucinous features,otherwise they were similar in many common features.

Colorectal cancer surveillance in inflammatory bowel disease:Practice guidelines and recent developments

Patients with long-standing inflammatory bowel disease(IBD)involving at least 1/3 of the colon are at increased risk for colorectal cancer(CRC).Advancements in CRC screening and surveillance and improved treatment of IBD has reduced CRC incidence in patients with ulcerative colitis and Crohn’s colitis.Most cases of CRC are thought to arise from dysplasia,and recent evidence suggests that the majority of dysplastic lesions in patients with IBD are visible,in part thanks to advancements in high definition colonoscopy and chromoendoscopy.Recent practice guidelines have supported the use of chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies.Endoscopists are encouraged to endoscopically resect visible dysplasia and only recommend surgery when a complete resection is not possible.New technologies such as virtual chromoendoscopy are emerging as potential tools in CRC screening.Patients with IBD at increased risk for developing CRC should undergo surveillance colonoscopy using new approaches and techniques.

Colorectal cancer in inflammatory bowel disease:The risk,pathogenesis,prevention and diagnosis

Patients with inflammatory bowel disease(IBD)are at increased risk for developing colorectal cancer(CRC),although the overall incidence of IBD-associated CRC has been diminishing in recent decades in western countries.As demonstrated in previous studies,the risk of CRC in IBD increases with longer duration,extent of colitis,a familial history of CRC,coexistent primary sclerosing cholangitis,and the degree of inflammation.The pathogenesis of CRC in IBD is poorly understood.Similar to sporadic CRC,IBD-associated CRC is a consequence of sequential episodes of genomic alteration.Multiple inter-related pathways,including immune response by mucosal inflammatory mediators,oxidative stress,and intestinal microbiota,are also involved the pathogenesis of IBD-associated CRC.Continuing colonic inflammation appears to be a factor in the development of CRC;therefore,anti-inflammatory agents such as5-aminosalicylate compounds and immune modulators have been considered as potential chemopreventive agents.Colonoscopic surveillance is widely accepted as being effective in reducing the risk of IBD-associated CRC,although no clear evidence has confirmed that surveillance colonoscopy prolongs survival in patients with extensive colitis.The traditional recommendation has been quadrantic random biopsies throughout the entire colon;however,several guidelines now have endorsed chromoendoscopy with a target biopsy because of increasing diagnostic yields and reduced workloads for endoscopists and pathologists.New technologies such as narrow band imaging,confocal endomicroscopy,and autofluorescence imaging have not yet been confirmed as surveillance strategies in IBD.

Has the risk of colorectal cancer in inflammatory bowel disease decreased?

The association between inflammatory bowel disease(IBD)and colorectal cancer(CRC)has been acknowledged for almost a century and is assumedly promoted by a chronic inflammation-driven carcinogenic process in the intestine in combination with a genetic predisposition.The magnitude of the risk of CRC in IBD remains a continuing subject of debate.The early,high risk estimates for CRC in IBD were most likely overestimated due to selected patient populations originating from tertiary referral centers with a disproportional high percentage of patients with severe disease.Later population-based studies calculating risk estimates from a broad spectrum of IBD patients have found the risk to be significantly lower.At present,there is evidence that IBD patients with longstanding and extensive disease with uncontrolled inflammation are those at increased risk.Additional,other recognized risk factors include early age at onset,family history of CRC,and concomitant primary sclerosing cholangitis.A significant amount of effort is put into identifying potential preventive factors of CRC in IBD,including surveillance programs and chemopreventive agents but the individual effect of these remains uncertain.Interestingly,recent studies have reported a decline in risk of CRC over time.Surveillance programs and the new treatment strategies,particular biological treatment might be part of the reason for the observed decline in risk of CRC in IBD over time but future studies will have investigate this assumption.

Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

AIM: To determine whether aspirin or non-aspirin nonsteroidal anti-inflammatory drugs(NA-NSAIDs) prevent colorectal cancer(CRC) in patients with inflammatory bowel disease(IBD).METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NANSAID use. Pooled odds ratios(OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger's test. Heterogeneity was assessed using Cochran's Q and the I2 statistic.RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80(95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66(95%CI: 0.06-1.39). There was significant heterogeneity(I2 > 50%) between the studies. There was no change in the effect estimates on subgroup a na ly s e s o f t he po pulat io n s t udie d o r w he t he r adjustment or matching was performed.CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

Gut microbiota,inflammatory bowel disease and colorectal cancer

The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the host.Dysbiosis,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and carcinogenesis.The increase in some specific groups of harmful bacteria,such as Escherichia coli(E.coli)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD patients.Therefore,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated CRC.Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand Bacteroidetes.Specific bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,E.coli,Enterococcus faecalis,Streptococcus gallolyticus,and ETBF.Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.

Colorectal cancer surveillance in patients with inflammatory bowel disease: What's new?

Several studies assessing the incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients have found an increased risk globally estimated to be 2 to 5 times higher than for the general population of the same age group. The real magnitude of this risk, however, is still open to debate. Research is currently being carried out on several risk and protective factors for CRC that have recently been identified in IBD patients. A deeper understanding of these factors could help stratify patient risk and aid specialists in choosing which surveillance program is most efficient. There are several guidelines for choosing the correct surveillance program for IBD patients; many present common characteristics with various distinctions. Current recommendations are far from perfect and have important limitations such as the fact that their efficiency has not been demonstrated through randomized controlled trials, the limited number of biopsies performed in daily endoscopic practice, and the difficulty in establishing the correct time to begin a given surveillance program and maintain a schedule of surveillance. That being said, new endoscopic technologies should help by replacing random biopsy protocols with targeted biopsies in IBD patients, thereby improving the efficiency of surveillance programs.However, further studies are needed to evaluate the cost-effectiveness of introducing these techniques into daily endoscopic practice.

Inflammatory bowel disease-related colorectal cancer:Past,present and future perspectives

Inflammatory bowel disease-related colorectal cancer(IBD-CRC)is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients.IBD is often associated with diet and lifestyle-related gut microbial dysbiosis,the interaction of genetic and environmental factors,leading to chronic gut inflammation.According to the“common ground hypothesis”,microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC.Among the many underlying factors known to increase the risk of IBD-CRC,perhaps the most important factor is chronic persistent inflammation.The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability.Multiple pathways have been identified,regulated by many positive and negative factors involved in the development of cancer,which in this case follows the‘inflammation-dysplasia-carcinoma’sequence.Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC,among which colonoscopic surveillance is the most widely accepted and implemented modality,forming part of many national and international guidelines.However,the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons—cost-benefit to health systems,resource requirements,and also because of studies showing conflicting long-term data.Our review provides a comprehensive overview of past,present,and future perspectives of IBD-CRC.We explore and analyse evidence from studies over decades and current best practices followed globally.In the future directions section,we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.

Colorectal cancer in inflammatory bowel disease:What is the real magnitude of the risk?

The association between inflammatory bowel disease(IBD) and colorectal cancer(CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in IBD.IBD-associated CRC(IBD-CRC) affects patients at a younger age than sporadic CRC.The prognosis for sporadic CRC and IBD-CRC is similar,with a 5-year survival of approximately 50%.Identifying at risk patients and implementing appropriate surveillance for these patients is central to managing the CRC risk in IBD.The increased risk of colorectal cancer in association with IBD is thought to be due to genetic and acquired factors.The link between inflammation and cancer is well recognised but the molecular biology,immune pathobiology and genetics of IBD-CRC are areas of much ongoing research.This review examines the literature relating to IBD-CRC,focusing on the incidence of IBD-CRC and examining potential risk factors including age at diagnosis,gender,duration and extent of colitis,severity of inflammation,family history of sporadic CRC and co-existent primary sclerosing cholangitis(PSC).Confirmed risk factors for IBD-CRC are duration,severity and extent of colitis,the presence of co-existent PSC and a family history of CRC.There is insufficient evidence currently to support an increased frequency of surveillance for patients diagnosed with IBD at a younger age.Evidence-based guidelines advise surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis,with the interval for further surveillance guided by risk factors(extent of disease,family history of CRC,post-inflammatory polyps,concomitant PSC,personal history of colonic dysplasia,colonic strictures).There is a move away from using random colonic biopsies towards targeted biopsies aimed at abnormal areas identified by newer colonoscopic techniques(narrow band imaging,chromoendoscopy,confocal microendoscopy).

Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease

AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticulitis. METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium (4.94 and 5.91 vs 6.96 log Cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis. CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

Screening for colorectal cancer in patients with inflammatory bowel disease. Should we already perform chromoendoscopy in all our patients?

Patients with inflammatory bowel disease(commonly known as IBD) have a greater risk of colorectal cancer than the general population. Therefore, they are included in special programs for screening and followup. Chromoendoscopy, which has a high diagnostic yield in the detection of neoplasia, is generally the recommended endoscopy technique. However, this procedure does have some disadvantages(long examination time, need for optimal bowel preparation, specialist training), which increase its cost. How then can we overcome these barriers? First, it is necessary to educate hospital managers and directors of the advantages of chromoendoscopy in patients with IBD. Second, at least one endoscopist per center should be a specialist in the technique. Third, we should train nursing staff in the preparation of the dye. Finally, each examination should be given the time it needs. Even though clinical practice guidelines do not yet recommend the use of virtual imaging techniques such as narrow band imaging, a recent study reported no differences between the two approaches for the detection of tumors. Therefore, we believe that all patients should undergo chromoendoscopy. In the future, centers without access to dyes or where other barriers exist should at least perform narrow band imaging.

Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes

Patients with inflammatory bowel disease(IBD)have an increased risk of 10%-15%developing colorectal cancer(CRC)that is a common disease of high economic costs in developed countries.The CRC has been increasing in recent years and its mortality rates are very high.Multiple biological and biochemical factors are responsible for the onset and progression of this pathology.Moreover,it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health.The gut microflora,or microbiota,has an extensive diversity both quantitatively and qualitatively.In utero,the intestine of the mammalian fetus is sterile.At birth,the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms,ultimately developing into a stable community,with marked variations in microbial composition between individuals.The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora(dysbiosis).The healthy human gut harbours about10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract.The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC.In healthy subjects,the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature,competition between different bacterial strains,peristalsis and drugs can influence the intestinal microenvironment.The microbiota exerts diverse physiological functions to include:growth inhibition of pathogenic microorganisms,synthesis of compounds useful for the trophism of colonic mucosa,regulation of intestinal lymphoid tissue and synthesis of amino acids.Furthermore,mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity.Changes in the microbiota composition are mainly influenced by diet and age,as well as genetic factors.Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response whichpromotes and sustains inflammation in IBD leading to carcinogenesis.A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue.The associated chronic inflammatory process associated increases the risk of developing CRC.Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations,such as rheumatoid arthritis.The pathogenesis of both diseases is complex and not yet fully known.However,it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.

Colorectal cancer surveillance in inflammatory bowel disease: The search continues

Patients with infl ammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease, age at time of diagnosis, severity of inflammation, family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately, surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy, and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management. Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes. Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC.

Colorectal cancer screening and surveillance in patients with inflammatory bowel disease in 2021

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.

Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: A review of the literature

To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer(CRC) development in inflammatory bowel disease(IBD)-primary sclerosing cholangitis(PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review. Recent evidence increasingly points to PSC as a significant risk factor in the development of CRC in patients with concomitant IBD. PSC may be an important risk factor for CRC in different populations worldwide. The mechanism for this increase in risk is still unclear. The efficacy of UDCA as a chemopreventive agent remains controversial. Liver transplantation does not halt the development of CRC, although there is not enough evidence to suggest that it is associated with increased incidence of CRC. While routine colonoscopic surveillance should be performed in patients with concurrent PSC and IBD, more high-level evidence is required to support the benefits of the procedure. While many new developments have taken place in the last decade, the pathogenesis and optimal management of CRC development in IBD-PSC patients remain unclear.

Colorectal cancer in patients with inflammatory bowel disease:Can we predict risk?

The inflammatory bowel diseases(IBD),Crohn's disease(CD) and ulcerative colitis(UC),may be complicated by colorectal cancer(CRC).In a recent populationbased cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation.The overall risk of CRC among patients with UC and CD was comparable with that of the general population.However,patients diagnosed with UC during childhood or as adolescents,patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk.In this commentary,we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients.Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC.The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD.The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients.The achieved knowledge may also be relevant for other inflammation-associated cancers.

Colorectal cancer surveillance in inflammatory bowel disease: A critical analysis

Colonoscopic surveillance is advocated in patients with inflammatory bowel disease(IBD) for detection of dys-plasia. There are many issues regarding surveillance in IBD: the risk of colorectal cancer seems to be de-creasing in the majority of recently published studies, necessitating revisions of surveillance strategy; surveil-lance guidelines are not based on concrete evidence; commencement and frequency of surveillance, cost-effectiveness and adherence to surveillance have been issues that are only partly answered. The traditional technique of random biopsy is neither evidence-based nor easy to practice. Therefore, highlighting abnormal areas with newer technology and biopsy from these areas are the way forward. Of the newer technology, digital mucosal enhancement, such as high-definition white light endoscopy and chromoendoscopy(with magnification) have been incorporated in guidelines. Dyeless chromoendoscopy(narrow band imaging) has not yet shown potential, whereas some forms of digital chromoendoscopy(i-Scan more than Fujinon intelligent color enhancement) have shown promise for colonoscopic surveillance in IBD. Other techniquessuch as autofluorescence imaging, endomicroscopy and endocytoscopy need further evidence. Surveillance with genetic markers(tissue, serum or stool) is at an early stage. This article discusses changing epidemiology of colorectal cancer development in IBD and critically evaluates issues regarding colonoscopic surveillance in IBD.