Extent Of Colitis Research Articles

PMO-251 A retrospective audit of colorectal cancer surveillance in inflammatory bowel disease in secondary care

IntroductionPatients with colitis are at increased risk of colorectal cancer (CRC). Colonoscopic surveillance to detect dysplasia and early cancers has been advocated by the BSG since 2002.1 Our aims were...

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).

Colorectal carcinoma at diagnosis of UC in a 17 year old

IBD is a known risk factor for colorectal cancer (CRC). The degree of risk is related to the duration and extent of colitis, as well as the severity of inflammation over time. Other risk factors include PSC and a family history of sporadic CRC. ACG and AGA guidelines suggest surveillance based on duration of disease, not chronological age. Surveillance colonoscopies are recommended starting 8 years after onset of symptoms. We present a 17 year old female diagnosed with carcinoma in situ associated with UC at 1st colonoscopy for suspected IBD. She presented with non-bloody diarrhea of 3 years' duration. Physical exam and routine lab tests were unremarkable. A clinical diagnosis of IBS was suggested elsewhere and her symptoms improved with loperamide. Hematochezia triggered an investigation for IBD. The colonoscopy (6/2008) revealed pancolitis, with edematous and hyperemic mucosa, mucopurulent exudate and friability. No tumor was seen. Histology confirmed characteristic signs of chronic colitis with focal ulcerations, crypt branching and abscesses and dense acute and chronic inflammatory infiltrates. Biopsies (ascending, transverse, descending and rectum) showed signs of definite dysplasia, as well as the presence of P53 and k167 expression. In the descending, high grade dysplasia with carcinoma in situ was confirmed by two independent pathologists. A proctocolectomy with ileo-anal J pouch anastomosis was performed (8/2008). The pathology specimen confirmed a diagnosis of UC without skip lesions. Carcinoma in situ in the descending was found. Recurrent episodes of pouchitis have occurred despite probiotics, and were successfully treated with antibiotics. CRC in pediatric UC was first reported by Lagercrantz in 1949. Other cases were published over the ensuing 2 decades. In 1961 the Mayo Clinic reported that 10% of UC patients below 21 years of age died of CRC. Over the last 40 years improvements in the treatment and increased awareness of risk of CRC in IBD has impacted favorably on the incidence of CRC. Nevertheless, rare cases of CRC at or shortly after diagnosis of IBD exist. The first CRC associated with Crohn's disease in childhood was reported in 2001 in an adolescent with undiagnosed chronic abdominal pain for 5 years. Recently, an adolescent male with CRC after only 3 years of UC was reported in a Danish population-based study. Our case is exceptional in that CRC was found at the time of initial colonoscopy for suspected IBD. This emphasizes the fact that CRC can be present early after the onset of symptoms and may be delayed or missed when conducting surveillance strictly according to formal guidelines. It was recently suggested that surveillance with mucosal biopsies for dysplasia alone may be inadequate, as aneuploidy was found without dysplasia in patients as young as 16. Further research to optimize detection of pre-cancerous changes in high risk IBD patients is needed.

Managing chronic disease in Ireland: hospital admission rates and clinical outcomes in a large ulcerative colitis population

Health care planning demands a detailed knowledge of the course of chronic diseases in the Irish population. This study describes hospital admission rates, medication use and outcomes in a large cohort of patients with ulcerative colitis attending a tertiary referral centre in Ireland. Four hundred and twenty-four patients who attended during the 18-year period from January 1991 to January 2009 were identified. Baseline demographics, hospital admission, medications required, extent of colitis and date of colectomy were recorded. More than half (55.4%) of the patients were managed exclusively in an outpatient setting throughout diagnosis and follow-up. Systemic corticosteroids, thiopurines and infliximab were required by 70, 29.5 and 5% of the patients, respectively. Overall 5-year colectomy rate due to failure of medical therapy was 15.8%. Independent predictors of colectomy were hospital admission at first presentation (odds ratio 3.6, p<0.0001) and pancolitis at diagnosis (odds ratio 2.3, p<0.01). The majority of patients with colitis have an uncomplicated disease course and do not require thiopurines, biologic agents or hospital admission. Principal management at a primary care level may be appropriate in many cases. Colectomy rates at a specialist centre in Ireland compare favourably with international figures.

Intestinal Inflammation and Cancer

Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer (CRC). Chronic inflammation is believed to promote carcinogenesis. The risk for colon cancer increases with the duration and anatomic extent of colitis and presence of other inflammatory disorders (such as primary sclerosing cholangitis), whereas it decreases when patients take drugs to reduce inflammation (such as mesalamine and steroids). The genetic features that lead to sporadic CRC-chromosome instability, microsatellite instability, and DNA hypermethylation-also occur in colitis-associated CRC. Unlike the normal colonic mucosa, cells of the inflamed colonic mucosa have these genetic alterations before there is any histologic evidence of dysplasia or cancer. The reasons for these differences are not known, but oxidative stress is likely to be involved. Reactive oxygen and nitrogen species produced by inflammatory cells can affect regulation of genes that encode factors that prevent carcinogenesis (such as p53, DNA mismatch repair proteins, and DNA base excision-repair proteins), transcription factors (such as nuclear factor-κB), or signaling proteins (such as cyclooxygenases). Administration of agents that cause colitis in healthy rodents or genetically engineered, cancer-prone mice accelerates development of colorectal tumors. Mice genetically prone to inflammatory bowel disease also develop CRC, especially in the presence of bacterial colonization. Individual components of the innate and adaptive immune response have also been implicated in carcinogenesis. These observations offer compelling support for the role of inflammation in colon carcinogenesis.

Influence of Interleukin-13 in 5-HT Synthesis and Severity of Experimental Colitis

BACKGROUND: Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5hydroxytryptamine, 5-HT) content in the gut. In our previous studies, we have shown that 5-HT plays an important role in the pathogenesis of experimental colitis. Dendritic cells (DC) are important innate immune cells and play a key role in the activation of the immune response and generation of gut inflammation. DCs express the 5-HT7 receptor, and we have recently demonstrated that 5-HT plays an important role in DC activation in relation to gut inflammation. In this study, we have evaluated the effect of inhibiting 5-HT signaling by using a 5-HT7 receptor antagonist or 5-HT7 receptor knockout mice in experimental colitis. METHODS: Mice (C57BL/6) were treated with selective 5-HT7 receptor antagonist SB266970 (40mg/kg, ip) or vehicle (saline) starting one day prior to administration of 5% dextran sulfate sodium (DSS) in drinking water and were sacrificed on day 5 post-DSS to assess the extent of colitis, myeloperoxidase (MPO) activity and pro-inflammatory cytokines. Colitis was also induced in 5-HT7 receptor deficient mice on C57BL/6 background (5HT7KO) and wild type mice either by 5% DSS or intrarectal administration of dinitrobenzene sulfonic acid (DNBS, 5mg/mouse) and were sacrificed on day 5 post-DSS and day 3 postDNBS to assess the extent of colitis, MPO activity and pro-inflammatory cytokines. RESULTS: Inhibition of 5-HT signaling by blocking 5-HT7 receptor function with a 5-HT7 antagonist ameliorated DSS-induced colitis. Compared to saline treated mice, we observed significantly lower macroscopic (4.0±0.28 vs. 2.6±0.43) and histological damage scores (4.8±0.59 vs. 2.4±0.54) in antagonist treated mice on day 5 post-DSS. This was associated with downregulation of MPO activity (16.9±0.88 vs. 12.32±1.21, P<0.05) and lower production of IL-1β, TNF-α and IL-6 (P<0.05) post-DSS. There were also significantly lower histological scores, MPO and pro-inflammatory cytokine levels in 5-HT7KOmice as compared to controls post-DSS. DCs isolated from 5-HT7KO mice post-DSS produced lower levels of IL-12 and IL-1β when stimulated with LPS as compared to wild-type mice (P<0.05). We also observed significant reduction in severity of colitis in 5-HT7KO mice following induction of DNBScolitis. CONCLUSION: These results demonstrate that disruption of 5-HT7 receptor function reduces the severity of gut inflammation and identifies a key role of 5-HT7 receptor mediated signaling in the pathogenesis of experimental colitis. These observations provide us with novel information on the role of the 5-HT7 receptor in gut inflammation and highlight the potential benefit of targeting this receptor to alleviate disease severity in intestinal inflammatory conditions including inflammatory bowel disease.

Colorectal cancer surveillance in inflammatory bowel disease: a primary care perspective

IntroductionPatients with colitis are at increased risk of colorectal cancer (CRC). The British Society of Gastroenterology (BSG) has been advocating colonoscopic surveillance to detect dysplasia and early CRC since 20021....

PillCam COLON capsule endoscopy: recent advances and new insights

Capsule endoscopy for the colon was introduced to allow an alternative screening method to the invasive classic colonoscopy. The results of initial studies have shown inferior detection rates of colonic polyps by the colon capsule. In this paper we aim to review and summarize the recent advances in wireless capsule endoscopy of the colon. Publications regarding the use of colon capsule with new technology, as well as personal experience, were reviewed. Since the introduction of the first generation of the colon capsule, many improvements have been made to create a better capsule endoscope. These include a wider angle of view, a faster adaptable frame rate and a new data recorder which is able to control the capsule activity during the transit through the bowel. Recent studies show these improvements had a direct effect on the colon capsule performance, leading to a better diagnostic yield. Recent advancements in the technology of the wireless colon capsule endoscope offer the option to screen patients for colonic polyps noninvasively. Colon capsule endoscopy may become relevant for assessment of extent of inflammatory bowel disease.

Outcome of Sporadic Adenomas and Adenoma-Like Dysplasia in Patients with Ulcerative Colitis Undergoing Polypectomy§†

Ulcerative colitis (UC) patients are at increased risk of colorectal dysplasia and cancer. Few studies have examined the clinical outcomes of dysplastic polyps resembling sporadic adenomas that are removed with endoscopic polypectomy. A centralized diagnostic index identified patients evaluated between 1994 and 2004 with UC and polypoid dysplasia who were followed from the time of polypectomy until the most recent colonoscopy. They were stratified into two groups by polyp occurrence, either within (adenoma-like dysplasia) or outside (sporadic adenoma) the most proximal endoscopic or histologic extent of colitis. The endpoints of interest were the development of subsequent colorectal neoplasia, flat dysplasia, or cancer. The cumulative probabilities of these endpoints were estimated using the Kaplan-Meier method, and the association with clinical factors assessed using Cox proportional hazards regression. Ninety-five patients were found to have polypoid dysplasia; of these, 77 underwent polypectomy. The cumulative probability of subsequent colorectal neoplasia in polypectomy patients was 18% at 1 year and 69% at 5 years. After polypectomy, cumulative incidence of cancer or flat dysplasia was 2% at 1 year and 13% at 5 years. The proportional hazards models indicated that these outcomes were not significantly associated with polyp type, primary sclerosing cholangitis, family history of colorectal cancer, 5-aminosalicylate use, extent of colitis, or duration of disease. While polypectomy may be safe for the management of adenomas occurring in most UC patients, the 5-year cumulative incidence of a combined endpoint (cancer or flat dysplasia) was 13%. Such patients should be followed closely.

Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain, colon wet weight, and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant-2, and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore, GL-p inhibited the oxidative activity of mucosal and purified MPO. GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

Krüppel-Like Factor 5 Protects Against Dextran Sulfate Sodium−Induced Colonic Injury in Mice by Promoting Epithelial Repair

Krüppel-like factor 5 (KLF5) is a transcription factor that promotes proliferation, is highly expressed in dividing crypt cells of the gastrointestinal epithelium, and is induced by various stress stimuli. We sought to determine the role of KLF5 in colonic inflammation and recovery by studying mice with dextran sulfate sodium (DSS)-induced colitis. Wild-type (WT) and Klf5(+/-) mice were given DSS in the drinking water to induce colitis. For recovery experiments, mice were given normal drinking water for 5 days after DSS administration. The extent of colitis was determined using established clinical and histological scoring systems. Immunohistochemical and immunoblotting analyses were used to examine proliferation, migration, and expression of the epidermal growth factor receptor. Klf5 expression was increased in colonic tissues of WT mice given DSS; induction of Klf5 was downstream of mitogen-activated protein kinase signaling. In DSS-induced colitis, Klf5(+/-) mice exhibited greater sensitivity to DSS than WT mice, with significantly higher clinical and histological colitis scores. In recovery experiments, Klf5(+/-) mice showed poor recovery, with continued weight loss and higher mortality than WT mice. Klf5(+/-) mice from the recovery period had reduced epithelial proliferation and cell migration at sites of ulceration compared to WT mice; these reductions correlated with reduced expression of epidermal growth factor receptor. Epithelial repair is an important aspect of recovery from DSS-induced colitis. The transcription factor KLF5 regulates mucosal healing through its effects on epithelial proliferation and migration.

Rectal Sparing and Skip Lesions in Ulcerative Colitis: A Comparative Study of Endoscopic and Histologic Findings in Patients Who Underwent Proctocolectomy

Ulcerative colitis (UC) is generally considered an inflammatory disorder that always involves the rectum and may also involve more proximal portions of the colon, but always in a diffuse and continuous (non-segmental) fashion. Earlier biopsy studies have shown that both rectal sparing and patchy disease may occur during the natural history of UC and may, in fact, be accentuated by oral or enema therapy; but these features have never been evaluated in resection specimens. The purpose of this study was to evaluate the prevalence rates and degree of endoscopic and histologic patchiness of disease and rectal sparing in preoperative endoscopic biopsies and to compare the findings with those observed in colectomy specimens. In addition, we evaluated the effects of immunomodulators and anti-TNF-alpha therapy on normalization of mucosa. Cases of 56 UC patients, all of whom had at least 1 preoperative endoscopy with biopsies, and who subsequently underwent a colectomy for nonneoplastic complications, were collected and reviewed for a variety of inflammatory histologic features, such as patchiness of disease and rectal sparing. Both of these features were categorized as either absolute or relative according to predetermined criteria. All biopsies and resection specimens were graded for their inflammatory activity on a 5-point scale. An independent score was provided for each portion of the colon, and a mean colitis score of the entire colon was calculated by adding all inflammatory grades for each colonic segment and dividing this number by the number of segments. Endoscopic, biopsy, and resection specimen findings were correlated with each other and with clinical and demographic features, such as duration of colitis, extent of colitis, and types of medications used for at least 6 months before resection. Overall, the mean colitis score in biopsies was significantly lower than in resection specimens (2.7+/-0.9 vs. 3.2+/-0.8, P<0.01). Evidence of rectal sparing and patchy disease occurred in 32.1% and 30.4% of patients by endoscopy, and 30.4% and 25% of patients by analysis of biopsies. Only 3 patients (5.4%) showed rectal sparing, and all of these were considered "relative" after evaluation of the patients' colectomy specimens. Six (10.7%) showed patchiness of disease in the colon resection specimen, 4 of which were absolute. After evaluation of all of the patients' preresection biopsy specimens and colectomy specimens, none of the patients (0%) showed complete absence of rectal involvement (absolute rectal sparing) after all of the tissue sections were evaluated. A significant correlation was noted between endoscopic and biopsy findings and between biopsy and colectomy findings, but poor correlation was noted between the patients' endoscopic features and the pathologic features in the patients' colectomy specimens. No correlation was noted between any specific type or combination of medication use and the presence or frequency of rectal sparing or patchiness of disease. These data indicate that absolute rectal sparing does not occur in UC patients even after long-term use of antiinflammatory medications. The presence of 1 (or more) tissue sections from an IBD patient's colectomy specimen showing complete absence of histologic features of chronicity or activity, but bordered on both sides by chronic or chronic active disease, should not represent a reason to change the patient's diagnosis from UC to Crohn disease.

Similarity in the metabolic profile in macroscopically involved and un-involved colonic mucosa in patients with inflammatory bowel disease: an in vitro proton ( 1H) MR spectroscopy study

Background The histological extent of inflammatory bowel disease (IBD) is greater than that evident by colonoscopic evaluation. We hypothesized that metabolic profile in macroscopically un-involved colonic mucosa in IBD is similar to that of controls with healthy colon. We thus assessed the differences in metabolic profile in macroscopically involved and un-involved colonic mucosa of IBD patients to further substantiate the extent of disease. Patients and Methods Colonic mucosal biopsies were obtained and snap frozen from both the macroscopically un-involved and involved colonic mucosa of IBD patients and macroscopically normal colonic mucosa of controls and were subjected to in-vitro high-resolution proton ( 1H) magnetic resonance (MR) spectroscopy and the concentrations of metabolites were determined. Results Thirty-two metabolites were assigned in the proton MR spectrum of colonic mucosa of IBD patients. The concentrations of amino acids (isoleucine, leucine, valine, arginine, lysine, glutamine/glutamate, alanine), membrane metabolites (choline, glycerophosphorylcholine/phosphorylcholine), glycolytic product (lactate) and short chain fatty acid (formate) were significantly lower while significantly high level of glucose were observed in the macroscopically un-involved colonic mucosa of IBD patients compared to the macroscopically normal mucosa of controls. There was no significant difference in the concentrations of metabolites in macroscopically involved and un-involved colonic mucosa of IBD patients. Conclusions The metabolic profile in macroscopically un-involved colonic mucosa of IBD patients is similar to that of macroscopically involved mucosa but different from colonic mucosa of controls. This suggests that even macroscopically un-involved colonic mucosa is metabolically abnormal and may explain the increase in extent of disease with time.

Colectomy for Fulminant Clostridium difficile Colitis: Predictors of Mortality

The purpose of this study was to define clinical and radiographic variables associated with postoperative mortality after urgent colectomy for fulminant Clostridium difficile colitis. Data were obtained regarding patients undergoing colectomy for fulminant C. difficile colitis at two institutions (1997-2005). Univariate analysis of factors predicting 30-day mortality was performed using chi2 and Student's t tests. Multivariable logistic regression was done to include all variables whose P value was < 0.20. Clinical variables analyzed included: age, gender, recent operation, comorbidities, preoperative multisystem organ failure, vasopressors, symptom duration, time to surgery, serum albumin, change in serum albumin, serum creatinine, white blood cell count, and extent of colectomy. Computed tomography variables included: ascites, megacolon, and extent of colitis. Thirty-five patients (mean age 70 years, 46% male) underwent urgent colectomy for C. difficile colitis. The 30-day mortality rate was 45.7 per cent (16/35). The only clinical variable associated with mortality was preoperative multisystem organ failure (nonsurvivors 9/16 vs survivors: 4/19; P = 0.037). None of the three patients undergoing partial colectomy survived, although the difference in survival versus those undergoing subtotal colectomy was not significant. Patients with fulminant C. difficile colitis undergoing colectomy have a high mortality rate. Preoperative presence of multisystem organ failure was independently predictive of mortality.

Lymphoid tyrosine phosphatase R620W variant and inflammatory bowel disease in Tunisia

To assess the possible association between PTPN22 (R620W) gene polymorphism and inflammatory bowel disease (IBD). One hundred and sixty-four patients with IBD [105 Crohn's disease (CD) and 59 ulcerative colitis (UC)] and 100 healthy controls were recruited. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by restriction fragment length polymorphism-polymerase chain reaction with RsaI digestion. The genotypic and allelic frequencies of (R620W) PTPN22 gene polymorphism reveal a significant association of the PTPN22 620-W allele with IBD, compared to the healthy control group (OR: 17.81, 95% CI: 4.18-21.86, P = 0.00001). Nevertheless, no difference in this polymorphism was found between CD and UC patients. No significant association was found between the frequencies of genotypes of the PTPN22 gene with either the clinical features such as sex, age, age at disease onset, and extent of colitis, or the production of serological markers (anti-Saccharomyces cerevisiae antibody in CD and perinuclear anti-neutrophil cytoplasmic antibody in UC). These observations confirm the association of IBD susceptibility with the PTPN22 1858T (620-W) allele in Tunisian patients.

Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?

The relationship between a predisposition to obesity and the development of colitis is not well understood. Our aim was to characterize the adipokine response and the extent of colitis in diet-induced obese (DIO) rats. DIO and control, diet-resistant (DR) animals were administered either saline or trinitrobenzene sulfonic acid (TNBS) to induce colitis. Macroscopic damage scores and myeloperoxidase (MPO) activity were measured to determine the extent of inflammation. Trunk blood was collected for the analysis of plasminogen activator inhibitor-1 (PAI-1) as well as leptin, ghrelin, and adiponectin. Colonic epithelial physiology was assessed using Ussing chambers. DIO rats had a modestly increased circulating PAI-1 before TNBS treatment; however, during colitis, DR animals had more than a fourfold increase in circulating PAI-1 compared with DIO rats. Circulating leptin was higher in DIO rats compared with DR animals, in the inflamed and noninflamed states. These changes in TNBS-induced adipokine profile were accompanied by decreased macroscopic tissue damage score in DIO animals compared with DR tissues. Furthermore, TNBS-treated DR animals lost significantly more weight than DIO rats during active inflammation. Colonic epithelial physiology was comparable between groups, as was MPO activity. The factors contributing to the decreased colonic damage are almost certainly multifold, driven by both genetic and environmental factors, of which adipokines are likely to play a part given the increasing body of evidence for their role in modulating intestinal inflammation.

More right-sided IBD-associated colorectal cancer in patients with primary sclerosing cholangitis

Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone.

Decreasing Time-Trends of Colorectal Cancer in a Large Cohort of Patients With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). There have been marked changes in the management and treatment of IBD over the past decades, but little is known about how these changes have impacted morbidity and mortality (time trends in risk) of CRC in patients with IBD. We assessed cancer occurrence and mortality in a large population-based cohort of patients with IBD who were diagnosed from 1954 to 1989 (n = 7607). Through register links, we collected data on vital status of all registered cases of CRC, as well as intestinal surgeries and mortalities from CRC through 2004. Relative risks for CRC incidence and mortality, by calendar period of follow-up evaluation, were assessed within the cohort (using Poisson regression and taking age, sex, extent of IBD, and time since IBD diagnosis into account) and also compared with the general population using standardized incidence and mortality ratios. During 198,227 person-years of follow-up evaluation for the 7607 patients with IBD, 188 new cases of CRC were observed (crude incidence, 95 per 100,000; 95% confidence interval, 82-109); 92 deaths from CRC were registered. Within the IBD cohort, as well as vs the general population, the incidence of CRC showed a tendency towards a decline whereas the mortality from CRC decreased several-fold from the 1960s through 2004. Over the past 35 years, the risk of diagnosis of CRC in patients with IBD has not declined significantly, but the risk of dying of CRC has decreased substantially.

Correlation of serum biomarkers with clinical severity and mucosal inflammation in Chinese ulcerative colitis patients

Serum biomarkers are commonly used for diagnosing and monitoring the disease activity of ulcerative colitis (UC) patients. However, their role in predicting active mucosal inflammation on Chinese patients is unknown. Our aim was to determine the sensitivity and correlation of these biomarkers with clinical severity and mucosal inflammation. Patients who had been newly diagnosed or who had developed a clinical relapse were identified. Active mucosal inflammation was confirmed by colonoscopy and histology. Those patients who had routine serum biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], white cell count, hemoglobin, platelet count and albumin) checked within 14 days of the index colonoscopy were recruited for a retrospective analysis. The disease severity was graded clinically and the positive rate of each marker was determined. The correlation of these markers with the clinical severity and extent of colitis were assessed by the Mann-Whitney U-test or the Kruskal-Wallis test. For the categorical variable, chi(2) or the Fisher's exact test were adopted. From January 2001 to December 2006, 49 Chinese UC patients fulfilled the inclusion criteria. There were 78 acute mucosal inflammatory episodes (24 at diagnosis and 54 clinical relapses). Abnormal CRP, ESR, white cell count, hemoglobin, platelet count and albumin occurred in 42.3%, 55.1%, 23.1%, 21.8%, 32.1% and 25.6% of these mucosal inflammatory episodes, respectively. For the severity of the clinical disease, all serum biomarkers demonstrated a good correlation with the severity grading. On the other hand, the serum biomarkers correlated well with endoscopic extensive colitis but not with proctitis or left-sided colitis. Routine serum biomarkers are not sensitive in predicting mucosal inflammation. However, they are helpful in identifying patients with extensive colitis or clinically severe disease.

Colorectal Cancer in Inflammatory Bowel Disease

Patients with long-standing inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC). CRC risk increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and severity of inflammation of the colon. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid. To reduce CRC mortality in IBD, colonoscopic surveillance remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.