Advances in Pharmacological Research on Active Components of Traditional Chinese Medicine in the Treatment of Inflammatory Bowel Disease-related Bowel Cancer

In recent years,with the modern development of traditional medicine,the research on the treatment of inflammatory bowel disease and bowel cancer is increasingly deep.This paper reviews the pharmacological research progress of flavonoids,alkaloids,polyphenols,polysaccharides,steroids and saponins in the treatment of inflammatory bowel disease and canceration.

METABOLISM PATTERN OF FECAL BILE ACIDS IN PATIENTS WITH LARGE BOWEL CANCER

The feca! bite acids were extracted from 21 patients with large bowel (colonic and rectal) cancer and 21 controls, and the bile acid composition and concentration were measured by gas chromatography. The total bile acid concentration and concentration of individual bile acids were not statistically different between colonic and rectal cancer. Bat the concentration and the percentage composition of secondary bile acids (deoxycholic and lithocholic acids) were significantly higher than that in controls. However the percentage composition of primary bile acids (cholic and chenocholic acids) were significantly lower than that in controls. The results suggest that incidence of large bowel cancer is closely related to the metabolism of fecal bile acids, and the etiology of colonic and rectal cancers may be the same.

Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment

In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.

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.

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.

5-aminosalicylicacid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.

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.

Cancer in inflammatory bowel disease

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins. To reduce CRC mortality in IBD, colonoscopic surveillance with random biopsies remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Patients with small intestinal Crohn’s disease are at increased risk of small bowel adenocarcinoma. 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. Other extra intestinal cancers, such as hepatobiliary and hematopoietic cancer, have shown variable incidence rates. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.

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.

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.

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).

Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis

AIM: To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD). METHODS: Data from 75 PSC-IBD patients evaluated in our tertiary center between 1963 and 2006 were collected and compared to 150 IBD patients without PSC, matched for sex, birth date, IBD diagnosis date and initial disease location regarding ileal, different colonic segments, and rectum, respectively. RESULTS: While PSC-IBD patients received more 5-aminosalicylates (8.7 years/patient vs 2.9 years/ patient, P < 0.001), they required less immuno-suppressors (24% vs 46% at 10 years; P < 0.001) and less intestinal resection (10% vs 44% at 10 years, P < 0.001). The 25-year cumulative rate of colectomy was 25.1% in PSC-IBD and 37.3% in controls (P = 0.004). The 25-year cumulative rate of colorectal cancer was 23.4% in PSC-IBD vs 0% in controls (P = 0.002). PSC was the only independent risk factor for the development of colorectal cancer (OR = 10.8; 95% CI, 3.7-31.3). Overall survival rate without liver transplantation was reduced in PSC-IBD patients (67% vs 91% in controls at 25 years, P = 0.001).CONCLUSION: This study confirms that patients with PSC-IBD have a particular disease phenotype independent of the initial disease location. Although their disease is less active and they use more 5-aminosalicylates, they present a higher risk of colorectal cancer.

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.

Surgical management of patients with bowel obstructions secondary to gastric cancer

AIM: To assess whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the management of small bowel obstructions (SBOs) secondary to gastric cancer and its role in treatment strategies. METHODS: The medical records of all of the patients who were admitted for an intestinal obstruction after curative resection for gastric cancer were retrospectively reviewed. PET/CT was performed before a clinical treatment strategy was established for each patient. The patients were divided into 2 groups: patients with no evidence of a tumor recurrence and patients with evidence of a tumor recurrence. Tumor recurrences included a local recurrence, peritoneal carcinomatosis or distant metastases. The primary endpoint was the 1-year survival rate, and other variables included patient demographics, the length of hospital stay, complications, and mortality. RESULTS: The median time between a diagnosis of gastric cancer and the detection of a SBO was 1.4 years. Overall, 31 of 65 patients (47.7%) had evidence of a tumor recurrence on the PET/CT scan, which was the only factor that was associated with poor survival. Open and close surgery was the main type of surgical procedure reported for the patients with tumor recurrences. R0 resections were performed in 2 patients, including 1 who underwent combined adjacent organ resection. In the group with no evidence of a tumor recurrence on PET/CT, bowel resections were performed in 7 patients, adhesiolysis was performed in 7 patients, and a bypass was performed in 1 patient. The 1-year survival curves according to PET/CT evidence of a tumor recurrence vs no PET/CT evidence of a tumor recurrence were significantly different, and the 1-year survival rates were 8.8% vs 93.5%, respectively. There were no significant differences (P = 0.71) in the 1-year survival rates based on surgical vs nonsurgical management (0% with nonoperative treatment vs 20% after exploratory laparotomy). CONCLUSION: 18 F-FDG PET/CT can be used to identify the causes of bowel obstructions in patients with a history of gastric cancer, and this method is useful for planning the surgical management of these patients.

Split-dose bowel preparation improves adequacy of bowel preparation and gastroenterologists' adherence to National Colorectal Cancer Screening and Surveillance Guidelines

AIM To quantify the impact of split-dose regimen on endoscopists' compliance with guideline recommendations for timing of repeat colonoscopy in patients with normal colonoscopy or 1-2 small polyps(< 10 mm).METHODS A retrospective chart review of all endoscopy reports was undertaken in average-risk individuals > 50 years old with a normal screening colonoscopy and 1-2 small polyps. Data were abstracted from two time periods, pre and post-split-dose bowel preparation institution. Main outcome measurements were recommendation for timing of repeat colonoscopy and bowel preparation quality. Bivariate analysis by χ~2 tests and Student's t-tests were performed to assess differences between the two cohorts. Multivariable logistic regression was used with guideline consistent recommendations as the dependent variables and an indicator for 2011 cohort as the primary predictor. RESULTS Four thousand two hundred and twenty-five patients were included in the study; 47.0%(1987) prior to the institution of split dose bowel preparation, and 53.0%(2238) after the institution of split dose bowel preparation. Overall, 82.2%(n = 3472) of the colonoscopies were compliant with guideline recommendations, with a small but significantly increased compliance rate in year 2011(83.7%) compared to year 2009(80.4%, P = 0.005), corresponding to an unadjusted odds ratio of 1.25(95%CI: 1.07-1.47; P = 0.005). Colonoscopies with either "Adequate" or "Excellent" had increased from 30.6% in year 2009 to 39.6% in year 2011(P < 0.001). However, there was no significant difference in poor/inadequate category of bowel preparation as there was a mild increase from 4.6% in year 2009 to 5.1% in year 2011(P = 0.50). CONCLUSION Split-dose bowel regimen increases endoscopists' compliance to guidelines in average-risk patients with normal colonoscopy or 1-2 small polyps.

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.

Protective links between vitamin D,inflammatory boweldisease and colon cancer

Vitamin D deficiency has been associated with a wide range of diseases and multiple forms of cancer including breast, colon, and prostate cancers. Relatively recent work has demonstrated vitamin D to be critical in immune function and therefore important in inflammatory diseases such as inflammatory bowel disease(IBD). Because vitamin D deficiency or insufficiency is increasingly prevalent around the world, with an estimated 30%-50% of children and adults at risk for vitamin D deficiency worldwide, it could have a significant impact on IBD. Epidemiologic studies suggest that low serum vitamin D levels are a risk factor for IBD and colon cancer, and vitamin D supplementation is associated with decreased colitis disease activity and/or alleviated symptoms. Patients diagnosed with IBD have a higher incidence of colorectal cancer than the general population, which supports the notion that inflammation plays a key role in cancer development and underscores the importance of understanding how vitamin D influences inflammation and its cancer-promoting effects. In addition to human epidemiological data, studies utilizing mouse models of colitis have shown that vitamin D is beneficial in preventing or ameliorating inflammation and clinical disease. The precise role of vitamin D on colitis is unknown; however, vitamin D regulates immune cell trafficking and differentiation, gut barrier function and antimicrobial peptide synthesis, all of which may be protective from IBD and colon cancer. Here we focus on effects of vitamin D on inflammation and inflammation-associated colon cancer and discuss the potential use of vitamin D for protection and treatment of IBD and colon cancer.

Colorectal cancer and dysplasia in inflammatory bowel disease

Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia- carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia.

Papillary thyroid cancer and inflammatory bowel disease:Is there a relationship?

AIM:To formally study age of diagnosis of papillary thyroid cancer(PTC) in inflammatory bowel disease(IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population.pothesis that patients with IBD are more likely to be diagnosed with PTC than a control population.A retrospective cohort analysis was performed using the University of Pennsylvania Health System's electronic database.Outpatients from 1998-2009 were included in the search,and patients in the cohort were selected based on ICD-9 codes.Inclusion criteria included the diagnosis of Crohn's disease(CD) or ulcerative colitis(UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population.Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls.Statistics were performed using corrected chisquare analysis.The primary outcome for this study was the diagnosis of PTC.Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania.RESULTS:The mean age was 47.5 years(range:18-102 years) and 66% patients were female.An analysis of variance model was used to compare the age of PTC diagnosis between the CD,UC,asthma and diverticulitis groups,and a statistically significant difference in age at PTC diagnosis was noted across all groups(F = 6.35,df = 3,P = 0.0006).The age of PTC diagnosis in CD patients was statistically significantly lower than UC,asthma,and diverticulitis patients(average PTC diagnosis age for CD 25,UC 49,asthma 45,diverticulitis 63).After covarying for sex and age in 2009,the difference in age at PTC diagnosis remained statistically significant(F = 4.13,df = 3,P = 0.0089).A total of 86 patients were diagnosed with PTC.Nine patients(0.5%) with UC were diagnosed with PTC.Patients with UC were not shown to be more likely to develop PTC [odds ratio(OR):1.544,95%CI 0.767-3.108] compared to asthma controls.Four patients(0.4%) with CD were diagnosed with PTC.Patients with CD were not shown to be more likely to develop PTC(OR:1.334,95%CI 0.485-3.672) compared to a control population with asthma.Nine patients(0.5%) with a history of diverticulitis were diagnosed with PTC.Patients with diverticulitis were not shown to be more likely to develop PTC(OR:1.673,95%CI 0.831-3.368) compared to asthma controls.Patients with CD or UC were not less likely to develop PTC compared to those with diverticulitis(CD OR:0.80,95%CI 0.25-2.60;UC OR:0.92,95%CI 0.37-2.33).None of the patients used immunosuppressant medications prior to the diagnosis of PTC(azathioprine,6-mercaptopurine,and methotrexate).CONCLUSION:There is a significant difference in age of diagnosis of PTC in patients with CD compared to patients with UC and the control populations studied.

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.