The Cancer “Fear” in IBD Patients: Is It Still REAL?

Increased rates of colorectal cancer (CRC) with high rates of progression from dysplasia to CRC are well documented in the inflammatory bowel disease (IBD) population. This increased risk in the presence of currently improving but still inadequate surveillance techniques confirms that the cancer “fear” in IBD patients is still real. The majority of data on the cancer risk in IBD has been gathered from ulcerative colitis (UC) patients as these patients are generally better studied. Thus surveillance and treatment protocols for Crohn’s disease (CD) are frequently modeled on UC paradigms. Dysplasia in the IBD cohort frequently is a harbinger of local, distant, or metachronous neoplasia. Therefore, frequent surveillance and referral for surgical intervention when dysplasia is detected are justified in both the CD and UC patient.     

Colorectal carcinoma in inflammatory bowel disease: a comparison between Crohn’s and ulcerative colitis

Aim The study assessed the clinicopathological features and survival rates of inflammatory bowel disease (IBD) patients with colorectal carcinoma (CRC), which accounts for ～15% of all IBD associated death. Method The medical records of patients operated on for CRC in three institutions between 1992 and 2009 were reviewed, and those with Crohn’s colitis (CC) and ulcerative colitis (UC) were identified. Data on age, gender, disease duration, colitis severity, surgical procedure, tumour stage and survival were retrieved. Results Fifty‐three patients (40 UC and 13 CC, 27 men, mean age at operation 54 years) were found. All parameters were comparable between the groups. Mean disease duration before CRC was 22.7 years for UC and 16.6 years for CC patients (P = 0.04). CRC was diagnosed preoperatively in 43 (81%) patients. Twenty‐eight patients had colon cancer, 23 had rectal cancer and two patients had more than one cancer. All malignancies were located in segments with colitis. Over one‐half were diagnosed at an advanced stage (36% stage III; 17% stage IV). At a mean follow up of 56 ± 65 months, 60% were alive (54% disease free) and 40% were dead from cancer‐related causes. The 5‐year survival rate was 61% for the UC and 37% for the CC patients (P = NS). Conclusion CRC in IBD patients is frequently diagnosed at an advanced stage, a factor that contributes to poor prognosis. The risk of CRC in CC patients is comparable to those with UC. Long‐term surveillance is recommended for patients with long‐standing CC and UC.     

Evolving endoscopic technologies for the detection of dysplasia in inflammatory bowel diseases

Patients with long-standing and extensive ulcerative colitis (UC) and colonic Chron's disease (CD) have an increased risk of CRC compared with the general population. Although no large controlled trials have proven that surveillance reduces mortality, cancer prevention in inflammatory bowel disease depends on the detection of dysplasia during scheduled surveillance colonoscopy and is widely recommended by gastroenterological associations. Dysplasia in IBD may occur in flat mucosa or in raised lesions (DALM) which have sometimes endoscopic features similar to adenoma (adenoma-like DALM). Recently, new endoscopic techniques to facilitate the distinction between dysplastic and actively inflamed or normal mucosa have been proposed. Chromoendoscopy significantly increases the sensitivity of detecting subtle dysplastic lesions and has emerged as the new standard of cancer surveillance in patients with IBD. Confocal laser endomicroscopy (CLE) is a novel technique that enables the endoscopist to obtain real time in vivo microscopic images of the gastrointestinal mucosa and can be used for targeting biopsies to relevant areas. CLE in conjunction with chromoendoscopy proved able to increase the diagnostic yield of dysplasia in ulcerative colitis and reduce the number of biopsies needed. The role of digital filtering technologies (virtual chromoendoscopy) and autofluorescence in IBD surveillance will be also discussed.     

The histological diagnosis of dysplastic and neoplastic lesions in inflammatory bowel disease: a pathological perspective

Patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), are at an increased risk for developing colorectal carcinoma (CRC). The accurate diagnosis of dysplasia in biopsies taken during periodic surveillance of long-standing IBD patients is most important in prevention of UC and CD related cancer. Distinction of low from high grade IBD-related dysplasia and differential diagnosis between IBD-related dysplasia and dysplasia in sporadic adenoma as well as distinction from pseudodysplastic lesions in inflammatory pseudopolyps or reparative lesions is often very subtle and difficult and demands expertise of second experienced gastrointestinal pathologist. Although surveillance colonoscopy with multiple biopsies does not reduce the cancer mortality, it offers a reasonable chance of detecting precancer and performed prophylactic colectomy. Novel methods of detecting dysplasia are continuously being evaluated, including chromoscopy and molecular biology markers. In the future, one may expect, from these new markers to detect the dysplasia in IBD patients before development of histological evidence of neoplastic changes.     

Dysplasia in ulcerative colitis: still a challenge

As duration of inflammatory bowel disease (IBD), in particular ulcerative colitis (UC), is a major risk factor for the development of colorectal cancer (CRC), it is rational to propose a screening colonoscopy when the risk starts to increase, i.e., after 8-10 years from the onset of disease. If low-grade dysplasia is detected, the 9-fold increased risk of developing CRC reported in the most recent meta-analysis could reasonably be viewed as justification for colectomy even if some follow-up studies have shown a lower rate of CRC. A reasonable compromise could be to continue surveillance with extensive biopsy sampling at shorter (perhaps 3-6 month) intervals. If high grade dysplasia is present, the decision is easier, because the risk of concomitant CRC may be as high as one third, assuming that the biopsies were indeed obtained from flat mucosa and not from an adenoma. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the most commonly performed procedure for patients with ulcerative colitis requiring elective surgery for dysplasia. Nevertheless, a recent systematic review alerted that the risk of dysplasia in anal transition zone and rectal cuff in patients undergone to restorative proctocolectomy was remarkable, mainly in patients operated on for dysplasia or colorectal cancer.     

Premalignant and malignant changes in idiopathic inflammatory bowel disease

It is well known that patients with long-standing inflammatory bowel disease (IBD), ulcerative colitis (UC) or Crohn's disease(CD) are at increased risk for developing colorectal cancer (CC). Before adenocarcinoma develops, the intestinal epithelium progress through a premalignant phase of dysplasia, which can be identified via mucosal biopsy and routine tissue histology. Surveillance colonoscopy and prophylactic colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Many physicians suggests that surveillance for extensive colitis should begin after 8 to 10 years of disease, and surveillance for left-sided colitis should begin after 15-20 years. Colonoscopy is recommended with frequent biopsies, at least every 10 cm in all four quadrants, and with biopsy of any suspicious lesion. The emerging field of colon cancer genetics has identified several important tumor markers that have potential to improve sensitivity for detection of early neoplasia.     

Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. PATIENTS AND METHODS: A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n=17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. RESULTS: The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P<0.001). All CRCs in the PSC group were in patients with IBD and an intact colon. The cumulative risk of developing CRC in the 83 patients with an intact colon and IBD was 14% and 17% after 5 and 10 years, respectively (PSC non-IBD group 0% risk after 10 years, P<0.06). The multivariate analysis showed three significant variables related to the risk of developing CRC: colonic dysplasia after LT (P<0.0003), duration of colitis more than 10 years (P<0.002), and pancolitis (P<0.004). The cause of death in patients with CRC was cancer related in 75% of cases with a reduced 5-year survival of 55% versus 75% without CRC (not significant). CONCLUSION: Patients with PSC undergoing LT with a long history of ulcerative colitis and pancolitis have an increased risk of developing CRC with reduced survival. We advocate long-term aggressive colonic surveillance and colectomy in selected high-risk patients with longstanding severe colitis.     

Colorectal cancer complicating inflammatory bowel disease: a comparative study of Crohn’s disease vs ulcerative colitis in 34 patients

Aim Colorectal cancer (CRC) complicating inflammatory bowel disease (IBD) accounts for 10–15% of all IBD deaths. Survival of patients with IBD‐related CRC was reviewed to analyse differences between ulcerative colitis (UC) and Crohn’s disease (CD). Method We analysed (24 men and 10 women) patients with CD (n = 14) or UC (n = 20) with CRC, who presented between 1990 and 2007, and were followed to October, 2009. Results The mean age of patients was 56 ± 12 years for patients with UC and 49 ± 17 years for patients with CD, and the mean duration of symptoms was 22 ± 11 and 16 ± 8 years, respectively. The median duration of follow up after the diagnosis of CRC was 49 (1–157) months. Recurrence occurred in five patients with UC and in nine with CD (P = 0.02). The overall and disease free five year survivals were significantly higher in patients with UC than CD [70%vs 43% (P = 0.01) and 63%vs 31% (P = 0.01), respectively]. Conclusion The results showed a poorer prognosis of CRC in patients with CD than with UC.     

Dysplasia in ulcerative colitis—clinical consequences?

Background The overall absolute risk of colorectal cancer (CRC) in longstanding extensive or total ulcerative colitis (UC) is estimated to be 10%–15%. The size of this risk is 6- to 10-times that expected in the background population. By performing complete colonoscopies with multiple biopsies from the entire colon and rectum at regular intervals, surveillance programmes for high-risk UC patients aim at detecting mucosal dysplasia in order to select CRC-prone individuals for prophylactic colectomy.Material and methods In many of the hitherto reported surveillance programmes, the UC patients surveyed have a much lesser risk of dying from CRC than do non-surveyed patients, although randomized studies are lacking. The inter- and intra-observer variability of dysplasia among pathologists is a major pitfall in the surveillance of these patients, as well as the influence of active inflammation, making dysplasia assessment difficult. The practical issues discussed here are, to a large extent, based on the recommendations from the Swedish Gastroenterological Association.Results Screening colonoscopy should be performed approximately 8–10 years after onset of disease. After negative results for screening or surveillance colonoscopy, the intervals between colonoscopies should not exceed 2 years. Biannual investigations of between 8 and 20 years duration have been adopted in the Swedish studies, with annual colonoscopies from that point. Findings of CRC, a dysplasia-associated lesion or mass (DALM) with high-grade dysplasia (HGD) or low-grade dysplasia (LGD), or HGD in flat mucosa, are considered as indications for proctocolectomy, as well as repeated, confirmed findings of multifocal LGD. The management of unifocal LGD in flat mucosa is controversial (e.g. proctocolectomy or increased surveillance). Polyps may be handled with snare polypectomy.Conclusions The safest way of handling UC patients at high risk of developing CRC is by performing regular colonoscopic surveillance. Dysplasia is a useful prognostic marker for subsequent cancer development but has its limitations. A combination of enhanced colonoscopic surveillance using markers that are more sensitive than dysplasia might be the optimal way to manage the increased CRC risk in these patients.     

Use of a microsatellite marker in predicting dysplasia in ulcerative colitis

BACKGROUND: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. The current screening protocol involves an annual colonoscopy and biopsy after the patient has had the disease for 8 years. This, however, does not prevent the development of colorectal cancer. HYPOTHESIS: A microsatellite marker for IBD1 may identify individuals who are at greater risk of developing dysplasia and therefore colorectal cancer. DESIGN: Case-control study. SETTING: Single surgical practice. PATIENTS AND METHODS: DNA was extracted from peripheral leukocytes of 152 patients: 22 with UC and dysplasia; 48 with UC and no dysplasia; 24 with colorectal cancer; and 58 with noninflammatory bowel disease, nonmalignant gastrointestinal tract disease who were used as control patients. A microsatellite marker for IBD1 (D16S541) was amplified by polymerase chain reaction. Genotypes were identified using autoradiography. RESULTS: Six alleles and 15 genotypes were identified for marker D 16S541. Genotype CC was found in 33% (8/24) of cancer patients but only 12% (7/58) of controls (chi2 = 5.5; P = .02). Thirty-two percent (7/22) of patients with dysplastic UC also had this genotype, whereas only 8% (4/ 48) of patients with nondysplastic UC had the genotype (chi2 = 4.6; P = .03; vs controls: chi2 = 3.1; P = .08). CONCLUSIONS: This microsatellite marker for IBD1, when combined with other markers, has the potential to be used as a screening tool for colorectal cancer and dysplasia in patients with UC. Such a marker would be of particular use in improving the sensitivity and specificity of the current screening protocol for dysplasia and colorectal cancer for patients with UC.     

Proctocolectomy for colon cancer associated with ulcerative colitis a few months after living donor liver transplantation for primary sclerosing cholangitis: Report of a case

Colorectal cancer (CRC) frequently develops in patients with ulcerative colitis (UC). We report a case of CRC treated successfully by proctocolectomy 8 months after living donor liver transplantation (LDLT) for primary sclerosing cholangitis (PSC). The lesion was detected early, probably as a result of colonoscopic surveillance after LDLT. Thus, patients with a long history of UC, who undergo LDLT for PSC, should be followed up with regular surveillance colonoscopy. Moreover, surgery, such as radical resection of the colon and rectum should be performed without delay, even shortly after LDLT. To our knowledge, this is the first report of a patient undergoing proctocolectomy after LDLT.     

Inflammatory bowel disease in the pediatric patient

Inflammatory bowel disease (IBD) is a general term used to describe two chronic bowel disorders, Crohn's disease (CD) and ulcerative colitis (UC), both of which are characterized by autoimmune-related inflammation of the intestines. UC is limited to the colonic mucosa, whereas CD can involve any part of the intestinal tract from the mouth to the anus. The true etiology of UC and CD is still unknown, although extensive research has identified some genetic and environmental factors. This article discusses current clinical concepts of both diseases in the pediatric population.     

Management of Crohn’s disease and ulcerative colitis

Crohn’s disease and ulcerative colitis (UC) are complex, contrasting disease processes that require multidisciplinary team management. The treatment modalities in inflammatory bowel disease are varied and the indications and threshold for surgery quite different in patients with UC compared with Crohn’s disease. We discuss the panoply of surgical techniques available to the surgeon and IBD patient while highlighting the potential sequelae, complimentary medical therapies, nutritional considerations and innovative techniques for reconstruction of the gastrointestinal tract.     

Disease Characteristics of Inflammatory Bowel Disease (IBD)

Background  

Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn’s disease (CD), which are chronic inflammatory conditions affecting the gastrointestinal tract. There are only few published data on disease characteristics of IBD related to South Asia.     

Surgical Site Infection Following Surgery for Inflammatory Bowel Disease in Patients with Clean-Contaminated Wounds

Background  It is generally believed that the accompanying conditions in patients with inflammatory bowel disease (IBD) are associated with a high incidence of surgical site infection (SSI), and sometimes these patients are classified as compromised hosts without definitive clinical evidence. The aim of this study was to clarify the impact of IBD on the occurrence and features of SSI in patients with clean-contaminated wounds. Methods  We conducted prospective SSI surveillance of 580 patients with clean-contaminated wounds who underwent surgery between March 2006 and December 2007 using the National Nosocomial Infection Surveillance system. Multivariate analyses using stepwise logistic regression were performed to determine risk factors for SSI. Results  A total of 562 patients with clean-contaminated wounds who underwent surgery for IBD [ulcerative colitis (UC), n = 173; Crohn’s disease (CD), n = 122] or colorectal cancer [(CA), n = 267] were identified for evaluation. SSI was observed in 12.6% of all patients and there was no significant difference in infection rate by type of disease (UC, 14.5%; CD, 13.9%; CA, 10.9%). Multivariate logistic regression analysis yielded an ASA score ≥3 [odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.06–3.93] and rectal surgery (OR = 2.35; 95% CI = 1.28–4.31) as independent risk factors for SSI. IBD surgery was not an independent risk factor for overall SSI (OR = 1.62; 95% CI = 0.94–2.80). However, there was a significant difference in the incidence of incisional SSI [IBD, 11.9% (UC, 12.7%; CD, 10.7%); CA, 4.9%, p = 0.003]. In the analysis of rectal surgery, the incidence of incisional SSI was 5.3% in CA patients, 12.0% in UC patients, and 26.3% in CD patients. In contrast to overall SSI data, IBD surgery was found to be an independent risk factor for incisional SSI (OR = 2.59; 95% CI = 1.34–5.03). Conclusions  In patients of surgery restricted to clean-contaminated wounds, IBD was shown to be an independent risk factor for incisional SSI. With the use of proper operative procedures and techniques, the incidence of organ/space SSI should not be high in patients who undergo an uncomplicated IBD surgical procedure.     

NOD2 mutations and colorectal cancer - Where do we stand?

Due to the overwhelming burden of colorectal cancer(CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2(NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases(IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.     

Immune responses triggering colitis and colitis-associated carcinoma

Inflammatory bowel diseases compromise of two forms of chronic intestinal inflammatory disorders: Crohn's disease and ulcerative colitis. Both forms of inflammatory bowel disease result from inappropriate inflammatory responses to the intestinal microbiota, but have different underlying immune responses. The connection between inflammation and cancer has long been established and longstanding inflammatory bowel diseases are an important risk factor for developing colorectal cancer. Colitis-associated colorectal cancer pathogenesis is highly influenced by specific inflammatory processes during inflammatory bowel disease. This article reviews the immunological responses affecting Crohn's disease and ulcerative colitis as well as the linkage of inflammatory bowel disease to the development of colitis-associated cancer. Finally, we discuss the prospects of using new research efforts to devise new immunotherapeutic approaches.     

An Updated Approach to Dysplasia in IBD

Introduction  Long-standing inflammation of the colorectum in ulcerative colitis (UC) and Crohn’s disease (CD) has been associated with an increased risk of subsequent dysplasia and colorectal cancer. Historically, it was described that the neoplastic transformation in these inflammatory bowel diseases (IBDs) occurred via a different biologic pathway and not by the non-IBD polyp-cancer pathway and predictable lag time of progression. Therefore, prevention strategies have focused on the detection of dysplasia in flat mucosa, and existing guidelines have recommended performance of interval surveillance colonoscopies with random biopsies to identify such lesions with proctocolectomy when they are confirmed. Discussion  The use of a new technology higher-resolution colonoscopies has led to the appreciation more recently that dysplasia in IBD may be visible with standard optical colonoscopy and can be identified in an even more sensitive manner using chromoendoscopy. Furthermore, emerging evidence favors the intuitive understanding that neoplastic transformation in IBD is linked to the degree of inflammation and that disease control may therefore modify this risk and its subsequent prevention approaches. Conclusion  Future IBD cancer prevention strategies and timing of surgery in at-risk patients will require a better understanding of this evolving field. This paper was originally presented as part of the SSAT/AGA/ASGE State-of-the-Art Conference on Optimal Timing of Surgery for IBD at the SSAT 49th Annual Meeting, May 2008, in San Diego, CA. The other articles presented in the conference were Hodin RA, Introduction: Optimal Timing of Surgery for Inflammatory Bowel Diseases; McLeod RS, Ileal Pouch Anal Anastomosis: Pregnancy—Before, During and After; Sands BE, Fulminant Colitis; and Fleshman JW, Pyogenic Complications of Crohn’s Disease, Evaluation and Management.     

Associated neoplastic disease in inflammatory bowel disease

The development of intestinal carcinoma in the setting of inflammatory bowel disease (IBD) has been recognized as an unsavory outcome of chronic inflammation of the bowel. Numerous studies have recently documented the clinical and morphologic features of malignant transformation in this closely-followed group of patients. This article highlights the recent findings of these population-based studies with specific attention to surgical concepts and frames these data in the context of surgical approaches to cancer arising in inflammatory disease. Specifically, the authors address the pathobiology of malignant transformation, the management of colorectal cancer in inflammatory bowel disease, the development of dysplasia in ulcerative colitis, surveillance of patients who have IBD, chemoprevention of cancer, and special features of surgical oncologic management.