Dysplasia-carcinoma sequence in the small bowel. 

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... a contrast gradient that enhances visualization. Chemoendoscopy seems to improve the sensitivity of detecting neoplasia and in addition to this offers potential to improve specifity as well, by facilitating enhanced endoscopic characterization of lesions. This allow the endoscopist to perform fewer biopsies more targeted. The combination of chemoendoscopy with magnification permits a detailed analysis of the mucosal helping to differentiate between benign and malignant lesions. Despite the promising information about this technique chemoendoscopy is not yet considered a standard of care approach to surveillance because of its cost and lack of training (Zisman & Rubin, 2008). 5-aminosalicylates are currently the most acknowledged treatment for colorectal cancer prevention in patients with Crohn’s disease and the evidence of this protective role for 5-aminosalicylates against colitis-associated colorectal cancer is known since several years (Pinczowski et al., 1994; Viennot et al., 2009). Several recent studies confirmed this evidence (Van Staa et al., 2005; Velayos et al., 2005) even if not all authors are agree on this protective effect, because there is an important heterogeneity of individual study results and the best avaible data interpretation appears to be that of published meta-analysis (Viennot et al., 2009). Similar roles are played by non-steoroidal antinflammatory drugs and ursodeoxycholic acid (Itzkowitz, 2002). Is now generally accepted that Crohn’s disease is associated with an increased risk of cancer. An increased risk of cancer in the intestinal tract is in fact detectable in patients with Crohn’s disease, although not specifically have seen increases in incidence or relative risk of oropharynx, esophagus and stomach cancer than the general population; an upward trend has been documented for anus cancer. The risk of developing lymphoma is also increased. Controversial and difficult to interpret are the data on the association between Crohn’s disease and other cancers. The colorectal cancer in patients with Crohn’s disease has particular characteristics that set it apart from sporadic cancer. Generally diffuse, with multiple characters, it may not be obvious macroscopic observation or involve the entire bowel wall with stricture formation, remaining silent with regard to the symptoms until an advanced stage: at this point is generally manifested by obstructive type symptoms , weight loss and presence of abdominal mass. Sometimes it can occur in association with fistulas or may occur in loops. The colorectal cancer in Crohn’s disease frequently affects younger patients (48 vs. 70 years) and is localized preferably in the right colon (45% vs. 20% of cases), compared with the cancers arose de novo (Figure 1). A diagnosis of Crohn’s disease prior to age 25 is associated with an increased risk of cancer (Weedon et al., 1973; Greenstein et al., 1981), as well as a long-standing Crohn’s disease (Fireman et al., 1989). Patients with severe Crohn’s disease with extensive involvement of the large intestine and diagnosed before 25 years of age, not previously subjected to an intervention of prophylactic colectomy are at high risk for the development of a colorectal surveillance examinations is dependent on each individual’s personal risk factors. In patients with a previous history of primary sclerosing cholangitis, active inflammation, dysplasia or stenosis, family history of bowel cancer annual surveillance is raccomanded (Kiran et al., 2010). Colectomy is strictly raccomanded for patients who were diagnosed with flat high-grade dysplasia or colorectal cancer and where diagnosis was confirmed by expert gastrointestinal pathologists. In patients with a biopsy indefinite for dysplasia, guidelines suggests colonscopy between 3 and 12 months. Multifocal low grade dysplasia is a stronger indication for colectomy. The optimal colonscopic surveillance interval for patients who were diagnosed with a flat low grade dysplasia is still unknown, but 3-6 months is often recommended (Lukas, 2010). Although guidelines currently exist, limitations of these guidelines indicate the need to continue research into the molecular pathogenesis of Crohn’s disease associated colorectal cancer with the hope to identify targets for prevention. Advances in endoscopic imaging are alredy underway and may potentially aid in detection of dysplasia and improve surveillance. Management of dysplasia depends above all on the focality of dysplasia itself with the mainstay of involving proctocolectomy or continue endoscopic surveillance. Continued research on additional chemopreventive agents may reduce the incidence of Crohn’s disease colorectal cancer but further studies are necessary to get this goal (Ahmadi et al., 2009). Most tumors of the small intestine in patients with Crohn’s disease are composed of adenocarcinoma of the jejunum and terminal ileum, rarely diagnosed at an early stage likely to care (Fornaro et al., 1994, Figure 4). The most common clinical presentation of small bowel cancer is intestinal obstruction (Greenstein et al., 1978). Other important symptoms are diarrhea, weight loss and fistulae. They, too, such as colorectal cancer, differ from the adenocarcinomas occurred de novo in several respects. The mean age of patients is generally lower (45 vs. 60 years), the cancer occurs more often distally with multiple characters (76% vs. 20% of cases) or in loops (Greenstein et al., 1978), attributable to the postoperative life even reduced to 8 months (Greenstein, 2000). Sarcomas are rarely seen in the small intestine in patients with Crohn’s disease: these rather represent a third of cancers arose de novo. Risk factors for developing carcinoma in small bowel segments of involved mucosa in patients with Crohn’s disease are poorly defined but numerous case reports document them in strictured mucosa and fistulae. Surgery must be considered if it’s difficult to examine fistulae and strictures or if symptoms worsen (Xie & Itzkowitz, 2008). A long-standing history of Crohn’s disease is most frequently associated with the appearance of small intestine tumors. Small intestine cancers occurs, as told above, in two thirds of cases with symptoms of obstructive (Greenstein et al., 1978; Greenstein, 2000); diarrhea, weight loss, fistulas, abdominal masses, may also be present. A delay in diagnosis may be partly justified by a non-specific accompanying symptoms and the presence of such symptoms in patients with quiescent Crohn’s disease for a long time, however, must lead early on the implementation of appropriate diagnostic tests. The prognosis of small intestine cancer in patients with Crohn’s disease is poor (Crohn et al., 1932). The relative risk of developing small intestine cancer in Crohn’s disease patients is higher than in the general population (Von Roon et al., 2007), increasing in relation to the anatomical segment affected by chronic inflammation (Greenstein et al., 1981; Jess et al., 2004). Patients with Crohn’s disease exclusively localized to the ileum only have a higher risk of developing a small intestine cancer (Von Roon et al., 2007). Although the risk of developing small intestine cancer is higher in patients with Crohn’s disease compared with that found in the general population, it remains, in absolute terms, rather than restricted. In fact the absolute number of cases of small bowel adenocarcinoma is low because of the rarity of this cancer in the general population but in patients with Crohn’s disease the risk is greater than in the general population. This risk vary in the different studies reported in literature. Based on the stated, hypothesis of a correlation between a chronic inflammation and cancer seems reasonable (Itzkowitz & Yio 2004). The different modes of clinical presentation, with symptoms often generic and nonspecific, and the difficulties of endoscopic evaluation of the small intestine, now partly overcome by modern techniques videocapsulo-tele-endoscopy, the difficult exploration of strokes or bypassed affected by stenosis or possibility of an occult malignancy are important limitations to the surveillance of these patients. Outpatient visits, with particular emphasis on examination of the abdomen and the perineal skin, accompanied by a careful anamnestic investigation aims to investigate the occurrence or the modification of old and new symptoms, especially if it occurred after a long period of quiescence of the disease, could be a viable alternative to more cumbersome methods of surveillance. Segmental resection is preferable to surgery in patients with Crohn’s disease complicated by small intestine carcinoma (Greenstein, 2000). The risk of developing squamous cell carcinoma of the anus is increased (Von Roon et al., 2007). Worsening perianal symptoms in these patients should warrant vigilance for this tumor which often requires examination under anesthesia for adequate tissue diagnosis. An increased risk for hepatobiliary cancers in patients with primary sclerosing cholangitis (Xie & Itzkowitz, 2008). There is nothing, however, statistically significant increases with regard to the oropharynx , esophagus and stomach cancer. These data find ample confirmation in the literature (Mellemkjaer et al., 2000; Von Roon et al. 2007). There is also an association between Crohn’s disease and carcinoid tumors, found primarily in the appendix (Fornaro et al 1998; Szabo et al. 1999; Fornaro et al., 2007). The onset of cancer in loops is described in the literature (Greenstein et al., 1978): This complication has led to the abandonment of the internal bypass interventions, largely carried out until the 60s, now played only in exceptional cases, urgently. Patients with perianal Crohn’s disease out to meet the development of squamous cell carcinoma of the anus are usually treated with an abdominal- perineal resection (Greenstein, 2000; Sjodahl et al., 2003), or alternatively can be treated with ...