(1)
Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
Keywords
IBDUlcerative colitisCrohn’s diseaseIntestinal cancerRisk13.1 Ulcerative Colitis
13.1.1 Epidemiology
Colorectal cancer (CRC) has long been a major clinical problem in ulcerative colitis (UC), and many studies have examined its incidence and risk factors. Eaden et al. conducted a meta-analysis of CRC in UC and reported that the rate of complicating CRC was 3.7 % in all UC cases, and the cumulative cancer incidence rate was 1.6 % at 10 years after onset of UC, increasing to 8.3 % after 20 years and 18 % after 30 years [1]. As disease duration increases, so does the risk of developing CRC [2, 3]. Many recent studies have reported that this risk of acquiring CRC has decreased over recent decades. In 2004, Winther et al. reported that the risk of developing CRC at 30 years after onset of UC was 2.1 % [4], while Lakatos et al. reported a risk of 7.5 % [5]. From a surveillance study of about 600 subjects, Rutter et al. reported that the cumulative CRC onset rate was 2.5 % at 20 years, 7.6 % at 30 years, and 10.8 % at 40 years [6]. The risk of acquiring CRC has thus decreased over the decades (Table 13.1). The causes of this are thought to be advances in pharmacotherapy, increased excision of premalignant lesions, and better techniques in colon resection, as well as the spread of surveillance colonoscopy (SC).
Table 13.1
Cumulative incidence of colitis-associated cancer in UC
Author, year, area | Subject | Year after UC | |||
---|---|---|---|---|---|
10 | 15 | 20 | 30 | ||
Gilat T, 1988, Israel | Population | 0.2 % | 2.8 % | 5.5 % | 13.5 % |
Lennard-Jones JE, 1990, UK | Institutional | 3.0 % | 5 % | ||
Eden JA, 2001 | Meta-analysis | 2 % | 8 % | 18 % | |
Winther, 2004 | Population | 2.1 % | |||
Lakatos, 2006 | Population | 0.6 % | 5.4 % | 7.5 % | |
Rutter, 2006 | Institutional | 2.5 % | 7.6 % | ||
Herrinton, 2012 | Institutional | 60 % higher than GP | |||
Hata, 2003, Japan | Institutional | 0.5 % | 4 % | 6 % |
13.1.2 Risk Factors
The clinical characteristics of UC-associated CRC are similar in Western and Eastern countries. Long-standing disease represents an important risk factor, and since the age of UC onset is young, CRC occurs at a younger age (40s) than in the general population. CRC is estimated to be the cause of death in about 20 % of UC cases [7, 8]. The incidence of multiple cancers is about 30 %. Since UC is present in the background mucosa, the morphology and histological findings vary and present different appearances from general CRC. There is a high incidence of flat and invasive types. Histologically, a characteristic of these cancers is that poorly differentiated adenocarcinoma and mucinous carcinoma account for about half of cases. A relationship with the severity of colitis has been indicated, and attention has been directed to the relationship with tissue inflammation [9, 10]. Factors raising the risk of CRC have recently been considered to be disease duration, extent of the diseased colon, family history of colon cancer, concomitant primary sclerosing cholangitis, and persistence of colitis. Conversely, factors that lower the risk are reported to be prophylactic colectomy, regular examination by a doctor, SC, chemical prevention, and adherence to treatment.
13.1.3 Purpose and Targets of SC
As mentioned above, patients with long-standing UC have a high risk of complicating CRC against a background of chronic inflammation. There is also a high rate of dysplasia, which is thought to represent a precancerous lesion. For that reason, surveillance for dysplasia as a cancer marker is recommended. Regular SC is thought to be essential for early detection of cancer or dysplasia. In fact, it has been shown that with regular SC, cancer or the related dysplastic lesions can be detected and treated at an early, curable stage [11, 12].
The main purpose of surveillance is to reduce deaths from CRC by detecting and excising precancerous lesions. A study by Choi et al. [13] looked at 41 patients who developed cancer, comprising 19 in an SC group and 22 in a non-SC group. A significant difference was seen between groups in 5-year survival, confirming the efficacy of SC [13]. In a recent study by Lutgens et al., 149 patients who developed cancer were studied, including an SC group of 23 patients. This SC group included many early-stage tumors than in non-SC group (52 % vs. 24 %), the mortality rate was lower (4 % vs. 24 %), and the 5-year survival rate was significantly higher than in the non-SC patients [14]. Based on the above studies, the decrease in mortality rate was concluded to be as much as 63 %. The largest study was one by Rutter et al. at St. Mark’s Hospital [6]. As a result of long-term SC, cancer was detected in 5 % of patients, and their prognosis was shown to be fair. The method of SC used was not perfect but was judged to be effective.
13.1.4 Endoscopic Images
The macroscopic picture of CRC in UC is thought to be protruding cancer in many cases, but few accurate statistics are available. Matsumoto et al. classified and reported endoscopic findings of UC-associated CRC using a dye method [15] (Table 13.2).
Table 13.2
Endoscopic classification for colorectal cancer associated with UC
1 | Protruded lesion (DALM) | Most common, irregularity, uneven redness, surrounded by slightly elevated mucosa |
2 | Slightly elevated lesion | Irregular granular surface, uneven redness |
3 | Flat lesion | Reddish lesion with defined boundary |
4 | Depressed lesion | Uncommon, accompanied by slightly elevated lesion |
5 | Mixed-type lesion |
They divided cancers into protruded lesions (Figs. 13.1 and 13.2), slightly elevated lesions (Figs. 13.3, 13.4, and 13.5), flat lesions (Figs. 13.6, 13.7, 13.8, and 13.9), depressed lesion (Fig. 13.10), and mixed-type lesions (Fig. 13.2) and presented endoscopic images of each. Appropriate endoscopic classifications like this are needed. Of course, the protruded lesion called dysplasia-associated lesion or mass (DALM) (Figs. 13.2, 13.3, 13.4, and 13.5) is the most important finding [16]. DALM presents diverse morphologies, including villiform, coarsely granular, and irregular flat-elevated shapes, with margins that are often indistinct. Changes in color tone have been confirmed in flat dysplasia, but differentiation from surrounding inflammatory regenerated mucosa is difficult (Figs. 13.5, 13.6, 13.7, 13.8, and 13.9). In endoscopy, abnormalities are seen even in non-tumor areas because of the inflammation in UC, making detection and definitive diagnosis of neoplastic lesions tricky. As mentioned above, a special care is needed in stenotic portions (Figs. 13.11 and 13.12).
Fig. 13.1
Protruded-type cancer in long-standing UC. Endoscopic view of a protruded-type cancer showing an irregular and nodular surface (a). Histologic picture of a protruded-type cancer with UC (b). Resected specimen shows IIa-like protrusion, and histologically, this tumor was diagnosed as well-differentiated adenocarcinoma and tumor invaded down to the subserosa (Quoted from Nishimura et al. [30], under permission of publisher)
Fig. 13.2
Protruded-type cancer in UC. A 29-year-old patient with long-standing refractory UC, disease duration 11 years, total colitis. Colonoscopic view of a reddish, protruded-type cancer (Is) in the sigmoid colon (a). The lesion seemed to be soft, and the surface is covered by granular or papillary mucosa, but surrounding mucosa has abnormal granularity. Histological examination showed very well to poorly differentiated adenocarcinoma (b) with mucinous degeneration invading into the deeper portion of the submucosa and surrounding area of dysplastic epithelium
Fig. 13.3
(a) Endoscopic view of a slightly elevated tumor with granular surface in the transverse colon. (b) Histologic picture of a slightly elevated lesion. Histologically, the tumor showed IIa + Is-like advanced cancer invading down to deeper parts of the muscularis propria (Quoted from Nishimura et al. [30], under permission of publisher)
Fig. 13.4
Slightly elevated lesion in the rectum was polypectomized. A 60-year-old; disease period, 22 years; total colitis. The slightly elevated lesion of the rectum consisted of very well- to well-differentiated adenocarcinoma confined to the mucosa
Fig. 13.5
Slightly elevated lesion. A patient in their 40s at diagnosis; disease period, 25 years; total colitis. A surveillance colonoscopy detected malignant elevations in the descending colon. The tumors comprised well- to moderately differentiated adenocarcinoma invading into the subserosa
Fig. 13.6
Flat lesion. A 46-year-old patient; disease period, 18 years; total colitis. Surveillance colonoscopy detected a flat lesion with superficial irregularity. Histological diagnosis was a mucosal lesion with moderately to severely dysplastic epithelium highly suggestive of well-differentiated adenocarcinoma
Fig. 13.7
Flat lesion. A 76-year-old patient; disease period, 4 years; left-sided type. Extremely difficult to diagnose as cancer. Endoscopic findings showed a flat lesion with low-grade inflammation and ill-defined margins. Histologically, the tumor consisted of adenocarcinoma and dysplastic epithelium in the sigmoid colon
Fig. 13.8
Macroscopic picture of a flat lesion and a protrusion. A 46-year-old patient; disease period, 26 years; left-sided colitis type. Schematic illustration of the resected colon and rectum. In Rb there is a protrusion which is composed of well-differentiated adenocarcinoma with mucinous change invading into the adventitia. In Ra there showed a broad, flat lesion with well-differentiated adenocarcinoma invading into the superficial part of the submucosa