Precancerous Lesions and Conditions

Dysplasia is the precancerous lesion from which CRC develops [3]. More than 70% of patients with CRC on UC show the presence of dysplasia on colorectal

Table 1. Risk of CRC and duration of the disease

Risk (%)

Duration of the disease (years)

0.7

10

3.4

15

7.2

20

11.6

25

Table 2. Risk of CRC and duration of the disease

Risk (%)

Duration of the disease (years)

2

10

8

20

18

30

mucosa [4, 5] with a transformation rate of 45% for severe dysplasia; for mild-low dysplasia there is less evidence in the literature to make a similar analysis [6, 7]. Furthermore, high grade dysplasia on rectal mucosa is a marker for the presence of CRC anywhere in the colon in 45% of the patients [8]. For these reasons, long-standing colitis with a history of 7 years or more warrants close follow-up.

Ullman et al. [8], in a review from the Mayo Clinic experience from 1990 to 1993, studied 18 patients with a mean follow-up of 32 months with a low-grade dysplasia; nine patients showed a neoplastic lesion (high-grade dysplasia or CRC) in the follow-up with a progression rate of 33% at 5 years. One patient developed a CRC 20 months after the last colono-scopy performed 74 months after the diagnosis of low-grade dysplasia. So, the Authors' conclusion was that a prophylactic colectomy should be performed for patients with long-standing colitis and dysplasia.

Moreover, about 25-68% of the patients with UC developed a CRC without any evidence of dysplasia; for these patients a different pattern of neoplastic growth should be hypothesised, with the need for new clinical and biological markers for transformation [4, 5, 9-11].

Sclerosing cholangitis (SC) is an additional and independent prognostic factor of CRC on UC. From a meta-analysis on 11 comparative studies, SC has been shown to be a significant risk factor for dysplasia or CRC in patients with UC [12].

Shetty et al. [13] compares two groups of patients, 132 with SC and 196 controls with UC without SC; CRC and dysplasia were more frequent in patients with SC (25 vs. 5.6%) and the tumours were localised more proximally and of a more advanced stage. Furthermore, the CRC related mortality for patients in the SC group was significantly higher (4.5 vs. 0%; p<0.01).

Similar results were obtained by Linberg et al. [14]: of 143 patients with UC followed for 20 years (19 SC), those with SC showed a predisposition for developing CRC and/or dysplasia with tumours located proximally (p=0.02).

Table 3. Stage and CRC on UC

CRC (%)

Dukes' stage

40 on UC

A-B

60 on UC

C-D

63 without UC

A-B

36 without UC

C-D

Habermann et al. [15] studied many biological risk factors; aneuploid DNA distribution patterns, laminin-5 gamma2 chain and cyclin A expression can identify a group of UC patients with an increased risk for cancer development (p=0.006, p=0.002, p=0.014 respectively).

CRC on UC is correlated to a more advanced stage compared with CRC without UC (Table 3).

Van Heerden et al. [16] showed that 5-year survival in 70 patients with diagnosis of CRC on UC was worse compared with patients operated on for prophylactic colectomy with incidentally diagnosed CRC (72 vs. 35%).

Connell et al. [5], in a study of 120 patients operated on for 157 CRC on UC (CRC located in the sigmoid or rectum in 67.5% of the patients) showed that five-year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p=0.024).

An important issue in the diagnosis and treatment of patients with or at risk for CRC on UC is the management of the stenosis. Lashner et al. [17] studied 15 patients with stenosis on UC (3.2% of all UC); eleven patients showed the presence of dysplasia and two patients had a CRC at colonoscopy biopsy. Ultimately, six patients showed a carcinoma found at colonoscopy or colectomy. All cancers were at the site of a stricture. These findings indicate that a true colonic stricture in UC is frequently associated with dysplasia and cancer. For this reason a stricture should be considered a strong risk factor for cancer and, if dysplasia is discovered or if the stricture cannot be adequately biopsied, consideration should be given to total colectomy [17].

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