Colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis

PURPOSE: Most patients with primary sclerosing cholangitis also have ulcerative colitis. It has been suggested that in the presence of primary sclerosing cholangitis the risk of colorectal dysplasia and carcinoma is greater than in patients with ulcerative colitis alone. METHODS: In a retrospective study, we evaluated the possibility of colorectal cancer or dysplasia in 35 consecutive patients with primary sclerosing cholangitis and ulcerative colitis seen at The Johns Hopkins Hospital between 1979 and 1991. RESULTS: Thirteen of the 35 patients (37 percent) with ulcerative colitis and primary sclerosing cholangitis had colorectal neoplasia (5 with adenocarcinoma and 8 with dysplasia). In the 27 patients undergoing colonoscopic biopsy surveillance, the cumulative incidence at 28 years of colorectal cancer was 18.5 percent and for colorectal dysplasia it was 29.6 percent. The high incidence of colorectal cancer was less than the rate of colorectal cancer in patients with extensive colitis of childhood onset without primary sclerosing cholangitis (35 percent), but the rate of colorectal cancer and dysplasia (48.1 percent) is similar to the highest rates of cancer noted in the comparison group. Because patients had subtle, quiescent colitis, a short time from diagnosis of ulcerative colitis to diagnosis of colorectal neoplasia was noted (mean, 12.2±9 years; less than 8 years in 5/13 (38.5 percent) patients). CONCLUSION: Ulcerative colitis patients with primary sclerosing cholangitis appear to have a high frequency of colorectal cancer but a rate lower than expected in patients with extensive quiescent ulcerative colitis of childhood onset alone. However, exact conclusions are complicated by the high incidence of colorectal dysplasia found, which portends malignant transformation. Because of the subtle nature of colitis, the diagnosis of ulcerative colitis is often delayed, and surveillance programs should start as soon as ulcerative colitis is diagnosed.     

Increased expression of proliferative Ki-67 nuclear antigen is correlated with dysplastic colorectal epithelium in ulcerative colitis

Because patients with ulcerative colitis have an increased long-term risk of colorectal cancer, colonoscopic surveillance with multiple biopsies is commonly performed for histopathological detection of dysplasia to select high-risk patients for prophylactic colectomy. Improved differentiation between neoplastic vs. nonneoplastic changes is needed because active inflammation may cause significant misinterpretation of nonneoplastic reactive/regenerative changes in the epithelium. We investigated whether the expression of proliferative antigens is correlated with various degrees of epithelial dysplasia and inflammatory changes in biopsy specimens from patients with long-standing ulcerative colitis. Colorectal biopsy specimens from patients undergoing colonoscopic surveillance were analyzed immunohistochemically using two types of monoclonal antibodies: MIB-1 against Ki-67 and NCL-PCNA against proliferating cell nuclear antigen for structural, active inflammatory, and dysplastic changes. Specimens from patients without inflammatory bowel disease or neoplasia were used as controls; these showed no increased proliferation. However, increased staining with the MIB-1 monoclonal antibody was detected in 9% of the specimens from patients with long-standing ulcerative colitis without active inflammation or dysplasia; this was significantly more common in specimens indefinite for dysplasia, probably positive (24%), and in those with definite dysplasia of low (47%) or high grade (67%; P = 0.008). For increased PCNA staining, there was a nonsignificant correlation (P = 0.30) with increasing degrees of dysplasia. Increased MIB-1 immunostaining was found in 50% and increased PCNA immunostaining in 75% of the specimens displaying mild inflammation. Both antibodies had a 100% increased staining in specimens with moderate or severe inflammation. Increased proliferation as expressed by MIB-1 is thus better correlated with increasing degree of dysplasia than is PCNA. Neither staining method is able to differentiate neoplastic from inflammatory epithelial changes. However, in the absence of active inflammation, immunostaining for MIB-1 may be a valuable adjunct in the confirmation of dysplastic epithelial changes in long-standing ulcerative colitis, particularly in the indefinite changes category. Accepted: 26 February 1999     

Flow cytometric and histologic evaluation in a large cohort of patients with ulcerative colitis: correlation with clinical characteristics and impact on surveillance

PURPOSE: To examine the prevalence of DNA aneuploidy as a function of the extent of ulcerative colitis and to study the correlation of aneuploidy with clinical characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during colonoscopic surveillance was studied in a subset of these patients. METHODS: By analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have evaluated the importance of DNA ploidy measured by flow cytometry. We have also investigated the influence of extent (219 patients with extensive or total colitis vs. 149 patients with localized colitis) and duration of colitis on the development of dysplasia (patients with biopsy specimens that showed inflammation alone were compared with those with biopsy specimens that were equivocal or positive for dysplasia) and aneuploidy. Included was a subgroup of patients with ulcerative colitis and primary sclerosing cholangitis (n = 16). RESULTS: Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of aneuploidy increased by the extent of ulcerative colitis (2 percent localized, 6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of aneuploidy was higher in patients with disease duration longer than 10 years (P = 0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than patients without primary sclerosing cholangitis. CONCLUSION: Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.     

Dysplasia and carcinoma in longstanding ulcerative colitis: an endoscopic and histological surveillance programme.

From 1976 to 1989 a total of 66 patients with longstanding ulcerative colitis were entered in a colonoscopic surveillance programme in order to detect dysplasia. Thirty patients had extensive or total ulcerative colitis and 36 left sided colitis. The median duration of the disease at the end of the follow up was 15.0 years. Altogether 182 colonoscopies (2.8 per patient), each involving approximately 20 biopsies from different sites of the colon, were performed. In the total or extensive colitis group, five patients had low grade and one patient had high grade dysplasia. In the left sided colitis group, three patients had low grade dysplasia. In three patients low grade dysplasia was detected in a macroscopic lesion or mass of colonic mucosa. Sixty per cent of the dysplasia specimens were from the right colon. The incidence of dysplasia was higher in patients with extensive colitis and increased with the duration of the disease. None of the patients have so far developed colorectal carcinoma. Our results indicate that a colonoscopic surveillance programme is a safe alternative to prophylactic colectomy in longstanding ulcerative colitis.     

Proximal colorectal dysplasia or cancer in ulcerative colitis. The impact of primary sclerosing cholangitis and sulfasalazine

PURPOSE: Known risk factors for the development of colorectal dysplasia or cancer in ulcerative colitis are total colonic involvement and long duration of the disease. It has recently been suggested that presence of primary sclerosing cholangitis is another independent risk factor—especially for proximal colorectal dysplasia or cancer—and that treatment with sulfasalazine might reduce the frequency of colorectal cancer in ulcerative colitis; the present study was undertaken to shed light on the validity of these theories. METHODS: A total of 143 patients with ulcerative colitis underwent regular colonoscopies and multiple biopsies in a 20-year surveillance program for studies of long-standing total ulcerative colitis. Fifty-one of the patients developed colorectal dysplasia or cancer. Patient records were scrutinized retrospectively for information of presence of primary sclerosing cholangitis, site of the colorectal malignancy, and results of sulfasalazine treatment. RESULTS: Nineteen of the patients had primary sclerosing cholangitis; these ran a significantly higher risk of developing colorectal dysplasia or cancer than patients with ulcerative colitis only. All colorectal cancers (n=3) and 75 percent of all colorectal dysplasias or cancers among patients with primary sclerosing cholangitis were located in the proximal part of the colon, whereas 36 percent were found in that same region among the patients with ulcerative colitis without primary sclerosing cholangitis (P=0.02). Sulfasalazine treatment showed no significant protective effect on the development of colorectal dysplasia or cancer in patients with ulcerative colitis. CONCLUSION: The risk evaluation, as assessed by multivariate analysis, shows that primary sclerosing cholangitis proves to be an additional and independent risk factor for the development of colorectal dysplasia or cancer in patients with ulcerative colitis—particularly in the proximal part of the colon. The findings do not support the theory that sulfasalazine treatment exerts a protective effect against colorectal dysplasia or cancer.     

Diagnostic Value of DNA Image Cytometry in Ulcerative Colitis

The increased risk of colorectal cancer in patients with extensive, long-standing ulcerative colitis is well established. The interpretation of dysplasia as the common precursor lesion of colorectal cancer in ulcerative colitis is, however, subject to inter- and intraobserver variation. The histologic diagnosis is particularly difficult in the presence of acute inflammation. Therefore, the analysis of ploidy patterns might be a more objective diagnostic tool. In the present study, the correlation of ploidy and dysplasia of the colonic mucosa was evaluated in the absence and presence of inflammation. Image cytometry was performed on 561 fixed, paraffin-embedded tissue specimens from 67 patients with ulcerative colitis. Twenty patients had long-standing and extensive disease, including eight patients in whom the colitis was associated with colorectal cancer. Dysplasia was only found in patients with long-standing colitis or with colorectal cancer and was significantly more often diagnosed in the case of concomitant inflammation. On the other hand, aneuploid patterns were shown to occur independent of inflammatory activity. Aneuploidy was present in all colorectal carcinomas associated with ulcerative colitis and in 46.2% of specimens with dysplasia. Moreover, aneuploidy was detectable in four of 12 samples with low-grade dysplasia as well as in one case devoid of any dysplastic alteration. Ulcerative colitis patients with low-grade dysplasia plus aneuploidy probably represent a subgroup that might be at higher risk of developing colorectal cancer than patients with low-grade dysplasia alone. All in all, image cytometry analysis might be instrumental in identifying neoplastic lesions even in cases of increased inflammatory activity or regenerative change.     

Crohn’s Colitis: The Incidence of Dysplasia and Adenocarcinoma in Surgical Patients

Purpose Data supporting an increased risk of colorectal cancer in patients with Crohn’s colitis are inconsistent. Despite this, clinical recommendations regarding colonoscopic screening and surveillance for patients with Crohn’s colitis are extrapolated from chronic ulcerative colitis protocols. The primary aim of our study was to determine the incidence of dysplasia and carcinoma in pathology specimens of patients undergoing segmental or total colectomy for Crohn’s disease of the large bowel. In addition, we sought to identify risk factors associated with the development of dysplasia and carcinoma. Methods We performed a retrospective review of all patients operated on at our institution for Crohn’s colitis between January 1992 and May 2004. Data were retrieved from patient charts, operative notes, and pathology reports. Logistic regression was used to model the probability of having dysplasia or adenocarcinoma. Results Two hundred twenty-two patients (138 females) who underwent surgical resection for the treatment of Crohn’s colitis were included in the study. Mean age at surgery was 41 (range, 15–82) years and the mean duration of disease was 10 (range, 0–53) years. There were five cases of dysplasia (2.3 percent) and six cases of adenocarcinoma (2.7 percent). Three patients with dysplasia and one with adenocarcinoma were diagnosed on preoperative colonoscopy; while the other cases were discovered incidentally on pathologic examination of resected specimens. Factors associated with the presence of dysplasia or adenocarcinoma included older age at diagnosis (38.2 vs. 30.3 years, P = 0.02), longer disease duration (16.0 vs. 10.1 years, P = 0.05), and disease extent (90 percent extensive vs. 59 percent limited, P = 0.05). Conclusions Patients with severe Crohn’s colitis requiring surgery are at significant risk for developing dysplasia and adenocarcinoma, particularly when diagnosed at an older age, after longer disease duration, and with more extensive colon involvement. Presented at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005. Reprints are not available     

Dysplasia in chronic ulcerative colitis: Implications for colonoscopic surveillance

Mucosal dysplasia has been used as a marker for patients with chronic ulcerative colitis considered to be most at risk of developing cancer, and its identification is the basis for colonoscopic surveillance programs. To evaluate the reliability of this premise, colectomy specimens from two groups of patients who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50 without) were retrieved. The groups were matched by age, sex, duration of disease, disease extent, and symptoms at the time of surgery. Using a standard technique of multiple random biopsies, we utilized the standard colonoscopic biopsy forceps to obtain four biopsies from mucosa that was not macroscopically suspicious for dysplasia or cancer in eight defined regions in each of the 100 colon specimens. This technique mimicked exactly the methods used in our clinical surveillance program. All 3,200 biopsies were evaluated blindly by one pathologist for presence and grade of dysplasia. Twenty-six percent of colons with an established cancer harbored no dysplasia in any biopsy from any region in the colon. While an overall association between the presence of cancer and high-grade dysplasia was detected (relative risk = 900; 95 percent CI of 2.73-29.67), the sensitivity and specificity of random colonic biopsies to detect concomitant carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that reliance on random biopsies, obtained during colonoscopic surveillance, may be misplaced.Supported in part by Research Grant DK37990 from the National Institutes of Health and by the Mayo Foundation.     

Screening and surveillance colonoscopy in chronic Crohn's colitis

BACKGROUND & AIMS: Unlike ulcerative colitis, there are few reports on the efficacy of surveillance colonoscopy in patients with chronic Crohn's colitis and therefore little agreement as to whether routine surveillance is indicated. We report on 259 patients with chronic Crohn's colitis who underwent screening and subsequent surveillance colonoscopy and biopsy since 1980. METHODS: Biopsies were performed at 10-cm intervals and from strictures and polypoid masses. Pathology was classified as normal, dysplasia (indefinite, low-grade, high-grade), or carcinoma. RESULTS: A total of 663 examinations were performed on 259 patients. The median interval between examinations was 24 months; examinations were performed more frequently (1-6 months) in patients with dysplasia on biopsy. A thinner-caliber colonoscope was required to complete 12% of screening examinations and 23% of surveillance examinations. The pediatric colonoscope helped increase our yield of neoplasia by 19%. The screening and surveillance program detected dysplasia or cancer in 16% (10 indefinite, 23 low-grade, and 4 high-grade dysplasias and 5 cancers). A finding of definite dysplasia or cancer was associated with age >45 years and increased symptoms. By life table analysis, the probability of detecting dysplasia or cancer after a negative screening colonoscopy was 22% by the fourth surveillance examination. CONCLUSIONS: Colonoscopic surveillance should be strongly considered in chronic extensive Crohn's colitis.     

Surveillance colonoscopy for colitic cancer in inflammatory bowel disease

Patients with inflammatory bowel disease are known to be at increased risk for the development of colorectal cancer, especially those with long‐standing extensive ulcerative colitis. Although some recommend prophylactic total proctocolectomy for these high‐risk patients, surveillance colonoscopy to detect ulcerative colitis‐associated colorectal cancer is, instead, generally performed. Dysplasia has been considered to be a useful marker to detect colorectal cancer at surveillance colonoscopy. High‐grade dysplasia is a definite indication for total proctocolectomy, while management of low‐grade dysplasia is still controversial. Patients with Crohn's disease are also considered to be at higher risk for the development of colorectal cancer, although the risk may be lower than in extensive ulcerative colitis. Molecular biology‐based surveillance and chemoprevention for ulcerative colitis‐associated colorectal cancer are also reviewed.     

Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis

BACKGROUND & AIMS: Long-standing ulcerative colitis has long been recognized as a risk factor for colorectal cancer, but there is still no universal consensus on the optimal management of ulcerative colitis patients with low-grade dysplasia in flat mucosa. Some authorities favor prompt colectomy, whereas others recommend continued surveillance. The purpose of our study was to determine the frequency with which flat low-grade dysplasia in ulcerative colitis progresses to advanced neoplasia (high-grade dysplasia or colorectal cancer) and whether specific variables could predict such progression. METHODS: We reviewed the medical histories, colonoscopic findings, and surgical and pathology reports of 46 patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a surveillance colonoscopy. The rates of neoplastic progression, as well as the frequency of advanced neoplasia, were tabulated. We correlated progression with several clinical and colonoscopic variables: the number of biopsy samples positive for flat low-grade dysplasia, the duration and anatomic extent of disease, patient age, and medication use. RESULTS: Among these 46 patients, there were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic progression was 53% at 5 years. No clinical features predicted progression to advanced neoplasia. Cancers, including 2 at advanced stages, developed despite frequent follow-up surveillance examinations. CONCLUSIONS: A finding of flat low-grade dysplasia during ulcerative colitis surveillance is a strong predictor of progression to advanced neoplasia. Early colectomy should be recommended for such patients.     

Liver involvement in patients operated for ulcerative colitis, with special reference to the association of cholangitis with colorectal dysplasia and carcinoma

This study classified liver changes found in patients undergoing proctocolectomy for ulcerative colitis and examined whether patients with cholangitis have an increased risk of colorectal dysplasia and carcinoma. The patients were 152 who underwent liver biopsy during surgery for ulcerative colitis. Prior surveillance colonoscopy specimens and operative liver and proctocolectomy specimens were examined histologically. Patients with dysplasia or carcinoma in colorectal specimens were pair-matched to patients without such neoplasia. Sixteen (10.5%) patients had histological features consistent with small-duct primary sclerosing cholangitis on liver biopsy, five of them showing normal liver function values. Of the 152 patients 4 were found to have colon carcinoma (2.6%) and another 4 low-grade dysplasia (2.6%) either upon colonoscopy or in colectomy specimens. The median duration of the colitis in the 8 patients with colorectal neoplasia was 12 years (range 2–29) and in the other 142 patients 4 years (0.1–33; P=0.007). The prevalence of primary sclerosing cholangitis (PSC) or cholangitis was 50% in cases with colorectal neoplasia and 13% in pair-matched controls without colorectal neoplasia. In this selected group of patients operated on for ulcerative colitis the prevalence of histological cholangitis was thus higher than that of PSC in previous epidemiological studies. In addition, the prevalence of PSC or cholangitis was much higher in cases with colorectal neoplasia than in pair-matched controls without colorectal neoplasia. Our results support the view that cholangitis constitutes an additional risk factor underlying colorectal dysplasia or carcinoma. Accepted: 17 April 2000     

How gastroenterologists screen for colonic cancer in ulcerative colitis: an analysis of performance

BACKGROUND: The aim of this study was to assess the colorectal cancer surveillance practices of British gastroenterologists for patients with ulcerative colitis. METHODS: A questionnaire that investigated aspects of surveillance in patients with ulcerative colitis was mailed to all consultant gastroenterologists in the U.K. (n = 413). RESULTS: Three hundred forty-one questionnaires were returned (response rate 83%). Ninety-four percent of consultants practice cancer surveillance in ulcerative colitis, with 35% maintaining a registry of patients in surveillance programs. All gastroenterologists perform surveillance in patients with pancolitis, 24% in those with left-sided colitis and 2% in patients with proctitis. The mean duration of disease before surveillance is commenced is 9.2 years for pancolitis and 12.4 years for left-sided colitis (p < 0.0001). Only 4% of gastroenterologists routinely offer patients with disease of more than 10 years' duration a prophylactic colectomy. Colonoscopies are conducted by an accredited gastroenterologist in 65% of cases and biopsies are reviewed by specialists in gastrointestinal pathology in 45%. When histology reveals low-grade dysplasia only 4% advise colectomy and when high-grade dysplasia is found 53% recommend colectomy. Sixteen percent of gastroenterologists were unaware of the significance of a dysplasia associated lesion or mass. CONCLUSION: The majority of gastroenterologists practice surveillance on a disorganized basis. There is inconsistency in the management of patients with dysplasia and education of gastroenterologists is needed.     

Incidence,risk factors,and treatment of dysplasia in the anal transitional zone after ileal pouch-anal anastomosis

Preservation of the anal transitional zone (ATZ) after restorative proctocolectomy and stapled ileal pouch-anal anastomosis (IPAA) for ulcerative colitis is controversial. PURPOSE: To evaluate the incidence, risk factors, and treatment options for dysplasia and/or cancer after restorative proctocolectomy and stapled IPAA. METHODS: We reviewed the records of all 254 patients operated on for ulcerative colitis who had a restorative proctocolectomy, stapled IPAA, and annual postoperative biopsies of ATZ. Follow-up studies included an annual questionnaire and physical examination. RESULTS: During a follow-up of 2.3±1.4 (mean ± standard deviation) years, low-grade dysplasia was found in eight patients (3.1 percent), 16 (median: range, 6–56) months after surgery. Repeated biopsies revealed dysplasia in only two of eight patients, and completion mucosectomy was performed. Dysplasia in ATZ was associated with a preoperative (P=0.02) or postoperative (P=0.04) pathologic diagnosis of ulcerative colitis with concurrent dysplasia or cancer. No association (P>0.05) was found between dysplasia and the following: age, sex, preoperative length of disease, use of a double-stapledversus single-stapled technique, or anastomotic distance from the dentate line. CONCLUSIONS: Incidence of low-grade dysplasia in ATZ was low. Restorative proctocolectomy with total mucosectomy of the anal canal and handsewn IPAA is recommended for patients with preoperative diagnosis of ulcerative colitis and concurrent cancer or dysplasia. Frequent follow-up with biopsies is recommended for patients with incidental finding of cancer or high-grade dysplasia after restorative proctocolectomy and stapled IPAA with preservation of ATZ. For persistent or recurrent low-grade dysplasia, we recommend a completion mucosectomyRead at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Dysplasia complicating chronic ulcerative colitis

PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77 vs. 5/513; P < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.     

Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration

Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question.     

DNA content in ulcerative colitis

Sixty patients with ulcerative colitis of more than nine years' duration and 13 patients with a shorter disease duration were examined over a three-year period with flow cytometric DNA analysis and conventional histologic investigation of biopsy specimens obtained by colonoscopy. The patient series included all patients with ulcerative colitis from a colonic cancer surveillance program in a defined area. There were five patients-one who developed colonic cancer, one with high-grade dysplasia, and three with low-grade dysplasia. None of these showed aneuploidy (abnormal DNA stem lines). There were six patients with aneuploidy in one to six locations in the colorectum. On consecutive examinations, there was a high reproducibility of the abnormal DNA pattern for ploidy levels and location in the bowel. In these patients, there was no obvious relationship with definite dysplasia. It is concluded that flow cytometric DNA analysis in ulcerative colitis may become a valuable complement to evaluation of dysplasia in cancer surveillance, but assessment of the cancer risk in individual patients with aneuploidy needs further investigation.     

Ulcerative colitis. Cancer surveillance in an unselected population

An unselected series of patients with chronic ulcerative colitis from a defined catchment area underwent endoscopic and histologic cancer surveillance from 1977 to 1985. At the end point of the study, which included a total of 93 patients, there were 38 patients with total colitis of more than 10 years' duration. There was one case of colonic carcinoma, two cases of high-grade dysplasia, and no death due to colorectal cancer. We conclude that in an unselected group of patients with ulcerative colitis, the risk for colorectal dysplasia and cancer is low and that a surveillance program is reliable and can be performed at a community hospital.     

Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis

Patients with extensive ulcerative colitis have a high risk of developing colon cancer. The etiology of mucosal dysplasia, a premalignant lesion that is used as a screening test in surveillance programs, is unknown. Previously, a case-control study [Lashner et al. (1989) Gastroenterology 97:255–259] suggested that folate supplementation was associated with a 62% reduction in the risk of developing dysplasia or cancer. The current case-control study was performed to obtain a better definition of this risk.All 67 patients with chronic ulcerative pancolitis having surveillance colonoscopy during a 1-year period were entered. There were 6 cases (4 with dysplasia and 2 with cancer) and 61 controls (no cancer or dysplasia). Red blood cell folate, reflecting intermediate-term stores, was a mean of 66.2 ng/ml lower in cases compared to controls. Serum folate, reflecting short-term stores, was not different between groups. Adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68–0.99). Vitamins A, D, and E and carotene were lower in cases than in controls, but no water-soluble vitamin other than red blood cell folate was associated with an increased cancer risk. Depressed red blood cell folate is associated with an increased risk of dysplasia and cancer in patients with ulcerative colitis and may be a risk factor for neoplastic transformation.Research supported by the Washington Square Health Foundation, the University of Chicago Clinical Nutrition Research Unit, and the Gastrointestinal Research Foundation Junior Board     

Efficiency of colorectal cancer surveillance in patients with ulcerative colitis: 26 years’ experience in a patient cohort from a defined population area

Objective. Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). The current procedure to diminish this risk is colonoscopic surveillance and histopathological evaluation of biopsy specimens. This method is not unquestioned and is undergoing continuous evaluation. The present study is a major update of an earlier reported investigation from an ongoing surveillance programme.Material and methods. In 1977 a colonoscopic surveillance programme comprising all patients with UC from a defined area was started in Örnsköldsvik. Three principal investigators performed regular colonoscopy with mucosal sampling for histopathological evaluation. Some 211 patients were studied from 1977 to 2002. At the end of the study period, 90 patients, including those operated on, had total colitis (TC) for more than 10 years, 74 patients had left the study, 31 after panproctocolectomy (PPC), 6 owing to advanced biological age, 1 because of intercurrent disease, 23 patients had moved out of the area and 13 patients were excluded because of poor compliance. In all, 928 colonoscopies were performed.Results. It was found that 135 patients had radiologically or morphologically defined TC and 69 patients had left-sided colitis (LC). Nine CRCs were diagnosed in 8 patients, one of whom died of CRC, while another two were included in the programme with a diagnosis of CRC. Morphological alterations classified as dysplasia or indefinite for dysplasia (ID) were found in 52 patients, 5 of whom were later found to have CRC. In total, 49 patients were operated on; in 15 of these patients the indication for surgery was dysplasia or CRC. Eighteen of the patients were operated on for different kinds of colonic resections and in 31 patients a PPC was performed.Conclusions. Colonoscopic surveillance is an effective method in preventing death from CRC among patients with UC. A conservative approach to surgery seems to be justified. The burden of the surveillance programme has been acceptable. The outcome depends on good patient compliance as well as the involvement of as few investigators as possible.