Cancer surveillance in ulcerative colitis: critical analysis of long-term prospective programme

BACKGROUND: Patients with longstanding ulcerative colitis are at increased risk of colorectal cancer. In the literature, no agreement has yet been reached regarding prevention strategies. Our report sums up a prospective study started in 1980. METHODS: A total of 65 patients affected by ulcerative colitis for more than seven years were admitted to a regular colonoscopic and biopsy follow-up programme. RESULTS: Some 20 years after the beginning of the study, 23 (35.3%) patients have been operated upon, 2 patients have died but not from cancer 29 (44.66%) patients have abandoned the programme. Only 11 (16.9%) patients have remained under colonoscopic surveillance. CONCLUSION: These results cast some doubts on the significance of such a programme and on its long-term feasibility.     

Dysplasia in the mucosal biopsy specimen is still a warning sign of cancer in ulcerative colitis

Abstract

Objectives

Patients with ulcerative colitis are at increased risk for colorectal cancer, especially at younger ages. Our aim was to determine, in our patient cohort, the clinicopathological features, incidence, and prognosis of ulcerative colitis-associated colorectal cancer.     

溃疡性结肠炎相关性结肠癌差异表达的miRNA的筛选研究

[目的]分析结肠癌与正常结肠黏膜、结肠炎肠黏膜的微小RNA（miRNA）表达谱差异.[方法]通过建立溃疡性结肠炎（ulcerative colitis,UC）及UC相关性结肠癌（ulcerative colitis related colorectal cancer,UCRCC）小鼠模型,抽提、纯化RNA,加入荧光标记后与miRNA寡核甘酸基因芯片（Affymetrix公司）杂交,应用SAM软件进行数据分析,对有显著差异的miRNA进行实时荧光定量PCR验证,采用靶基因分析软件分析miRNA功能.[结果]has-miR-194、has-miR-215、has-miR-93、has-miR-192、has-miR-92a、has-miR-29b、has-miR-20a等7个miRNA在肿瘤组织中显著上调[中位假基因验出率（FDR）＜5％],has-miR-1231、has-miR-195、has-miR-143、has-miR-145等4个miRNA显著下调（FDR＜5％）.[结论]UCRCC与正常结肠黏膜、UC肠黏膜之间存在明显的miRNA差异表达,这些miRNA的差异性表达可能与UCRCC的发病有关.     

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.     

Acute onset of ulcerative colitis following an operation for sigmoid colon cancer

We describe a case of ulcerative colitis (UC) where clinical symptoms began abruptly within a few weeks after colon resection. The patient, a 44-year-old woman, was first referred to our hospital for the treatment of colon cancer. During the past several years, she had not had any inflammatory bowel disease-like clinical symptoms, such as frequent diarrhea or abdominal discomfort. Before the operation, both macroscopic and microscopic examination revealed that no remarkable inflammatory change was associated with the cancer in any area of her colon. At 10 days after the operation, she started to complain of frequent watery diarrhea. Two weeks after the operation, she was readmitted to our hospital because of frequent bloody diarrhea, fever, and abdominal discomfort. Based on endoscopic and histological examinations, she was diagnosed as having severe UC and was treated with hyperalimentation, predonisolone, mesalazine, and granulocyte apheresis. However, she did not respond to this combination therapy. At 45 days after the first operation, owing to sudden onset hemorrhagic shock, she underwent a second colectomy. The resected specimen of the entire colon showed severe pancolitis, and histological examination revealed severe inflammatory changes in the lamina propria together with crypt distortion, all of which were consistent with UC.     

The risk of colorectal cancer in ulcerative colitis: a meta-analysis

BACKGROUND AND AIMS: Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS: A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS: The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS: Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.     

Therapeutic effect of nimesulide on colorectal carcinogenesis in experimental murine ulcerative colitis

BACKGROUND: Patients with ulcerative colitis (UC) exhibit an increased risk for the development of cancer of the colon and rectum. Cyclooxygenase (COX)-2 inhibitors are known to suppress sporadic colorectal cancer, but it is unknown whether selective COX-2 inhibitors exhibit a preventive effect in UC-associated neoplasia. This study investigated the preventive effect of nimesulide, a selective COX-2 inhibitor, on colorectal carcinogenesis in an experimental model of murine UC. METHODS: Chronic colitis was induced in mice by administration of four cycles of dextran sulfate sodium (DSS) (each cycle: 5% DSS for 7 days and then distilled water for 14 days). The mice were killed 120 days after the completion of the fourth cycle. The mice were divided into the following five groups: group A served as a disease control; group B received a diet mixed with 400 p.p.m. of nimesulide during the whole period; group C received nimesulide during the four cycles of DSS administration (active phase); group D received nimesulide for 120 days from the end of the fourth cycle (remission phase); group E received no agents including DSS and served as a normal control. RESULTS: The incidence of dysplasia and/or cancer was 28%, 15%, 11.8%, 6.7% and 0% in groups A-E, respectively. In group D, nimesulide significantly suppressed the occurrence of dysplasia and/or cancer (P < 0.05). Strong COX-2 expression was detected by immunohistochemistry in cancer and dysplastic lesions while diffusely weak COX-2 expression was also found in the residual colon (i.e. lesion-free colon). The mucosal concentration of prostaglandin E(2) was significantly lower in groups B and D than in group A. CONCLUSIONS: The administration of the selective COX-2 inhibitor nimesulide (especially during the remission phase) exerts a suppressive effect on the development of dysplasia and/or cancer in a murine model of DSS-induced colitis. These findings may have relevance to long-standing UC in humans.     

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.     

High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis

Objective. The management of high-grade dysplasia (HGD) in polypoid lesions in patients with ulcerative colitis (UC) is not well characterized. The purpose of this study was to characterize the clinical course of patients with HGD in adenoma-like dysplasia-associated lesion or masses (DALMs) in the absence of any synchronous flat dysplasia. We hypothesize that colectomy is not warranted in patients who undergo complete excision of adenoma-like DALMs with HGD in UC. Material and methods. Pathology and clinical databases were systematically searched for the presence of dysplastic lesions in inflammatory bowel disease from 1997 to 2004. Patients with UC who had adenoma-like DALMs were identified, and a subset with HGD lesions was defined as our study cohort. Results. A total of 102 patients with UC were identified. Thirty of them (29%) had adenoma-like DALMs without synchronous flat dysplasia; 9 of these patients (30%) had HGD in these lesions. Thirty-two surveillance colonoscopies were performed in this cohort (mean 3.6 colonoscopies/patient). The patients were followed for a mean of 76.5 months (52–99 months). Three out of 9 patients (33%) had colectomy. None of the patients in this cohort was detected to have carcinoma in surveillance biopsies and/or in the resection specimens. Conclusions. Our data suggest that the presence of HGD in DALMs does not warrant colectomy. Continued close observation is suggested in this patient cohort after complete excision of polyps. Further prospective evaluation of this patient population is merited.     

Difference in the clinical characteristic and prognosis of colitis-associated cancer and sporadic neoplasia in ulcerative colitis patients

BackgroundAlthough various studies have been conducted on colitis-associated cancer (CAC), few have assessed the differences in the clinical and endoscopic features, treatment, and prognosis of CAC and sporadic neoplasia (SN) in the inflamed mucosa of ulcerative colitis (UC) patients.AimsTo compare the characteristics of CAC and SN within the previously or currently inflamed mucosa.MethodsBetween 1997 and 2017, we retrospectively analyzed the endoscopic chart data of 348 colonic lesions from 266 UC patients. Non-dysplastic lesions and lesions located outside the inflamed mucosa were excluded. The diagnosis of CAC or SN was confirmed by conventional histopathological and immunohistochemical evaluation of p53 and Ki67.ResultsIn total, 74 patients with CAC (97 lesions) and 46 with SN (58) were enrolled. The proportions of patients with a younger age of onset of UC, with chronic persistent UC, and with severe inflamed mucosa were significantly higher in the CAC group. In the SN group, no flat lesions were found, whereas 26% of the lesions in the CAC group were flat. Sixteen patients died during a median follow-up of 6.1 years (interquartile range (IQR) 1.8–11.1)in the CAC group, whereas 1 patient died during a median follow-up 3.2 years(IQR 1.4–4.6) in the SN group. Mortality from colorectal cancer was significantly higher (P = 0.015) in the CAC group (12/68; 17.6%) than in the SN group (1/44; 2.3%). The 5-year survival rate was 100% in the SN group and 97% in the CAC group for lesions located in the mucosa or submucosa.ConclusionRecognizing differences in the characteristics of CAC and SN within the inflamed mucosa is critical to avoid unnecessary total colectomy in patients with SN.     

Risk of colorectal cancer in ulcerative colitis in India

BACKGROUND: The risk for colorectal cancer (CRC) in ulcerative colitis (UC) in India is not known. METHOD: Retrospective cohort from a tertiary level hospital in South India. Analysis of archived records of all patients with UC who underwent colonoscopy and segmental biopsies over the last 25 years. Incidence densities and risk of developing high grade dysplasia or CRC was calculated and chi-squared test was performed for risk factors of interest. RESULTS: Complete records were available for 532 patients, 336 (63.2%) male. The mean (+/- SEM) duration of illness was 6.04 +/- 0.29 years. In total, 234 patients (44%) had pancolitis, 121 (22.7%) had left-sided colitis and 177 (33.3%) had proctitis or proctosigmoiditis. Overall, five (0.94%) patients developed carcinoma and one (0.19%) patient had high grade dysplasia. The incidence density and risk of developing either CRC or high grade dysplasia was zero in the first 10 years of disease. In those with disease duration of 10-20 years, incidence density was 2.34 per 1000 person years' duration (PYD) for all patients with colitis and 4.5 per 1000 PYD for patients with pancolitis alone. This corresponded to risks of 2.3% and 4.4%, respectively. For those with disease duration longer than 20 years, incidence density was 2.73 per 1000 PYD for all patients and 4.9 per 1000 PYD for patients with pancolitis. This corresponded to risks of 5.8% and 10.2%, respectively. Duration of disease beyond 10 years and extent of colitis were the only risk factors significantly associated with CRC. CONCLUSIONS: The risk of developing CRC is Indian patients with UC is lower than that reported from the West. Strategies for cancer surveillance in Indian patients with UC need to be tailored accordingly.     

Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model

BACKGROUND: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. METHODS: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. RESULTS: Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. CONCLUSION: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia-invasive carcinoma sequence in ulcerative colitis.     

Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with methylprednisolone pulse therapy and cyclosporine

A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative colitis had been well controlled with oral prednisolone, but ulcerative colitis relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but relapsed when prednisolone was tapered. A second trial of pulse therapy combined with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and no recurrence was recognized after prednisolone was tapered. This is a very rare case of successful treatment with methylprednisolone pulse therapy combined with cyclosporine for pyoderma gangrenosum complicating ulcerative colitis. (Received May 6, 1997; accepted Sept. 26, 1997)     

Colonic cancer in a patient with primary sclerosing cholangitis and long-standing ulcerative colitis

A 27-year-old woman with a 9-year history of ulcerative colitis involving the entire colon was admitted to our hospital in August 1992 because of bloody stools and left lower abdominal pain. She had been treated with sulfasalazine since 1983 and the colitis had been clinically quiescent or mild for 7 years. She had also been diagnosed as having primary sclerosing cholangitis (PSC) 4 years prior to this admission, based on the clinical, laboratory, and cholangiographic findings. A barium enema and colonoscopy showed an irregular mass obstructing the bowel lumen in the distal portion of the descending colon. Biopsy specimens taken from the mass revealed moderately differentiated adenocarcinoma, and a subtotal colectomy was performed. Histologic examination of the mass lesion showed moderately differentiated adenocarcinoma invading the pericolic adipose tissue. She is currently alive 3 years after surgery. PSC has recently been reported as a risk factor for colonic neoplasia in patients with longstanding ulcerative colitis. In Japan, however, colorectal cancer associated with PSC and ulcerative colitis has rarely been reported. The present case suggests that the risk of colonic cancer is higher in patients with ulcerative colitis and PSC than in patients with ulcerative colitis alone.     

Serrated neoplasias and de novo carcinomas in ulcerative colitis: a histological study in colectomy specimens

BACKGROUND AND AIM: Cancer in ulcerative colitis (UC) originates in dysplastic crypts, adenomatous growths (UCAG), and UC-associated adenomas (UCAD). The aim of the present study was to compare the histological phenotypes between UCAG, UCAD, and sporadic colorectal adenomas in non-colitics (non-UCAD), as well as between UC-associated carcinomas (UCC) and carcinomas in non-colitic patients (non-UCC). METHODS: Three thousand and forty nine sections from 96 colectomy specimens in patients with UC-pancolitis and carcinoma were reviewed. RESULTS: Villous phenotypes were more frequent in UCAG (48%) than in UCAD (26%) and non-UCAD (11%), and serrated phenotypes more frequent in UCAD (29%) than in UCAG (12%) and non-UCAD (8%). Tubular phenotypes were far less frequent in UCAG (14%) than in UCAD (45%) and non-UCAD (80%). Villous and signet ring cell cancer phenotypes were more frequent in UCC (22% and 8%, respectively) than in non-UCC (9% and 0.8%, respectively). Six UCC (5.6%) were de novo carcinomas. CONCLUSIONS: Invasive carcinomas were found in one-half of the UCAG and in one-third of the UCAD, indicating that both lesions are important in cancer development in UC. The different proportions of histological phenotypes found in UCAG, UCAD, and non-UCAD on the one hand, and UCC and non-UCC on the other, suggest that chronic protracted inflammation might have modified the stem cell receptors that receive the molecular signals that program structural configurations in neoplastic glands. This is the first study reporting the occurrence of serrated and microtubular UCAG and of de novo carcinomas in UC.     

Carcinoma of the colon and rectum complicating chronic ulcerative colitis

Patients with pancolonic chronic ulcerative colitis are at increased risk to develop carcinoma of the colon. Controversy continues, however, as to whether this carcinoma is more “virulent” than “type ordinaire” carcinoma of the colon and as to the best way to manage these patients. This study reviews the characteristics and survival of 70 patients with cancer of the colon superimposed on chronic ulcerative colitis. Patients with carcinoma identified incidentally during prophylactic colectomy for chronic ulcerative colitis fared well (5-year survival of 72 per cent), while those with clinical symptoms or radiographic suggestion of cancer had a poor survival rate (5-year survival of 35 per cent). Patients with panproctocolitis, 10 years of disease, and early onset of disease are most likely to have cancer superimposed on chronic ulcerative colitis. This cancer is likely to have a poorer prognosis than type ordinaire cancer of the colon. Prophylactic proctocolectomy should be considered before evidence suggesting carcinoma develops. Read at the meeting of the American Society of Colon and Rectal Surgeons, Atlanta, June 10 to 14, 1979. This paper received the Harry E. Bacon Foundation Award.     

Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations.

BACKGROUND: K-ras mutation is one of the first genetic alterations in classical colorectal carcinogenesis. AIMS: To investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis. METHODS: A total of 161 microdissected and 100 DNA samples from 13 patients were analysed for K-ras codons 12 and 13 mutations by means of a combination of enriched polymerase chain reaction amplification and temporal temperature gradient electrophoresis. RESULTS: K-ras mutations were found in 21/161 (13%) microdissected samples in 7/13 large bowels (16 and five in codons 12 and 13, respectively), and in 10/100 (10%) mucosal DNA samples (six and four, respectively). One of four patients with six adenocarcinomas had a K-ras mutation in a carcinoma, as well as one of two patients with large dysplasia associated lesion or mass (DALM). Eight of 13 (61%) areas with villous architecture and large, distended goblet cells, had a K-ras mutation, which was significantly more frequent than in low grade dysplasia (one of 23, 4%) but did not reach significance versus high grade dysplasia (four of 14, 28.5%). K-ras mutations were found in one of 20 (5%) flat lesions indefinite for dysplasia, two of 14 (14%) in non-villous, hypermucinous mucosa, and in one of 57 flat areas negative for dysplasia. CONCLUSION: The highest K-ras mutation frequency was found in villous, hypermucinous mucosa. We suggest that this entity should be investigated further as a potential risk lesion for cancer development. It may represent a pathway directly from non-classical dysplasia to cancer, not previously described.     

Right-sided ulcerative colitis

This report describes a case of right-sided ulcerative colitis in which multiple shallow ulcers and erosion with symmetric luminal stenosis were distributed segmentally from the ascending colon to the cecum, with a skip lesion composed of superficial erosions in the right half of the transverse colon. Both the rectum and the left colon were spared at the time of onset. Biopsies taken from the lesions showed non-specific inflammation, while those from the rectum and sigmoid colon showed no abnormal findings. A 5-year follow-up study was made based on radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's disease, tuberculosis, Yersinosis, Behçet's disease, and ischemic colitis were all ruled out, based on the macroscopic and microscopic findings as well as the clinical course. To our knowledge, this is the first report of right-sided ulcerative colitis that has been followed for a long period.     

A decision analysis of surveillance for colorectal cancer in ulcerative colitis

BACKGROUND: Patients with long standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. AIMS: To assess the feasibility of surveillance colonoscopy in preventing death from colorectal cancer. PATIENTS: A hypothetical cohort of patients with chronic ulcerative colitis. METHODS: The benefits of life years saved were weighted against the costs of biannual colonoscopy and proctocolectomy, and the terminal care of patients dying from colorectal cancer. Two separate Markov processes were modelled to compare the cost-benefit relation in patients with or without surveillance. The cumulative probability of developing colorectal cancer served as a threshold to determine which of the two management strategies is associated with a larger net benefit. RESULTS: If the cumulative probability of colorectal cancer exceeds a threshold value of 27%, surveillance becomes more beneficial than no surveillance. The threshold is only slightly smaller than the actual cumulative cancer rate of 30%. Variations of the assumptions built into the model can raise the threshold above or lower it far below the actual rate. If several of the assumptions are varied jointly, even small changes can lead to extreme threshold values. CONCLUSIONS: It is not possible to prove that frequent colonoscopies scheduled at regular intervals are an effective means to manage the increased risk of colorectal cancer associated with ulcerative colitis.