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.     

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.     

Dysplasia and cancer complicating strictures in ulcerative colitis

Previous studies have found a widely variable prevalence of dysplasia and cancer in colonic strictures in patients with ulcerative colitis. Consequently, therapeutic recommendations are conflicting. To better assess the prevalence, we reviewed the clinical and pathological findings in all 27 patients with ulcerative colitis complicated by stricture who were entered into our Inflammatory Bowel Disease Registry. A true stricture was defined as a persistant localized narrowing of the colon found on air-contrast barium enema or on colonoscopy. Upon careful review, 12 of 27 patients were found to have transient colonic spasm, not a stricture, and were excluded. The remaining 15 patients with true strictures represented 3.2% of all ulcerative colitis patients in the registry. Strictures were identified at 13.3± 9.9 years following the diagnosis of ulcerative colitis. Eleven patients had multiple strictures that were principally located in the left colon. Of the 15 patients, 11 had dysplasia and two had cancer found on colonoscopic biopsy. Ultimately, six patients had carcinoma found at colonoscopy or colectomy (three modified Dukes' stage A, one stage B, and two stage D). All cancers were at the site of a stricture. These findings indicate that a true colonic stricture in ulcerative colitis is frequently associated with dysplasia and cancer, which can be diagnosed with colonoscopic biopsy. A stricture should be considered a strong risk factor for cancer, requiring intensive colonscopic surveillance. If dysplasia is discovered, or if the stricture cannot be adequately biopsied, consideration should be given to total colectomy.Research supported by the David and Reva Logan Gastrointestinal Clinical Research Center and the Gastrointestinal Research Foundation Junior Board.     

Colonic malacoplakia: Unusual association with ulcerative colitis

Abstract A 44 year old Chinese female with malacoplakia of the colon associated with ulcerative colitis was presented. The patient showed typical histological, electron microscopic and X-ray micro-analysis findings of malacoplakia. The malacoplakia gradually disappeared after discontinuation of high-dose systemic steroid prescribed by private practitioner for the ulcerative colitis. A review of the 26 previously reported cases of malacoplakia of the colon is also included. Coupled with the clinical events of this patient, it appears that malacoplakia is likely to be secondary to immunosuppression, due to drugs, malignant or debilitating diseases.     

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.     

Advances in endoscopic imaging in ulcerative colitis

Modern strategies for the treatment of ulcerative colitis require more accurate tools for gastrointestinal imaging to better assess mucosal disease activity and long-term prognostic clinical outcomes. Recent advances in gastrointestinal luminal endoscopy are radically changing the role of endoscopy in every-day clinical practice and research trials. Advanced endoscopic imaging techniques including high-definition endoscopes, optical magnification endoscopy, and various chromoendoscopy techniques have remarkably improved endoscopic assessment of ulcerative colitis. More recently, optical biopsy techniques with either endocytoscopy or confocal laser endomicroscopy have shown great potential in predicting several histological changes in real time during ongoing endoscopy. Here, we review current applications of advanced endoscopic imaging techniques in ulcerative colitis and present the most promising upcoming headways in this field.     

Flicking method: A novel colonoscope insertion method for surveillance colonoscopy in ulcerative colitis patients

Aim: Periodic surveillance colonoscopy is required for patients with ulcerative colitis to detect colitis‐associated dysplasia at an early stage. However, sometimes colonoscopy may damage the fragile mucosa of patients with ulcerative colitis. The aim of this study was to devise a new method of surveillance colonoscopy for patients with mild to moderate ulcerative colitis. Methods: The ‘flicking method’ of colonoscope insertion was recently developed by our team. It is a completely novel method that involves using the elastic force of the colonoscope to introduce it into the deeper regions while using colon mucosa patterns as a guide. The subjects were 66 hospital outpatients with ulcerative colitis who underwent colonoscopies during a 2‐year period, from April 2006 to March 2008, with both the conventional insertion method and the flicking method. Results: Cecal intubation rate, insertion time, patient pain level, change in number of defecations pre‐ and post‐colonoscopy, and change in severity pre‐ and post‐colonoscopy were compared between the conventional and flicking methods. The flicking method was superior in all respects. Conclusions: The flicking method is a novel colonoscope insertion method that is regarded as particularly useful in cases when the intestinal mucosa is fragile, as is the case with ulcerative colitis patients.     

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.     

Lethal neuroendocrine carcinoma in ulcerative colitis

A 48-year old male with longstanding and extensive pancolitis developed a high grade and rapidly lethal malignant lesion in the ascending colon characterized by a neuroendocrine carcinoma. Prior biopsies obtained from multiple sites in the colon during endoscopic surveillance were reported to show only inflammatory changes without dysplasia. Although operator-dependent, repeated endoscopic studies may have limitations during surveillance programs because the biological behavior of some colonic neoplastic lesions may have a rapid and very aggressive clinical course.     

Telomere shortening in the colonic mucosa of patients with ulcerative colitis

Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 ± 0.36 kb versus 8.77 ± 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 ± 3.35% in UC patients, compared with 0.8 ± 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC. (Received May 6, 1997; accepted Sept. 26, 1997)     

结肠灌洗透析机治疗全结肠溃疡性结肠炎疗效观察

2005年12月～2008年8月采用结肠灌洗透析机对39例溃疡性急慢性结肠炎患者进行保留灌肠治疗,疗效显著,现报道如下。     

Adenoma‐like and non‐adenoma‐like dysplasia‐associated lesion or mass in ulcerative colitis

Ulcerative colitis (UC) patients have an increased risk of colorectal cancer. UC has two general patterns of dysplasia, which are commonly classified as adenoma‐like dysplasia‐associated lesion or mass (DALM) and non‐adenoma‐like DALM. The latter has a high risk of concurrent malignancy and often requires a colectomy. Unfortunately, non‐adenoma‐like DALMs sometimes have endoscopic features similar to those of adenoma‐like DALMs. Therefore, new endoscopic techniques to distinguish between these two kinds of DALM have been proposed.     

Colonic biogeography in health and ulcerative colitis

The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.     

Low incidence of colorectal dysplasia and cancer among patients with ulcerative colitis: A Turkish referral centre study

Abstract

Objectives. To determine the incidences of dysplasia, adenomatous polyp and colon cancer in patients with ulcerative colitis (UC) and to evaluate the risk factors. Material and methods. We retrospectively reviewed the medical records of patients with UC admitted to the Turkiye Yuksek Ihtisas Hospital between 1994 and 2008 and who subsequently developed colorectal cancer (CRC). Results. Between 1994 and 2008, a total of 844 UC patients were followed in our clinic. A total of 275 patients entered our surveillance programme. The duration of UC was as follows: 10–15 years, n = 173 (62.9%); 15–20 years, n = 55 (20.0%); 20–25 years, n = 26 (9.5%), 25–30 years, n = 9 (3.3%); and >?30 years, n = 12 (4.4%). In terms of localization, 80 patients (29.1%) had distal disease, 107 (38.9%) had left-sided disease and 88 (32.0%) had extensive colitis. Adenomatous polyp was found in six patients (2.2%). Five cases (83.3% of the polyps) were in the diseased segment and one case (16.7%) was in the non-diseased segment. Endoscopy revealed dysplasia in 11 cases (4.0%). Of the 275 UC patients, CRC was diagnosed in only three (1.1%) during follow-up. Adenomatous polyp was not found in cases with colon cancer. Conclusions. In our cases with UC, rates of dysplasia and CRC were much lower than in other reports. The difference in rates may be explained by racial factors, specific environmental factors, intensive control of disease activity through medical therapy and effective colonoscopic surveillance programmes.     

Screening for dysplasia and TP53 mutations in closed rectal stumps of patients with ulcerative colitis or Crohn disease

Background: Patients who undergo colectomy due to intractable chronic inflammatory bowel disease (IBD) may keep a closed rectal stump for several years, which may be at increased risk of malignant transformation owing to residual inflammatory activity. We examined a hospital series of patients with ulcerative colitis or Crohn colitis to describe the clinical, endoscopical and histological features of the closed rectal stump and to screen for dysplasia and mutations in the TP53 tumour suppressor gene. Methods: During rigid proctoscopy, rectal mucosal biopsy specimens and rectal lavage fluid were collected from 42 patients. Biopsy specimens were examined histologically, and genomic DNA extracted from frozen biopsies and lavage fluid was analysed for mutations in TP53 exons 4–9. Results: The median disease duration was 8.5 years (range 1.3–34 years). No endoscopic or histological signs of dysplasia or carcinoma were seen and no mutations in the TP53 gene were detected in any biopsy or lavage fluid specimens. Histological moderate to severe mucosal inflammation was present in 78% (33/42) of the patients, however, and rectal stump involution was noted in 43% (18/42). Conclusion: No signs of malignancy or premalignant degeneration were detected in this prospective series of IBD patients with a closed rectal stump. Although this is reassuring for patients, the presence of moderate to severe inflammation in the majority of rectal stumps indicates a role for adjuvant molecular markers to improve colorectal cancer surveillance on this subgroup of IBD patients.     

Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requiring surgery

BACKGROUND AND AIMS: Up to one-third of patients with ulcerative colitis (UC) need to undergo surgery, but the factors that exacerbate inflammation remain unclear. The authors hypothesize that excessive apoptosis reported in active UC may disrupt epithelial defenses and exacerbate the disease. The aim of the present study was to clarify whether apoptotic epithelial cells and histiocytes engulfing them increased in patients with active UC who ultimately require surgery (UC-S) rather than those receiving medication alone (UC-M). METHODS: The study included 29 patients with UC-S, 35 with UC-M, 18 with infectious colitis, and 16 healthy controls. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Using biopsy specimens taken from the most severely inflamed rectosigmoid mucosa as determined endoscopically, the apoptotic index (apoptotic cells/epithelial cells,%) and density (per mm2) of lamina propria histiocytes positive for CD68 were then evaluated. Statistical differences were tested with the Mann-Whitney U-test. RESULTS: The apoptotic indices in UC-M patients were significantly higher than those in controls (P < 0.05) but almost equal to those in infectious colitis patients. In the upper and lower halves of the mucosa, both apoptotic indices and histiocyte densities were significantly higher for UC-S than in UC-M (P < 0.01). Ratios of the mean apoptotic index for UC-S to that for UC-M exceeded 3.4, while ratios of the mean histiocyte density were limited to approximately 1.6. CONCLUSIONS: The results suggest that epithelial apoptosis is a non-specific phenomenon and that an increased number of apoptotic cells exceeding histiocyte phagocytic capacity may play a part in the disruption of epithelial defenses and further accelerate mucosal inflammation.