Minute findings by magnifying colonoscopy are useful for the evaluation of ulcerative colitis

BACKGROUND: Colonoscopy has an important role in the diagnosis of ulcerative colitis. However, colonoscopic findings are inadequate for the prediction of relapse without histologic examination. In this study, the role of magnifying colonoscopy in ulcerative colitis was evaluated. METHODS: One hundred sixteen magnifying colonoscopy observations were made in 61 patients with ulcerative colitis between January 1994 and October 1998. A simple classification of magnifying colonoscopic findings into 5 categories was devised as follows: regularly arranged crypt openings, villous-like, minute defects of epithelium, small yellowish spots, and coral reef-like appearance. The colonoscopic findings by classification were compared with histopathologic findings, and the usefulness of the classification for predicting relapse was prospectively analyzed in 18 patients. RESULTS: Compared with grade as determined by conventional colonoscopy, there was a better correlation between the classification of findings by magnifying colonoscopy and histopathologic findings (r(2) = 0.665, 0.807, respectively). Of 18 patients studied prospectively, 7 of 9 with minute defects of epithelium relapsed within 6 months, and the cumulative nonrelapsing rate was significantly lower in patients with minute defects of epithelium compared with those without minute defects of epithelium (p = 0.0059). Moreover, minute defects of epithelium was found to be a significant independent predictive factor for relapse (multivariate analysis, Cox proportional hazards model; p = 0.0203). CONCLUSIONS: Our proposed classification of magnifying colonoscopic findings in patients with ulcerative colitis is useful for the evaluation of disease activity and for the prediction of periods of remission.     

Histologic and colonoscopic assessment of disease extension in ulcerative colitis

A comparison between histologic and colonoscopic extension of ulcerative colitis was made in 107 examinations (83 patients). During colonoscopy signs of inflammation were registered, and biopsy specimens were taken from the following gut segments: rectum, left colon, transverse colon, and right colon. Inflammatory activity in the specimens was graded in accordance with severity in a scale from one to five. Endoscopically, total colitis was seen in 40 examinations but was present in 70 examinations histologically. In 34 of 107 examinations the extension of disease was underestimated at colonoscopy. A slight inflammation existed in those segments that appeared normal colonoscopically. Our conclusion is that the extension of ulcerative colitis often is underestimated endoscopically and that inflammatory activity can be present in mucosa assessed as normal on colonoscopy.     

Gastral antral biopsy in the differentiation of pediatric colitides

OBJECTIVES: Differentiation of Crohn's disease (CD) from ulcerative colitis (UC) is problematic, primarily when inflammation is confined to the colon. In a historical cohort study, we evaluated the usefulness of baseline gastric antral biopsies in the differentiation of pediatric chronic colitides. METHODS: During initial investigation for suspected inflammatory bowel disease, 39 children and adolescents with colitis but normal small bowel radiography underwent pretreatment upper endoscopy concurrently with colonoscopy. Two reviewers assigned a colonoscopic diagnosis (colonic CD, UC, or indeterminate colitis) based on the macroscopic and microscopic appearances of the colonic mucosa. Antral histological findings were compared between groups using Fisher's exact test. RESULTS: Five (14%) of colonoscopic diagnoses (four indeterminate, one UC) were changed to CD by the finding of granulomatous inflammation in antral biopsies. Nonspecific antral gastritis was found in similar proportions of children and adolescents with Crohn's colitis and UC (92% vs 75%). Focal antral gastritis was more common in patients with Crohn's colitis than UC (52% vs 8%). CONCLUSIONS: Nonspecific antral gastritis is common in all forms of chronic colitis. Nevertheless, upper gastrointestinal endoscopy with biopsy is useful in the differentiation of inflammatory bowel disease confined to the colon, particularly when colonoscopic findings are indeterminate.     

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.     

Subclinical time span of inflammatory bowel disease in patients with primary sclerosing cholangitis

PURPOSE: This study is designed to describe colonic histology in patients with primary sclerosing cholangitis (PSC) without clinical symptoms of inflammatory bowel disease (IBD) and to do a follow-up study of these patients to find the time span from first detection of histologic signs until development of clinical symptoms of IBD. METHODS: In a cohort of 76 patients with PSC treated at Huddinge University Hospital, 11 patients did not have any clinical symptoms of IBD at the time of PSC diagnosis. Nine of these patients underwent diagnostic colonoscopy with multiple biopsies. RESULTS: In the group of nine PSC patients, without clinical signs of IBD undergoing colonoscopy, histologic signs of IBD were found in seven patients (6 ulcerative colitis and 1 Crohn's disease). Among them one had dysplasia, and another had epithelial changes probably positive for dysplasia. Two other patients had histologic signs of inflammation, however, not fully compatible with IBD. Three of 11 patients developed clinical symptoms of IBD after one, three, and seven years of follow-up since diagnostic colonoscopy. CONCLUSIONS: In patients with PSC, histologic signs of IBD, including premalignant changes, may precede development of clinical symptoms of IBD by as much as seven years. This indicates that IBD onset may have a substantial subclinical phase of IBD far longer than previously appreciated. This finding may be of clinical importance because underestimation of disease duration may delay inclusion of PSC patients with extensive colitis in colonoscopic surveillance programs. The subclinical phase may also allow the studies of early pathogenesis in vivo.Supported by grants from the Nanna Svartz Scholarship.     

Appendiceal Involvement in Patients with Ulcerative Colitis

Abstract: There have been few case reports of ulcerative colitis with appendiceal involvement because the appendix has generally received little attention in ulcerative colitis patients. We encountered an inflammatory appendiceal lesion in a patient with ulcerative colitis, which piqued our interest in endoscopic findings of the appendix in these patients. Subsequently, we carefully observed the appendiceal orifice during colonoscopy in patients with ulcerative colitis. From December 1994 to December 1996, 44 patients with ulcerative colitis underwent colonoscopy in Nagaoka Red Cross Hospital. Among these 44, there were three in whom it had not been possible to observe the cecum. During this period, we encountered inflammatory appendiceal lesions in eight cases. Therefore, 20% (8/41) of patients with ulcerative colitis undergoing colonoscopy had appendiceal involvement. Five of these eight patients showed a colonoscopically normal cecum, such that appendiceal involvement thought to be a colonoscopic skip lesion was seen in five (12%: 5/41). There was only one case who had an appendiceal lesion without a microscopically diseased cecum. Appendiceal involvement may be frequent in ulcerative colitis. We thus recommend that endoscopists meticulously examine the appendiceal orifice during colonoscopy in patients with ulcerative colitis.     

MINUTE FINDINGS DETECTED BY MAGNIFYING COLONOSCOPY IN ULCERATIVE COLITIS

In order to detect flat‐type dysplastic and cancerous lesions associated with longstanding ulcerative colitis, it is important to understand the minute findings detected by magnifying colonoscopy in active and quiescent stage of ulcerative colitis. The severity of mucosal findings by magnifying colonoscopy could be categorized as follows: polypoid mucosal tag which has severe ulceration and hemorrhage; coral‐reef‐like appearance which has coarse or nodular mucosa with ulcerations; minute defect of epithelia which has minute or shallow depressions surrounded by edematous mucosa; small yellowish spots which has minute whitish or yellowish coats; villi‐like appearance which has shaggy appearance like small intestinal villi; and regularly arranged crypt opening which has round shaped and regularly arranged crypt.     

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.     

Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis

BACKGROUND: Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns. AIMS: To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations. METHODS: MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse. RESULTS: A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4. CONCLUSION: MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.     

Ultrasonographic Assessment of Inflammatory Bowel Disease

Ultrasound examinations were performed in 36 patients with Crohn's disease, 28 with ulcerative colitis, and 50 with no bowel disease. The pathological findings were classified into three types and compared with the radiographic and/or colonoscopic findings. Crohn's disease and ulcerative colitis could be detected by ultrasonography with a sensitivity of 86% and 89%, respectively. The ultrasonographic features correlated with the radiographic/colonoscopic findings and with disease activity, but did not help much in making a differential diagnosis, although the location of the pathologic changes was helpful to some extent. In conclusion, ultrasonography can serve as a useful alternative diagnostic procedure that permits us to obtain information about transmural changes in inflammatory bowel disease.     

527例溃疡性结肠炎临床与病理分析

目的 评价临床、内镜及活检三者在溃疡性结肠炎(UC)诊断中的作用。方法 总结我院10年间经肠镜诊断为UC的病例，分析其临床、内镜表现及部分活检资料。结果 527例确诊为UC，其中误诊34例，结肠镜诊断正确率为93．9％。UC临床主要表现为腹泻(88％)、粘液脓血便(52％)。结肠镜表现以粘膜充血水肿(94％)、糜烂溃疡(75％)最多见，病变部位以直、乙结肠为主(51％)，呈弥漫性、连续性分布。活检特征性表现为炎症程度重(49％)，固有层弥漫性混合性炎细胞浸润(76％)、杯状细胞减少(71％)、隐窝扭曲(63％)、萎缩(47％)、隐窝炎(45％)、隐窝脓肿(36％)及绒毛状表面(39％)。结论 UC的诊断应强调临床、内镜及活检相结合。     

Changes in Colonoscopic Findings in Longstanding Ulcerative Colitis

Abstract: A total of 44 patients with long-standing ulcerative colitis were studied to elucidate changes over time in colonoscopic and histological inflammatory activity. More than two years of symptomatic remission without melena or bloody diarrhea was achieved in 63.6% (28/44). All patients underwent total colonoscopic examinations. Compared with findings of the previously involved area, 70.5% (31/44) showed a reduction or disappearance of the inflammatory area on endoscopic and histological examinations; however, the rectal inflammation disappeared in 31.8% (14/44) of patients. Moreover, it became apparent that the remaining active inflammatory area tended to show discontinuous spread with patchy inflammatory foci. Thus, the mucosal inflammation in long-standing ulcerative colitis may be characterized by a reduction in both extent and degree.     

Safety of Surveillance Colonoscopy in Long-standing Ulcerative Colitis

Objective: Because of the increased risk of colorectal cancer in patients with long-standing ulcerative colitis, colonoscopic surveillance for the detection of dysplasia is currently recommended as a method of identifying high-risk patients. However, the hazard of colonoscopy with multiple hiopsies in such patients is not well known. Our objective was to assess the safety of surveillance colonoscopy in patients with long-standing ulcerative colitis. Methods: To accomplish our objective, we conducted a retrospective analysis of results and follow-up of surveillance colonoscopies. Resutts: A total of 6,727 biopsies were obtained during 384 colonoscopies, with a median of 17 biopsies per colonoscopy. Nineteen studies were performed in a setting of underlying stricture. A single complication of a silent perforation occurred in a patient with an underlying stricture. No instances of bleeding, infection, respiratory distress, myocardial infarction, or death resulted from the procedure. Conclusion: Our findings suggest that surveillance colonoscopy with multiple biopsies is a relatively safe procedure. Given increasing evidence of the survival benefit derived from the procedure, we believe these results render further support for the current practice of surveillance colonoscopy in patients with ulcerative colitis.     

Serial carcinoembryonic antigen (CEA) blood levels in patients with ulcerative colitis

Fifty-seven patients with ulcerative colitis were followed 1–49 months (mean, 18 months) with serial CEA determinations during periods of remission, mild relapses, and severe relapses. Elevated CEA titers correlated with activity and possibly extent of disease: 12% of patients with proctitis, 47% of patients with left-sided colitis, and 60% of patients with transverse or universal colitis had elevated CEA titers during a flare. Moreover, 24% of patients with mild flares and 86% of patients with severe flares had elevated CEA titers. Ninety-two percent of patients with extensive disease and severe flares had elevated CEA titers. Elevated CEA titers were correlated with histologic findings in three patients. Inflammation of mucosa was demonstrated by colonoscopy and confirmed by biopsy in one patient with persistently elevated CEA titers during clinical remission. In two other patients with active disease whose CEA titers fell prior to colectomy, marked denudation of colonic mucosa was noted. In this study, a transiently elevated CEA titer indicated either clinically active ulcerative colitis or active inflammation of colonic mucosa.     

Clinical significance of erosive and/or small ulcerative lesions in the colon and terminal ileum--short-term follow-up study]

BACKGROUND/AIMS: Various etiologies and diseases may be related to erosions and/or small ulcers without gross inflammatory changes in the surrounding mucosa found in the colon and terminal ileum during colonoscopy. However, studies on follow-up of these lesions are rare. Thus, we investigated the clinical significance of these lesions and their characteristics helpful for differential diagnosis. METHODS: We reviewed the data of 183 patients with colonoscopically observed erosive or small ulcerative lesions (<2 cm), and analyzed them according to the location, number, and size of lesions, histopathologic findings, chief complaints, laboratory findings, changes of symptoms, and changes in lesions during 4-12 week follow-up period. RESULTS: Histopathologic findings of these lesions included acute nonspecific inflammation, chronic nonspecific inflammation, Crohn's disease, tuberculous colitis, ischemic colitis, Behcet's disease, cytomegalovirus infection, eosinophilic colitis, ulcerative colitis or pseudomembranous colitis, but most of them were nonspecific (84%). In patients with nonspecific inflammation, histopathologic findings, symptoms, location and multiplicity of the lesions were not prognostic factors for the persistency of symptoms and lesions during follow-up period. Two patients with acute inflammation, who showed no improvement in symptoms and lesions, were later diagnosed as Crohn's disease. CONCLUSIONS: Erosive or small ulcerative lesions without macroscopic inflammatory changes in the surrounding mucosa during colonoscopy, are mainly nonspecific. However, careful follow-up is required when the symptoms and/or lesions are not improved.     

Catheter probe assisted endoluminal US in inflammatory bowel disease.

BACKGROUND: Use of an echocolonoscope to examine patients with inflammatory bowel disease is technically difficult. Catheter probe assisted endoluminal ultrasonography (US) may be a feasible alternative. METHODS: Determination of demographic information and clinical disease activity was followed by colonoscopy with biopsy. Catheter probe assisted endoluminal US was performed with measurements of thickness of the intestinal wall and evaluation of the structure of the sonographic layers. RESULTS: Twenty-eight patients, 7 with ulcerative colitis, 11 with Crohn's disease, and 10 healthy control subjects participated in a prospective study. Mean colonic wall thickness was 2.2 +/- 0.1 mm (controls) compared with 4. 1 +/- 0.4 mm (ulcerative colitis) (p < 0.001) and 4.4 +/- 0.4 mm (Crohn's disease) (p < 0.001). Among patients with ulcerative colitis, colonic wall thickness correlated with severity of colonoscopic changes (r = 0.84, p = 0.02). Among patients with Crohn's disease, loss of endosonographic layer structure correlated with disease activity score (r = 0.8, p = 0.003), and colonic wall thickness correlated with the severity of histologic changes (r = 0. 62, p = 0.04). CONCLUSIONS: Catheter probe assisted endoluminal US is technically feasible in the care of patients with inflammatory bowel disease. Endosonographic measurements of colonic wall thickness and layer structure provide clinically significant information.     

Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?

The aetiology of ulcerative colitis is unknown. Two patientswithout pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in thedefunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features ofulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggestthat diversion colitis may be a risk factor for ulcerative colitis inpredisposed individuals and that ulcerative colitis can be triggered byanatomically discontinuous inflammation elsewhere in the large intestine.

Keywords:ulcerative colitis, diversion colitis

     

Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis

BACKGROUND & AIMS: Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. METHODS: We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). RESULTS: Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). CONCLUSIONS: In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs.     

Significance of appendiceal involvement in patients with ulcerative colitis

BACKGROUND: The appendix is occasionally involved in patients with distal ulcerative colitis. This study investigated the clinical significance of patchy involvement at the appendiceal orifice in ulcerative colitis. METHODS: Colonoscopy was performed in 40 patients with active distal ulcerative colitis of mild to moderate severity. Patients were divided into 2 groups based on the presence or absence (positive or negative) of involvement at the appendiceal orifice at colonoscopy. Clinical activity, histologic grade of inflammation, and subsequent clinical course were compared between patients who were positive (appe(+)) and negative (appe(-)). RESULTS: Twenty-three patients had involvement at the appendiceal orifice (reddish mucosa with mucinous exudate). The proximal-most extent of involvement by ulcerative colitis, the endoscopic grade, and clinical activity were not different between appe(+) and appe(-) groups. However, histologic grade of inflammation in the ascending colon was higher in the appe(+) group than in the appe(-) group. The endoscopic remission rate at 12 months was higher in the appe(+) group than in the appe(-) group (84% vs. 40%, p < 0.05). CONCLUSIONS: In patients with distal ulcerative colitis, involvement at the appendiceal orifice may be indicative of histologically active disease, which responds reasonably well to pharmacotherapy.     

Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease

INTRODUCTION: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). METHODS: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. RESULTS: One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. CONCLUSIONS: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.