Analysis of direct tissue isoelectric focused protein profiles of resected intestinal mucosa and endoscopic biopsies from patients with inflammatory bowel disease.

Direct tissue isoelectric focusing was used as a procedure to analyze differences in soluble tissue protein profiles of resected intestinal segments and endoscopic biopsies from patients with ulcerative colitis, Crohn's disease, and colonic cancer. Extraction of tissue proteins was accomplished by electrophoresis of mucosal cryostat sections on agarose gels across a broad pH gradient. The inflamed colonic mucosa from Crohn's disease patients showed similar isoelectric focusing protein patterns. Small bowel mucosa from a patient with both colonic diverticular disease and Crohn's disease showed protein patterns identical with that of the mucosa from a patient with only Crohn's disease. The inflamed mucosae from ulcerative colitis patients revealed identical protein patterns but were distinct from those of non-inflamed ulcerative colitis mucosa and from the inflamed mucosae from Crohn's disease patients. Non-inflamed small bowel mucosae from cancer, ulcerative colitis, and Crohn's disease patients showed distinct protein patterns which were absent in the non-inflamed large bowel mucosae. The inflamed resected ileum of a Crohn's disease patient exhibited protein patterns similar to those of the biopsy of an inflamed mid-transverse large bowel. Mucosal biopsies from inflamed sigmoid colon of a Crohn's disease patient showed different protein patterns than those in biopsies from the inflamed mid-transverse colon. Thus, distinctive isoelectric focusing protein patterns may be useful in differentiating Crohn's colitis and ulcerative colitis when granulomata are absent, and in resolving indeterminant colitis to one of these classic inflammatory bowel diseases.     

Depletion of non specific esterase activity in the colonic mucosa of patients with ulcerative colitis

BACKGROUND: Non specific esterases (NSE) are a group of cellular carboxylesterases, enzyme markers of monocytes/macrophages, whose tissue distribution in the human body and changes in various disease states have not been adequately studied. We investigate the presence and localization of NSE, in the normal and inflamed human colonic mucosa. DESIGN: NSE were studied histochemically and biochemically using alpha-naphthyl acetate as the substrate, in the colonic mucosa from 67 patients with colitis of various aetiologies and 10 normal controls. In addition, esterase activity was studied biochemically in serum from colitic patients and normal controls. RESULTS: Histochemical study of the colonic tissue demonstrated that NSE were localised in the epithelial brush border, the goblet cells of the glands and a macrophage population of the lamina propria in the colonic mucosa of normal controls and patients with non specific colitis. In active ulcerative colitis, esterase depletion and esterase negative macrophages were identified in parallel with goblet cell disappearance. Gradual reappearance of esterase activity was found after successful treatment. Biochemical study of NSE activity showed that serum and colonic tissue esterase levels were greatly (P < 0.001) reduced in active ulcerative colitis compared to the normal controls or non specific colitis patients and they were increased after successful treatment. Despite this increase, the esterase activity in the colonic tissue from ulcerative colitis patients after treatment was significantly reduced compared to the normal controls. Interestingly, the enzyme levels from non-inflamed areas of the bowel of patients with ulcerative colitis were also significantly (P < 0.01) decreased compared to the normal controls. CONCLUSIONS: These data suggest that esterase reduction in ulcerative colitis is not a simple result of the inflammatory process but rather it precedes its development. This enzyme depletion might have an important pathogenetic implication in the inflammatory process.     

Mitomycin C-induced colitis in rats: a new animal model of acute colonic inflammation implicating reactive oxygen species.

The mechanism of the tissue damage induced by colonic inflammation in ulcerative colitis is not established. We therefore developed and characterized a simple new rat model of acute colonic inflammation induced by a single systemic injection of mitomycin C. After an intraperitoneal injection of mitomycin-C, colon histologic examination revealed transient (3 to 14 days) diffuse, colonic inflammation and injury that, like human ulcerative colitis, was limited to the mucosal layer. The rest of the gastrointestinal tract was spared. Gut permeability, as measured by urinary excretion of orally administered lactulose and mannitol, was unchanged 3 days after injection, when inflammation was already present; permeability was increased at 7 days, when inflammation was maximal. Mitomycin C did not produce inflammation in experimentally bypassed segments of small bowel despite the presence of colonic-type bacteria, suggesting that lack of intraluminal bacteria was not responsible for the absence of inflammation in the small intestine. Chemiluminescence, a means of estimating levels of reactive oxygen species, was greater in the intact, inflamed colon of mitomycin C-treated rats than in bypassed segments. Moreover, inflamed mucosal scrapings produced more in vitro luminol-enhanced chemiluminescence. Furthermore, the reactive oxygen species scavengers allopurinol, catalase, and WR-2721 decreased inflammation severity. We therefore conclude: (1) the mitomycin C-treated rat is a novel, easy to prepare animal model of acute inflammation of colonic mucosa, with morphologic similarities to the acute phase of ulcerative colitis in human beings; (2) increased gut permeability in mitomycin C-treated rats is the result, not the cause, of the inflammation; and (3) reactive oxygen species play an important role in colonic inflammation and tissue injury in this model, and possibly in human ulcerative colitis.     

Phospholipase A2 in serum and colonic mucosa in ulcerative colitis.

Group II phospholipase A2 is involved in the pathogenesis of various inflammatory diseases and in the host defence against bacteria. The enzyme is expressed in the epithelial cells of colonic mucosa in ulcerative colitis. In this study, we measured the concentration of group II phospholipase A2 in serum and colonic mucosa of patients with ulcerative colitis of different severity and of control patients without any inflammatory disease. The activity of ulcerative colitis was assessed by endoscopy. The concentration of group II phospholipase A2 was measured with an immunoassay. The concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher in patients with active and inactive ulcerative colitis than in controls. However, the group II phospholipase A2 levels did not separate patients with different disease activity. The concentration of group II phospholipase A2 in colonic mucosa corresponded with the mucosal inflammatory activity (higher in active colonic areas) intra-individually, but not between different patients with ulcerative colitis. Serum group II phospholipase A2 values were above the normal reference range more often than the values of 11 standard laboratory blood tests widely used for the follow-up of inflammatory activity in ulcerative colitis. These results indicate that the concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with ulcerative colitis. The clinical value of the measurement of group II phospholipase A2 in the follow-up of ulcerative colitis remains to be clarified.     

Beneficial effects of ropivacaine in rat experimental colitis.

Ropivacaine, a new, long-acting local anesthetic agent, has been shown to have beneficial effects in the treatment of ulcerative colitis. Treatment with this drug results in prompt symptomatic relief. The aim of this study was to examine the effects of ropivacaine on mucosal healing and to investigate whether ropivacaine can restore the decreased colonic contractility seen in the diseased state. Colitis was induced in rats by a single intrarectal administration of trinitrobenzene sulfonic acid. Mucosal healing was assessed after 1 week of therapy. The effects on colonic contractility were examined either after 1 week of treatment or by application of the drugs to untreated, inflamed rat colon segments placed in organ baths. After the induction of colitis, daily intracolonic treatment with ropivacaine for 1 week reduced morphological damage and myeloperoxidase activity. One week of treatment also restored the contractile response to acetylcholine. By adding ropivacaine directly to untreated inflamed colonic segments in organ baths, the contractile response to acetylcholine was increased compared with controls. For comparison, the effects of budesonide and 5-aminosalicylic acid were also examined. Ropivacaine improved mucosal healing and restored colonic motor activity in experimental colitis, similar to budesonide but superior to 5-aminosalicylic acid.     

活动期溃疡性结肠炎患者结肠黏膜中生长抑素受体的表达及其临床意义

目的:研究生长抑素受体(somatostatin receptor,SSTR)在活动期溃疡性结肠炎(ulcerative colitis,UC)中的表达及其临床意义.方法:取36份活动期UC患者的结肠黏膜标本(结肠炎组)及30份体检者的结肠黏膜标本(对照组),采用免疫组织化学法检测两组SSTR的表达情况.结果:SSTR的表达主要定位于结肠黏膜的上皮细胞、纤维细胞、淋巴细胞和小血管的内皮细胞的细胞质中.SSTR在UC结肠黏膜中的阳性表达率为92%,明显高于对照组的73%(P＜0.05).中、重度UC患者结肠黏膜SSTR的阳性表达率均明显高于轻度UC患者(均为P＜0.05).便血明显(肉眼可见)的UC患者结肠黏膜SSTR的阳性表达率明显高于便血不明显(肉眼不可见,但潜血试验阳性)的UC患者(P＜0.05).结论:活动期UC患者结肠黏膜的SSTR的表达上调,其上调程度在病情较重或伴明显便血患者中更高.     

溃疡性结肠炎结肠粘膜HLA－DR抗原表达

本文检测了６０例溃疡性结肠炎和３０例正常结肠粘膜上皮细胞ＨＬＡ－ＤＲ抗原表达。结果显示，３０例正常结肠粘膜上皮及腺体不表达ＨＬＡ－ＤＲ抗原；而６０例ＵＣ中有３２例结肠粘膜上皮和腺体不同程度表达该抗原。其中，４２例活动性ＵＣ中２９例表达，１８例非活动性ＵＣ仅３例表达。同时发现ＵＣ结肠粘膜上皮表达ＨＬＡ－ＤＲ抗原还与粘膜炎症程度成正比。结果提示，细胞免疫机制在ＵＣ的发病机理中起重要作用。     

Cancer in chronic ulcerative colitis. Diagnostic role of segmental colonic lavage.

Saline colonic lavage in 74 patients with chronic ulcerative colitis was performed utilizing a commercially available dental irrigating unit through a polyethylene catheter in the biopsy channel of a colonoscope or through a sigmoidoscope via a lavage-aspirating double-lumen probe. Six patients were found with colonic carcinoma. Two diagnoses of malignancy were established by cytologic smears and cell block alone. Two patients had positive mucosal biopsies and cell block. One patient with a hepatic flexure carcinoma and a second patient with a malignancy proximal to the left colon stricture were missed by these techniques. Considering the established proclivity for carcinoma in these patients, it is felt that segmental lavage in areas of stricutre, grossly dostorted mucosa, or endoscopically inaccessible areas represents a valuable adjunct in the diagnosis of carcinoma in chronic ulcerative colitis.     

Elevated cell-associated levels of interleukin 1β and interleukin 6 in inflamed mucosa of inflammatory bowel disease

The aim of this study was to investigate the involvement of the monocyte-derived cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) in idiopathic inflammatory bowel disease. Endoscopic biopsies of normal and inflamed intestinal mucosa were obtained from patients with ulcerative colitis ( n  = 11) and with Crohn's disease ( n  = 10). Intestinal mucosal cells were isolated by collagenase digestion. Cell viability, morphology and CD14 expression were determined. To measure cell-associated cytokine levels, cells were lysed and analysed for IL-1β and TNF-α in specific radioimmunoassays and for IL-6 using a biological assay. Compared with mucosal cells from control patients without inflammatory bowel disease the inflamed intestine in ulcerative colitis and Crohn's disease displayed markedly enhanced levels of IL-1β (median 245 pg 10⁻⁶ cells, range 30–1275) and IL-6 (median 22 U 10⁻⁶ cells, range 1–298). Non-inflamed mucosa in patients with ulcerative colitis and Crohn's disease did not shown elevated levels of IL-1β (median 50 pg 10⁻⁶ cells, range 33–90) or IL-6 (mean below detection limit of assay, i.e. 1 U 10⁻⁶ cells). In contrast, no clear cut difference between inflamed and non-inflamed mucosa could be detected for TNF-α. High tissue levels of IL-6 were associated with a high endoscopic grade of local inflammation. These results suggest that the monocyte-derived cytokines IL-1β and IL-6 are mediators of inflammation in inflammatory bowel disease.     

T lymphocyte subpopulations and immunoglobulin-containing cells in the colonic mucosa of ulcerative colitis; a morphometric and immunohistochemical study

T lymphocyte subpopulations and immunoglobulin containing cells in the colonic mucosa of 25 patients with ulcerative colitis have been studied using an indirect immunoperoxidase technique. In ulcerative colitis a marked increase in the population of Leu 3a positive cells (helper/inducer T cells) and IgG containing cells was observed in the mucosal lamina propria. In the intraepithelial spaces, a remarkable decrease in the population of Leu 2a positive cells (suppressor/cytotoxic T cells) and a marked increase in the number of Leu 3a positive cells were revealed. There was a very significant correlation between the population of IgG containing cells and the ratio of Leu 3a positive cells to Leu 2a positive cells in the lamina propria of patients with ulcerative colitis. These results suggest that an imbalance of mucosal immunoregulatory T cells and an increased production of IgG occurred in correlation with inflammatory activities of ulcerative colitis.     

Low frequency of colorectal dysplasia in patients with long-standing inflammatory bowel disease colitis: detection by fluorescence endoscopy

BACKGROUND AND STUDY AIM: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colonic dysplasias. Dysplastic changes in flat mucosa are likely to be missed by conventional colonoscopy. Endoscopic fluorescence imaging, using 5-aminolevulinic acid (5-ALA) as photosensitizer, has evolved as a new technique to differentiate between normal colonic mucosa and dysplasia. We combined this technique with random biopsies to prospectively evaluate the occurrence of dysplasias in patients with long-standing IBD. PATIENTS AND METHODS: 52 colonoscopies were performed in 42 consecutive patients (n = 28 with ulcerative colitis, n = 11 with Crohn's colitis, n = 3 with indeterminate colitis; mean age 43 years, range 21 - 78) with long-standing IBD colitis (median disease duration 14 years, range 3 - 40). All patients were in clinical remission. Patients were examined using both conventional white light and by fluorescence colonoscopy using oral 5-ALA. Four biopsies were taken every 10 cm from mucosa of normal appearance. In addition, macroscopically suspicious and fluorescence-positive areas were biopsied. RESULTS: A total of 688 biopsies of red-fluorescent (n = 20) and nonfluorescent (n = 662) areas of mucosa were taken. Dysplasia was detected histopathologically in only two of the biopsies. These biopsies were taken from two polypoid lesions which were fluorescence-negative. CONCLUSIONS: The rate of colonic dysplasia in patients with long-standing IBD colitis may be lower than previously reported.     

Transrectal ultrasound in the diagnosis and management of inflammatory bowel disease

BACKGROUND AND STUDY AIMS: To aim of the present study was to determine the value of transrectal ultrasonography (TRUS) in the assessment of disease activity in ulcerative colitis patients, and in differentiating between mucosal inflammation and transmural inflammation. PATIENTS AND METHODS: TRUS examinations were used to study 30 control individuals and 76 patients with inflammatory bowel disease, including 50 cases of ulcerative colitis and 26 of Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall. RESULTS: In the 30 control individuals, the rectal wall showed five layers, with a mean total diameter of 2.6 mm. There were significant differences between patients with quiescent ulcerative colitis, active ulcerative colitis, and control individuals with regard to the total rectal wall thickness (P<0.001), submucosal thickness (P<0.001) and mucosal thickness (P<0.001). Using cut-off values, differentiation between active ulcerative colitis and remission ulcerative colitis was found to be 100% specific and 73 % sensitive for submucosal thicknesses. TRUS revealed a 100% specificity in differentiating between remission ulcerative colitis and control cases based on the total rectal wall thickness, submucosal, and mucosal thicknesses. In the differential diagnosis of active and remission ulcerative colitis, an increase in submucosal wall thickness and the existence of arterial and venous capillary flow in the submucosa were found to be specific and more sensitive than the other parameters. TRUS examination revealed transmural inflammation in 21 of the 26 Crohn's disease patients, and mucosal inflammation in all 50 of the ulcerative colitis patients. CONCLUSION: TRUS is a reliable and easy method of assessing ulcerative colitis activity and differentiating between rectal diseases.     

Glycoprotein Synthesis and Secretion by Mucosal Biopsies of Rabbit Colon and Human Rectum

Elucidation of mechanisms involved in the control of colonic production of mucus requires direct examination of glycoprotein synthesis and secretion by colonic mucosa. In the past, the limited viability of intestinal mucosa in vitro has hampered such investigations. When maintained in an organ culture system, mucosal biopsies of rabbit colon and human rectum remained viable for 24 h as documented by morphologic appearance and a steady rate of protein synthesis and secretion. These biopsies also incorporated (14)C-labeled glucosamine into tissue glycoproteins and secreted labeled glycoproteins at a steady rate for 24 h. Glucosamine was predominantly incorporated into macromolecules that were ultimately secreted, in contrast to leucine, which was predominantly incorporated into tissue macromolecules. When studied by autoradiography, cultured rabbit colonic biopsies synthesized and secreted glycoproteins in vitro at cellular sites and over a time-course similar to those previously described for the intestine of intact animals. Acetylcholine consistently stimulated secretion of labeled glycoproteins but did not alter glycoprotein synthesis. In contrast, cycloheximide inhibited glycoprotein synthesis but had no effect on the secretion of newly synthesized glycoproteins. Rectal biopsies from patients with active ulcerative colitis incorporated increased amounts of [(14)C]glucosamine into glycoproteins during organ culture and secreted labeled glycoproteins more rapidly into the incubation medium when compared to biopsies obtained from healthy volunteers These findings indicate that organ culture provides a useful means of directly examining the synthesis and secretion of glycoproteins by healthy and diseased colonic mucosa.     

Composition of human colonic mucin. Selective alteration in inflammatory bowel disease.

Human colonic mucin has been isolated from mucosal scrapings of fresh surgical specimens of normal controls as well as patients with Crohn's colitis and ulcerative colitis. Following sonication and ultracentrifugation, mucin fractions were separated from other soluble colonic glycoproteins by Sepharose 4B chromatography. After nuclease digestion, cesium chloride gradient centrifugation of the excluded material yielded colonic mucin with an average buoyant density of 1.52 g/ml. Subsequent chromatography of the apparently homogeneous colonic mucin on DEAE-cellulose revealed the presence of at least six distinct mucin species (mucin I-VI). Each mucin species was found to have a distinctive hexose, hexosamine, sialic acid, and sulfate content as well as blood group substance activities. Mucin from five patients with Crohn's colitis was found to represent a mixture of at least six discrete species comparable to those isolated from normal colonic specimens. However, in mucin from eight patients with ulcerative colitis there was a marked and selective reduction of one component mucin subclass, designated species IV. Normal mucin and mucin from patients with Crohn's disease contained 48 +/- 17 and 42 +/- 12 mg of species IV/g, while mucin from patients with ulcerative colitis had 5 +/- 3 mg/g solubilized glycoprotein. The selective absence of species IV was found in preparations from both sigmoid (n = 7) and ascending (n = 4) colon and could not be accounted for by an overall decrease in total mucin content. The selective reduction of species IV was also found in mucin isolated from relatively noninflamed colonic mucosa of patients with ulcerative colitis. The carbohydrate composition and blood group activities of the remaining five mucin species were similar to their normal counterparts. Based on the results to date, there appears to be an underlying selective decrease of one colonic mucin subclass in ulcerative colitis.     

益生菌CMS-H002和CMS-H003联用对小鼠急性溃疡性结肠炎的影响

目的：研究肠道益生菌CMS-H002和CMS-H003对小鼠溃疡性结肠炎（UC）的治疗作用。方法：建立硫酸葡聚糖胺（DSS）诱导的小鼠急性UC模型。观察益生菌CMS-H002和CMS-H003治疗后，疾病活动指数（DAI）、肠道菌群及丙二醛（MDA）的变化。结果：肠道益生菌CMS-H002和CMS-H003均可明显降低DAJ的水平及结肠组织的MDA水平。疗效均优于或等于巴柳氮阳性治疗药物。治疗后，各益生菌治疗组粪便乳酸杆菌、双歧杆菌菌数均有不同程度增加；而大肠杆菌及金黄色葡萄球菌菌数均有不同程度减少；其中用CMS-H003和合用组治疗后，丁酸梭菌菌数也有增加。以合用组小鼠粪便菌群更趋近于正常小鼠粪便菌群构成。而巴柳氮阳性治疗组对小鼠粪便的菌群菌数无明显影响。结论：口服肠道益生菌CMS-H002和CMS-H003可明显改善5％DSS诱导的Balb／c小鼠急性UC的一般表现及组织学损伤。两茼舍用效果尤为明显。减少自由基的产生及逆转病态菌群是它们发挥治疗UC作用的部分机制。     

Biosynthesis and secretion of human colonic mucin glycoproteins.

Synthesis and secretion of colonic mucin glycoprotein species were assessed during in vitro culture of colonic mucosal explants. DEAE-cellulose chromatography of endogenously labeled mucin glycoproteins from explant tissue demonstrated the presence of six mucin species (I-VI) similar to those identified earlier in surgical specimens of human colonic tissue. The relative proportions of mucin species I-VI in tissue explants remained constant throughout a 30-h culture period. However, the proportional representation of the various mucin species in media was significantly different from that found in tissue, which suggests that some mucin species (I, II, and III) are differentially secreted, whereas others (IV and V) are retained within intracellular pools. Radiolabeled precursors were incorporated into mucin species I, II, and III at a 2.0-2.6-fold greater rate than their concentration in tissue, supporting the concept that these glycoproteins were both synthesized and secreted at a greater rate than species IV and V. Colonic mucosal explants from patients with ulcerative colitis showed greater than 90% reduction of species IV. However, the amount of species IV recovered from culture media of ulcerative colitis explants was comparable to normal controls. It appears that mucin species IV is differentially secreted rather than retained within intracellular pools in mucosa of patients with ulcerative colitis.     

Probiotics and prebiotics for the treatment of inflammatory bowel disease

Although the causes of inflammatory bowel disease including ulcerative colitis and Crohn's disease remain incompletely understood, increasing evidence implicates intestinal microflora in the pathogenesis of this disorder. Therefore, modulation of microflora with probiotics or prebiotics may offer a plausible therapeutic approach. While recent data support a potential therapeutic efficacy, such treatments need to be further assessed by large scale studies. A better understanding of the intestinal microflora and the mechanisms of their action may help us to develop more effective treatment for inflammatory bowel disease.     

Cytomegalovirus colitis in intensive care unit patients: Difficulties in clinical diagnosis

Purpose

Cytomegalovirus (CMV) infection occurs increasingly in critically ill patients in intensive care units (ICUs). We reported CMV colitis which has rarely been recognized in the ICU patients.

Methods

CMV DNA was detected by polymerase chain reaction (PCR) for blood and/or stool samples. Definite diagnosis of CMV colitis required histopathology or CMV immunohistochemical staining of colorectal biopsies. We reviewed ICU patients characterized by positive blood or stool CMV-PCR with colorectal bleeding or water diarrhea.

Results

We identified 18 patients (biopsy-proved, n = 8; probable cases, n = 10). The most common comorbidities were chronic renal disease, diabetes mellitus, and coronary artery disease. Stool CMV-PCR was positive in 7 of 10 patients (2 of 3 biopsy-proved and 5 of 7 probable cases). Colonoscopy was performed for 15 patients, revealing ulcerative or polypoid lesions. The endoscopists obtained colonic biopsies from 9 patients. Yet, the pathologists reported CMV colitis for 4 patients. Additional 4 patients were confirmed using immunohistochemical stain by the request of clinical physicians. Pseudomembranous colitis was found in 4 patients.

Conclusion

Diagnosis of CMV colitis seems difficult in clinical practice and need persistent communication between clinicians. The positive stool CMV-PCR result was a useful hint for adding immunohistochemical stain in mucosal biopsies to make a definite diagnosis of CMV colitis.     

Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis.

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis. 2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetylglucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into pure mucin was assessed. 3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305-0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959-1.111, P < 0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378-0.829) did not quite reach statistical significance (P = 0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26). 4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618-1.022) than in their paired proximal colonic biopsies (0.602, 0.421-0.861; P < 0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262-0.773; right colon: 0.470, 0.321-0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260-0.815; right colon: 0.492, 0.260-0.929, P = 0.8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Indigo carmine-assisted high-magnification chromoscopic colonoscopy for the detection and characterisation of intraepithelial neoplasia in ulcerative colitis: a prospective evaluation

BACKGROUND AND STUDY AIMS: Recent data suggest that panchromoscopy using methylene blue can improve the detection of intraepithelial neoplastic lesions in the context of surveillance colonoscopy for patients with chronic ulcerative colitis. This method has also been shown to provide a more accurate diagnosis of the extent of disease and inflammatory activity. Interval cancers are known to occur in patients with chronic ulcerative colitis despite the adoption of currently accepted surveillance biopsy protocols. We hypothesised that targeted chromoscopy alone, with high-magnification imaging, may increase the total number of intraepithelial neoplastic lesions detected, compared with conventional colonoscopy and biopsy surveillance according to current protocols. PATIENTS AND METHODS: A total of 350 patients with long-standing ulcerative colitis (>or=8 years) underwent surveillance colonoscopy using high-magnification chromoscopic colonoscopy (HMCC). Quadrantic biopsies at 10-cm intervals were taken on extubation in addition to targeted biopsies of abnormal mucosal areas. Defined lesions were further evaluated using modified Kudo crypt pattern analysis. These data were compared with data from 350 disease duration- and disease extent-matched control patients who had undergone conventional colonoscopic surveillance between January 2001 and April 2005. RESULTS: Significantly more intraepithelial neoplastic lesions were detected in the magnification chromoscopy group compared with controls (69 vs. 24, P<0.0001). Intraepithelial neoplasia was observed in 67 lesions, of which 53 (79%) were detected using magnification chromoscopy alone. Chromoscopy increased the number of flat lesions with intraepithelial neoplasia detected compared with controls (P<0.001). Twenty intraepithelial neoplastic lesions were detected from 12,850 non-targeted biopsies in the HMCC group (0.16%), while 49 intraepithelial neoplastic lesions were detected from the 644 targeted biopsies in the HMCC group (8%). From 12,482 non-targeted biopsies taken in the control group patients, 18 (0.14%) showed intraepithelial neoplasia. The yield of intraepithelial neoplastic lesions from targeted biopsies in the control group (i. e. without HMCC imaging), however, was only modestly improved at 1.6% (6/369). Using modified Kudo criteria, the sensitivity and specificity for differentiating neoplastic from non-neoplastic lesions using HMCC were 93% and 88% respectively. The total procedure time was significantly longer in the HMCC group compared with controls (P<0.02). CONCLUSIONS: Magnification chromoscopy improves the detection of intraepithelial neoplasia in the endoscopic screening of patients with chronic ulcerative colitis. Neoplastic and non-neoplastic mucosal change can be predicted with a high overall accuracy using magnification techniques. These adjunctive endoscopic techniques have important clinical implications and may lead to changes in current practice guidelines.