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[Differential diagnosis of acute inflammatory colon diseases by colonic sonography].

Colon sonography enables imaging of the colon from the beginning of the rectosigmoid transition up to the cecum. Colon sonographic investigations in 29 patients (normal findings n = 15, ulcerative colitis n = 6, Crohn's disease n = 8) with a finding verified by coloscopy and biopsy show that acute ulcerative colitis and florid Crohn's disease lead to different sonographic alterations. Formation of haustra can no longer be detected in the two diseases. In Crohn's disease, the typical sonographically discernible wall layering has been abolished, and the wall is markedly thickened. In contrast to this, the wall layering is preserved in acute ulcerative colitis and the wall is only moderately thickened. The results show that differential diagnosis of acute inflammatory diseases of the large intestine is possible using colon sonography.

Adult↗

Slow-release pellets of sodium butyrate increase apoptosis in the colon of rats treated with azoxymethane, without affecting aberrant crypt foci and colonic proliferation.

We investigated whether sodium butyrate, administered orally as gastroresistant slow-release pellets to rats, could affect markers of colon carcinogenesis. F344 male rats were fed a high-fat diet (230 g/kg corn oil, wt/wt) and treated with two injections (1 wk apart) of azoxymethane (15 mg/kg sc) or saline. Rats were then divided into two groups: one received the diet with 1.5% (wt/wt) sodium butyrate for 10 weeks to provide 150 mg butyrate/day, and one group received no butyrate. At the end of this period, rats were sacrificed, and colonic proliferative activity, number of aberrant crypt foci (ACF), and apoptosis were assessed in the colon. The proliferative activity and ACF induction were not affected by butyrate pellet administration. On the contrary, in rats treated with butyrate, apoptotic index increased from 0.12 +/- 0.12 to 0.81 +/- 0.10 (means +/- SE, p < 0.05). The short-chain fatty acid concentration was significantly increased in the feces of rats treated with butyrate. In conclusion, the increase in the mucosal apoptotic index suggests that gastroresistant butyrate pellets have a beneficial effect against colon carcinogenesis. However, because butyrate pellets did not modify proliferation or ACF induction, this conclusion should be confirmed in long-term carcinogenesis experiments.

Animals↗

Diverticulitis of the sigmoid colon. A comparison of CT, colonic enema and laparoscopy.

PURPOSE: To evaluate the use of laparoscopy, CT, colonic enema (CE), and laboratory tests (white blood cell count (WBC), sedimentation rate (SR), and C-reactive protein (CRP) in diagnosing diverticulitis of the sigmoid colon. MATERIAL AND METHODS: The diagnostic methods were prospectively evaluated in 88 patients, 30 of whom were referred for laparoscopy. RESULTS: Fifty-two patients were found to have sigmoid diverticulitis: 20 patients by laparoscopy, 21 by CT, and 11 by CE combined with one positive laboratory test. Laparoscopy proved to be superior to the other diagnostic methods in diagnosing diverticulitis of the sigmoid colon. CT had a high specificity (1.0; 95% CI: 0.92-1.0) but low sensitivity (0.69; 95% CI: 0.56-0.79) in detecting diverticulitis. CE had a higher sensitivity (0.82; 95% CI: 0.71-0.90) but a lower specificity (0.81; 95% CI: 0.67-0.91) than CT. CONCLUSION: CT was the best method for diagnosing abdominal pathology outside the colon. CT can be recommended as the first examination in seriously ill patients where abscesses and other causes of the symptoms than diverticulitis must first be ruled out. Laparoscopy is probably the most accurate method in diagnosing diverticulitis.

Adult↗

Colon cancer prevalence and estimation of differing care needs of colon cancer patients.

BACKGROUND: Cancer prevalence-the proportion of people in a population with a diagnosis of cancer-includes groups with widely differing cancer care needs. We estimated the proportions of the prevalent colon cancer cases requiring initial care, terminal care and follow-up. PATIENTS AND METHODS: Prevalence by year since diagnosis was estimated from incidence and vital status data on 243,471 colon cancer cases collected by EUROPREVAL from 36 European population-based cancer registries. The proportions of cured and fatal cases were estimated by applying 'cure' survival models to the dataset. The proportion of recurrence-free cases was estimated by analysis of a representative sample of 278 colon cancer patients from the Lombardy Cancer Registry (LCR), northern Italy. RESULTS: The proportions of total prevalence requiring initial care was estimated at 12% in the LCR and 10% in Italy and Europe. Recurrence-free patients formed 89% of the total prevalence in the LCR and 91% in Italy and Europe. Eleven per cent (LCR) and 9% (Italy, Europe) of the total prevalence had recurred and consisted of patients in the terminal phase of their illness. CONCLUSIONS: In 1992, 660,000 people were living with a diagnosis of colon cancer in Europe. We have estimated the proportions of this prevalence requiring particular types health care in the years following diagnosis, providing data useful for planning the allocation of health-care resources.

Algorithms↗

Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis.

Apples contain several classes of polyphenols: monomers (catechins, epicatechins) and oligomers/polymers, such as the procyanidins. Our aim was (i) to study anti-proliferative mechanisms on human metastatic colon carcinoma (SW620 cells) of apple polyphenol fractions (monomers or procyanidins) and (ii) to evaluate their anti-carcinogenic properties in vivo. Two polyphenol-enriched fractions were isolated from apples. Fraction non-procyanidins contained 73% phenolic monomers and no procyanidins, while fraction procyanidins contained 78% procyanidins and no monomers. Inhibition of SW620 cell growth was only observed with fraction P (IC50 = 45 microg/ml). After a 24-h exposure of cells to fraction P, protein kinase C activity was inhibited by 70% and a significant increase in extracellular signal-regulated kinases 1 and 2 and c-jun N-terminal kinases expression was observed together with the down-regulation of polyamine biosynthesis and the activation of caspase-3. Colon carcinogenesis was induced in rats by intraperitoneal injections of azoxymethane, once a week for 2 weeks. Seven days after the last injection, Wistar rats received fraction P (0.01%) dissolved in drinking water. After 6 weeks of treatment, the colon of rats receiving procyanidins showed a significant (P < 0.01) reduction of the number of preneoplastic lesions when compared with controls receiving water. The total number of hyperproliferative crypts and of aberrant crypt foci was reduced by 50% in rats receiving 0.01% apple procyanidins in their drinking water. Our results show that apple procyanidins alter intracellular signaling pathways, polyamine biosynthesis and trigger apoptosis in tumor cells. These compounds antagonize cancer promotion in vivo. In contrast with absorbable drugs, these natural, non toxic, dietary constituents reach the colon where they are able to exert their antitumor effects.

Administration, Oral↗

Urinary pH and urea concentration correlate to the bacterial colonization rate in gastric, colonic, ileal and myoperitoneal bladder augmentation.

We investigated how various types of augmentation cystoplasty alter the native bacteriostatic properties of urine, particularly urinary urea and pH, in the Sprague-Dawley rat. The augmentation cystoplasties studied included 1 cm.2 and 2 cm.2 patches of colon, ileum and stomach as well as myoperitoneal bladder flaps. Augmentations in order of decreasing incidence of bacteriuria and urinary pH are 2 cm.2 ileal greater than 1 cm.2 ileal greater than 2 cm.2 colonic greater than 1 cm.2 colonic greater than myoperitoneal greater than cystotomy alone greater than 1 cm.2 gastric greater than 2 cm.2 gastric. Urinary urea concentrations were similar between cystotomy alone, and myoperitoneal and gastric augments. In contrast, all colonic and ileal augments had significantly lower urea concentrations compared to the aforementioned groups. Our findings suggest that the type and size of augmentation directly affect urinary pH and urea nitrogen concentration, and the incidence of bacteriuria.

Animals↗

Repeated coaxial colonic stenting in the palliative management of benign colonic obstruction.

In inflammatory bowel disease, strictures of the colon, causing bowel obstruction, is not uncommon. Usually an operative procedure can deal with these strictures. We describe a case of an unfit patient with pulmonary malignancy having a Crohn's stricture of the recto-sigmoid junction in which repeated coaxial placement of self-expanding metallic stents eliminated the need to perform an operation. This is the first report of multiple coaxial colonic stenting. It shows that there is a place for stents in selected cases of inflammatory bowel disease with a limited life expectancy and that repeated colonic stenting makes colonic stenting possible also in patients requiring stents for longer time periods.

Aged↗

Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk.

Clinical studies reveal concomitant occurrence of several gastrointestinal and urologic disorders, including irritable bowel syndrome and interstitial cystitis. The purpose of this study was to determine the mechanisms underlying cross-organ sensitization at the level of dorsal root ganglion (DRG) after acute and subsided gastrointestinal inflammation. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and Fast Blue were injected into the distal colon and urinary bladder of male rats, respectively. Convergent DRG neurons were found in L1-L3 and L6-S2 ganglia with an average distribution of 14% +/- 2%. The resting membrane potential (RMP) of cells isolated from upper lumbar (UL) ganglia was -59.8 +/- 2.7 mV, whereas lumbosacral (LS) neurons were more depolarized (RMP = -49.4 +/- 2.1 mV, P < or = 0.05) under control conditions. Acute trinitrobenzene sulfonic acid (TNBS) colitis (3 days) decreased voltage and current thresholds for action potential firing in LS but not UL convergent capsaicin-sensitive neurons. This effect persisted for 30 days in the absence of overt colonic inflammation. The current threshold for action potential (AP) firing in UL cells was also decreased from 165.0 +/- 24.5 pA (control) to 85.0 +/- 19.1 pA at 30 days (P < or = 0.05), indicating increased excitability. The presence of a subpopulation of colon-bladder convergent DRG neurons and their persistent hyperexcitability after colonic inflammation provides a basis for pelvic organ cross-sensitization.

Action Potentials↗

Involvement of N-acetyl-lactosamine-containing sugar structures in the liver metastasis of mouse colon carcinoma (colon 26) cells.

Histochemical aspects of the process of experimentally induced metastasis were examined by light and electron microscopy with labelled lectins employed as a probe. Mouse colon carcinoma cells (colon 26) were injected into the spleen of Balb/c mice and liver metastasis was induced. Among the lectins tested, Erythrina cristagalli agglutinin (ECA) stained the metastasized colon 26 cells strongly compared with the heterogeneous and faint staining in non-metastasized tumour foci in the spleen or in the subcutaneous space. Other lectins, such as Phaseolus vulgaris leucoagglutinin (PHA-L), Phaseolus vulgaris erythroagglutinin (PHA-E) and Datura stramonium agglutinin (DSA), having specificity for branched complex type sugar chains, did not show any differences between metastasized cells and non-metastasized tumour foci. In addition, N-acetyl-lactosamine, a specific inhibitor of ECA binding, significantly inhibited the attachment of suspended colon 26 cells to sectioned unfixed normal liver tissue. These results indicate that the expression of galactose (Gal) beta 1-4 N-acetyl-glucosamine (GlcNAc) residues of branched complex type sugar chains having specificity for ECA are important for the interaction process of carcinoma cells with hepatic cells in the process of liver metastasis.

Amino Sugars↗

Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.

OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Aneuploidy↗

In vitro colonization ability of human colon mucosa by exogenous Lactobacillus strains.

We have tested five Lactobacillus strains for their in vitro colonization ability in a human colon epithelium culture model. Positive colonization occurred in different degrees in the presence of four Lactobacillus strains. We have found that L. casei GG and L. acidophilus NCFB 1748 induce an intermediate colonization. These two strains, largely investigated by others, have been reported to be beneficial to humans. The use of human intestinal tissue in our study partially reconstitutes the complex architectural specificity of human epithelium with the mucus layer and more closely simulates the in vivo situation.

Colon↗

Degradation of pig gastric and colonic mucins by bacteria isolated from the pig colon.

Mucin degradation was studied with one Clostridium (RS42) and two Bacteroides (RS2 and RS13) strains isolated from the pig colon mucosa. Mucins from pig colon and stomach were prepared in their subunit forms for use as growth substrates, and the loss of the individual sugars from the mucins was measured after bacterial growth. Colonic mucin was more resistant to degradation than gastric mucin. The strains differed in their competence in degrading the mucins. Carbohydrate plus sulfate removal from gastric mucin varied from 63 to 76% for RS2, 37 to 46% for RS13, and 37 to 53% for RS42. All three strains removed more fucose (67 to 87%) and less sulfate (22 to 63%) than the average carbohydrate plus sulfate loss. Under the same conditions of growth, a mixed pig fecal culture removed 78% of sulfate and 96% of each sugar. Of the two major glycoprotein types present in the subunit pig gastric mucin preparation (R. A. Stanley, S. P. Lee, and A. M. Roberton, Biochim. Biophys. Acta 760:262-269, 1983), the less highly sulfated mucin was more susceptible to RS42 degradation. The degradation of gastric mucin by RS2 was not affected by glucose or high sulfate concentrations in the growth medium. The results show that the three strains of colon bacteria are capable of significant hydrolysis of mucin carbohydrate and that the extent of degradation seen with pure cultures is determined in part by the subunit glycoprotein type(s) present in the mucin.

Animals↗

Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption.

Lactobacillus rhamnosus GG is one of the most thoroughly studied probiotic strains. Its advantages in the treatment of gastrointestinal disorders are well documented. The aim of the present study was to demonstrate with colonic biopsies the attachment of strain GG to human intestinal mucosae and the persistence of the attachment after discontinuation of GG administration. A whey drink fermented with strain GG was fed to human volunteers for 12 days. Fecal samples were collected before, during, and after consumption. L. rhamnosus GG-like colonies were detected in both fecal and colonic biopsy samples. Strain GG was identified by its characteristic colony morphology, a lactose fermentation test, and PCR. This study showed that strain GG was able to attach in vivo to colonic mucosae and, although the attachment was temporary, to remain for more than a week after discontinuation of GG administration. The results demonstrate that the study of fecal samples alone is not sufficient in evaluating colonization by a probiotic strain.

Administration, Oral↗

Colonic polyps: effect of attenuation of tagged fluid and viewing window on conspicuity and measurement--in vitro experiment with porcine colonic specimen.

PURPOSE: To investigate effect of attenuation of tagged fluid and viewing window on polyp conspicuity and measurement with porcine colonic specimen. MATERIALS AND METHODS: Eleven (3-10-mm-diameter) polyps were created in porcine colon and the specimen submerged in saline. Four-detector row CT was performed after gas distension and after filling with six barium sulfate suspensions (attenuation, 100-1000 HU). Two readers independently measured maximal two-dimensional polyp diameter on each data set with the following four viewing windows and window levels and window widths, respectively: colon (-150 HU, 1500 HU), lung (-500 HU, 1500 HU), bone (500 HU, 2500 HU), and abdomen (40 HU, 400 HU). In consensus, polyp conspicuity (compared with air data set) was assigned a grade of 1-4 for each viewing window (grade 1, not seen or barely visible; grade 4, optimally seen). For statistical analysis, conspicuity grades were collapsed to a two-point scale. Data were analyzed with Mann-Whitney, Kruskal-Wallis, and chi2 tests. RESULTS: Accuracy of polyp measurement was independent of viewing window for attenuation of tagged fluid of 100-300 HU but differed significantly for 500-1000 HU (P < .001); that for colonic and bone viewing windows was superior (median size difference, 1.0 mm; interquartile range, 0.5-1.5). Conspicuity differed significantly according to viewing window at all attenuation values (P < .001). For 100-300 HU with abdominal viewing window, 83% (24 of 29) of observations were assigned grade 3 or 4 (best). For 500-1000 HU with bone viewing window, 94% (30 of 32) of observations were assigned grade 3 or 4 (superior). Overall conspicuity was best with bone viewing windows at 700 HU. CONCLUSION: Polyp conspicuity and measurement in tagged data sets were optimized at 700 HU with bone viewing windows. At less than 300 HU, conspicuity improved with abdominal viewing windows.

Animals↗

Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer.

HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as the colon. In CaCo-2 colonic epithelial cells, the expression of this gene increases with cell differentiation. Accordingly, immunohistochemistry with specific antibodies shows that HMGCS2 is expressed mainly in differentiated cells of human colonic epithelium. Here, we used a chromatin immunoprecipitation assay to study the molecular mechanism responsible for this expression pattern. The assay revealed that HMGCS2 is a direct target of c-Myc, which represses HMGCS2 transcriptional activity. c-Myc transrepression is mediated by blockade of the transactivating activity of Miz-1, which occurs mainly through a Sp1-binding site in the proximal promoter of the gene. Accordingly, the expression of human HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. HMGCS2 protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors. Based on these findings, we propose that ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2.

Acetylation↗

A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene.

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.

Adenoma↗

A report of 27 cases of congenital short colon with an imperforate anus: so-called 'pouch colon syndrome'.

This is a retrospective study of 27 cases of congenital short colon with anorectal malformation (pouch colon syndrome) treated during the last 5 years (from January 1991 to December 1995). The radiological feature of enormously dilated colonic pouch occupying more than half the width of abdomen was diagnostic in almost all cases. Excision of pouch and end enterostomy was associated with maximum survival (92.3%) in good risk patients. Proximal diverting enterostomy with decompression and irrigation of pouch is a preferable alternative to pouch colostomy in poor risk patients. Tapering coloplasty and colostomy should be reserved only for types I and II cases of pouch colon.

Abnormalities, Multiple↗

Calcium or resistant starch does not affect colonic epithelial cell proliferation throughout the colon in adenoma patients: a randomized controlled trial.

Patients with a history of sporadic adenomas have increased epithelial cell proliferative activity, an intermediate risk marker for colorectal cancer. Reduction of proliferation by dietary intervention may reflect a decreased colorectal cancer risk. To evaluate whether calcium or resistant starch could reduce proliferative activity throughout the colon, we performed a randomized controlled trial in 111 sporadic adenoma patients. Patients received two placebos, 1 g of calcium + placebo, or 30 g of amylomaize (19 g of resistant starch) + placebo. After 2 mo, biopsies were collected from the cecum, transverse and sigmoid colon, and rectum during colonoscopy. Epithelial cell proliferation was determined by dividing the number of 5-bromo-2-deoxyuridine-labeled nuclei by the total number of nuclei x 100 (labeling index, LI). LI of luminal, mid, and basal compartments was determined. Twenty-five patients dropped out. In the remaining 86 patients (28 treated with placebo, 30 with calcium + placebo, and 28 with resistant starch + placebo), no difference was observed in total LI, the LI of the three compartments, or the crypt length in the four areas of the colorectum. Colonic epithelial cell proliferative activity throughout the colon of sporadic adenoma patients is not affected by supplementation with 1 g of calcium or 19 g of resistant starch.

Adenoma↗