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PubMed2002

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.

Biomarkers, Tumor↗
PubMed2000

Acute diverticulitis of the cecum and ascending colon: the value of thin-section helical CT findings in excluding colonic carcinoma.

OBJECTIVE: The purpose of this study was to assess the value of characteristic thin-section helical CT findings of acute diverticulitis involving the cecum and ascending colon in excluding colonic carcinoma. MATERIALS AND METHODS: Thin-section helical CT scans (5-mm collimation) of 19 consecutive patients with proven diverticulitis and 21 consecutive patients with surgically proven carcinoma involving the cecum and ascending colon were reviewed retrospectively. Two radiologists independently analyzed these parameters: degree of pericolic infiltration, mesenteric fluid, vascular engorgement, arrowhead-shaped wall thickening, air-filled diverticula, inflamed diverticula, and preserved enhancement pattern of involved colonic wall. Inter-observer agreement was assessed with a kappa statistical analysis, and the features that most distinguished diverticulitis from colonic carcinoma were selected with a stepwise logistic-regression analysis. RESULTS: The two CT findings of right-sided colonic diverticulitis that most distinguished it from colonic carcinoma were inflamed diverticula and the preservation of an enhancement pattern of the involved colonic wall. Excellent interobserver agreement (kappa > 0.60) was obtained for both findings. Inflamed diverticula (kappa = 0.80) had a mean sensitivity, specificity, and accuracy for diverticulitis of 86.8%, 92.9%, and 90.0%, respectively, in differentiating right-sided colonic diverticulitis from colonic carcinoma. Preserved wall enhancement pattern (kappa = 0.70) had a mean sensitivity, specificity, and accuracy of 89.5%, 95.3%, and 92.5%, respectively. CONCLUSION: On thin-section helical CT, an inflamed diverticula and a preserved enhancement pattern of the thickened colonic wall were the two most statistically significant CT findings of acute diverticulitis involving the cecum and ascending colon that distinguished diverticulitis from colonic carcinoma.

Acute Disease↗
PubMed1985

Ileal and colonic mucosal bile acids in Crohn's disease and right colonic carcinoma.

Bile acids are supposed to promote colonic cancer. In Crohn's disease, colonic carcinomas are relatively rare. We, therefore, compared ileal and right colonic mucosal bile acids analysed by gas-liquid chromatography in 8 patients with ileal Crohn's disease (14-48 yrs.) and 7 patients with right colonic carcinoma (28-77 yrs.) who underwent surgery. In both ileal and colonic mucosa, nonsulphated bile acid concentrations were somewhat higher in Crohn's disease (20.98 micrograms/g +/- 4.77 SEM; 12.09 micrograms/g +/- 2.55) than in colonic carcinoma (16.06 micrograms/g +/- 3.46; 7.75 micrograms/g +/- 4.28). In ileal mucosa, percentages of lithocholic and deoxycholic acids were slightly higher in colonic carcinoma (3.9%; 23.2%) than in Crohn's disease (1.1%; 14.9%). In colonic mucosa, carcinoma patients had more lithocholic (7.6%) and less deoxycholic acid (11.9%) than patients with Crohn's disease (1.7%; 20.3%). Bile acid sulphate esters were similar in both diseases (ca. 3.0 micrograms/g in ileal, 1.4 micrograms/g in colonic mucosa). Our results show that ileal and right colonic mucosal nonsulphated bile acids tend to be even lower in right colonic carcinoma than in Crohn's disease. This agrees well with our earlier findings of low mucosal bile acid concentrations in patients with left colonic carcinoma (Tokai J Exp Clin Med 8: 59-69, 1983) and does not support the assumption that bile acids are envolved in right colonic carcinogenesis.

Adolescent↗
PubMed1993

[Diagnosis of colonic tumors and chronic inflammatory colonic diseases by hydrocolonic sonography].

Retrograde instillation of water into the colon makes it possible to visualize the colon sonographically from the rectosigmoid transition to the cecum in 97% of the patients examined. The sonographic views obtained using this technique, which is called hydrocolonic sonography, show the echo-free intestinal lumen, the five individual layers of the colon wall and the connective tissue surrounding the colon. Colonic polyps and carcinomas appear sonographically as echogenic structures projecting from the intestinal wall into the lumen. Colonic polyps larger than 7 mm diameter can be identified in 91% of cases, and the sensitivity of the technique in the detection of carcinomas of the colon is 97%. In addition, detailed evaluation of the structure of the bowel wall permits more precise staging of tumors of the colon. Aside from such localized changes, hydrocolonic sonography can also demonstrate typical changes in the wall structure in chronic inflammatory large-bowel diseases. In acute Crohn's disease the normal stratified appearance of the colonic wall is no longer in evidence and the wall appears visible thickened. In contrast, in patients with acute ulcerative colitis the normal sonographic stratified appearance of the colonic wall is maintained. Hydrocolonic sonography enables a detailed sonographic examination of the colonic lumen and the colon wall, thus providing additional information and allowing more precise diagnosis of many diseases of the colon.

Colonic Neoplasms↗
PubMed2002

Small colonic J-pouch improves colonic retention of liquids--randomized, controlled trial with scintigraphy.

PURPOSE: A small 6-cm colonic J-pouch improves stool frequency and continence, without stool evacuation problems. However, the reservoir function is not improved on physiologic studies. Hence, a scintigraphy technique was devised to study the transit of solid and liquid colonic contents in these patients. METHODS: Patients were randomly assigned to straight or colonic J-pouch anal anastomoses after ultralow anterior resection. At 1 year after surgery, they were studied by bowel questionnaire, anorectal manometry, and technetium TC 99m tin-colloid liquid test meal/I-131 microcapsule scintigraphy. In the latter, technetium TC 99m tin-colloid was ingested orally to image the colonic liquids. I-131 microcapsules taken simultaneously imaged the solid stools. After ingestion of the radioisotopes, imaging was performed at intervals of 7 to 8, 24, and 56 hours later. Two independent observers noted the presence of technetium TC 99m tin-colloid liquid and I-131 microcapsules in various areas of interest drawn over the colon. RESULTS: There were six patients (5 males, mean age, 61.5 (SE mean, 1.9) years) in the straight, and six patients (5 males, mean age, 63.2 (4.5) years) in the colonic J-pouch group. Stool frequency was more in the straight group (4.8 (0.4) vs. 3 (0.2) stools/day; P <.001). Continence, evacuation problems, and anorectal physiologic findings were not different. Technetium TC 99m tin-colloid (imaging liquids) transited significantly faster than I-131 microcapsules (imaging solids), at various areas of interest in the colon. In the colonic J-pouch patients, technetium TC 99m tin-colloid liquid was retained significantly longer in the descending colon at 24 hours (P <.05). Stool frequency was higher when technetium TC 99m tin-colloid was not retained in the descending colon at 56 hours (3.3 (0.5) vs. 4.3 (0.4) stools/day) but this did not reach statistical significance. There were no significant differences in the distribution of the ingested I-131 microcapsules between colonic J-pouch and straight groups. CONCLUSIONS: Reduced stool frequency after colonic J-pouch may be related to factors causing better retention of liquid stools in the distal colon. No difference in solid stool transit could possibly account for minimal evacuation problems in small pouches.

Aged↗
PubMed1997

K-ras and p53 mutations in aberrant crypt foci and colonic tumors from colon cancer patients.

Aberrant crypt foci (ACF) are microscopic lesions which can be detected, after methylene blue staining, in the overtly normal looking colonic mucosa of cancer patients. ACF have been postulated to be precursor lesions which develop into colorectal cancer. Mutations of K-ras and p53 are two important genetic events implicated in colon carcinogenesis. Mutations in K-ras are detectable at earlier stages, while mutations in p53 are detectable at later stages of colon carcinogenesis. Our objective was to compare the nature of genetic alterations in K-ras (codon 12 and 13) and in p53 (exon 4-9) between ACF and corresponding colonic tumors from cancer patients. ACF with > or =20 crypts/focus were harvested from overtly normal looking colonic mucosa of cancer patients at a distance of (approx.) 5 cm from the site of colonic tumors. The colonic tumors and ACF samples were compared for K-ras codon 12 and 13 base pair sequence, using DNA sequencing and for p53 (exon 5-9) allelic types, using PCR-SSCP and DNA sequencing. The results demonstrated a perfect correlation in terms of the type of K-ras allele (wild or mutated) between the ACF (> or =20 crypts/focus) and corresponding colonic tumors in 11/13 cancer patients. Analyses of p53 mutations demonstrated the presence of p53 mutations in colonic carcinomas from 10/13 patients. However, p53 mutations could be detected in an ACF from only 1/13 patient. The results provides further evidence to the role of ACF as precursor to colon cancer. The presence of an identical K-ras as well as p53 mutation in an ACF and the corresponding colonic carcinoma in a patient suggests the possibility of existence of ACF that may be at a more advanced stage in the sequence of colonic tumorigenesis than others. In conclusion, the results suggest that a subset of ACF with higher multiplicity might be considered more likely to progress to more advanced lesions and should be explored as markers of colon cancer risk.

Adenoma↗
PubMed1990

Effects of androgen manipulations on chemically induced colonic tumours and on macroscopically normal colonic mucosa in male Sprague-Dawley rats.

Epidemiological and experimental studies suggest that androgens influence colonic carcinogenesis. We investigated the effects of hormonal manipulations (surgical and chemical castration, hormone substitution) on colonic tumour development, tumour and mucosal histopathology, and epithelial proliferation in macroscopically normal colonic mucosa in male rats, after induction of chemical colon carcinogenesis by subcutaneous injections of azoxymethane (AOM). Chemical castration with cyproterone acetate, but not surgical castration, resulted in increased colonic tumorigenesis, which was accompanied by decreased crypt length, decreased number of cells per crypt, and increased crypt epithelial mitotic index in the right colon. Chemically castrated rats also had crypt hyperplasia and increased numbers of dysplastic foci in the left colon which were not seen with surgical castration. By contrast, rats given testosterone after surgical castration showed decreased colonic tumorigenesis with an increased proportion of tumours in the left colon and lower percentage of tumours with invasion. The grossly normal mucosa of the testosterone-substituted castrated rats showed decreased crypt length in the right colon similar to the other groups of castrated rats, but no significant increase in mitotic index. Our results suggest that the anti-androgenic progestin cyproterone is a potent enhancer of colonic tumorigenesis and epithelial proliferative abnormalities after AOM administration. Exogenous testosterone after castration alters tumour distribution and characteristics and suppresses epithelial proliferative abnormalities. Finally, androgen effects on the colonic mucosa are more prominent in the right than in the left colon, suggesting different influences of hormones on the epithelium of these anatomical sites.

Adenocarcinoma↗
PubMed2005

Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological marker of colon neoplasia.

Cancers of the colon and rectum are the second leading cause of cancer death among adult Americans. When detected at early stages, colon cancer is highly curable. Colonoscopy, an effective but invasive screening test, has been limited in its public acceptance. The goal of this study was to identify novel serum markers of colon cancers and precancerous colon adenomas as potential candidates for noninvasive detection of early colon neoplasms. Employing expression microarrays, we identified colon cancer secreted protein-2 (CCSP-2) as a novel transcript whose expression is generally absent in normal colon and other normal body tissues, but that is induced an average of 78-fold in Stage II, III, and IV colon cancers, as well as in colon adenomas and colon cancer cell lines. These findings were validated by real-time PCR analysis in an independent panel of colon cancer cases. Moreover, CCSP-2 was shown to encode a secreted protein that circulates stably and is detectable in the blood of mice bearing human cancer xenografts transfected with epitope-tagged CCSP-2. As a novel secreted protein that is markedly induced in colon adenomas and cancers, CCSP-2 is a novel candidate for development as a diagnostic serum marker of early stage colon cancer.

Amino Acid Sequence↗
PubMed1997

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea-pigs: comparisons with caecum and descending colon.

A systematic examination has been made of the active and passive electrophysiological properties and synaptic inputs of forty-four randomly impaled submucosal neurones in the proximal colon of the guinea-pig to compare these characteristics directly with those of submucosal neurones in the caecum (n = 70) and descending colon (n = 45). Within each of the three electrophysiological classes of submucosal neurones identified (S, S/AH and AH), no statistically significant regional differences were found with respect to the resting membrane potential, membrane time constant or input resistance between neurones of the proximal colon, descending colon and caecum. Of submucosal neurones from the proximal colon, forty-three of forty-four (98%) received fast excitatory synaptic potentials (fast EPSPs); thirty-nine (91%) were S neurones and the others were S/AH neurones; only one of the forty-four cells (2%) was an AH neurone. An idazoxan-sensitive slow inhibitory postsynaptic potential (slow IPSP) was induced in thirty of forty-three S and S/AH neurones (70%) of the proximal colon, compared with sixty-one of sixty-six caecal neurones (92%) and twelve of forty-one neurones (29%) in the descending colon. The mean (+/- S.E.M.) amplitude of the slow IPSP in proximal colonic neurones was 17 +/- 1 mV (range, 6-30 mV; n = 30), compared with the significantly larger synaptic response (25 +/- 1 mV; range, 7-38 mV; n = 66; P < 0.05) recorded in the caecum; the mean slow IPSP amplitude in the descending colon was significantly smaller (12 +/- 2 mV; range, 5-27 mV; n = 12; P < 0.05) than that in the caecum. In the proximal colon and caecum, only those neurones with a slow IPSP had a hyperpolarizing response to noradrenaline, whereas about 50% of those neurons of the descending colon that lacked a slow IPSP were hyperpolarized by noradrenaline, acting via alpha 2-adrenoceptors. Thus, the electrophysiological characteristics of the submucosal neurones of the proximal colon more closely resemble those of the caecum than those of the descending colon, of which many do not have a functional noradrenergic synaptic input. Furthermore, the results confirm that there are fundamental regional differences in the guinea-pig large intestine with respect to the synaptic organization of submucosal neurones of particular electrophysiological classes.

Adrenergic alpha-Agonists↗
PubMed1999

Attitudes toward colon cancer gene testing: survey of relatives of colon cancer patients.

OBJECTIVES: Various studies have identified psychosocial factors that may influence attitudes toward colon cancer gene testing. Whereas family history of colon cancer has been associated with interest in gene testing, this has not been examined extensively. We hypothesized that the strength of family history of colon cancer is associated with risk perception and willingness to undergo gene testing. MATERIALS AND METHODS: We evaluated attitudes toward colon cancer gene testing among persons who had at least one first-degree relative with colon cancer. A total of 2680 at-risk relatives in 863 kindreds were identified and mailed an extensive survey regarding sociodemographic variables, family history, health behaviors and knowledge, and willingness to take a colon cancer gene test. A total of 56.6% of persons completed and returned surveys. We conducted a brief telephone survey of a random sample of 200 persons who did not respond to the mail survey. RESULTS: The combined study sample of 1373 people was 42% male, had a mean age of 55 +/- 15 years, was 96% white, and had moderate-to-high SES. A total of 77.4% were very likely to take the gene test, and 92.4% were somewhat or very likely to take the gene test. A total of 78% of the sample perceived a higher colon cancer risk, although patterns of risk perception and worry differed significantly between mail survey and telephone survey respondents. More of the telephone survey respondents were also somewhat unlikely or very unlikely to take the gene test compared to the mail survey respondents (13.7% versus 6.9%). In the combined sample, concern about developing colon cancer and risk perception increased with number of relatives with colon cancer (P < 0.0001). Eight percent expressed no concern about developing colon cancer; 4.8% felt their chance of developing colon cancer was lower than others of the same age, sex, and race; and 3.3% felt that they were very unlikely to develop colon cancer in their lifetime. However, there was strong interest in gene testing regardless of the number of affected relatives, and persons with more affected relatives were generally willing to pay more for the gene test (up to $1000). CONCLUSIONS: The strength of family history of colon cancer is associated with risk perception but not with willingness to undergo gene testing.

Aged↗
PubMed2004

Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines.

Caveolin-1, -2, and -3 are the principal proteins of caveolae, the vesicular invaginations of the plasma membrane. Recent studies suggest that caveolins play an important role in cellular signaling and, possibly, in tumorigenesis. We examined the expression of the three caveolins in azoxymethane-induced rat colon adenocarcinoma and normal-appearing colonic mucosa, and also in human colon cancer cells with inherently different proliferation rates. Expression of caveolins was assessed in experimental rat colon adenocarcinoma and normal-appearing colonic tissues by RT-PCR, immunoblot and immunohistochemistry. Expression of caveolin-1, -2, and -3 at protein and mRNA levels in human colon cancer cell lines Caco-2, HT-29 and HCT-116 was assessed by immunoblot and RT-PCR, respectively. While caveolin-1 was overexpressed in all experimental adenocarcinoma tissues by comparison to normal-appearing colonic mucosa at both the mRNA and protein level, caveolin-2 was expressed equally only at the mRNA level in both tissues. Immunohistochemical analysis of experimental rat colon tissues also revealed a similar pattern with caveolin-1 being overexpressed in adenocarcinomas as compared to normal-appearing colonic mucosa. Caveolin-1 protein expression was observed in HT-29 and HCT-116 cell lines but not in the Caco-2 cell line or the macrophage Raw 264.7 cell line. Caveolin-1 mRNA expression was evident in all colon carcinoma cell lines tested; however, caveolin-2 mRNA was found only in HT-29 and HCT-116. Caveolin-1 protein and mRNA transcript levels in human colon cancer cell lines were observed to be concordant with the growth rate of the cells, and followed the pattern of HCT-116 > HT-29 > Caco-2. Taken together, our results indicate that caveolin-1 is overexpressed in experimental colon adenocarcinoma by comparison to adjacent normal mucosa, and its expression in human colon cancer cells is directly associated with the growth rate.

Adenocarcinoma↗
PubMed1976

The effects of mechanical preparation and acidification of the colon on the healing of colonic anastomoses.

The results of clinical studies have suggested that inadequate preoperative mechanical preparation of the colon is a significant factor in the pathogenesis of disruption of colonic and colorectal anastomoses. A possible explanation for the adverse effect of poor mechanical preparation is that ammonia released from feces has a cytotoxic effect on the healing anastomosis. It has been suggested that acidification of the colonic lumen prevents the release of fecal ammonia and protects the anastomoses. The effects of mechanical preparation of the colon and colonic acidification were studied in anastomoses in the left colon of rats. Colonic acidification was produced by the oral administration of a synthetic disaccharide lactulose solution. Mechanical preparation resulted in a significant increase in the bursting wall tension in anastomoses on the seventh postoperative day. The oral administration of lactulose resulted in a reduction in the colonic mucosal pH, but this was not accompanied by improved healing of anastomoses, as judged by measurements of colonic bursting pressure, bursting wall tension and total challagen content. Mechanical preparation of the colon is an important factor in the safety of colonic anastomosis. However, the results do not suggest that acidification of the colonic lumen significantly improves the quality of colonic healing.

Administration, Oral↗
PubMed1986

Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas.

The expression of LeY (Fuc alpha 1----2Gal beta 1----4 [Fuc alpha 1----3]GlcNAc beta 1----R) (in which Fuc is fucose, Gal is galactose, and GlcNAc is N-acetylglucosamine) defined by monoclonal antibody AH6 in various locations of human colonic epithelia, colonic polyps, and adenocarcinomas has been studied. In normal colonic mucosa, strong staining by AH6 was observed in the proximal regions such as the terminal ileum and cecum. The staining was, however, greatly reduced in the epithelia of the ascending colon and became very weak in the epithelia of transverse, descending, and sigmoidal colon as well as the rectum. Of 481 crypts in 40 biopsy samples of the epithelia of normal sigmoidal colon, 421 crypts did not show any staining, and only a weak staining of the lowest crypt area was observed in 60 crypts (12%); of 474 crypts in 40 biopsy samples of normal rectal epithelia, 110 crypts (26%) showed a weak staining. At the fetal stage, the LeY staining was much more intense in all locations of the colon than in corresponding locations of adult epithelia, and staining was observed in the epithelia of the sigmoidal colon and rectum. A strong staining was observed in 24 of 25 cases of colorectal adenocarcinomas, irrespective of their original location. The expression of LeY in polyps was correlated with histological type as well as the degree of dysplasia of the polyps. Of various adenomas examined, tubular adenomas, many of which showed mild or moderate dysplasia and less malignant potentials, displayed the least LeY expression. Tubulovillous and villous adenomas, which have higher malignant potential and showed a higher incidence of severe dysplasia, showed a greater area and intensity of LeY expression. No LeY was detectable in juvenile polyps, and only a very weak staining was observed in the dysplastic area of hyperplastic polyps. The extent and intensity of staining in various adenocarcinomas and adenomas could not be correlated with blood group ABO status of the hosts nor with location of the tumors. These results suggest that LeY in colonic adenocarcinomas and polyps at the distal region of the colon and rectum is a typical oncofetal antigen and is a useful marker for diagnosis of colonic cancer. Its expression in colonic polyps can be correlated with the degree of dysplasia and may indicate the degree of malignant potential of the polyp. Thus, LeY expression in polyps may have prognostic value.

Adenocarcinoma↗
PubMed2003

Colonization and infection with multiple nosocomial pathogens among patients colonized with vancomycin-resistant Enterococcus.

OBJECTIVE: To test the hypothesis that patients colonized with vancomycin-resistant Enterococcus (VRE) have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. DESIGN: A rectal swab culture survey was conducted to determine the point-prevalence of stool colonization with ceftazidime-resistant gram-negative bacilli in hospitalized patients with or without VRE stool colonization. For a 6-month period, the frequency of Clostridium difficile diarrhea and isolation of antibiotic-resistant (ie, ceftazidime-, piperacillin/tazobactam-, levofloxacin-, or trimethoprim/sulfamethoxazole-resistant) gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA), and non-albicans Candida species from clinical specimens other than stool was examined. SETTING: A Department of Veterans Affairs medical center. PATIENTS: All patients hospitalized in the acute care facility and one nursing home unit during a 1-week period in February 2001. RESULTS: VRE-colonized patients had a higher point-prevalence of rectal colonization with ceftazidime-resistant gram-negative bacilli than did patients not colonized with VRE (17% vs 4%; P = .026). During a 6-month period,the VRE-colonized patients were more likely to have Clostridium difficile-associated diarrhea (26% vs 2%; P = .001), MRSA infection (17% vs 4%; P = .017), or colonization or infection with gram-negative bacilli resistant to 4 different antibiotics. CONCLUSION: VRE-colonized patients in our institution have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. This suggests that isolation measures implemented to control VRE could help limit the dissemination of other, coexisting pathogens.

Aged↗
PubMed2005

Altered gene expression in normal colonic mucosa of individuals with polyps of the colon.

PURPOSE: Expression levels of many genes are altered in colon cancer, relative to normal colonic mucosa. We recently reported that such differences also exist between grossly normal colonic mucosa of individuals with and without colon cancer, and between individuals with and without a family history of colon cancer. Here we report a study of individuals with no cancer but with polyps in the transverse, ascending/descending, or rectosigmoid colon. METHODS: Biopsies of grossly normal-appearing colonic mucosa from the rectosigmoid colon were taken from individuals with polyps, with or without personal/family history of colon cancer, and gene expression profiles compared with those from biopsies of control patients, with no polyps or known personal/family history. A global expression analysis was conducted of the same 15 genes used in our previous studies. RESULTS: We found significant differences in gene expression in normal-appearing rectosigmoid colonic mucosa between individuals with polyps and controls, regardless of whether personal or family history of cancer was present. CONCLUSIONS: Alterations in gene expression patterns in morphologically normal-appearing colonic mucosa are associated with the presence of adenomatous polyps. Prospective studies will be required to determine whether these alterations in gene expression can be used to predict risk of developing colon cancer.

Adult↗
PubMed2004

Colonic stent vs. emergency surgery for management of acute left-sided malignant colonic obstruction: a decision analysis.

BACKGROUND: Acute colonic obstruction because of malignancy is often a surgical emergency. Surgical decompression with colostomy with or without resection and eventual re-anastomosis is the traditional treatment of choice. Endoscopic colonic stent insertion effectively decompresses the obstructed colon, allowing for surgery to be performed electively. This study sought to determine the cost-effectiveness of colonic stent vs. surgery for emergent management of acute malignant colonic obstruction. METHODS: Decision analysis was used to calculate the cost-effectiveness of two competing strategies in a hypothetical patient presenting with acute, complete, malignant colonic obstruction: (1) emergent colonic stent followed by elective surgical resection and re-anastomosis; (2) emergent surgical resection followed by diversion (Hartmann's procedure) or primary anastomosis. Cost estimates were obtained from a third-party payer perspective. Primary outcome measures were mortality, stoma requirement, and total number of operative procedures. RESULTS: Colonic stent resulted in 23% fewer operative procedures per patient (1.01 vs. 1.32 operations per patient), an 83% reduction in stoma requirement (7% vs. 43%), and lower procedure-related mortality (5% vs. 11%). Colonic stent was associated with a lower mean cost per patient ($45,709 vs. $49,941). CONCLUSIONS: Colonic stent insertion followed by elective surgery appears more effective and less costly than emergency surgery under base-case conditions. This finding remains robust over a wide range of assumptions for clinical inputs in sensitivity analysis. Our findings suggest that colonic stent insertion should be offered, whenever feasible, as a bridge to elective surgery in patients presenting with malignant colonic obstruction.

Acute Disease↗
PubMed2004

Through-the-scope double colonic stenting in the management of inoperable proximal malignant colonic obstruction: a pilot study.

BACKGROUND AND STUDY AIMS: Particularly in cases of proximal colonic obstruction, the long distance and tortuosity of the bowel make it difficult for gastroenterologists and radiologists to advance the stent to the point of the obstruction. The purpose of this study was to evaluate the clinical usefulness and efficacy in preventing stent migration and tumor ingrowth of a new self-expanding through-the-scope (TTS) double colonic stent in the palliative management of patients with inoperable proximal malignant colonic obstruction. PATIENTS AND METHODS: A total of seven patients (four men, three women; mean age 62 years, range 57 - 68) underwent placement of a newly developed through-the-scope self-expanding double colonic stent. The etiologies of the obstructions at the time of stent insertion were colonic adenocarcinoma (no previous surgical resection) in five cases and metastatic adenocarcinoma from gastric carcinoma in two. The locations of the obstructions were the ascending colon in three cases, the hepatic flexure in two, and the transverse colon in two. To prevent tumor ingrowth and stent migration, an uncovered Niti-S stent (Taewoong Medical Co., Ltd., Seoul, South Korea) was inserted into the stenotic area; a partly membrane-covered Niti-S stent was then again inserted into the stenotic area inside the uncovered Niti-S stent. RESULTS: The self-expanding TTS double colonic stents were placed in the colon in seven patients with acute malignant colonic obstruction. Double stenting was successful in traversing the lesion in six of the seven cases. In one patient, the stent was not successfully placed across the lesion due to a very acute angle at the hepatic flexure. There were no significant complications relating to the insertion, with no clinical or radiographic evidence of perforation or bleeding during or after the procedures, and there were no cases of stent migration or tumor ingrowth during the mean follow-up period of 13 months. CONCLUSIONS: Placement of these new self-expanding through-the-scope double colonic stents for the management of inoperable proximal malignant colonic obstruction is a feasible, effective, and safe form of palliative treatment for the prevention of stent migration and tumor ingrowth.

Adult↗
PubMed2000

Site-dependent production of transforming growth factor beta1 in colonic mucosa: its possible role in tumorigenesis of the colon.

Transforming growth factor (TGF) beta1 has an antitumorigenic role in the gastrointestinal tract and may be associated with the development of colon neoplasia. In the present study we investigated whether TGF-beta1 production in mucosa is lower in the distal colon, which is where clinical evidence shows that the incidence of colon neoplasia is higher, and whether TGF-beta1 levels were lower in the mucosa of patients with colon adenoma. Production of colon mucosa TGF-beta1 was investigated by means of a 24-hour organ culture with biopsy specimens taken from different segments of the colon of 58 normal subjects by using an enzyme immunoassay. TGF-beta1 production in colon mucosa from locations near the site of sporadic adenoma was also investigated in 46 patients. TGF-beta1 production gradually increased from the rectum to the ascending colon in a statistically significant manner in both normal (r = 0.77, P < .0001) and adenoma-bearing (r = 0.8, P < .0001) mucosa. When TGF-beta1 production was compared between normal and adenoma-bearing mucosa, levels were lower in the latter, although statistically significant results were seen only in the transverse colon (P < .05). TGF-beta1 production has clear site dependency, being lowest in the rectum and highest in the ascending colon. Furthermore, low levels of TGF-beta1 are associated with the development of adenoma. Our results suggest the possibility that this site dependency is associated with the higher epidemiologic incidence of colon neoplasia in the distal colon.

Actins↗