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PubMed1990

Induction of carcinoembryonic antigen and its crossreactive gene products in human colonic adenomas and carcinomas by transforming growth factor-beta.

The inducing effect of transforming growth factor-beta (TGF-B) on carcinoembryonic antigen (CEA) secretion and the cellular expression of CEA and CEA crossreactive glycoproteins (CEA-GLY) was examined from a panel of human colonic cell lines with different phenotypic classification. This panel included carcinomas with dissimilar differentiation characteristics and metastatic behavior, and premalignant adenomas derived from colonic polyps. A great degree of heterogeneity was observed in the endogenous levels of CEA secretion and the cellular expression of CEA and CEA-GLY species. The response profiles of the different cell lines to TGF-B treatment were also found to be heterogenous. However, TGF-B was able to induce CEA secretion and up-modulated the cellular expression of CEA and CEA-GLY from a majority of the cells tested. More importantly, TGF-B was able to exert these effects on carcinoma cells that secrete or express minimal or nondetectable amounts of these glycoproteins. These biologic modifying effects of TGF-B may have potential in augmenting the efficacy of CEA as a colon cancer marker, and in antibody-directed radioimaging and therapeutics. Further investigation in vivo in an experimental animal model system is warranted.

Adenoma↗

PubMed2003

Molecular dimensions of gastrointestinal tumors: some thoughts for digestion.

Topics discussed here include PTEN mutations and colonic polyps; WNT signaling, APC, beta-catenin, and gastrointestinal neoplasms; mismatch-repair genes (MLH1, MSH2, PMS1, MSH6) and hereditary nonpolyposis colorectal cancer; MYH mutations and autosomal recessive colorectal tumors; STK11 mutations and Peutz-Jeghers syndrome; TGFbeta and gastrointestinal cancer; BMPR1A mutations and juvenile polyposis; FGF/FGFR alterations in gastrointestinal neoplasms; PTCH mutations and gastrointestinal neoplasms; RUNX3 expression and gastric cancer; role of mucins in gastric carcinogenesis; KIT, PDGFRalpha, and gastrointestinal stromal tumors; intestinal neurofibromatosis; and gastrointestinal tumors in other disorders.

Colonic Polyps↗

PubMedDate not supplied

Lines of curvature for polyp detection in virtual colonoscopy.

Computer-aided diagnosis (CAD) is a helpful addition to laborious visual inspection for preselection of suspected colonic polyps in virtual colonoscopy. Most of the previous work on automatic polyp detection makes use of indicators based on the scalar curvature of the colon wall and can result in many false-positive detections. Our work tries to reduce the number of false-positive detections in the preselection of polyp candidates. Polyp surface shape can be characterized and visualized using lines of curvature. In this paper, we describe techniques for generating and rendering lines of curvature on surfaces and we show that these lines can be used as part of a polyp detection approach. We have adapted existing approaches on explicit triangular surface meshes, and developed a new algorithm on implicit surfaces embedded in 3D volume data. The visualization of shaded colonic surfaces can be enhanced by rendering the derived lines of curvature on these surfaces. Features strongly correlated with true-positive detections were calculated on lines of curvature and used for the polyp candidate selection. We studied the performance of these features on 5 data sets that included 331 pre-detected candidates, of which 50 sites were true polyps. The winding angle had a significant discriminating power for true-positive detections, which was demonstrated by a Wilcoxon rank sum test with p < 0.001. The median winding angle and inter-quartile range (IQR) for true polyps were 7.817 and 6.770 - 9.288 compared to 2.954 and 1.995 - 3.749 for false-positive detections.

Algorithms↗

PubMed1975

Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. II. Variations in surface architecture found by scanning electron microscopy.

We have used the high resolution and the great depth of focus possible with the scanning electron microscope to define the surface features of normal human colon and human colonic polyps. This technique demonstrates that the surface of the normal colon has a territorialization which encompasses multiple crypts. The surface of the normal colon is covered with both absorptive cells and goblet cells. Hyperplastic polyps are covered with overdeveloped absorptive cells and the normal teritorialization is present but is distorted. Adenomatous polyps are covered with immature cells and, except for the villous adenomas, goblet cells are strikingly absent from the surface. The territorial patterns are totally obliterated in the adenomas.

Adenoma↗

PubMed2005

Low-dose CT colonography in children: initial experience, technical feasibility, and utility.

BACKGROUND: CT colonography (CTC) is utilized as a diagnostic tool in the detection of colon polyps and early colorectal cancer in adults. Large studies in the literature, although focused on adult populations, have shown CTC to be a safe, accurate, non-invasive technique. OBJECTIVE: We evaluated the technical feasibility of CTC in children using a low-dose technique. MATERIALS AND METHODS: From November 2001 to April 2004 we evaluated eight patients (3-17 years) with non-contrast CTC. Seven of the patients had CTC, followed by standard colonoscopy (SC) the same day; in one patient, CTC followed a failed SC. CTC results were compared to results of SC. The estimated effective dose from each CTC was calculated and compared to that of standard barium enema. RESULTS: CTC results were consistent with those of SC. Sensitivity for polyps 5-10 mm was 100%, and sensitivity for polyps 10 mm and larger was 66.7%. The estimated mean effective dose was 2.17 mSv for CTC, compared to the 5-6 mSv for a standard air-contrast barium enema in a small child. CONCLUSION: Our initial experience shows CTC in children is well-tolerated, safe, and useful. The procedure can be performed successfully with a low radiation dose, and preliminary results compare well with SC.

Adenomatous Polyposis Coli↗

PubMed1991

Mycotic aortic aneurysm infected by Clostridium septicum--a case history.

The authors describe a sixty-seven-year-old hypertensive, diabetic man with a mycotic abdominal aortic aneurysm infected with Clostridium septicum. The patient had colonic polyps but no malignant disease. They could find only one other report of a mycotic aneurysm infected with C. septicum. In that case, as in most other cases of C. septicum bacteremia, the patient had gastrointestinal cancer. Their case suggests that treatment for a clostridial infection should be considered in patients with known gastrointestinal disease, signs and symptoms of sepsis, and abdominal pain. Conversely, patients known to have a C. septicum infection should be evaluated for gastrointestinal lesions.

Aged↗

PubMed2001

Current attitudes in laparoscopic colorectal surgery.

BACKGROUND: In this study, we set out to examine the current attitudes among surgeons toward laparoscopic colorectal surgery (LCS). METHODS: A total of 3628 questionnaires were sent to all North American members of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) and the American Society of Colon and Rectal Surgeons (ASCRS); 40% of the members of each society responded (B15 respondents). RESULTS: Currently, 85% of the respondents perform laparoscopic surgery; LCS was performed by 48% of the respondents in 21% of their patients. Although 35% of the members of SAGES have increased the number of laparoscopic colorectal operations they perform in the last 3 years, only 26% of ASCRS members did so. Our findings showed that 74% of the surgeons who perform LCS do so for diverticular disease, 68% for colonic polyps, 61% for villous adenoma, and 36% for ileal Crohn's disease. However, only 15% operate for the cure of carcinoma of any stage (16% of SAGES members and 11% of ASCRS members), whereas 8.5% and 7% operate for the cure of all upper and lower rectal carcinomas, respectively. Thirty-six percent of the surgeons who perform LCS for cancer have done between one and 10 curative resections, 8% have done 11-20 procedures, and 14% have done >20 procedures. There were 80 cases of port site recurrence reported by 4.4% of surgeons. Although 56% of the respondents would themselves undergo laparoscopic colorectal surgery for a rectal villous adenoma, only 9% would do so for a distal-third rectal carcinoma (12% of SAGES and 5% of ASCRS respondents). CONCLUSIONS: The overall percentage of respondents performing LCS has decreased over the last 3 years; moreover, surgeons are more hesitant to perform laparoscopic surgery for the cure of colonic cancer. Due to the overall low response rate, the fact that 4.4% of those surgeons who did respond have seen port site recurrences does not allow any conclusions to be drawn about the prevalence of this problem.

Adenoma↗

PubMed1999

Morules with biotin-containing optically clear nuclei in colonic tubular adenoma.

Morules have been reported in pulmonary endodermal tumors (PET) resembling fetal lung, in thyroid carcinoma, and in endometrial and colonic neoplasms. A morule has biotin-containing optically clear nuclei (OCN) in PET and thyroid carcinoma. Biotin-containing OCN have been also reported in endometrial tissue during pregnancy and in endometrioid carcinoma of the ovary, and it has been postulated that morules or OCN develop under the influence of female sex hormones. The authors report here the first case, to their knowledge, of morules with OCN in a colonic adenoma from a 68-year-old man. The colonic polyp consisted of ordinary tubular adenomatous tissue and morules. Many cells in the morules contained OCN. The OCN were immunopositive for biotin and reacted with streptavidin. The neoplastic cells in the morules were immunopositive for oncofetal antigens. Serum levels of female sex hormones were within the normal range, and no cells in the adenoma were immunopositive for receptors for progesterone and estrogen. The results indicate that OCN are rich in biotin and that morules may be embryologically immature elements that develop independently of influence by female sex hormones.

Adenoma↗

PubMed2000

Troglitazone prevents fatty changes of the liver in obese diabetic rats.

BACKGROUND AND AIMS: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats. METHODS: A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age. RESULTS: Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue. CONCLUSION: Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes.

Age Factors↗

PubMed2005

Incidental lesions found on CT colonography: their nature and frequency.

CT colonography has been used to detect colonic polyps and cancers, but its effect in practice will also be influenced by the frequency with which extracolonic lesions of various types are detected. We performed a systematic review of the types of incidental lesions found on CT colonography. This is necessary to model the benefits and harms of detecting extracolonic lesions. Primary clinical studies of extracolonic findings on CT colonography were identified from electronic databases, scanning reference lists and hand searches of relevant journals and conference proceedings. A data collection proforma was used to collect information on extracolonic findings. 17 discreet studies were identified, involving 3488 patients. In total 40% of patients were recorded to have abnormalities and many had more than one abnormality. Nearly 14% of patients had further investigations and 0.8% were given immediate treatment. Extracolonic cancers were detected in 2.7% (0.9% had N0M0 cancers) and 0.9% had an aortic aneurysm. The number of extracolonic findings was high in all studies. While only a small population were judged "important", the prevalence of serious lesions outside the colon was nevertheless higher than in many other screening programs.

Adult↗

PubMed1984

Genetics of rectal cancer.

Two operational subdivisions of hereditary colorectal cancer susceptibility are those with and those without premalignant adenomatous colonic polyp expression. In both of these subdivisions, reliable biomarkers of gene carriage would be of value in patient management as we have previously emphasized. Consideration must also be given to the familial (hereditary) occurrence of inflammatory bowel diseases associating with colorectal cancer susceptibility. The occurrence of rectal cancers should therefore alert the physician to investigate the possibility of a significant family medical history in order to fully elucidate the genetic heterogeneity of susceptibility to this disease. Clinicians should also be alert to the possibility of extracolonic malignancies where probable genetic colorectal cancer susceptibility is evident. Whenever possible, all potential biomarkers should be investigated to aid in definition of genetic heterogeneity.

Colitis↗

PubMed2004

Elastosis and elastofibromatous change in the gastrointestinal tract: a clinicopathologic study of 13 cases and a review of the literature.

We describe 13 cases in which the submucosa and muscularis mucosae of the gastrointestinal tract exhibited a focal or diffuse increase of elastin fibers. This elastosis or elastofibromatous change most commonly manifested as a colonic polyp and usually was found during screening colonoscopy. Gastric and small intestinal cases were less frequent and associated with ulcers or an inflammatory process. The literature includes reports of 13 gastrointestinal elastotic lesions with a topographic distribution similar to that in our series. Histologically, elastosis appears as finely granular and/or fibrillar amphophilic material, sometimes with a fibrous component (elastofibromatous change). The changes occasionally appear centered around blood vessels and often are mistaken for amyloid but are negative for Congo red stain and strongly positive for elastin stain. We believe that this lesion might be more underrecognized than rare. In 2 of 26 cases, elastotic lesions also were present in nongastrointestinal sites.

Aged↗

PubMedDate not supplied

[Tissue expression of carbohydrate antigen 19-9 (CA 19-9) in adenomatous lesions of the colorectum].

Serum levels of tumor markers almost not detectable in precancerous states or early cancer, the behavior of the tumor associated antigen CA 19-9 in colorectal carcinogenesis was analysed. In order to investigate the adenoma-carcinoma sequence, tissue antigenic expression was measured in adenomas, characterized by different size and histology, and compared with that found in normal colonic mucosa. Tissue content of CA 19-9 was determined by an immunoperoxidase technique (ABC-POD) in 88 colonic polyps, and correlated to the degree of histological dysplasia, and dimension of adenoma. Tissue content of CA 19-9 was also evaluated in non-adenomatous mucosa obtained by endoscopic biopsy. Among the 88 polyps, 50 showed the tubular histological type, while 31 resulted tubulovillous and 7 villous. High degree of dysplasia was present in 7 adenomas (7.9%) and focal carcinoma was observed in 6 (6.8%). Positivity for CA 19-9 was registered in 60.2% of adenomas. No correlation was found between tissue-CA 19-9 and degree of dysplasia, size of adenoma and villous component. However, a statistically significant correlation was observed between expression and cellular distribution of the antigen (chi 2 = 98.07, p < 0.00001). Our data confirmed CA 19-9 expression in adenomas, but it is unlikely this tissue antigen proves to be a reliable marker of adenoma-carcinoma sequence.

Adenoma↗

PubMed1986

Colorectal adenomas. Distribution, incidence of malignant transformation, and rate of recurrence.

In 282 patients, 731 colon polyps (643 adenomas and 88 hyperplastic polyps) were extirpated endoscopically or biopsied and investigated histologically. Localization of the adenomas with various degrees of atypia and the hyperplastic polyps, as well as their size distribution, were determined. In 66 patients with adenoma polypectomy on the first examination, one or more control colonoscopies were carried out (in all, 107). The median period of follow-up observation was 31 months. Thirty percent of the one-year control colonoscopies after polypectomy revealed new adenomas. The statistical analyses showed that patients with singular adenomas, on initial investigation, develop significantly fewer adenomas in the further course than patients with multiple initial findings, especially in negative results in the one-year control. The size of new adenomas found during the first 24 months after polypectomy does not exceed 10 mm. On the basis of these results and the literature data available so far, a follow-up program is presented for discussion.

Adenoma↗

PubMed2006

Patient retention in a clinical trial: a lesson from the rofecoxib (VIOXX) study.

A high retention rate of patients and control subjects is an important criterion for the credibility and accuracy of prospective, randomized, controlled clinical trials. Retention and adherence depend on a combination of patient-, physician- and coordinator-related factors, and these need to be carefully evaluated to ensure success. The aim of the study was to evaluate predictive factors for patient retention in a clinical trial. Questionnaires containing items on demographic and clinical data and specific questions related to patient motivation were distributed to 31 patients participating in a clinical study comparing rofecoxib (Vioxx) and placebo for the prevention of colonic polyp recurrence. Adherence of the group with the rofecoxib study and the questionnaire was 100%. The sample included 24 men (77%) and 7 women of mean age 66+/-9 years; 90% were married, 42% were employed. A family history of colorectal cancer (CRC) was reported by 29%. The main reasons for adherence reported by the patients (on an analog scale of 0-10) were 24-hour availability of a nurse (9.2+/-1.9), the chance to prevent CRC (9.1+/-1.9), and participation in a multicenter study (9.1+/-2.2). The least important factor was support of the family physician (5.8+/-4.1). In conclusion, retention in a clinical trial mainly depends on the subject of the trial and the scientific/professional setting where it takes place, and less on the support of the family physician.

Aged↗

PubMed1987

Monoclonal small (well-differentiated) lymphocytic proliferations of the gastrointestinal tract resembling lymphoid hyperplasia: a neoplasm of uncertain malignant potential.

Three histologically benign-appearing or diagnostically equivocal small lymphocytic proliferations of the gastrointestinal tract were examined by fresh-frozen section immunohistologic techniques. In one case, a dense infiltrate in the small intestine, consisting of small lymphocytes with round nuclei, was limited almost entirely to the mucosa. In another case, a localized colonic polyp was formed by mucosal and submucosal lobules of benign-appearing lymphoid aggregates with centrally located germinal centers. The third case, a penetrating gastric ulcer, was surrounded by histologically hyperplastic lymphoid tissue which included germinal centers. The small lymphocytes in all three cases were strongly positive for B-cell-associated antigens (B1, B2, BA-1), and all exhibited monoclonal light-chain restriction. Even though treatment consisted only of surgical resection of the lesions, no patient has had progressive disease during follow-up periods ranging from 24 to more than 50 months. We believe that the infiltrates in these cases are analogous to the morphologically benign monoclonal small lymphocytic proliferations common to the lung and orbit and that they have an uncertain, but probably low, malignant potential.

Adult↗

PubMedDate not supplied

[Mutation in the MSH2 gene in Muir-Torre syndrome].

BACKGROUND: The Muir-Torre syndrome is an autosomal dominant hereditary condition predisposing to cancer. It is characterized by skin tumors associated with adenocarcinoma of the colon or other neoplasias observed in the context of hereditary non-polyposis colorectal cancer (HNPCC). The Muir-Torre syndrome is also characterized by the frequent presence of multiple colonic polyps and the relatively moderate aggressivity of the tumors. CASE REPORT: We studied a family with Muir-Torre syndrome. We sequenced the exons of the hMSH2 gene in this family and identified heterozygous germinal mutation by G insert at position 2427 (2427insG). This mutation changes the lecture phase producing a premature codon stop. DISCUSSION: Our study confirms the predominant responsibility of the hMSH2 gene in Tuir-Torre syndrome. This clinical case and data reported in the literature demonstrate the importance of searching for a history of non-polyposis colorectal cancer in patients and relatives and the unstable genome characteristic of these tumors found in sebaceous tumors or keratoacanthomas. Sequencing the hMSH2 gene should be a priority when clinical features, history and laboratory tests suggest Muir-Torre syndrome.

Adenocarcinoma↗

PubMedDate not supplied

Inactivity of fecapentaene-12 as a rodent carcinogen or tumor initiator.

The possible carcinogenic activity of synthetic fecapentaene-12 (FP-12) was studied in several mammalian test systems: (a) for carcinogenicity by intrarectal instillation in male F344/NCr rats as well as by intrarectal and subcutaneous application in male B6C3F1 mice; (b) for initiation by skin painting in female SENCAR mice followed by repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), with 7,12-dimethylbenz[a]anthracene (DMBA) followed by TPA as positive control; (c) in a rat subcutaneous granuloma pouch assay in which mutagenicity was measured by induction of 6-thioguanine (6-TG) resistance and carcinogenicity was determined by induction of subcutaneous tumors in the pouch. There was no significant increase in tumor incidence after 72-78 weeks in test (a), although 2 rats receiving FP-12 intrarectally developed colon polyps. FP-12 did not initiate any skin tumors in test (b), nor did it significantly convert DMBA-initiated papillomas into carcinomas when 8 of the positive control mice were given FP-12 weekly for 10 weeks after 10 weeks on the DMBA-TPA regimen. Although FP-12 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were comparably mutagenic in test (c), FP-12 induced no tumors after more than a year in 133 rats at risk while MNNG induced 7 tumors in 107 rats. These rodent assays provide no evidence that FP-12 is a strong carcinogen, although the possibility remains that it may possess weak carcinogenic activity not revealed by these experiments.

9,10-Dimethyl-1,2-benzanthracene↗