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PubMed1987

Serial observations of colonic carcinogenesis in the rat. Premalignant mucosa binds Ulex europeus agglutinin.

We evaluated certain histochemical tests for their ability to detect premalignant mucosa in the dimethylhydrazine model of colonic carcinogenesis. Biweekly colonoscopic biopsies of the descending colon were performed for 29 wk in control and dimethylhydrazine-treated rats. Biopsy specimens of the splenic flexure, rectum, and any visualized tumors were taken. The specimens were stained with periodic acid-Schiff to detect neutral mucins, high-iron diamine alcian blue to detect sialylated and sulfated mucins, fluoresceinated peanut agglutinin, and fluoresceinated Ulex europeus agglutinin. None of the first three tests consistently detected premalignant mucosa. However, Ulex europeus agglutinin, which bound to only 3% of control biopsy specimens throughout the course of the study, bound to increasing numbers of biopsy specimens in the dimethylhydrazine-treated animals, reaching a maximum of 90% positivity by 13-16 wk. Moreover, Ulex europeus agglutinin bound strongly to all biopsy specimens from tissues adjacent to tumors and to 93% of tumors. Mucosal atrophy and focal dysplasia were present more frequently in specimens taken from the rectum (but not the splenic flexure) of dimethylhydrazine-treated animals than of control animals, but there was no correlation between the histochemical markers and either atrophy or dysplasia. We conclude that Ulex europeus agglutinin binding is a consistent feature of premalignant colonic mucosa in dimethylhydrazine-treated rats.

Animals↗
PubMed1989

Isolation of colonic crypts that maintain structural and metabolic viability in vitro.

The aim of this study was to develop a method by which colonic epithelial cells can be isolated from resected mucosa or colonoscopic biopsy specimens and viability maintained in the short term. The principles of the technique are to digest the lamina propria from the epithelium with Dispase and collagenase, to disrupt the epithelium by trituration, and to purify the epithelial cells by seiving and differential sedimentation. Whole and partial crypts were isolated with consistently high purity of 93.5% +/- 1.2% (excluding red cells). Structural integrity was confirmed by light and electron microscopy, exclusion of trypan blue, minimal leakage of lactic dehydrogenase over 5 h (4.1% +/- 1.7%), and 51Cr leakage of less than 2% per hour over 16 h. Functional integrity was supported by continued deoxyribonucleic acid synthesis [( 3H]thymidine uptake) over 16 h and the formation of epithelial monolayer cultures on plastic. Thus, this simple method yields a highly enriched cell population that maintains high viability in vitro for at least 16 h. Such cells may be useful for the study of the biology of colonic epithelial cells.

Autoradiography↗
PubMed1991

Distribution of aneuploid cell populations in ulcerative colitis with dysplasia or cancer.

Flow cytometry was used to detect the presence and assess the distribution of aneuploid cell populations in eight proctocolectomy specimens from patients with ulcerative colitis. Mucosal samples were taken according to a systematic protocol for flow cytometry, the surrounding tissue was examined histologically, and the distributions of flow cytometric and histologic abnormalities were "mapped" within each resected colon. Two resection specimens that were negative for dysplasia lacked aneuploid cell populations. Four resection specimens with final case diagnoses of dysplasia or Dukes' stage A carcinoma had 1-5 regions of aneuploidy or increased 4N (G2/tetraploid) cell populations located in discrete areas of the colon. Two specimens with dysplasia or Dukes' stage C carcinoma each had 14-15 different, often overlapping, regions of aneuploidy or increased 4N (G2/tetraploid) cell populations involving large portions of the colonic mucosa. Analysis of the DNA content of the invasive portion of the tumor from the specimen with a Dukes' stage C carcinoma showed a single aneuploid cell population. The results show that single or multiple aneuploid cell populations are often present in colons resected for ulcerative colitis with dysplasia or early cancer. The distribution of these aneuploid cell populations suggests that each represents a clone of cells that has expanded to occupy a discrete region of colonic mucosa. Additional genetic errors may result in multiple aneuploid cell populations that may be associated with an increased risk of developing cancer. These data, therefore, are consistent with the hypothesis that genomic instability and clonal evolution are associated with the progression to dysplasia and carcinoma in ulcerative colitis. Because flow cytometry can measure aneuploid cell populations in colonoscopic mucosal biopsies, it may prove to be complementary to histology for detecting patients with ulcerative colitis who are at risk for neoplastic progression.

Adult↗
PubMed1991

Perendoscopic manometry of the distal ileum and ileocecal junction in humans.

Previous manometric studies of the ileocolonic junction were performed without assessing the precise spatial relationship between recording sensors and ileocolonic junction. In the present study, the motor activity of the ileocolonic junction was recorded using manometric sensors localized under direct colonoscopic control in 11 patients (4 men, 7 women; mean age, 55 years) referred for hematochezia with normal stool frequency. No medications were administered before and during endoscopy. A perfused catheter (OD 1.7 mm, with three side holes 4 mm apart and marked by evenly spaced black rings in the distal 6 cm) was passed through the biopsy channel of the endoscope and advanced through the ileocolonic junction and 6 cm into the ileum. The catheter was then withdrawn into the cecum by 1-cm steps, and motor activity was recorded for 4-6 minutes at each station. A single catheter taped to the endoscope continuously recorded cecal pressure. An ileocecal pressure gradient could not be identified in the majority of subjects; individual values ranged from -8 to +4 mm Hg, and gradients were maintained over the entire length of the ileum. In the distal ileum, tonic and phasic pressure waves were detected. Tonic variations were present for 70.1% of the recording time, either alone (44%) or together with phasic waves (56%). Phasic waves were present for 10.3% of the recording time and, according to their duration, were subdivided into those compatible with the rate of ileal slow waves and prolonged waves not compatible with the rate of ileal slow waves. Regular phasic waves could be either isolated or in clusters; prolonged waves were always isolated. A similar proportion of regular (27.9%) and prolonged (31.2%) phasic waves propagated aborally along the ileum or from ileum to cecum. Clusters presented an average of 8.7 +/- 0.6 peaks/min, and 44% of them propagated aborally. The manometric characteristics did not vary between the segments 5-3 cm and 2-0 cm proximal to the ileocecal junction. In conclusion, a powerful ileocecal sphincter was not detected at the human ileocecal junction, and motor activity of the distal ileum was characterized by tonic changes and rapid phasic contractions.

Adult↗
PubMed1991

Granulocytic sarcoma of the colon.

Granulocytic sarcoma is an extramedullary tumor consisting of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myelogenous leukemia, or acute myelogenous leukemia. This tumor may involve nodes, cervix, bone and periosteum, and infrequently the small intestine. Granulocytic sarcoma rarely occurs in the colon and has not been previously described endoscopically. We encountered a 73-year-old man with myelodysplastic syndrome who presented with fever, diarrhea, and abdominal pain. Colonoscopic evaluation (focal ulceration, friability, and nodularity) was compatible with Crohn's disease, although histology showed a dense myeloid cell infiltrate characteristic of granulocytic sarcoma. In patients with myelodysplastic syndrome or acute or chronic myelogenous leukemia presenting with diarrhea, abdominal pain, and/or fever, colonoscopy and biopsy are indicated to determine if the colon is affected by granulocytic sarcoma.

Aged↗
PubMed1991

Acute abdomen as the first presentation of pseudomembranous colitis.

Acute abdomen was the presenting manifestation of pseudomembranous colitis in six men who had previously been treated with antibiotics and presented with abdominal distention, pain, fever, and leukocytosis with absent or mild diarrhea. Plain abdominal radiographs revealed megacolon in two, combined small and large bowel dilation in three, with one of them showing volvuluslike pattern, and isolated small bowel ileus in one. Emergency colonoscopy was performed successfully in all patients and revealed pseudomembranes in five and nonspecific colitis in one. All patients had positive latex test results for Clostridium difficile, and two tested positive for cytotoxicity. All patients were treated with IV metronidazole, resulting in resolution of symptoms and abdominal findings. In addition, two patients underwent colonoscopic decompression with improvement. Endoscopically, complete resolution of the pseudomembranes occurred at 4 weeks in all cases. No patient had a recurrence. It is concluded that (a) pseudomembranous colitis may present as abdominal distention mimicking small bowel ileus. Ogilvie's syndrome, volvulus, or ischemia; (b) in such cases, emergency colonoscopy is safe and useful for diagnosis and therapeutic decompression and may obviate the need for surgery; and (c) treatment with IV metronidazole is effective. Colitis due to C. difficile should be considered in the differential diagnosis of acute abdomen in patients previously treated with antibiotics.

Abdomen, Acute↗
PubMed1991

Comparative evaluation of carcinoembryonic antigen, secretory component, and mucins in index and metachronous adenomas of the colorectum.

Of 124 patients who underwent endoscopic polypectomy, 70 were colonoscopically reevaluated during a mean period of 10 years. On the basis of the clinical outcome, the patients were divided into three groups: group 1, 31 patients who had a colon still with no adenomas or cancer; group 2, 35 patients in whom one or more metachronous adenomatous polyps developed; and group 3, 4 patients in whom a carcinoma of the colon subsequently developed. In addition to the clinical and pathological features, the pattern of the immunohistologic staining for carcinoembryonic antigen and secretory component was studied. Moreover, the mucin histochemical staining intensity of neutral mucins, sulfomucins, and sialomucins was evaluated. The features of the 40 index adenomas obtained from patients in group 1 were compared with the features of the 51 index adenomas from patients in group 2. Furthermore, these characteristics of the index adenomas were compared with those in the 69 metachronous adenomas of the group 2 patients. It was found that male sex (P less than 0.005) and a history of colorectal neoplasia (P less than 0.02) are main factors for the development of new adenomas. The neutral mucins were less abundant in the group 2 index adenomas (r = -0.21; P less than 0.05). The expression of the other evaluated markers was not significantly different between both groups, although the group 2 index adenomas were significantly smaller (r = -0.22; P less than 0.05) and showed a trend toward a more pronounced cytoplasmic expression of carcinoembryonic antigen than the index adenomas from group 1 (22% vs. 12.5%). Moreover, it was found that in comparison with the index adenomas, metachronous adenomas were significantly smaller (r = -0.24; P less than 0.01) and more sessile (r = 0.20; P less than 0.002). Significant negative correlations, i.e., decrease, were also found in the expression of carcinoembryonic antigen (surface P less than 0.001; cytoplasmic P less than 0.05) and neutral mucins (P less than 0.005) between the index adenomas and the metachronous adenomas, whereas positive correlations were found for secretory component (P = 0.0001) and sulfomucins (P less than 0.05). These findings suggest that a limited production of neutral mucins in the goblet cells of a small index adenoma from a male patient with a history of colorectal neoplasia is indicative of an increased risk for the development of new colorectal adenomas. Furthermore, the clinical, mucin histochemical, and immunohistochemical findings of the metachronous adenomas show less malignancy-associated features than those of the index adenomas.

Adenocarcinoma↗
PubMed1992

Primary sclerosing cholangitis in ulcerative colitis--a risk factor for the development of dysplasia and DNA aneuploidy?

In a 15-year surveillance program for long-standing, total ulcerative colitis (UC), 72 patients were followed up with colonoscopic biopsies. Seventeen patients developed definite dysplasia, carcinoma, and/or DNA aneuploidy. Alkaline phosphatase and transaminases were examined in all patients. In the group with dysplasia, carcinoma, and/or DNA aneuploidy, 5 patients (28%) were found to have primary sclerosing cholangitis (PSC) based on histological and/or cholangiographic criteria. In the group without definite dysplasia or DNA aneuploidy, no patient with PSC appeared, although two patients with other forms of chronic liver disorders were found. The difference in distribution of PSC between the two groups was statistically significant (P = 0.0004). Using logistic regression, the presence of PSC and the duration of UC were identified as independent risk factors associated with dysplasia and/or DNA aneuploidy. Thus, UC patients with PSC seem to run an increased risk of developing colonic dysplasia and/or DNA aneuploidy. Although the reason for the increased risk is still unclear, these results warrant increased surveillance among patients with both PSC and longstanding, total UC.

Adolescent↗
PubMed1992

Neoplasia and hyperplasia of large bowel: focal lesions in an abnormal epithelium.

Expression of brush border hydrolases can reflect the state of differentiation of an epithelium. To determine if expression of these enzymes is disordered in patients with neoplastic or hyperplastic lesions, the activities of alkaline phosphatase, maltase, and dipeptidyl peptidase IV were measured spectrophotometrically in colonoscopic biopsies from the proximal and distal colon and rectum in 50 controls, 17 patients with large bowel adenomas, 29 with carcinoma, and 9 with hyperplastic polyps. In normal controls, a descending cecorectal gradient of alkaline phosphatase activities and an ascending gradient of maltase activities were seen (P < 0.001). Though regional patterns of expression were generally preserved in disease groups, there were significant differences of activities across patient groups for alkaline phosphatase (greater in cancer, adenoma, and hyperplastic groups than in normals; P < 0.05) and for dipeptidyl peptidase IV (greater in hyperplastic polyp group than normals, greater in adenoma than cancer group; P < 0.05). Compared with normal controls, abnormalities of site-specific activities were confined to the rectum in patients with adenoma (maltase decreased, P = 0.02; dipeptidyl peptidase IV increased, P < 0.01) or with carcinoma (alkaline phosphatase increased, P = 0.03) but dipeptidyl peptidase IV activities were increased in all regions in bowels bearing hyperplastic polyps (P < 0.01). These data suggest that neoplastic and hyperplastic lesions, while focal in nature, occur in large bowel epithelium, which is diffusely abnormal in terms of its expression of these enzymes.

Adenoma↗
PubMed1992

DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis.

The objective of the present study was to determine whether abnormal epithelial DNA content (aneuploidy) in colonic biopsy specimens from ulcerative colitis (UC) patients correlated with and predicted histological progression to dysplasia. Aneuploidy was absent in 20 low-cancer risk patients. In 81 high-cancer risk patients aneuploidy correlated significantly with the severity of histological abnormality (negative, indefinite, dysplasia, or cancer). Statistically our data suggest that many more biopsy specimens than are usually taken are needed to detect focal dysplastic lesions. Prospective study of 25 high risk patients without dysplasia revealed 5 with aneuploidy, all of whom progressed to dysplasia in 1-2.5 years, whereas 19 patients without aneuploidy did not progress to either aneuploidy or dysplasia within 2-9 years. Our data indicate that aneuploidy in mucosal biopsy specimens correlates with histological grade and identifies a subset of patients without dysplasia who are more likely to develop it. It was concluded that more frequent and extensive colonoscopic surveillance of this minority subset of high risk patients and less frequent surveillance in the remaining majority may reduce cost and detect more curable lesions.

Adolescent↗
PubMed1992

Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis.

Crohn's disease (CD) is characterized by granulomatous inflammation of the intestinal mucosa, but the etiology and pathogenesis of the inflammatory lesions are unknown. The aim of this study was to determine whether T-cell activation and lymphokine production occurs in the mucosal lesions of this disease. Total cellular RNA was isolated from peripheral blood lymphocytes and from colonoscopic mucosal biopsies of normal individuals and patients with CD of the colon or ulcerative colitis (UC). Levels of interleukin-2 (IL-2) messenger RNA (mRNA) transcripts in samples were determined using a quantitative reverse transcriptase polymerase chain reaction method. IL-2 mRNA transcripts were detected in histologically normal intestinal mucosal biopsies obtained from control subjects. In CD, higher levels of IL-2 mRNA transcripts were detected in the mucosa from areas of active inflammation, but in areas that were histologically normal, levels were similar to control subjects. The levels of IL-2 mRNA transcripts in biopsies from active and inactive UC were similar to control subjects. Levels of IL-2 mRNA in peripheral blood lymphocytes were low and not significantly different in all groups of subjects. In conclusion, the normal intestinal mucosa contains IL-2 mRNA transcripts and may be an important source of IL-2. Furthermore, the inflammatory lesions of CD, but not UC, have higher levels of IL-2 mRNA transcripts, suggesting that T-cell activation and lymphokine secretion in the intestine may be important in the pathogenesis of CD. These data provide further evidence that the pathogenesis of CD and UC are different.

Base Sequence↗
PubMed1993

Increased risk of 'high-risk' colorectal adenomas in overweight men.

BACKGROUND: Epidemiologic studies have suggested that the incidence of colorectal carcinoma may be related to overnutrition, but retrospective analysis of its relation to the body mass index (BMI: kg/m2) has produced conflicting data. METHODS: To avoid as many sources of statistical bias as possible, the relation between BMI and the presence of colorectal adenomas was investigated in a cross-sectional study. RESULTS: Two thousand twelve consecutive colonoscoped patients were investigated (532 patients with malignancies or other conditions associated with weight loss were excluded). The relation between BMI and observed colorectal adenomas was evaluated by a logistic model controlling for other prognostic factors such as age, sex, and serum cholesterol level. The subgroup of "high-risk" adenomas with an increased risk of malignant transformation was positively associated with the BMI in men of the age group 50.5-68.1 years (quintiles III and IV: odds ratio for the top quintile vs. the lowest quintile, 3.21; 95% confidence interval, 1.15-8.98). CONCLUSIONS: It was concluded that the risk of developing high-risk adenomas tends to be increased in men who are overweight and that this association is independent of the positive association with the serum cholesterol level recently described.

Adenoma↗
PubMed1994

Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection.

We report six cases of toxic megacolon in patients with human immunodeficiency virus (HIV). One case, at an early stage of HIV infection, mimicked a severe attack of Crohn's disease, with a negative search for infectious agents. Subtotal colectomy was successfully performed with an uneventful postoperative course. The five other cases concerned patients with acquired immunodeficiency syndrome at a late stage of immunodeficiency. They were related to Clostridium difficile or cytomegalovirus (CMV) intestinal infection in two and three patients, respectively. One case of CMV colitis presented macroscopically and histologically as pseudomembranous colitis. Emergency subtotal colectomy, performed in the first four patients with acquired immunodeficiency syndrome was followed by a fatal postoperative outcome. The last patient treated conservatively by colonoscopic decompression, in association with anti-CMV therapy, had a favorable short-term outcome. From the experience of our series and data from the literature, we discuss the best diagnostic and therapeutic approach to toxic megacolon in patients with HIV.

Adult↗
PubMed1995

Sialosyl-Tn antigen: initial report of a new marker of malignant progression in long-standing ulcerative colitis.

BACKGROUND & AIMS: Expression of the mucin-associated carbohydrate antigen sialosyl-Tn (STn) correlates with malignant transformation in sporadic colonic neoplasms. The aim of this study was to analyze STn antigen expression in patients with long-standing ulcerative colitis (UC). METHODS: STn antigen was assessed by immunohistochemistry in archival tissues. Study A was a retrospective chronological case-control study. Serial surveillance colonoscopic biopsy specimens without inflammation or dysplasia were analyzed in 7 patients who developed colon cancer and in 8 controls who did not develop colon cancer. Study B analyzed the anatomic distribution of STn expression in 17 cancer-bearing (case) and 6 cancer-free (control) colectomy specimens from patients with UC. In some colectomy specimens, STn was compared with aneuploidy, which was determined by flow cytometry. RESULTS: In study A, among the 7 patients with UC who developed cancer, 6 patients (86%) expressed STn in at least one prior nondysplastic surveillance biopsy specimen from the same site. Only 3 of 8 control patients (38%) expressed STn. In study B, STn was expressed in 40 of 82 specimens (49%) from cancer-bearing colons but only 8 of 62 specimens (13%) from cancer-free colons. STn was expressed in most aneuploid areas but was also found in diploid, nondysplastic mucosa. CONCLUSIONS: STn antigen seems to be a promising marker of cancer risk in patients with UC.

Aneuploidy↗
PubMed1995

Prophylactic colectomy or surveillance for chronic ulcerative colitis? A decision analysis.

BACKGROUND & AIMS: The treatment of patients with long-standing ulcerative colitis involving the entire colon is controversial. The aim of this study was to examine the effectiveness of surveillance colonoscopy or prophylactic colectomy on colon cancer mortality in patients with chronic ulcerative colitis. METHODS: Using decision analysis, computer cohort simulation of patients with ulcerative colitis was performed to evaluate 17 strategies including no colonoscopic surveillance, surveillance at varying intervals, and prophylactic proctocolectomy with ileal pouch-anal anastomosis. The model examined which biopsy results (low-grade dysplasia, high-grade dysplasia, or cancer) should lead to proctocolectomy and ileal pouch-anal anastomosis. Published data on the incidence of cancer with ulcerative colitis, the sensitivity and specificity of colonoscopy with biopsy, the risks of colonoscopy and surgery, and the prognosis with colon cancer were used. RESULTS: For a 30-year-old patient with pancolitis for 10 years, the model suggests that prophylactic colectomy would increase life expectancy by 2-10 months compared with surveillance and by 1.1-1.4 years compared with no surveillance. Surveillance would improve life expectancy by 7 months to 1.2 years compared with no surveillance. In sensitivity analysis, results were most affected by the cumulative incidence of cancer in patients with chronic ulcerative colitis. CONCLUSIONS: Either surveillance or prophylactic colectomy should increase life expectancy in patients with ulcerative colitis.

Adult↗
PubMed1993

Malignant risk in juvenile polyposis coli: increasing documentation in the pediatric age group.

The presence of juvenile polyps with resulting bleeding and abdominal pain has traditionally been considered a benign, self-limiting process which would resolve with age. The dictum that these polyps were usually solitary, were found predominantly in the rectosigmoid area, and were without malignant potential has been reconsidered in recent years with the increased use of colonoscopy. Several case reports in both adults and children have documented the presence of adenomatous changes in this syndrome. We report 3 cases of children, ages 3, 11, and 11 who were found to have adenomatous polyps in the midst of fields of juvenile polyps on evaluation for rectal bleeding. All three were treated definitively with endorectal pull-through. Two of these patients had atypia on histological evaluation, one of which was severe. We recommend a more aggressive approach to patients found to have multiple juvenile polyps on barium enema, including colonoscopic biopsies at several sites to determine the presence of adenomatous changes, with colectomy and endorectal pull-through should these be found.

Adenomatous Polyps↗
PubMed1995

The nonspecificity of histological findings reported for flat adenomas.

Flat adenomas have been reported to be associated with an increased risk of high grade dysplasia and with a genetic predisposition to numerous colonic polyps. Histological findings reported for flat adenomas are dysplastic glands superficial to nondysplastic glands and a thickness of dysplastic mucosa that does not exceed twice that of nondysplastic mucosa. We assessed the specificity of these histological findings with regard to a colonoscopically flat appearance in a series of 127 sequentially accessioned adenomas from 52 patients without adenomatous polyposis coli or inflammatory bowel disease. Thirty-two of the 127 adenomas (25%) from 20 of 52 patients (36%) showed the histological findings outlined above; none of these polyps was grossly flat and none had high grade dysplasia. The predictive values of these histological features for patients younger than 50 years old and for the presence of five or more polyps in a patient were 15% and 25%, respectively. We conclude that the histological findings previously reported for flat adenomas are not specific for that entity and are not uncommonly seen in grossly typical appearing adenomatous polyps. These histological findings also are not associated with high grade dysplasia. They can be seen in polyps from individuals without clinically recognized polyposis, and are relatively poor indicators of young age or increased polyp number, features that could potentially indicate a clinically unrecognized polyposis syndrome. The histological findings in and of themselves thus appear to confer no additional cancer risk to the individual or to the individual's family members over and above that associated with an adenoma.

Adenoma↗
PubMed1981

Pneumoscrotum after colonoscopy.

A case of pneumoscrotum after colonoscopy is reported. The patient recovered uneventfully with careful observation. This complication ws the result of perforation of retroperitoneal bowel by the colonoscope. As such, prophylactic antimicrobial therapy may be indicated.

Aged↗