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PubMed2000

Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK.

BACKGROUND: Flat and depressed colorectal tumours were originally thought to be unique to the Japanese population. Recently there have been reports of flat and depressed lesions in western countries but they have been thought to be uncommon. METHODS: In this prospective study, 1000 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions. The examinations were done by one European colonoscopist using methods developed in Japan. FINDINGS: 321 adenomas were found: 202 (63%) were polypoid, 36% (117) were flat and 2 (0.6%) appeared depressed. Most adenomas contained areas of mild or moderate dysplasia but 10% (31) were severely dysplastic. Six Dukes' A adenocarcinomas were identified together with 25 more advanced adenocarcinomas. The likelihood of Dukes' A cancer or severe dysplasia increased from 4% (3/70) in small flat lesions, to 6% (9/154) in small polyps, 16% (8/50) in larger polyps, 29% (14/49) in large flat lesions, and 75% (3/4) in depressed lesions. 54% (20/37) lesions containing severe dysplasia or Dukes' A carcinoma were flat or depressed. INTERPRETATION: The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for cancer, and many early colorectal neoplasms may therefore be missed. Colonoscopists require training in the recognition of flat and depressed lesions to detect colorectal tumours in the early stages.

Adenocarcinoma↗
PubMed1987

Screening before surgery for colon neoplasms with a flexible sigmoidoscope by surgical residents.

The value of flexible sigmoidoscopy to screen for colorectal neoplasms was determined in asymptomatic patients. One hundred sixty men (mean age 61 +/- 10), who denied a change in bowel habits or blood in their stools and who had guaiac-negative stools, had flexible sigmoidoscopic examinations performed by surgical residents with little previous endoscopy experience, while a staff surgeon continuously viewed the resident's progress through a teaching scope. Forty-nine benign neoplastic polyps were removed from 21% of the patients. The examination was well tolerated in 93% of these patients who received no medications. Resident endoscopists who had performed more than 15 examinations were more likely to reach 50 cm (79%) than those with less experience. The authors conclude that surgical residents are able to safely and effectively screen for colorectal neoplasms with a flexible sigmoidoscope when supervised.

Adult↗
PubMed1986

The mode of growth and compartmentalization of neoplastic glands during experimental colon carcinogenesis.

During the growth of 1,2-dimethylhydrazine (DMH)-induced colon neoplasms in mice from microscopic ones at 9 weeks to macroscopic, invasive ones at 25-26 weeks after the initiation of DMH treatments, the neoplastic glands became increasingly but variably elongated and tortuous, with epithelial evaginations and/or invaginations. For assessment of the mode of growth and genesis of heterogeneity of neoplasms, colon neoplasms induced by two different cumulative doses of DMH were compared at 25-26 weeks after the initial DMH injection. At this time they invaded the colonic wall similarly in depth. However, neoplasms that developed in mice given a higher cumulative dose of DMH had a more homogeneous cell population, a higher proliferative activity, and more apoptotic bodies than those with a lower dose. By 73 hours after multiple tritiated thymidine injections, most neoplastic cells became labeled. There were numerous foci of unlabeled cells seen among, or alternating with, areas of labeled cells. Epithelial evaginations into the glandular lumen consisted of proliferating cells and/or differentiated cells; whereas invaginations into the lamina propria contained only proliferating cells. These findings suggest a compartmentalization of neoplastic glands into multiple neoplastic clonogenic units during growth, from which cellular heterogeneity and architectural complexities of neoplastic glands develop.

1,2-Dimethylhydrazine↗
PubMed2003

Endoscopic mucosal resection using a pure cut and hemoclip method for colonic nonpolypoid neoplasms.

BACKGROUND: Colonic mucosal neoplastic lesions can be classified morphologically into polypoid and nonpolypoid types. The nonpolypoid type has a greater malignancy potential than does the polypoid type. Removing these lesions and obtaining an integral specimen for histopathologic assessment during colonoscopy are very important. This study evaluates the safety and integrity of specimens obtained by endoscopic mucosal resection (EMR) using the pure cut current and hemoclip method. METHODS: Fourteen nonpolypoid colonic neoplasms, which were removed by EMR using the pure cut and hemoclip method between April 2001 and April 2002, were studied. There were 9 male and 4 female patients and the mean age was 57.8 +/- 15.5 (range, 32 - 80) years. EMR was conducted in cases where the lesions were diagnosed as neoplastic tumors by magnification colonoscopy and the indigo carmine dye spray method. RESULTS: The study revealed 11 flat type neoplasms and 3 laterally spreading tumors. The mean size of the lesions was 10.7 +/- 5.6 (range, 6 - 25) mm. All lesions were completely removed. Histopathologically, there were 1 adenocarcinoma and 13 adenomas (3 with mild dysplasia, 7 with moderate dysplasia, and 3 with severe dysplasia). The mean number of hemoclips used was 2.14 +/- 0.66 (range, 1 - 3) pieces. No bleeding or perforation was noted following EMR. CONCLUSION: EMR using the pure cut and hemoclip method is a useful means of obtaining an integral specimen for accurate pathologic assessment. This method provides a safe and minimally invasive technique for managing colonic non-polypoid lesions.

Adult↗
PubMed1996

Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its difference from that of human colonic tissues.

Telomerase activity in tissues may be related to tumor development, especially malignant conversion, in humans. However, there are few reports about telomeres and telomerase activity in animals. In this study, we examined telomerase activity in rat colon carcinogenesis and in normal rat liver tissue and compared it with that of human colon cancer tissues. This is the first report concerning telomerase activity in rats. F344 rats were used, and colon neoplasms were induced with methylazoxymethanol acetate. There was telomerase activity in not only the induced colon neoplasms but also the colon mucosa and livers of untreated rats, in contrast with the results from normal human somatic tissues in previous reports. Indeed, we also observed negative results in normal human mucosa, despite the positive results in colon-cancer tissues. These findings suggest that there is a difference in the telomerase activities in humans and rats. Because rat telomeres are very long (20-100 kp, average 50 kp) compared with human telomeres (5-15 kp, average 12 kp), the difference in the telomere lengths of rats and humans might be related to their enzyme activities, although this is still unclear. Furthermore, because the inhibition of telomerase has been proposed as a novel cancer therapy for humans, the rat model presented here, in which telomerase is expressed in somatic tissues, may be useful for studies of telomerase inhibition, including inhibition by chemopreventive agents.

Adenocarcinoma↗
PubMedDate not supplied

Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods: a randomized controlled trial.

CONTEXT: Before the development of human colonic neoplasms, colonic epithelial cells showed altered growth and differentiation. These alterations characterized mucosa at risk for cancer formation and were termed intermediate biomarkers of risk. Modifications of the mucosa toward more normal features by nutrients or drugs are putative approaches to chemoprevention of colon cancer. OBJECTIVE: To determine whether increasing calcium intake via dairy products alters colonic biomarkers toward normal. DESIGN: Randomized, single-blind, controlled study. SETTING: Outpatient clinic. PARTICIPANTS: Seventy subjects with a history of polypectomy for colonic adenomatous polyps. INTERVENTION: Low-fat dairy products containing up to 1200 mg/d of calcium. Subjects were randomized to 4 strata by diet (control vs higher calcium) and age (<60 vs > or = 60 years). MAIN OUTCOME MEASURES: Changes in total colonic epithelial cells and number and position of thymidine-labeled epithelial cells and changes in the ratio of sulfomucins (predominantly secreted by distal colorectal epithelial cells) to sialomucins and expression of cytokeratin AE1, 2 markers of colonic cell differentiation. RESULTS: During 6 and 12 months of treatment, reduction of colonic epithelial cell proliferative activity (P<.05), reduction in size of the proliferative compartment (P<.05), and restoration of acidic mucin (P<.02), cytokeratin AE1 distribution (P<.05), and nuclear size (P<.05) toward that of normal cells occurred. Control subjects showed no differences from baseline proliferative values at 6 and 12 months (P>.05). CONCLUSION: Increasing the daily intake of calcium by up to 1200 mg via low-fat dairy food in subjects at risk for colonic neoplasia reduces proliferative activity of colonic epithelial cells and restores markers of normal cellular differentiation.

Adenomatous Polyposis Coli↗
PubMed1978

Histogenesis of symmetrical 1,2-dimethylhydrazine-induced neoplasms of the colon in the mouse.

CF-1 female adult mice were given weekly sc injections of 20 mg symmetrical 1,2-dimethylhydrazine (DMH)-2HCl/kg body weight and killed at various intervals after commencement of the injection. [3H]thymidine (TdR) was given before the animals were killed. The histogenesis of colon neoplasms was investigated by means of autoradiographs prepared from sections of Epon-embedded descending colon, which were stained with periodic acid-Schiff reaction and iron hematoxylin. By 9 weeks after initiation of DMH treatment, the distal 5 cm of the colon became enlarged, the mucosa thickened, and the crypts were elongated and hyperplastic. In the hyperplastic crypts, the number of proliferating cells increased, but the distribution of these cells followed a previously discussed slow cut-off model of Cairnie et al. as for the normal crypts. Differentiation and transformation of epithelial cells occurred, but somewhat aberrantly. Hyperplasia of the crypts occurred diffusely, but neoplastic lesions that began to appear by 9 weeks after the intiial treatment were isolated. An isolated crypt from which a neoplasm developed was first repopulated by what appeared to be altered, undifferentiated "stem" cells. These cells did not differentiate, continued to divide, and eventually upon migration accumulated in the upper part of the crypts, where an earliest identifiable neoplastic lesion was observed. Once such a lesion was formed, it expanded in various directions, depending on the local environments, and formed a polypoid or discoid lesion. The biologic behavior of the neoplasm seemed to be determined by the downward progression of its leading edge. When it penetrated the muscularis mucosae, the neoplasm became highly invasive. In the murine model, the invasive adenocarcinomas were observed by 26 weeks after commencement of DMH treatment.

Adenocarcinoma↗
PubMedDate not supplied

[Computed tomographic colonography: applications, advantages and disadvantages].

INTRODUCTION: Complete preoperative study of the colon is required in the management of colorectal cancer, due to the frequent association of primary colonic neoplasms with colonic adenomas (28%) and/or synchronous carcinomas (5%) of the colon. We present a series of patients who underwent computed tomographic colonography, the indications for this procedure, and the results. PATIENTS AND METHODS: We performed a descriptive prospective study. Between May 2003 and August 2004, 50 computed tomographic colonographies were performed in 50 patients with suspected stenosing colorectal cancer and incomplete conventional colonoscopy. RESULTS: Fifty computed tomographic colonographies were performed. The findings were as follows: three were normal (6%), and in the remainder, one was a false positive for a suspected neoplastic pelvic mass (3.125%) and two were false positives (11.7%) for colonic polyps. Fifty percent of the findings (n = 32) were related to peritoneal metastases and colonic neoplasms. There were 12 technical complications [lack of cleaning of the colon (5), lack of distension (2), little air insufflation (5)]. Patient complications included vegetative manifestations in one (vomiting) and rectal bleeding in another. The overall complication rate was 27.4% (23.4% corresponded to technical complications and the remaining 4% were patient-related). There was no mortality related to the procedure. CONCLUSION: Because computed tomographic colonography is safe, effective and well tolerated by the patient, it should be considered as a technical alternative in the study of stenosing neoplasms of the proximal colon with incomplete colonoscopy. In addition, it allows other associated findings, both intra- and extracolonic, to be obtained and improves the diagnostic and therapeutic management of the patient.

Adenocarcinoma↗
PubMed1984

Effect of BCG immunotherapy on N-nitroso-N-methylurea-induced carcinogenesis of guinea pig colon.

A total of 480 guinea pigs each received twice weekly intrarectal instillations of 1 mg N-nitroso-N-methylurea (NMU) during 14-35 weeks (total dose NMU, 28-70 mg) to induce colon neoplasms. At 24, 28, or 35 weeks after the start of NMU instillation, the distal colon was exposed by a ventral laparotomy and suspected neoplastic lesions were treated by one of four methods: A, intratumoral instillation of an emulsion of killed BCG cell walls attached to oil droplets; B, intratumoral instillation of a control emulsion of killed BCG cell walls in an aqueous phase rather than lipid phase; C, surgical excision of the colon lesion with formation of a ventral diverting colostomy; or D, sham operation (no treatment). All guinea pigs were allowed to recover from surgery and were then observed for a period of 1 year for the study of the effects of these treatments on NMU-induced colon neoplasms. Colon neoplasms were produced in 76% of all sham-operated control guinea pigs, and the frequency of such neoplasms was dependent on the total dose of NMU. Most neoplasms were adenocarcinomas with invasion of the bowel wall but only approximately 5% of them metastasized. Treatment with BCG failed to alter the course of NMU-induced colon carcinogenesis, as determined by the frequency of colon neoplasia, the number, the gross, or microscopic characteristics of colon neoplasms, or the rate of survival.

Animals↗